MATT-DDI: Predicting multi-type drug-drug interactions via heterogeneous attention mechanisms.

The joint use of multiple drugs can result in adverse drug-drug interactions (DDIs) and side effects that harm the body. Accurate identification of DDIs is crucial for avoiding accidental drug side effects and understanding potential mechanisms underlying DDIs. Several computational methods have been proposed for multi-type DDI prediction, but most rely on the similarity profiles of drugs as the drug feature vectors, which may result in information leakage and overoptimistic performance when predicting interactions between new drugs. To address this issue, we propose a novel method, MATT-DDI, for predicting multi-type DDIs based on the original feature vectors of drugs and multiple attention mechanisms. MATT-DDI consists of three main modules: the top k most similar drug pair selection module, heterogeneous attention mechanism module and multi­type DDI prediction module. Firstly, based on the feature vector of the input drug pair (IDP), k drug pairs that are most similar to the input drug pair from the training dataset are selected according to cosine similarity between drug pairs. Then, the vectors of k selected drug pairs are averaged to obtain a new drug pair (NDP). Next, IDP and NDP are fed into heterogeneous attention modules, including scaled dot product attention and bilinear attention, to extract latent feature vectors. Finally, these latent feature vectors are taken as input of the classification module to predict DDI types. We evaluated MATT-DDI on three different tasks. The experimental results show that MATT-DDI provides better or comparable performance compared to several state-of-the-art methods, and its feasibility is supported by case studies. MATT-DDI is a robust model for predicting multi-type DDIs with excellent performance and no information leakage.

Antihyperuricemic activity and inhibition mechanism of xanthine oxidase inhibitory peptides derived from whey protein by virtual screening.

Xanthine oxidase (XO), a rate-limiting enzyme in uric acid production, is the pivotal therapeutic target for gout and hyperuricemia. In this study, 57 peptides from α-lactalbumin and ß-lactoglobulin were obtained via virtual enzymatic hydrolysis, and 10 XO inhibitory peptides were virtually screened using molecular docking. Then toxicity, allergenicity, solubility, and isoelectric point of the obtained 10 novel peptides were evaluated by in silico tools. The XO activity of these synthetic peptides was tested using an in vitro assay by high-performance liquid chromatography. Their inhibitory mechanism was further explored by molecular docking. The results showed that 4 peptides GL, PM, AL, and AM exhibited higher inhibitory activity, and their half maximal inhibitory concentration in vitro was 10.20 ± 0.89, 23.82 ± 0.94, 34.49 ± 0.89, and 40.45 ± 0.92 mM, respectively. The peptides fitted well with XO through hydrogen bond, hydrophobic interaction, and van der Waals forces, and amino acid residues Glu802, Leu873, Arg880, and Pro1076 played an important role in this process. Overall, this study indicated 4 novel peptides GL, PM, AL, and AM from whey protein exhibited XO inhibitory activity, and they might be useful and safe XO inhibitors for hyperuricemia prevention and treatment.

Bovine milk osteopontin improved intestinal health of pregnant rats fed a high-fat diet through improving bile acid metabolism.

The main purpose of the current study was to investigate the ameliorative effects of bovine milk osteopontin (bmOPN) on the gut dysfunction of pregnant rats fed a high-fat diet (HFD). Bovine milk osteopontin was supplemented at a dose of 6 mg/kg body weight. Bovine milk osteopontin supplementation during pregnancy reduced colonic inflammation of HFD dams, and it also increased the colonic expression of ZO-1 and claudin-4 of HFD dams. Bovine milk osteopontin significantly enriched the relative abundance of Bacteroidetes, whereas it decreased Proteobacteria, Helicobacteraceae, and Desulfovibrionaceae in feces of HFD dams. The levels of isobutyric acid and pentanoic acid in the HFD + bmOPN group were higher than that of the HFD group. Functional predication analysis of microbial genomes revealed that bmOPN supplementation to HFD pregnancies changed 4 Kyoto Encyclopedia of Genes and Genomes pathways including bile acid biosynthesis. Further, bmOPN enriched hepatic taurochenodeoxycholic acid and tauroursodeoxycholic acid plus taurohyodeoxycholic acid in the gut of HFD maternal rats. Our findings suggested that bmOPN improved the gut health of HFD pregnant rats partially through modulating bile acid biosynthesis.

NeuroPpred-Fuse: an interpretable stacking model for prediction of neuropeptides by fusing sequence information and feature selection methods.

Neuropeptides acting as signaling molecules in the nervous system of various animals play crucial roles in a wide range of physiological functions and hormone regulation behaviors. Neuropeptides offer many opportunities for the discovery of new drugs and targets for the treatment of neurological diseases. In recent years, there have been several data-driven computational predictors of various types of bioactive peptides, but the relevant work about neuropeptides is little at present. In this work, we developed an interpretable stacking model, named NeuroPpred-Fuse, for the prediction of neuropeptides through fusing a variety of sequence-derived features and feature selection methods. Specifically, we used six types of sequence-derived features to encode the peptide sequences and then combined them. In the first layer, we ensembled three base classifiers and four feature selection algorithms, which select non-redundant important features complementarily. In the second layer, the output of the first layer was merged and fed into logistic regression (LR) classifier to train the model. Moreover, we analyzed the selected features and explained the feasibility of the selected features. Experimental results show that our model achieved 90.6% accuracy and 95.8% AUC on the independent test set, outperforming the state-of-the-art models. In addition, we exhibited the distribution of selected features by these tree models and compared the results on the training set to that on the test set. These results fully showed that our model has a certain generalization ability. Therefore, we expect that our model would provide important advances in the discovery of neuropeptides as new drugs for the treatment of neurological diseases.

Gut microbiota mediates the alleviative effect of polar lipids-enriched milk fat globule membrane on obesity-induced glucose metabolism disorders in peripheral tissues in rat dams.

BACKGROUND: Obesity during pregnancy and lactation not only increases the incidence of metabolic disorders and gestational diabetes in mothers, but also programs adiposity and related metabolic diseases in offspring. The aim of this study was to investigate the effects of milk polar lipids on gut microbiota and glucose metabolism in high-fat diet (HFD)-fed rat dams. METHODS: Sprague Dawley (SD) female rats were fed a HFD for 8 weeks to induce obesity, followed by HFD with or without oral administration of polar lipids-enriched milk fat globule membrane (MFGM-PL) at 400 mg/kg BW during pregnancy and lactation. At the end of lactation, fresh fecal samples of dams were collected, the gut microbiota was assessed, and the insulin-signaling protein expression in peripheral tissues (adipose tissue, liver and skeletal muscle) were measured. RESULTS: MFGM-PL supplementation attenuated body weight gain, ameliorated serum lipid profiles and improved insulin sensitivity in obese dams at the end of lactation. 16 S rDNA sequencing revealed that MFGM-PL increased the community richness and diversity of gut microbiota. The composition of gut microbiota was also changed after MFGM-PL supplementation as shown by an increase in the ratio of Bacteroidetes/Firmicutes and the relative abundance of Akkermansia, as well as a decrease in the relative abundance of Ruminococcaceae. The functional prediction of microbial communities by PICRUSt analysis showed that there were 7 KEGG pathways related to carbohydrate metabolism changed after MFGM-PL supplementation to HFD dams, including glycolysis/gluconeogenesis and insulin signaling pathway. Furthermore, MFGM-PL improved insulin signaling in the peripheral tissues including liver, adipose tissue and skeletal muscle. CONCLUSIONS: MFGM-PL supplementation during pregnancy and lactation improves the glucose metabolism disorders in HFD-induced obese dams, which may be linked to the regulation of gut microbiota induced by MFGM-PL.

Supplementation of milk polar lipids to obese dams improves neurodevelopment and cognitive function in male offspring.

Milk contains about 4% fat globules with its surface covered by polar lipids. Despite the abundant consumption of dairy products, the biological effects of dietary milk polar lipids on metabolic health have only been sparsely examined. Maternal obesity results in neurodevelopmental disorders and cognitive impairment in offspring. Considering the importance of maternal nutrition, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to dams during pregnancy and lactation on neurodevelopment and its long-term programming effects on offspring cognition were examined. Female Sprague-Dawley rats consumed 8-week control diet (CON) or high-fat diet (HFD) to induce obesity before mating. Then, female rats were fed CON or HFD with or without the supplementation of 400 mg/kg body weight MFGM-PL during pregnancy and lactation. The offspring were fed 11-week HFD after weaning. MFGM-PL supplementation to obese dams suppressed body weight gain and hyperinsulinemia in both dams and offspring. Offspring born to obese dams displayed delayed neurological reflexes development, impaired neurogenesis before weaning, and cognitive impairment in adulthood, which were recovered by maternal MFGM-PL supplementation. Insulin resistance and aberrant brain-derived neurotrophic factor signaling were induced in the hippocampus of neonatal and adult offspring due to maternal and progeny HFD, but recovered by maternal MFGM-PL administration. This study demonstrates that maternal MFGM-PL supplementation can promote neurodevelopment and exert long-term effects against HFD-induced cognitive impairment in offspring via alleviating hippocampal insulin resistance. Hence, MFGM-PL is a promising ingredient for exerting beneficial programming effects on the brain health of offspring.

Metabolism, absorption, and anti-cancer effects of sulforaphane: an update.

Cancer is one of the most devastating diseases, and recently, a variety of natural compounds with preventive effects on cancer developments have been reported. Sulforaphane (SFN) is a potent anti-cancer isothiocyanate originating from Brassica oleracea (broccoli). SFN, mainly metabolized via mercapturic acid pathway, has high bioavailability and absorption. The present reviews mainly discussed the metabolism and absorption of SFN and newly discovered mechanistic understanding recent years for SFN's anti-cancer effects including promoting autophagy, inducing epigenetic modifications, suppressing glycolysis and fat metabolism. Moreover, its inhibitory effects on cancer stem cells and synergetic effects with other anti-cancer agents are also reviewed along with the clinical trials in this realm.

Conditioned medium from the bone marrow mesenchymal stem cells modulates immune response via signal transduction and activator of transcription 6 signaling pathway in an allergic rhinitis mouse model.

BACKGROUND: Allergic rhinitis (AR) is a common immune disease of the nasal mucosa characterized with immunoglobulin E (IgE)-mediated allergic inflammation after exposure to allergens in susceptible population. Previous reports have demonstrated that the bone marrow mesenchymal stem cells (BMSCs) could reduce allergic inflammation. However, there is little knowledge about whether the culture supernatant of BMSCs (conditioned medium, CM) has similar anti- inflammatory potential in treating AR. OBJECTIVE: The study aimed to evaluate the immunoregulatory effects of conditioned medium derived from BMSCs (BMSC-CM) on allergic inflammation in an AR mouse model. MATERIAL AND METHODS: The AR murine model was induced by repeated sensitization and challenges with ovalbumin (OVA). Subsequently the allergic symptoms of AR mice, cytokine levels, the histopathological features of the nasal mucosa and T helper 1 (Th1) : T helper 2 (Th2) cells ratio were evaluated. RESULTS: Treatment with BMSC-CM was found as effective as BMSCs in reducing allergic symptoms and inhibiting eosinophilic infiltration in the nasal mucosa. After BMSC-CM or BMSCs administration, the OVA-specific IgE and interleukin 4 levels in serum decreased and interferon gamma level increased compared with AR mice treated with uncultured fresh medium. Flow cytometry analysis revealed a decrease in Th1:Th2 cells ratio after OVA-sensitization and the ratio was reversed by BMSC-CM and BMSCs treatments. Furthermore, the data revealed that BMSC-CM suppressed the production of signal transduction and activator of transcription 6 (STAT6) at messenger RNA and protein levels in the nasal mucosa. CONCLUSION: BMSC-CM could ameliorate allergic inflammation and regulate the balance of Th cells, and the underlying mechanism was closely related to STAT6 signaling pathway. The immunoregulatory effects of BMSCs could be achieved through paracrine function, and nasal dripping of BMSC-CM might be a novel approach for the treatment of AR.

Supplementation of polar lipids-enriched milk fat globule membrane in high-fat diet-fed rats during pregnancy and lactation promotes brown/beige adipocyte development and prevents obesity in male offspring.

Promoting brown adipose tissue (BAT) function or browning of white adipose tissue (WAT) provides a defense against obesity. The aim of the study was to investigate whether maternal polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to high-fat diet (HFD) rats during pregnancy and lactation could promote brown/beige adipogenesis and protect against HFD-induced adiposity in offspring. Female SD rats were fed a HFD for 8 weeks to induce obesity and, then, fed a HFD during pregnancy and lactation with or without MFGM-PL. Male offspring were weaned at postnatal Day 21 and then fed a HFD for 9 weeks. MFGM-PL treatment to HFD dams decreased the body weight gain and WAT mass as well as lowered the serum levels of insulin and triglycerides in male offspring at weaning. MFGM-PL+HFD offspring showed promoted thermogenic function in BAT and inguinal WAT through the upregulation of UCP1 and other thermogenic genes. In adulthood, maternal MFGM-PL supplementation reduced adiposity and increased oxygen consumption, respiratory exchange ratio, and heat production in male offspring. The enhancement of energy expenditure was correlated with elevated BAT activity and inguinal WAT thermogenic program. In conclusion, maternal MFGM-PL treatment activated thermogenesis in offspring, which exerted long-term beneficial effects against HFD-induced obesity in later life.

Noninvasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells.

PURPOSE: Prostate specific antigen testing results in unnecessary biopsy and over diagnosis with consequent overtreatment. Tissue biopsy is an invasive procedure associated with significant morbidity. More accurate noninvasive or minimally invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly to predict clinically significant prostate cancer in prebiopsy cases. MATERIALS AND METHODS: We enrolled 155 treatment naïve patients with prostate cancer and 98 before biopsy for circulating tumor cell enumeration. RNA was extracted from circulating tumor cells of 184 patients for gene expression analysis. The Kruskal-Wallis and Spearman rank tests, multivariate logistic regression and the random forest method were applied to assess the association of circulating tumor cells with aggressive prostate cancer. RESULTS: Of patients with localized prostate cancer 54% were scored as having positive circulating tumor cells, which was associated with a higher Gleason score (p=0.0003), risk group (p <0.0001) and clinically significant prostate cancer (p <0.0001). In the prebiopsy group a positive circulating tumor cell score combined with prostate specific antigen predicted clinically significant prostate cancer (AUC 0.869). A 12-gene panel prognostic for clinically significant prostate cancer was also identified. When combining the prostate specific antigen level, the circulating tumor cell score and the 12-gene panel, the AUC of clinically significant prostate cancer prediction was 0.927. Adding those data to cases with available multiparametric magnetic resonance imaging data significantly increased prediction accuracy (AUC 0.936 vs 0.629). CONCLUSIONS: Circulating tumor cell analysis has the potential to significantly improve patient stratification by prostate specific antigen and/or multiparametric magnetic resonance imaging for biopsy and treatment.

Prevention of breast cancer by dietary polyphenols-role of cancer stem cells.

Breast cancer is a common malignancy with poor prognosis. Cancer cells are heterogeneous and cancer stem cells (CSCs) are primarily responsible for tumor relapse, treatment-resistance and metastasis, so for breast cancer stem cells (BCSCs). Diets are known to be associated with carcinogenesis. Food-derived polyphenols are able to attenuate the formation and virulence of BCSCs, implying that these compounds and their analogs might be promising agents for preventing breast cancer. In the present review, we summarized the origin and surface markers of BCSCs and possible mechanisms responsible for the inhibitory effects of polyphenols on BCSCs. The suppressive effects of common dietary polyphenols against BCSCs, such as curcumin, epigallocatechin gallate (EGCG) and related polyphenolic compounds were further discussed.

Dipeptidyl Peptidase-IV Inhibitory Activity and Related Molecular Mechanism of Bovine α-Lactalbumin-Derived Peptides.

Identifying DPP-IV inhibitory peptides from dietary protein has attracted increased attention. In the present study, bovine α-lactalbumin hydrolysates were generated by alcalase for various hydrolysis times, and DPP-IV inhibitory activity of these hydrolysates was determined. The 4 h hydrolysates displayed the most potent DPP-IV inhibitory activity, with DPP-IV inhibition rate of 82.30 ± 1.39% at concentration of 1.0 mg/mL. DPP-IV inhibitory peptides were isolated from the 4 h-hydrolysates with gel filtration chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC). Using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS), two DPP-IV inhibitory peptides were identified, and their amino acid sequences were Glu-Leu-Lys-Asp-Leu-Lys-Gly-Tyr (ELKDLKGY) and Ile-Leu-Asp-Lys-Val-Gly-Ile-Asn-Tyr (ILDKVGINY), respectively. Furthermore, molecular docking analysis showed that peptides ELKDLKGY and ILDKVGINY could form hydrogen bonds, pi-cation interactions, and salt bridges with DPP-IV. These findings indicated that bovine α-lactalbumin may be a potential source of natural DPP-IV inhibitor.

Pyrazinamide resistance and mutations L19R, R140H, and E144K in Pyrazinamidase of Mycobacterium tuberculosis.

Pyrazinamide (PZA) is an important component of first-line antituberculosis drugs activated by Mycobacterium tuberculosis pyrazinamidase (PZase) into its active form pyrazinoic acid. Mutations in the pncA gene have been recognized as the major cause of PZA resistance. We detected some novel mutations, Leucine19Arginine (L19R), Arginine140Histidine (R140H), and Glutamic acid144 Lysine (E144K), in the pncA gene of PZA-resistant isolates in our wet lab PZA drug susceptibility testing and sequencing. As the molecular mechanism of resistance of these variants has not been reported earlier, we have performed multiple analyses to unveil different mechanisms of resistance because of PZase mutations L19R, R140H, and E144K. The mutants and native PZase structures were subjected to comprehensive computational molecular dynamics (MD) simulations at 100 nanoseconds in apo and drug-bound form. Mutants and native PZase binding pocket were compared to observe the consequence of mutations on the binding pocket size. Hydrogen bonding, Gibbs free energy, and natural ligand Fe +2 effect were also analyzed between native and mutants. A significant variation between native and mutant PZase structure activity was observed. The native PZase protein docking score was found to be the maximum, showing strong binding affinity in comparison with mutants. MD simulations explored the effect of the variants on the biological function of PZase. Hydrogen bonding, metal ion Fe +2 deviation, and fluctuation also seemed to be affected because of the mutations L19R, R140H, and E144K. The variants L19R, R140H, and E144K play a significant role in PZA resistance, altering the overall activity of native PZase, including metal ion Fe +2 displacement and free energy. This study offers valuable evidence for better management of drug-resistant tuberculosis.

DNA replication-dependent induction of gene proximity by androgen.

The male hormone androgen, working through the androgen receptor (AR), plays a major role in physiological process and disease development. Previous studies of AR mainly focus on its transcriptional activity. Here, we found that androgen-induced TMPRSS2 and ERG gene proximity is mediated by AR control of DNA replication rather than gene transcription. We demonstrate that, in both AR transactivation-positive and -negative prostate cells, androgen regulates DNA replication and androgen-induced gene proximity relies on both DNA replication-licensing and actual DNA replication activity. Androgen stimulation advances DNA replication timing of certain genomic regions, which may potentially increase gene proximity through sharing the same replication factory at a similar time. Therefore, we have revealed novel mechanisms of AR biological function, which will stimulate new research directions.

TMPRSS2:ERG fusion gene occurs less frequently in Chinese patients with prostate cancer.

Prostate cancer is the commonest male malignancy in the Western world, but its morbidity is much lower in China. The principal aim of this study was to evaluate the frequency of TMPRSS2:ERG fusion in Chinese prostate cancer patients using immunohistochemistry and reverse transcription polymerase chain (RT-PCR). In addition, we compared the ERG protein expression with TMPRSS2:ERG fusion gene. The relationship between ERG expression and clinicopathologic features was also examined. Samples from patients who underwent radical prostatectomies in Changhai Hospital (Shanghai, China) were collected and stored in ethically approved tissue banks. One hundred seventy-four prostate cancer tissue samples and 10 normal tissues were marked on standard hematoxylin-eosin (HE) sections, punched out of the paraffin blocks and inserted into a recipient block using tissue arrayer instruments. Immunohistochemistry and RT-PCR were employed to detect TMPRSS2:ERG fusion gene. ERG was highly expressed in the nuclei of endothelial cells of vessels and weak cytoplasmic staining was occasionally observed. ERG positive staining was present in 14.9 % (26/174) of the tumor samples in microarray. All benign prostate samples were found to be negative. RT-PCR results revealed that 11.1 % (15/135) were TMPRSS2:ERG fusion positive. Altogether, there was a good agreement of ERG immunostaining with the presence of TMPRSS2:ERG. However, no correlation was observed between ERG expression and age, Gleason score, stage, surgical margin, and seminal vesicle involvement in Chinese patients. In the present study, we identified a high correlation between ERG expression and ERG TMPRSS2:ERG, with 100 % sensitivity and 88.9 % specificity. The expression level of ERG was unrelated to the age, Gleason score, stage, surgical margin, and seminal vesicle involvement. Therefore, the association between ERG expression and prostate cancer based on Chinese population should be further investigated in the future.

Comparative Analysis of Volatile Composition in Chinese Truffles via GC × GC/HR-TOF/MS and Electronic Nose.

To compare the volatile compounds of Chinese black truffle and white truffle from Yunnan province, this study presents the application of a direct solvent extraction/solvent-assisted flavor evaporation (DSE-SAFE) coupled with a comprehensive two-dimensional gas chromatography (GC × GC) high resolution time-of-flight mass spectrometry (HR-TOF/MS) and an electronic nose. Both of the analytical methods could distinguish the aroma profile of the two samples. In terms of the overall profile of truffle samples in this research, more kinds of acids were detected via the method of DSE-SAFE. Besides, compounds identified in black truffle (BT), but not in white truffle (WT), or vice versa, and those detected in both samples at different levels were considered to play an important role in differentiating the two samples. According to the analysis of electronic nose, the two samples could be separated, as well.

Identification of ZDHHC14 as a novel human tumour suppressor gene.

Genomic changes affecting tumour suppressor genes are fundamental to cancer. We applied SNP array analysis to a panel of testicular germ cell tumours to search for novel tumour suppressor genes and identified a frequent small deletion on 6q25.3 affecting just one gene, ZDHHC14. The expression of ZDHHC14, a putative protein palmitoyltransferase with unknown cellular function, was decreased at both RNA and protein levels in testicular germ cell tumours. ZDHHC14 expression was also significantly decreased in a panel of prostate cancer samples and cell lines. In addition to our findings of genetic and protein expression changes in clinical samples, inducible overexpression of ZDHHC14 led to reduced cell viability and increased apoptosis through the classic caspase-dependent apoptotic pathway and heterozygous knockout of ZDHHC14 increased [CORRECTED] cell colony formation ability. Finally, we confirmed our in vitro findings of the tumour suppressor role of ZDHHC14 in a mouse xenograft model, showing that overexpression of ZDHHC14 inhibits tumourigenesis. Thus, we have identified a novel tumour suppressor gene that is commonly down-regulated in testicular germ cell tumours and prostate cancer, as well as given insight into the cellular functional role of ZDHHC14, a potential protein palmitoyltransferase that may play a key protective role in cancer.

Anti-anaemia efficacy of ß-lactoglobulin hydrolysate-iron complex on iron-deficient anaemic rats.

PURPOSE: The effects of orally administered ß-lactoglobulin hydrolysate-iron complex (ß-LGH-Fe) on haematological and biochemical parameters in anaemic rats were evaluated. Female weaning Sprague-Dawley rats were fed with iron-deficient diet to induce iron deficiency anaemia. After 6 weeks, the obtained anaemic rats were divided into five groups: iron deficiency control group (iron-deficient diet without ß-LGH-Fe complex supplementation, IDC); three groups supplemented with different dosages of ß-LGH-Fe complex (0.5 mg Fe/kg BW, iron-deficient diet with low ß-LGH-Fe, IDLFe; 2.0 mg Fe/kg BW, iron-deficient diet with medium ß-LGH-Fe, IDMF; 4.0 mg Fe/kg BW, iron-deficient diet with high ß-LGH-Fe, IDHFe); and ferrous sulphate-supplemented group at a dosage of 2.0 mg Fe/kg BW. RESULTS: ß-LGH-Fe complex could significantly improve hematocrit and haemoglobin decrease, and normalise the serum iron level, total iron-binding capacity and transferrin saturation of anaemic rats in a dose-dependent manner. Serum ferritin content and hepatic nonheme iron level were also increased. In addition, the antioxidant enzyme activities of superoxidase dismutase, catalase and glutathione peroxidase in both plasma and liver homogenate were improved. The production of malondialdehyde and pro-inflammatory cytokines (TNF-α and IL-6) decreased. CONCLUSIONS: It suggests that ß-LGH-Fe complex can ameliorate iron deficiency anaemia, which might make it a potential ingredient with anti-anaemia activity.

The enhanced affinity of moderately hydrolyzed whey protein to EGCG promotes the isoelectric separation and unlocks the protective effects on polyphenols.

The instability and discoloration of (-)-epigallocatechin-3-gallate (EGCG) constrain its application in functional dairy products. Concurrently, challenges persist in the separation and utilization of whey in the dairy industry. By harnessing the interactions between polyphenols and whey proteins or their hydrolysates, this study proposed a method that involved limited enzymatic hydrolysis followed by the addition of EGCG and pH adjustment around the isoelectric point to obtain whey protein hydrolysates (WPH)-EGCG. Over 92 % of protein-EGCG complexes recovered from whey while ensuring the preservation of α-lactalbumin. The combination between EGCG and WPH depended on hydrogen bonding and hydrophobic interactions, significantly enhanced the thermal stability and storage stability of EGCG. Besides, the intestinal phase retention rate of EGCG in WPH-EGCG complex was significantly increased by 23.67 % compared to free EGCG. This work represents an exploratory endeavor in the improvement of EGCG stability and expanding the utilization approaches of whey.