Changes in the functional properties of casein conjugates prepared by Maillard reaction with pectin or arabinogalactan.

The aim of this study was to prepare conjugates of casein (CA) with pectin (CP) or arabinogalactan (AG) by the Maillard reaction (wet-heating) and to investigate the effects of CP or AG on the structural and functional properties of casein. The results indicated that the highest grafting degree of CA with CP or AG was observed at 90 °C for 1.5 h or 1 h, respectively. Secondary structure showed that grafting with CP or AG reduced the α-helix level and increased the random coil level of CA. Glycosylation treatment of CA-CP and CA-AG exhibited lower surface hydrophobicity and higher absolute ζ-potential values, further significantly improving the functional properties of CA (e.g., solubility, foaming property, emulsifying property, thermal stability, and antioxidant activity). Accordingly, our results indicated that it is feasible for CP or AG to improve the functional properties of CA by the Maillard reaction.

W/O/W emulsions stabilized with whey protein concentrate and pectin: Effects on storage, pasteurization, and gastrointestinal viability of Lacticaseibacillus rhamnosus.

Probiotics have demonstrated various bioactive functions but poor storage and application stability, and encapsulation a promising method of increasing its viability. In this study, whey protein concentrate (WPC) and pectin (PEC) formed non-covalent complexes through electrostatic interaction at pH 3.0. The formed WPC-PEC complexes showed superior particle size, absolute potential, emulsification properties, and structural changes when PEC concentration was >0.8 % (w/v). This made them appropriate as a hydrophilic emulsifier to stabilize W/O/W emulsions. Then, Lacticaseibacillus rhamnosus, one representative of probiotics, was encapsulated in the internal aqueous phase of W/O/W emulsions. We obtained higher encapsulation efficiency (78.49 %) and smaller D4,3 (9.72 µm) with 0.8 % (w/v) PEC concentration. Encapsulation of Lacticaseibacillus rhamnosus in W/O/W emulsions improved its viability under harsh conditions, including 28 days storage at 4 °C, simulated pasteurization, and simulated gastrointestinal digestion. W/O/W emulsions stabilized by WPC-PEC non-covalent complexes further improved the survival of Lacticaseibacillus rhamnosus against various adverse conditions as compared to WPC. These findings suggest that the studied W/O/W emulsions systems have the potential to deliver probiotics in food substrates to enhance their viability during production processing, storage transportation, and digestion.

Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin pathway modulation.

Studies demonstrated that Ginkgo biloba extract (GBE) played a cardioprotective role in diabetic conditions. Impaired autophagy is one of the mechanisms underlying diabetic cardiomyopathy (DCM). The effect of GBE on autophagy has been observed in several diseases; however, whether GBE can ameliorate DCM by regulating autophagy remains unclear. Here, we investigated the effect of GBE on DCM and the potential mechanisms regarding autophagy using a streptozotocin (STZ)-induced diabetic rat model and a high-glucose (HG)-stimulated H9C2 cell model. We demonstrated that GBE attenuated metabolic disturbances, improved cardiac function, and reduced myocardial pathological changes in diabetic rats. Impaired autophagy as well as dysregulation of the adenosine monophosphate-activated protein kinase/ mammalian target of the rapamycin (AMPK/mTOR) signaling pathway were observed in diabetic hearts, as evidenced by the reduced conversion of LC3B-I to LC3B-II along with excessive p62 accumulation, decreased AMPK phosphorylation, and increased mTOR phosphorylation, which could be reversed by GBE treatment. In vitro, GBE reduced the apoptosis induced by HG in H9C2 cells by activating AMPK and inhibiting mTOR to restore autophagy. However, this effect was inhibited by the AMPK inhibitor Compound C. In conclusion, the ameliorative effect of GBE on DCM might be dependent on the restoration of autophagy through modulation of the AMPK/mTOR pathway.

Aristolochic acid mutational signature defines the low-risk subtype in upper tract urothelial carcinoma.

Rationale: Dietary exposure to aristolochic acids and similar compounds (collectively, AA) is a significant risk factor for nephropathy and subsequent upper tract urothelial carcinoma (UTUC). East Asian populations, who have a high prevalence of UTUC, have an unusual genome-wide AA-induced mutational pattern (COSMIC signature 22). Integrating mutational signature analysis with clinicopathological information may demonstrate great potential for risk ranking this UTUC subtype. Methods: We performed whole-genome sequencing (WGS) on 90 UTUC Chinese patients to extract mutational signatures. Genome sequencing data for urinary cell-free DNA from 26 UTUC patients were utilized to noninvasively identify the mutational signatures. Genome sequencing for primary tumors on 8 out of 26 patients was also performed. Metastasis-free survival (MFS) and cancer-specific survival (CSS) were measured using Kaplan-Meier methods. Results: Data analysis showed that a substantial proportion of patients harbored the AA mutational signature and were associated with AA-containing herbal drug intake, female gender, poor renal function, and multifocality. Field cancerization was found to partially contribute to multifocality. Nevertheless, AA Sig subtype UTUC patients exhibited favorable outcomes of CSS and MFS compared to the No-AA Sig subtype. Additionally, AA Sig subtype patients showed a higher tumor mutation burden, higher numbers of predicted neoantigens, and infiltrating lymphocytes, suggesting the potential for immunotherapy. We also confirmed the AA signature in AA-treated human renal tubular HK-2 cells. Notably, the AA subtype could be ascertained using a clinically applicable sequencing strategy (low coverage) in both primary tumors and urinary cell-free DNA as a basis for therapy selection. Conclusion: The AA mutational signature as a screening tool defines low-risk UTUC with therapeutic relevance. The AA mutational signature, as a molecular prognostic marker using either ureteroscopy and/or urinary cell-free DNA, is especially useful for diagnostic uncertainty when kidney-sparing treatment and/or immune checkpoint inhibitor therapy were considered.

Cordycepin ameliorates cardiac hypertrophy via activating the AMPKα pathway.

Increase of myocardial oxidative stress is closely related to the occurrence and development of cardiac hypertrophy. Cordycepin, also known as 3'-deoxyadenosine, is a natural bioactive substance extracted from Cordyceps militaris (which is widely cultivated for commercial use in functional foods and medicine). Since cordycepin suppresses oxidative stress both in vitro and in vivo, we hypothesized that cordycepin would inhibit cardiac hypertrophy by blocking oxidative stress-dependent related signalling. In our study, a mouse model of cardiac hypertrophy was induced by aortic banding (AB) surgery. Mice were intraperitoneally injected with cordycepin (20 mg/kg/d) or the same volume of vehicle 3 days after-surgery for 4 weeks. Our data demonstrated that cordycepin prevented cardiac hypertrophy induced by AB, as assessed by haemodynamic parameters analysis and echocardiographic, histological and molecular analyses. Oxidative stress was estimated by detecting superoxide generation, superoxide dismutase (SOD) activity and malondialdehyde levels, and by detecting the protein levels of gp91phox and SOD. Mechanistically, we found that cordycepin activated activated protein kinase α (AMPKα) signalling and attenuated oxidative stress both in vivo in cordycepin-treated mice and in vitro in cordycepin treated cardiomyocytes. Taken together, the results suggest that cordycepin protects against post-AB cardiac hypertrophy through activation of the AMPKα pathway, which subsequently attenuates oxidative stress.

High Incidence of Incidental Prostate Cancer in Transurethral Resection of Prostate Specimens in China. The Value of Pathologic Review.

OBJECTIVE: To identify the incidence and clinicopathologic features of prostate cancer incidentally detected in patients undergoing transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH), and to estimate the clinical value of pathologic review of all TURP specimens. STUDY DESIGN: A pathologic review was performed on all TURP specimens for each patient from May 1, 2004, to June 30, 2014, in our institute. A total of 1,024 men (ages 46-98) were identified by pathology specimen. Those with a known diagnosis of prostate cancer prior to TURP (n = 16) were excluded from the analysis. The tumor volume, Gleason score, pathologic stage, serum prostate-specific antigen (PSA) level, and follow-up data were evaluated for those who were found to have prostate cancer. RESULTS: A total of 87 (8.6%) patients (ages 50-88) were found to have prostate cancer. Significant prostate cancer was found in 25 patients. From May 1, 2004, to May 31, 2009, 30 (6.1%) patients (ages 57-83) were found to have prostate cancer. From June 1, 2009, to June 30, 2014, 57 (11.0%) patients (ages 50-88) were found to have prostate cancer. CONCLUSION: Our series demonstrates that 8.6% of patients were found to have prostate cancer and that the incidence was increasing in recent years. Even in some patients with T1a disease, the tumors were significant. The pathologic review of TURP specimens is valuable in China.

Combining Bone Marrow Stromal Cells with Green Tea Polyphenols Attenuates the Blood-Spinal Cord Barrier Permeability in Rats with Compression Spinal Cord Injury.

This study was performed to investigate the effect of bone marrow stromal cells (BMSCs) combined with green tea polyphenols (GTPs) on the blood-spinal cord barrier (BSCB) permeability after spinal cord injury (SCI) in the rat model. In the model of SCI rats, we found that the water content and the BSCB permeability were decreased by BMSCs and GTPs treatment, and their combination had a synergistic effect. Further, the motor function of rats was also greatly improved by BMSCs and GTPs administration. After treated by the combination of BMSCs and GTPs, SCI rats showed the up-regulated expression of tight junction (TJ) associated proteins claudin-5, occludin and ZO-1 by Western blot, which was more remarkable than that in the single treatment. The increased expression levels of claudin-5, occludin, and ZO-1 were the most obvious in the spinal cord microvessels using immunohistochemistry assay. This led to the conclusion that the combination of BMSCs and GTPs could decrease the BSCB permeability by up-regulating protein expression levels of claudin-5, occludin, and ZO-1. In addition, after BMSCs and GTPs administration, the results of Western blot and enzyme-linked immunosorbent assay (ELISA) revealed a significant decrease in protein expression level and the activation of nuclear factor-кB (NF-кB) p65. Our results indicated that combination of BMSCs and GTPs could improve motor function after SCI, which might be correlated with improvements in BSCB integrity, and that NF-кB might be involved in the modulating process.

Erastin sensitizes glioblastoma cells to temozolomide by restraining xCT and cystathionine-γ-lyase function.

Glioblastoma multiforme (GBM) is one of the most common encephalic malignant tumors. Due to a high recurrence rate and a lack of effective treatments, the average survival rate remains low. Temozolomide (TMZ), a class of alkylating agent, is widely used as a first-line therapeutic drug during the adjuvant treatment for GBM patients. However, most patients exhibit a palpable resistance to TMZ treatment. Additionally, the underlying mechanism remains to be clarified. In this study, glutathione (GSH) and reactive oxygen species (ROS) levels were found to be closely associated with the sensitivity of GBM cells to TMZ. We also found that TMZ markedly induced xCT, the subunit of glutamate/cystine transporter system xc- expression, which together with the GSH synthesis was increased while the TMZ-inducible ROS level was decreased in GBM cells. In addition, the cystathionine γ-lyase (CTH) acivity, a key enzyme in the transsulfuration pathway was enhanced by TMZ, which insured a cysteine supply and GSH synthesis in a compensatory manner when xCT was blocked. Thus, the individual inhibition of xCT by siRNA and a pharmacological inhibitor (sulfasalazine) only partially inhibited GSH synthesis and moderately enhanced the GBM cell sensitivity to TMZ. However, the TMZ­induced cytotoxicity was markedly increased along with a marked decrease in GSH levels as result of co-treatment with erastin, which inhibited cysteine uptake from xCT transporter and suppressed CTH activity, leading to impaired transformation from methionine to cysteine. In conclusion, to GBM therapy with a drug combination of TMZ and erastin may be beneficial.