Purification and identification of xanthine oxidase inhibitory peptides from enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein.

The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report on milk protein hydrolysates' XO inhibitory activity, with the mechanism of their interaction remaining elusive. Here, different commercial enzymes were used to hydrolyze α-lactalbumin and bovine colostrum casein. The two proteins hydrolyzed by alkaline protease exhibited the most potent XO inhibitory activity (bovine casein: IC50 = 0.13 mg mL-1; α-lactalbumin: IC50 = 0.28 mg mL-1). Eight potential XO inhibitory peptides including VYPFPGPI, GPVRGPFPIIV, VYPFPGPIPN, VYPFPGPIHN, QLKRFSFRSFIWR, LVYPFPGPIHN, AVFPSIVGR, and GFININSLR (IC50 of 4.67-8.02 mM) were purified and identified from alkaline protease hydrolysates by using gel filtration, LC-MS/MS and PeptideRanker. The most important role of inhibiting activity of peptides is linked to hydrophobic interactions and hydrogen bonding based on the results of molecular docking and molecular dynamics simulation. The enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein could be a competitive candidates for hyperuricemia-resisting functional food.

Chinese medicinal herbs for reducing endocrine therapy-induced side effects in patients with hormone receptor-positive breast cancer: a systematic review and meta-analysis.

CONTEXT: Chinese medicinal herbs (CMH) have been considered a potentially efficacious approach for patients with breast cancer that experience adverse effects from endocrine treatment. OBJECTIVE: To investigate the impact of CMH on endocrine therapy-induced side effects in patients with hormone receptor-positive (HR+) breast cancer. METHODS: Ten databases (e.g., PubMed, Web of Science, Cochrane Library, China National Knowledge Information Database and other databases) were searched up to 20 May 2022. The search terms included Chinese herb, breast cancer, endocrine therapy, clinical trial and their mesh terms. The study selection and data extraction were performed by two independent reviewers. The risk of bias was evaluated using the Cochrane risk of bias method. RESULTS: A total of 31 studies with 2288 patients were included. There were significant improvements in bone mineral density (BMD) [lumbar BMD (MD 0.08, 95% CI 0.07 to 0.09, p < 0.00001) and femoral neck BMD (MD 0.08, 95% CI 0.07 to 0.10, p < 0.00001)] and bone gal protein (BGP) (MD 0.24, 95% CI 0.17 to 0.31, p < 0.00001), with a significant reduction in triglycerides (MD -0.53, 95% CI -1.00 to -0.07, p < 0.05) and no effect on estradiol levels (MD 0.90, 95% CI -0.31 to 2.12, p = 0.15). CONCLUSIONS: CMH combined with complementary therapy can moderately reduce endocrine therapy-induced side effects, including bone loss and dyslipidemia in patients with HR + breast cancer, revealing the potential role of CMH in treating (HR+) breast cancer. More high-quality RCTs are warranted to further validate the effectiveness and safety of CMH.

Aqueous extracts of tree peony petals: renin and angiotensin I-converting enzyme inhibitory activities in different colours and flowering stages.

Tree peony (Paeonia suffruticosa Andr.) is an ornamental and medicinal plant from China. Previous studies have detected novel blood pressure-regulating substances in this species, which potentiate its value of utilization. To explore these substances, the aqueous extracts of 7 different colours of tree peony petals were assessed for inhibitory activity on renin and angiotensin-converting enzyme (ACE). The results showed that the activity of dark-coloured samples was significantly stronger than that of light-coloured ones. Furthermore, the inhibitory activity of the red tree peony petals 'Hong TaiYang' on renin and ACE indicated a downward trend from bud compaction to the full opening stage. The antioxidant activities of the aqueous extracts, on one side, and the correlations between phenolics and flavonoids functionalities and total contents, on the other, were also evaluated. In this regard, the extracts of different samples had ABTS free radical scavenging capacities of 17.28-210.41 mg TE per g DW, DPPH radical scavenging capacities of 35.45-150.78 mg TE per g DW, iron ion reduction capacities of 16.66-150.77 mg TE per g DW, and total phenolic content of 23.94-150.78 mg GAE per g DW. Correlation analysis revealed that the renin and ACE inhibitory activities, the DPPH and ABTS free radical scavenging capacities, and the iron reduction ability of different sample extracts were positively correlated with total phenolic contents (p < 0.01). Finally, the aqueous phenolic compounds in the sample extracts tended to show strong renin and ACE inhibitory activities and therefore exhibit a potential auxiliary blood pressure control prospect.

Covalent modification by phenolic extract improves the structural properties and antioxidant activities of the protein isolate from Cinnamomum camphora seed kernel.

In this study, protein isolate (PI) and purified phenolic extract (PPE) were prepared from Cinnamomum camphora seed kernel (CCSK). The effects of covalent modification of PI by PPE at different concentrations (1, 2, 3, 4 and 5%, w/w) were investigated with respect to structural properties and antioxidant activities of protein. Fifteen bioactive compounds in PPE were tentatively identified by UPLC-ESI-MSn. With the increase of PPE concentration, the turbidity, covalent binding rate, phenolic content and color intensity of the PI-PPE complexes were gradually increased. Fourier transform infrared spectroscopy and circular dichroism spectroscopy analysis showed that the secondary and tertiary structures of the complexes were changed and became greater order than PI. Furthermore, the complexes exhibited stronger thermal stability and antioxidant activities than those of PI. These results suggested that the protein-phenolic covalent complexes obtained from CCSK may have great potential to be used in food formulations as functional ingredients.

Design of long-wavelength emission carbon dots for hypochlorous detection and cellular imaging.

A facile strategy for the preparation of nitrogen and phosphorus co-doped carbon dots (N, P-CDs) with long-wavelength emission is attractively proposed in one-pot hydrothermal strategy. The resulting N, P-CDs hold exceptional optical features and display excitation wavelength-independent properties with the emission wavelength at 590 nm, which enable it with the satisfactory relative quantum yield (QY) of 15.6% in long-wavelength region. In addition, the proposed N, P-CDs demonstrates specific selectivity towards ClO- over other competitive reactive oxygen species and exhibits rapid fluorescence response time to ClO-. Moreover, the N, P-CDs exhibits low-cytotoxicity and excellent cell membrane permeability for recognizing ClO- in SMMC-7721 cells, which demonstrates their enormous potential in biological system.

Precision Molecular Diagnosis Defines Specific Therapy in Combined Immunodeficiency with Megaloblastic Anemia Secondary to MTHFD1 Deficiency.

BACKGROUND: Methylenetetrahydrofolate dehydrogenase (MTHFD1) deficiency has recently been reported to cause a folate-responsive syndrome displaying a phenotype that includes megaloblastic anemia and severe combined immunodeficiency. OBJECTIVE: To describe our investigative approach to the molecular diagnosis and evaluation of immune dysfunction in a family with MTHFD1 deficiency. METHODS: The methods used were exome sequencing and analysis of variants in genes involved in the folate metabolic pathway in a family with 2 affected siblings. Routine laboratory and research data were analyzed to gain an in-depth understanding of innate, humoral, and cell-mediated immune function before and after folinic acid supplementation. RESULTS: Interrogation of exome data for concordant variants between the siblings in the genes involved in folate metabolic pathway identified a heterozygous mutation in exon 3 of the MTHFD1 gene that was shared with their mother. In view of highly suggestive phenotype, we extended our bioinformatics interrogation for structural variants in the MTHFD1 gene by manual evaluation of the exome data for sequence depth coverage of all the exons. A deletion involving exon 13 that was shared with their father was identified. Routine laboratory data showed lymphopenia involving all subsets and poor response to vaccines. In vitro analysis of dendritic cell and lymphocyte function was comparable to that in healthy volunteers. Treatment with folinic acid led to immune reconstitution, enabling discontinuation of all prophylactic therapies. CONCLUSIONS: Exome sequencing demonstrated MTHFD1 deficiency as a novel cause of a combined immunodeficiency. Folinic acid was established as precision therapy to reverse the clinical and laboratory phenotype of this primary immunodeficiency.

Phosphorus and Nitrogen Dual-Doped Hollow Carbon Dot as a Nanocarrier for Doxorubicin Delivery and Biological Imaging.

Innovative phosphorus and nitrogen dual-doped hollow carbon dots (PNHCDs) have been fabricated for anticancer drug delivery and biological imaging. The functional groups of PNHCDs are introduced by simply mixing glucose, 1,2-ethylenediamine, and concentrated phosphoric acid. This is an automatic method without external heat treatment to rapidly produce large quantities of PNHCDs, which avoid high temperature, complicated operations, and long reaction times. The as-prepared PNHCDs possess small particle size, hollow structure, and abundant phosphate/hydroxyl/pyridinic/pyrrolic-like N groups, endowing PNHCDs with fluorescent properties, improving the accuracy of PNHCDs as an optical monitoring code both in vitro and in vivo. The investigation of PNHCDs as an anticancer drug nanocarrier for doxorubicin (DOX) indicates a better antitumor efficacy than free DOX owing to its enhanced nuclear delivery in vitro and tumor accumulation in vivo, which results in highly effective tumor growth inhibition and improved targeted therapy for cancer in clinical medicine.