Association of Dietary Retinol Intake and Serum Neurofilament Light Chain Levels: Results from NHANES 2013-2014.

BACKGROUND: There is increasing evidence suggesting that serum neurofilament light chain (sNfL) levels can be used as biomarkers for axonal injury. Retinol is recognized for its significant involvement in nervous system function, but the precise connection between dietary retinol and sNfL levels remains uncertain. OBJECTIVE: Our objective was to investigate the relationship between dietary retinol intake and sNfL, and to find an optimal retinol intake level for neurological health. METHODS: In the National Health and Nutrition Examination Survey (NHANES), conducted from 2013 to 2014, a cohort of 1684 participants who met the criteria were selected for the study. sNfL levels were measured from stored serum samples using a novel high-throughput immunoassay platform from Siemens Healthineers. Assessment of dietary retinol intake was performed by a uniformly trained interviewer through a 24 h dietary recall method. A generalized linear model was evaluated to assess the correlation between dietary retinol intake and sNfL concentrations. Furthermore, the nonlinear association between the two is further explored using restricted cubic spline (RCS) analysis. RESULTS: Upon adjusting for potential confounders, a 10% increase in dietary retinol intake was associated with a 3.47% increase in sNfL levels (95% CI: 0.54%, 6.49%) across all participants. This relationship was more pronounced in specific subgroups, including those under 60 years of age, non-obese, impaired estimated glomerular filtration rate (eGFR), and non-diabetic. In subgroup analysis, among those younger than 60 years of age (percent change: 3.80%; 95% CI: 0.43%, 7.28%), changes were found in non-obese participants (percent change: 6.28%; 95% CI: 2.66%, 10.02%), those with impaired eGFR (percent change: 6.90%; 95% CI: 1.44%, 12.65%), and non-diabetic patients (percentage change: 4.17%; 95% CI: 1.08%, 7.36%). RCS analysis showed a linear relationship between dietary retinol intake and sNfL levels. Furthermore, the positive correlation between the two was more significant after the inflection point, according to piecewise linear analysis. CONCLUSION: This current investigation uncovered a J-shaped relationship between dietary retinol and sNfL levels, suggesting that axonal damage can occur when dietary retinol intake increases more than a specific threshold. These findings need to be further confirmed in future prospective studies to determine the precise intake level that may trigger axonal injury.

Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. RESULTS: OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. CONCLUSIONS: We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.

The blockade of the TGF-ß pathway alleviates abnormal glucose and lipid metabolism of lipodystrophy not obesity.

TGF-ß is thought to be involved in the physiological functions of early organ development and pathological changes in substantial organ fibrosis, while studies around adipose tissue function and systemic disorders of glucolipid metabolism are still scarce. In this investigation, two animal models, aP2-SREBP-1c mice and ob/ob mice, were used. TGF-ß pathway showed up-regulated in the inguinal white adipose tissue (iWAT) of the two models. SB431542, a TGF-ß inhibitor, successfully increased inguinal white adipocyte size by more than 1.5 times and decreased the weight of Peripheral organs including liver, Spleen and Kidney to 73.05%/62.18%/73.23% of pre-administration weights. The iWAT showed elevated expression of GLUTs and lipases, followed by a recovery of circulation GLU, TG, NEFA, and GLYCEROL to the wild-type levels in aP2-SREBP-1c mice. In contrast, TGF-ß inhibition did not have similar effects on that of ob/ob mice. In vitro, TGF-ß blocker treated mature adipocytes had considerably higher levels of glycerol and triglycerides than the control group, whereas GLUTs and lipases expression levels were unchanged. These findings show that inhibiting the abnormally upregulated TGF-ß pathway will only restore iWAT expansion and ameliorate the global metabolic malfunction of glucose and lipids in lipodystrophy, not obesity.

Potential Correlation between Microbial Diversity and Volatile Flavor Substances in a Novel Chinese-Style Sausage during Storage.

A novel Chinese-style sausage with Chinese traditional fermented condiments used as additional ingredients is produced in this study. The aim of this study was to investigate the microbial community's structure, the volatile flavor substances and their potential correlation in the novel Chinese sausage. High-throughput sequencing (HTS) and solid-phase microextraction-gas chromatography-mass spectrometry (GC-MS) were, respectively, used to analyze the microbial diversity and volatile flavor substances of the novel Chinese-style sausage during storage. The results showed that Firmicutes, Proteobacteria and Actinobacteria were the predominant bacterial genera, and Hyphopichia and Candida were the predominant fungal genera. A total of 88 volatile flavor substances were identified through GC-MS, among which 18 differential flavor compounds were screened (VIP > 1), which could be used as potential biomarkers to distinguish the novel sausages stored for different periods. Lactobacillus exhibited a significant negative correlation with 2,3-epoxy-4,4-dimethylpentane and acetoin and a significant positive correlation with 2-phenyl-2-butenal. Hyphopichia significantly positively correlated with ester. Leuconostoc significantly positively correlated with ethyl caprate, ethyl palmate, ethyl tetradecanoate and ethyl oleate while it negatively correlated with hexanal. This study provides a theoretical basis for revealing the flavor formation mechanisms and the screening of functional strains for improving the flavor quality of the novel Chinese-style sausage.

Inverse J-Shaped Relationship of Dietary Carbohydrate Intake with Serum Klotho in NHANES 2007-2016.

BACKGROUND: The relationship between dietary carbohydrate intake and serum Klotho levels, an aging biomarker, remains uncertain. OBJECTIVE: This study aimed to investigate the association between dietary carbohydrate intake and serum Klotho levels among American adults aged 40-79. METHODS: We analyzed data from 10,669 adults aged 40-79 years who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Trained interviewers assessed dietary carbohydrate intake using a 24 h dietary recall. Serum Klotho concentrations were measured using commercially available ELISA kits provided by IBL International, Japan, which served as the study outcome. Generalized linear models were used to assess the relationship between the carbohydrate energy percentage and serum Klotho concentration, and restricted cubic spline (RCS) analysis was employed to explore any nonlinear associations. RESULTS: After adjusting for multiple variables, we observed a nonlinear inverse J-shaped relationship (p for non-linearity < 0.001) between the carbohydrate energy percentage and serum Klotho levels. Specifically, the highest serum Klotho levels were associated with a total carbohydrate energy percentage ranging from 48.92% to 56.20% (third quartile). When the carbohydrate energy percentage was evaluated in quartiles, serum Klotho levels decreased by 5.37% (95% CI: -7.43%, -3.26%), 2.70% (95% CI: -4.51%, -0.86%), and 2.76% (95% CI: -4.86%, -0.62%) in the first quartile (<41.46%), second quartile (41.46% to 48.92%), and fourth quartile (≥56.20%), respectively, compared to the third quartile. This relationship was more pronounced in male, non-obese and non-diabetic participants under 60 years of age. CONCLUSION: A non-linear inverse J-shaped relationship exists among the general U.S. middle-aged and older population between the carbohydrate energy percentage and serum Klotho levels, with the highest levels observed at 48.92% to 56.20% carbohydrate intake.

CUL4B functions as a tumor suppressor in KRAS-driven lung tumors by inhibiting the recruitment of myeloid-derived suppressor cells.

Lung cancer is the leading cause of cancer-related death worldwide. KRAS mutations are the most common oncogenic alterations found in lung cancer. Unfortunately, treating KRAS-mutant lung adenocarcinoma (ADC) remains a major oncotherapeutic challenge. Here, we used both autochthonous and transplantable KRAS-mutant tumor models to investigate the role of tumor-derived CUL4B in KRAS-driven lung cancers. We showed that knockout or knockdown of CUL4B promotes lung ADC growth and progression in both models. Mechanistically, CUL4B directly binds to the promoter of Cxcl2 and epigenetically represses its transcription. CUL4B deletion increases the expression of CXCL2, which binds to CXCR2 on myeloid-derived suppressor cells (MDSCs) and promotes their migration to the tumor microenvironment. Targeting of MDSCs significantly delayed the growth of CUL4B knockdown KRAS-mutant tumors. Collectively, our study provides mechanistic insights into the novel tumor suppressor-like functions of CUL4B in regulating KRAS-driven lung tumor development.

The Association between Dietary Fiber Intake and Serum Klotho Levels in Americans: A Cross-Sectional Study from the National Health and Nutrition Examination Survey.

BACKGROUND: Klotho is an aging-related marker closely associated with a number of diseases. A growing body of evidence suggests that dietary factors and lifestyle habits can impact serum Klotho levels. The effect of dietary fiber, a key component of a healthy diet, on the body's serum Klotho levels has not been fully elucidated. OBJECTIVE: The aim of this study was to explore the relationship between dietary fiber intake and serum Klotho levels in people aged 40-79 years in the United States. METHODS: A total of 11,282 participants were included in this study, all from the National Health and Nutrition Examination Survey from 2007 to 2016. Dietary fiber intake was assessed by uniformly trained interviewers using the 24 h dietary recall method. Serum Klotho was quantified using commercially available ELISA kits manufactured by IBL International, Japan. The relationship between dietary fiber intake and serum Klotho levels was analyzed using a multiple linear regression model. Subsequently, the non-linear dose-response relationship between the two was further explored using a restricted cubic spline (RCS) model. RESULTS: After adjusting for potential confounders, serum Klotho levels increased by 1.9% (95% confidence interval [CI]: 0.8%, 3.0%) for each interquartile range increase in dietary fiber intake in all participants. Considering dietary fiber intake as a categorical variable, serum Klotho levels were found to be 4.7% higher in participants in the highest quartile of dietary fiber intake than in those in the lowest quartile (95% CI: 1.8%, 7.6%). RCS plots depicted a non-linear positive correlation between dietary fiber intake and serum Klotho levels. Subgroup analysis revealed that the relationship between dietary fiber intake and serum Klotho levels was more pronounced in older (percentage change: 7.0%; 95% CI: 2.5%, 11.7%) and overweight and obese participants (percentage change: 4.9%; 95% CI: 1.5%, 8.4%). CONCLUSIONS: The results of this study showed that dietary fiber intake was significantly associated with serum Klotho levels in participants. This finding is yet to be further confirmed by prospective studies.

Corrigendum: Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome.

[This corrects the article DOI: 10.3389/fendo.2023.1122709.].

Garlic polysaccharide-Cr (III) complexes with enhanced in vitro and in vivo hypoglycemic activities.

This study aimed to prepare a complex of Cr (III) and garlic polysaccharides (GPs) and evaluate the in vitro and in vivo hypoglycemic activities of GPs and GP-Cr (III) complexes. The chelation of GPs with Cr (III) increased molecular weight, modified crystallinity, and altered morphological characteristics, through targeting the OH of hydroxyl groups and involving the C-O/O-C-O structure. The GP-Cr (III) complex had a higher thermal stability over 170-260 °C and higher stability throughout the gastrointestinal digestion. In vitro, the GP-Cr (III) complex exhibited a significantly stronger inhibitory effect against α-glucosidase compared with the GP. In vivo, the GP-Cr (III) complex at a high dose (4.0 mg Cr/kg body weight) generally had a higher hypoglycemic activity than the GP in (pre)-diabetic mice induced by a high-fat and high-fructose diet, based on indices like body weight, blood glucose levels, glucose tolerance, insulin resistance, insulin sensitivity, blood lipid levels, and hepatic morphology and function. Therefore, GP-Cr (III) complexes could be a potential Cr (III) supplement with an enhanced hypoglycemic activity.

Quercetin alleviates atherosclerosis by suppressing oxidized LDL-induced senescence in plaque macrophage via inhibiting the p38MAPK/p16 pathway.

Quercetin is a widely known and biologically active phytochemical and exerts therapeutic effects against atherosclerosis. The removal of senescent plaque macrophages effectively slows the progression of atherosclerosis and decreases the plaque burden. Still, whether quercetin alleviates atherosclerosis by inhibiting the senescence of plaque macrophages, including the potential mechanisms, remains unclear. ApoE-/- mice were fed with a normal chow diet or high-fat diet (HFD) supplemented or not with quercetin (100 mg/kg of body weight) for 16 weeks. An accumulation of senescent macrophages was observed in the plaque-rich aortic tissues from the mice with HFD, but quercetin supplementation effectively reduced the amount of senescent plaque macrophage, inhibited the secretion of key senescence-associated secretory phenotype factors, and alleviated atherosclerosis by inhibiting p38MAPK phosphorylation and p16 expression. In vitro, SB203580 (a specific inhibitor of p38 MAPK) significantly inhibited oxidized low-density lipoprotein (ox-LDL)-induced senescence in mouse RAW264.7 macrophages, as evidenced by decreased senescence-associated markers (SA-ß-gal staining positive cells and p16 expression). Furthermore, quercetin not only effectively reversed ox-LDL-induced senescence in RAW264.7 cells but also decreased the mRNA levels of several key senescence-associated secretory phenotype factors by suppressing p38 MAPK phosphorylation and p16 expression. The p38 MAPK agonist Asiatic acid reversed the effects of quercetin. In conclusion, these findings indicate that quercetin suppresses ox-LDL-induced senescence in plaque macrophage and attenuates atherosclerosis by inhibiting the p38 MAPK/p16 pathway. This study elucidates the mechanisms of quercetin against atherosclerosis and supports quercetin as a nutraceutical for the management of atherosclerosis.

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome.

Background: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated. Methods: A pseudo sterile mouse model was established during this four-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet-induced PCOS mice model. Female prepuberal mice were randomly divided into three groups; namely, the control group, PCOS group and YLTB (38.68 g·kg-1·day-1) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota, and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice. Results: Our results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc.) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis. Conclusion: These results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials.

The characteristics of dome-shaped macula in Chinese children aged 4-6 years using optical coherence tomography angiography.

PURPOSE: To evaluate the characteristics of dome-shaped macula (DSM) in children aged 4-6 years with normal visual acuity using optical coherence tomography angiography. METHOD: This is a cross-sectional study. A total of 19 children aged 4-6 years were included. The results of optical coherence tomography angiography images were analysed to identify and quantify retinal structural and vascular parameters in DSM children. The dome height, dome base, and sub-dome choroidal thickness were manually measured. Participants with DSM and those without DSM from our previous study were compared on these parameters. RESULTS: Nineteen eyes of the preschool subjects with normal visual acuity showed horizontal DSM on optical coherence tomography (OCT). The DSM was significantly smooth and low in the children, and we did not observe differences between sex and age. Compared to the children without DSM, the average axial length was longer, and the average macular vessel density was lower in the DSM group, especially in the deep retinal vascular density. Additionally, the dome height was positively correlated with the sub-dome choroidal thickness. When the dome base/height was increased, the fovea avascular zone (FAZ) area was larger. CONCLUSION: Dome-shaped macula was detected in the preschool children in the process of the emmetropization with normal visual acuity. The changes in macular structure and vasculature provide new ideas for further investigation into the characteristics of DSM formation.

Advancement and prospects of production, transport, functional activity and structure-activity relationship of food-derived angiotensin converting enzyme (ACE) inhibitory peptides.

Food-derived antihypertensive peptides have attracted increasing attention in functional foods for health promotion, due to their high biological activity, low toxicity and easy metabolism in the human body. Angiotensin converting enzyme (ACE) is a key enzyme that causes the increase in blood pressure in mammals. However, few reviews have summarized the current understanding of ACE inhibitory peptides and their knowledge gaps. This paper focuses on the food origins and production methods of ACE inhibitory peptides. Compared with conventional methods, the advanced technologies and emerging bioinformatics approaches have recently been applied for efficient and targeted release of ACE inhibitory peptides from food proteins. Furthermore, the transport and underlying mechanisms of ACE inhibitory peptides are emphatically described. Molecular modeling and the Michaelis-Menten equation can provide information on how ACE inhibitors function. Finally, we discuss the structure-activity relationships and other bio-functional properties of ACE inhibitory peptides. Molecular weight, hydrophobic amino acid residues, charge, amino acid composition and sequence (especially at the C-terminal and N-terminal) have a significant influence on ACE inhibitory activity. Some studies are required to increase productivity, improve bioavailability of peptides, evaluate their bio-accessibility and efficiency on reducing blood pressure to provide a reference for the development and application of health products and auxiliary treatment drugs.

Association of Dietary Vitamin C Consumption with Serum Klotho Concentrations.

BACKGROUND: Klotho is widely recognized as a protein that combats aging and possesses antioxidative characteristics, which have been implicated in the pathophysiology of numerous diseases. There is emerging evidence suggesting that the consumption of dietary nutrients, particularly those rich in antioxidants, could be associated with serum Klotho concentrations. Dietary vitamin C is one of the critical nutrients that possesses antioxidant properties. Nonetheless, the association between dietary vitamin C consumption and serum Klotho concentrations remains unclear. OBJECTIVE: Aiming to evaluate the relationship between serum Klotho concentrations and dietary vitamin C consumption among Americans aged 40 to 79, we conducted a population-based study. METHODS: From the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016, a grand total of 11,282 individuals who met the criteria were selected as eligible participants for the study. Serum Klotho concentrations were measured using an ELISA kit that is commercially available. Trained interviewers evaluated the consumption of dietary vitamin C in the diet through a 24-hour dietary recall technique. A generalized linear model was used to evaluate the correlation between the consumption of dietary vitamin C in the diet and serum Klotho concentrations. Further examination was conducted using restricted cubic spline (RCS) analysis to explore the non-linear correlation between dietary vitamin C consumption in the diet and serum Klotho concentrations. RESULTS: After accounting for possible confounding factors, serum Klotho concentrations rose by 1.17% (95% confidence interval (CI): 0.37%, 1.99%) with every standard deviation (SD) rise in dietary vitamin C consumption. With the first quintile of dietary vitamin C consumption as a reference, the percentage change of serum Klotho concentrations in the fifth quintile of dietary vitamin C consumption was 3.66% higher (95% CI: 1.05%, 6.32%). In older, normal-weight, and male participants, the subgroup analysis revealed a stronger correlation between dietary vitamin C consumption and serum Klotho concentrations. Analysis of RCS showed a linear positive association between dietary vitamin C consumption and the levels of serum Klotho concentrations. CONCLUSION: The findings of this research indicate a strong and positive correlation between dietary vitamin C consumption and serum Klotho concentrations among the general adult population in the United States. Further studies are needed to validate the present findings and to explore specific mechanisms.

Iron Restriction Alleviates Atherosclerosis in ApoE KO Mice: An iTRAQ Proteomic Analysis.

The "iron hypothesis" of atherosclerosis has long been controversial. Several studies have shown that dietary iron restriction or low-iron diets can effectively alleviate atherosclerosis in rabbits and mice. However, the underlying molecular mechanisms of these phenomena remain to be elucidated. In this study, we further evaluated possible correlations between a low-iron diet and atherosclerosis alleviation by using a quantitative proteomic approach. For this purpose, apolipoprotein E knockout (ApoE KO) mice were divided into three groups and fed a normal diet (ND), a high-fat diet (HFD), or a high-fat +low-iron diet (HFD + LI). Our results showed that the HFD-LI improved atherosclerosis by decreasing en face lesions of the aorta and reducing the accumulation of macrophages and disordered smooth muscle cells. HFD-LI also decreased iron levels, serum hepcidin levels and the serum concentration of low-density lipoprotein cholesterol (LDL-C). The use of the isobaric tag for absolute quantification (iTRAQ) proteomic method and subsequent multi-technique molecular validation indicated that many of the proteins involved in atherosclerotic inflammation, vascular remodeling, and focal adhesion had significant changes in their expression among the diet groups. Importantly, the proteins Gal-3 and VCAM1, which are key participants of atherosclerosis pathogenesis, revealed lower expression after a low-iron diet. The present findings widely support the "iron hypothesis" of atherosclerosis. Further studies are suggested to fully understand the implications of these results.

Digestive properties and prebiotic activity of garlic saccharides with different-molecular-weight obtained by acidolysis.

Garlic saccharides have prebiotic activity, but the association between their function and structure is still poorly known. In present study, four different garlic saccharides were obtained from garlic polysaccharides (GPs) after acidolysis by ultrafiltration. Obtained GPs were constituted by different monosaccharides, among which fructose and glucose were the main components, while galactose was a major component of GPs-U6. All four saccharides were partly degraded by the simulated digestive system, and most could reach the large intestine to be utilized by the gut microbiota. Except for GPs-U6, the other three garlic saccharide fractions had good prebiotic activity in vitro and in vivo. Furthermore, GPs-U0.3 with lower molecular weight (Mw) showed better prebiotic activity, including promoting the production of short-chain fatty acids (SCFAs), increasing the abundance of beneficial bacteria such as Bifidobacterium, Lachnospiraceae NK4A136 group and Phoscolarctobacterium, and inhibiting the growth of potentially harmful bacteria. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis showed that GPs-U0.3 could reduce the risk of cancer and cardiovascular diseases. Overall, this findings of the present study revealed the digestive properties of GPs, as well as the potential association between their chemical structures and fermentation characteristics by gut microbiota. Thus, it can be stated that GPs-U0.3 can be used as potential prebiotics in functional foods, which provides a theoretical basis for the targeted preparation of functionalized garlic saccharides.

Bovine-derived α-lactalbumin exhibits cardiovascular protection against aging by ameliorating the inflammatory process in mice.

Cardiovascular aging is the most important factor leading to cardiovascular disease (CVD), and the incidence and severity of cardiovascular events increase with age. Cardiovascular disease is one of the leading causes of death in the aging population. Therefore, it is extremely urgent to develop and explore effective drugs or bioactive molecules to prevent cardiovascular aging and related diseases. In the current work, the effect of bovine α-lactalbumin (α-lactalbumin is one of the major bioactive protein molecules in milk) on cardiovascular aging was investigated in vitro and in vivo. First, a cellular model of cardiovascular aging was established using H2O2-induced in vitro cellular models. It was found that α-lactalbumin could alleviate cardiovascular senescence by assessing Sa-ß-gal and senescence-related markers (such as p16/p21/p53) in in vitro cellular models. Bovine α-lactalbumin attenuated aging-related inflammation and oxidative stress. Furthermore, aged mice were used as an in vivo cardiovascular aging model. We explored the effect of α-lactalbumin on cardiovascular aging and found that cardiovascular aging was significantly attenuated by evaluating Sa-ß-gal staining and aging-related marker molecules. Mechanistically, we found that α-lactalbumin may alleviate cardiovascular aging by regulating the expression of Sirt1 (Sirtuin 1). In summary, in the current work, we systematically explored the potential biological activity of α-lactalbumin against cardiovascular aging and found that α-lactalbumin has good anti-aging potential in vitro and in vivo, suggesting that α-lactalbumin could be used as an antiaging functional food in the future.

GC-TOF-MS-Based Non-Targeted Metabolomic Analysis of Differential Metabolites in Chinese Ultra-Long-Term Industrially Fermented Kohlrabi and Their Associated Metabolic Pathways.

Fermented kohlrabi is a very popular side dish in China. Chinese kohlrabies industrially fermented for 0 years (0Y), 5 years (5Y), and 10 years (10Y) were employed and analyzed by non-targeted metabolomics based on GC-TOF-MS, and the differential metabolites were screened using multivariate statistical analysis techniques, including principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA). The results showed that 47, 38, and 33 differential metabolites were identified in the three treatment groups of 0Y and 5Y (A1), 0Y and 10Y (A2), and 5Y and 10Y (A3), respectively (VIP > 1, p < 0.05). The metabolites were mainly carbohydrates, amino acids, and organic acids. Furthermore, 13 differential metabolites were screened from the three groups, including L-glutamic acid, L-aspartic acid, γ-aminobutyric acid, and other compounds. Four metabolic pathways termed alanine, aspartate, and glutamate metabolism, arginine biosynthesis, arginine and proline metabolism, and glycolysis/gluconeogenesis were the most significant pathways correlated with the differential metabolites, as analyzed according to the Kyoto Encyclopedia of Genes and Genomes (KEGG). The odors for the three ultra-long-term industrially fermented kohlrabies were significantly different, as detected by E-nose. The present work describes the changes in metabolites between different ultra-long-term industrially fermented kohlrabies and the associated metabolic pathways, providing a theoretical basis for the targeted regulation of characteristic metabolite biosynthesis in Chinese fermented kohlrabi.

Acetyl-CoA Deficiency Is Involved in the Regulation of Iron Overload on Lipid Metabolism in Apolipoprotein E Knockout Mice.

The role of dietary iron supplementation in the development of nonalcoholic fatty liver disease (NAFLD) remains controversial. This study aimed to investigate the effect of excess dietary iron on NAFLD development and the underlying mechanism. Apolipoprotein E knockout mice were fed a chow diet, a high-fat diet (HFD), or an HFD containing 2% carbonyl iron (HFD + Fe) for 16 weeks. The serum and liver samples were acquired for biochemical and histopathological examinations. Isobaric tags for relative and absolute quantitation were performed to identify differentially expressed proteins in different groups. Excess dietary iron alleviated HFD-induced NAFLD, as evidenced by significant decreases in serum/the hepatic accumulation of lipids and the NAFLD scores in HFD + Fe-fed mice compared with those in HFD-fed mice. The hepatic acetyl-CoA level was markedly decreased in the HFD + Fe group compared with that in the HFD group. Important enzymes involved in the source and destination of acetyl-CoA were differentially expressed between the HFD and HFD + Fe groups, including the enzymes associated with cholesterol metabolism, glycolysis, and the tricarboxylic acid cycle. Furthermore, iron overload-induced mitochondrial dysfunction and oxidative stress occurred in mouse liver, as evidenced by decreases in the mitochondrial membrane potential and antioxidant expression. Therefore, iron overload regulates lipid metabolism by leading to an acetyl-CoA shortage that reduces cholesterol biosynthesis and might play a role in NAFLD pathogenesis. Iron overload-induced oxidative stress and mitochondrial dysfunction may impair acetyl-CoA formation from pyruvate and ß-oxidation. Our study provides acetyl-CoA as a novel perspective for investigating the pathogenesis of NAFLD.

Study on the antipruritic mechanism of Zanthoxylum bungeanum and Zanthoxylum schinifolium volatile oil on chronic eczema based on H1R and PAR-2 mediated GRPR pathway.

OBJECTIVE: To observe the antipruritic effect and mechanism of the volatile oil of Zanthoxylum bungeanum and Zanthoxylum schinifolium on chronic eczema to provide data support for clinical application and new drug development of Zanthoxylum bungeanum and Zanthoxylum schinifolium. METHODS: The model of chronic eczema was established by using 2-dinitrochlorobenzene (DNCB), and the composition and content of volatile oil in Zanthoxylum schinifolium and Zanthoxylum bungeanum was determined by gas chromatography-mass spectrometry (GC-MS). The antipruritic effect by (EASI) score of eczema area and severity index and scratching times was then evaluated. Then, the contents of histamine, gastrin-releasing peptide (GRP), interleukin-4 (IL-4), and immunoglobulin E (IgE) in serum of rats was determined by enzyme-linked immunosorbent assay (ELISA). The tissue morphology was observed by HE staining. The expressions of H1R, PAR-2, TRPV1, TRPA1, and GRPR was then detected by immunohistochemistry, Western blot, and QRT-PCR. RESULTS: The results revealed that there were differences in the composition of volatile oil between Zanthoxylum bungeanum and Zanthoxylum schinifolium. Compared to the model group, the medium-dose group of Zanthoxylum bungeanum and Zanthoxylum schinifolium group significantly increased the difference of EASI score and scratching times, significantly decreased the concentrations of IL-4, IgE, GRP, and histamine, and significantly decreased the expression levels of H1R, PAR-2, TRPV1, and GRPR. The degree of inhibition on the pathological manifestations of chronic eczema was evident. There was no significant difference in antipruritic effect between the two groups. The expression of TRPA1 was inconsistent at the protein and gene level, which needs to be further researched. CONCLUSION: The volatile oil of Zanthoxylum bungeanum and Zanthoxylum schinifolium can reduce the expression of H1R, PAR-2, TRPV1, and GRPR. The mechanism may be through the H1R and PAR-2-mediated GRPR pathway intervention to achieve the effect, both of which have the same antipruritic effect.