Dietary dicarbonyl compounds exacerbated immune dysfunction and hepatic oxidative stress under high-fat diets in vivo.

High-fat diets (HFDs) predispose to obesity and liver dysfunctions, and α-dicarbonyl compounds (α-DCs) present in highly processed foods are also implicated in relevant pathological processes. However, the synergistic harmful effects of α-DCs co-administered with HFDs remain to be elucidated. In this study, 6-week-old C57BL/6 mice were fed with a HFD co-administered with 0.5% methylglyoxal (MGO)/glyoxal (GO) in water for 8 weeks, and multi-omics approaches were employed to investigate the underlying toxicity mechanisms. The results demonstrated that the MGO intervention with a HFD led to an increased body weight and blood glucose level, accompanied by the biological accumulation of α-DCs and carboxymethyl-lysine, as well as elevated serum levels of inflammatory markers including IL-1ß, IL-6, and MIP-1α. Notably, hepatic lesions were observed in the MGO group under HFD conditions, concomitant with elevated levels of malondialdehyde. Transcriptomic analysis revealed enrichment of pathways and differentially expressed genes (DEGs) associated with inflammation and oxidative stress in the liver. Furthermore, α-DC intervention exacerbated gut microbial dysbiosis in the context of a HFD, and through Spearman correlation analysis, the dominant genera such as Fusobacterium and Bacteroides in the MGO group and Colidextribacter and Parabacteroides in the GO group were significantly correlated with a set of DEGs involved in inflammatory and oxidative stress pathways in the liver. This study provides novel insights into the healthy implications of dietary ultra-processed food products in the context of obesity-associated disorders.

MBD3 promotes epithelial-mesenchymal transition in gastric cancer cells by upregulating ACTG1 via the PI3K/AKT pathway.

BACKGROUND: Gastric cancer (GC) is a common malignancy and a leading cause of cancer-related death with high morbidity and mortality. Methyl-CpG binding domain protein 3 (MBD3), a key epigenetic regulator, is abnormally expressed in several cancers, participating in progression and metastasis. However, the role of MBD3 in GC remains unknown. METHODS: MBD3 expression was assessed via public databases and validated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The prognosis of MBD3 was analysed via bioinformatics based on the TCGA dataset. The migration, invasion and proliferation of GC cells were examined by transwell, wound healing, cell counting kit (CCK)-8, colony-formation and xenograft mouse models. Epithelial-mesenchymal transition (EMT) and phosphatidylinositide 3-kinases/ protein Kinase B (PI3K/AKT) pathway markers were evaluated by Western blotting. RNA sequencing was used to identify the target of MBD3. RESULTS: MBD3 expression was higher in GC tissues and cells than in normal tissues and cells. Additionally, high MBD3 levels were associated with poor prognosis in GC patients. Subsequently, we proved that MBD3 enhanced the migration, invasion and proliferation abilities of GC cells. Moreover, western blot results showed that MBD3 promoted EMT and activated the PI3K/AKT pathway. RNA sequencing analysis showed that MBD3 may increase actin γ1 (ACTG1) expression to promote migration and proliferation in GC cells. CONCLUSION: MBD3 promoted migration, invasion, proliferation and EMT by upregulating ACTG1 via PI3K/AKT signaling activation in GC cells and may be a potential diagnostic and prognostic target.

COVID-19 Research in Communication Journals: A Structural Topic Modeling-Assisted Bibliometric Analysis.

This article presents a bibliometric analysis of research on COVID-19 health communication. We reviewed and analyzed 1,851 articles published in 170 peer-reviewed communication journals between January 2020 and November 2022, to identify key bibliometric information and major research topics in this rapidly expanding field of research. The distribution of countries indicates that the United States is the most productive country, and researchers from Spain, China and the United Kingdom also play an important role. Health Communication is the most influential journal in terms of research productivity and impact. The analysis of highly cited references demonstrates the interdisciplinary nature of this research field. The topics generated by structural topic modeling show that scholars have responded to a variety of issues in COVID-19 communication, encompassing different levels of health communication, the effects of information dissemination, the impact on the general public as well as vulnerable populations, health preventive behaviors and communication technologies. This study aims to enhance researchers' understanding of the current state of this research field and provide insights for future studies.

Covalent and non-covalent interactions of cyanidin-3-O-glucoside with milk proteins revealed modifications in protein conformational structures, digestibility, and allergenic characteristics.

Currently, there is a need to explore the effects of different types of protein-anthocyanin complexations, as well as the possible changes in the nutrition and allergenicity of the formed complexes. Here, we systematically investigated the covalent and non-covalent interactions between cyanidin-3-O-glucoside (C3G) and two major milk proteins, α-casein (α-CN) and ß-lactoglobulin (ß-LG). Fluorescence quenching data showed that, under non-covalent conditions, C3G quenched the fluorescence of the two proteins via a static process, with the interaction forces being revealed; for covalent products, decreased fluorescence intensities were observed with red shifts in the λmax. Multiple spectroscopic analyses implied that C3G-addition induced protein structural unfolding through transitions between the random coil and ordered secondary components. With a two-stage simulated gastrointestinal (GI) digestion model, it was seen that covalent complexes, not their non-covalent counterparts, showed reduced protein digestibility, ascribed to structural changes resulting in the unavailability of enzyme cleaving sites. The GI digests displayed prominent 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation-scavenging abilities (3.8-11.1 mM Trolox equivalents per mL digest), in contrast to the markedly reduced 1,1-diphenyl-2-picrylhydrazyl radical-scavenging capacities. Additionally, covalent protein-C3G complexes, but not their non-covalent counterparts, showed lower IgE-binding levels in comparison to the native control. This study provides new understanding for the development of anthocyanin-milk protein systems as functional ingredients with health-beneficial properties.

The interfacial covalent bonding of whey protein hydrolysate and pectin under high temperature sterilization: Effect on emulsion stability.

In this study, the effect of high-pressure steam sterilization (121 °C for 15 min) on whey protein hydrolysate-pectin solutions and emulsions was studied. The interaction and emulsification characteristics of pectin and whey protein concentrate (WPC) were evaluated from the solution system to the emulsion system. Enzymatic hydrolysis of WPC (WPH, 2 % and 8 % degree of hydrolysis) increased the covalent binding with pectin, which reduced the heat-induced aggregation of protein and improved emulsification. The thermodynamic incompatibility between WPC and pectin was not conducive to the covalent bonding under high temperature sterilization and produced serious aggregates, which also made a rapid increase in particle size (up to ∼3 µm), compared to WPH-pectin emulsion (∼ 400 nm). In addition, if emulsion was stirred during the sterilization, the creaming and protein aggregation could be avoided. By comparing low methoxy pectin (LMP) and high methoxy pectin (HMP), it was found that the whey protein-HMP complex had better emulsification stability, and the steric stabilization played a more important role in emulsion stability than the electrostatic repulsion. The changes of whey protein and pectin at the oil-water interface of the emulsion during the sterilization process may provide a reference for the sterilized bioactive ingredient delivery system.

Ultrasonic pre-treatment modifies the pH-dependent molecular interactions between ß-lactoglobulin and dietary phenolics: Conformational structures and interfacial properties.

There is a need to understand the ultrasound-induced changes in the interactions between proteins and phenolic compounds at different pH. This study systematically explored the role of high-intensity ultrasound pre-treatment on the binding mechanisms of ß-lactoglobulin (ß-LG) to two common phenolic compounds, i.e., (-)-epigallocatechin-3-gallate (EGCG) and chlorogenic acid (CA) at neutral and acidic pH (pH 7.2 and 2.4). Tryptophan fluorescence revealed that compared to proteins sonicated at 20% and 50% amplitudes, 35%-amplitude ultrasound pre-treatment (ULG-35) strengthened the binding affinities of EGCG/CA to ß-LG without altering the main interaction force. After phenolic addition, ULG-35 displayed a similar but a greater extent of protein secondary and tertiary structural changes than the native protein, ascribed to the ultrasound-driven hydrophobic stacking among interacted molecules. The dominant form of ß-LG (dimer/monomer) played a crucial role in the conformational and interfacial properties of complexes, which can be explained by the distinct binding sites at different pH as unveiled by molecular docking. Combining pre-ultrasound with EGCG interaction notably increased the foaming and emulsifying properties of ß-LG, providing a feasible way for the modification of bovine whey proteins. These results shed light on the understanding of protein-phenolic non-covalent binding under ultrasound and help to develop complex systems with desired functionality and delivery.

Optimizing granular anammox retention via hydrocycloning during two-stage deammonification of high-solid sludge anaerobic digester supernatant.

High-solid sludge anaerobic digestion leads to increased organic matters in digester supernatant, which promotes heterotrophic competition and reduces anaerobic ammonium oxidation (anammox) retention. This research demonstrated effective anammox retention by hydrocycloning during a two-stage deammonification. Anammox retention was evaluated by dividing large (>0.425 mm), medium (0.25 to 0.425 mm), and small (<0.25 mm) aggregate fractions via a sieve, whereby Candidatus Kuenenia abundance in each size aggregate was measured to be 16.8%, 5.0%, and 0.9% respectively. After hydrocyclone separation, large particles took up only 1.7% to 2.7% in the overflow discharge (upper discharge from the reactor), whereas its initial proportion was 19.4%, indicating limited anammox loss. The volume ratio change of large particles to total aggregates was defined for particle breakdown evaluation. Breakdown (23% to 32% large particles) occurred mainly during pumping (influenced by pump frequency and type), while little happened in the hydrocyclone. This research provided methods to use a sieve to evaluate anammox retention by hydrocyclone during high-solid sludge anaerobic digester supernatant deammonification, and information for reducing particle breakdown, pumping selection, and separation optimization.

The efficacy of niacin supplementation in type 2 diabetes patients: Study protocol of a randomized controlled trial.

BACKGROUND: Dyslipidemia is a main risk factor of cardiovascular disease in the diabetic patients. Niacin was found acutely to decrease the plasma concentration of free fatty acids by inhibiting their mobilization from adipose tissue. This present study is a double blinded, randomized, and prospective trial to determine the effect of niacin during dyslipidemia in type 2 diabetic patients. METHODS: This randomized controlled, double-blinded, single center trial is carried out according to the principles of Declaration of Helsinki. This present study was approved in institutional review committee of the Second Affiliated Hospital of Dalian Medical University. All the patients received the informed consent. Diabetic patients were randomized (1:1) to receive 3-month treatment with extended-release niacin or matching placebo. The major outcome of our present study was the change in the level of HbA1c from the baseline to week 12. Secondary outcome measures contained the levels of fasting blood glucose, the concentrations of serum transaminase, the other laboratory variables, and self-reported adverse events. The P < .05 was regarded as statistically significant. RESULTS: We assumed that adding the niacin to the medication in patients with type 2 diabetes would reduce dyslipidemia and achieve target lipid levels. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5925).

Risk Factors of Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease: A Meta-Analysis of Case-Control Studies.

Previous studies have shown that children with Kawasaki disease (KD) who fail to respond to intravenous immunoglobulin (IVIG) therapy are at higher risk of developing coronary artery lesions (CALs). We aimed to conduct a meta-analysis to uncover the risk factors associated with IVIG resistance in children with KD. PubMed, Embase, and Cochrane Library databases were searched up to 31st October 2019, and 23 case-control studies were finally eligible, enrolling 2,053 patients of IVIG resistance and 16,635 patients of IVIG sensitivity. Potential factors were comprehensively analyzed by using stata15 software with a standard meta-analysis procedure and consequently found that in addition to patients with polymorphous rash or swelling of extremities symptoms had a tendency to be non-responders, IVIG resistance was more likely to occur in patients with severe anemia, hypoalbuminemia, decreased baseline platelet count, and elevated levels of erythrocyte sedimentation rate (ESR), total bilirubin, alanine aminotransferase (ALT) and neutrophils percentage. Particularly, male sex, hyponatraemia, increased aspartate aminotransferase (AST), and C-reactive protein (CRP) were confirmed as the risk factors favor IVIG resistance in Mongoloids from Asia countries, but not in Caucasians from non-Asia regions. In summary, we report several risk factors relevant to IVIG resistance in children with KD, which may provide guidance for the prediction of IVIG resistance. But a proposing of an optimal prediction system with high specificity and sensitivity needs further studies because of confounding factors.

Antiproliferation Activity and Mechanism of c9, t11, c15-CLNA and t9, t11, c15-CLNA from Lactobacillus plantarum ZS2058 on Colon Cancer Cells.

Conjugated linolenic acid (CLNA) is a type of ω-3 fatty acid which has been proven to have a series of benefits. However, there is no study about the function of Lactobacillus-derived CLNA isomer. Lactobacillus plantarum ZS2058 has been proven to manifest comprehensive functions and can produce CLNA. To investigate the specific functions of CLNA produced by this probiotic bacterium, two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated that lipid peroxidation was related to the antiproliferation activity of CLNAs. An examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. No sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first study on the function of Lactobacillus-derived CLNA isomer. The inhibition pathway of Lactobacillus-derived CLNA isomer on colon cancer cells were proved.

Lumped-Parameter Circuit Platform for Simulating Typical Cases of Pulmonary Hypertensions from Point of Hemodynamics.

Pulmonary hypertension (PH) presents unusual hemodynamic states characterized by abnormal high blood pressure in pulmonary artery. The objective of this study is to simulate how the hemodynamics develops in typical PH cases without treatment. A lumped-parameter circuit platform of human circulation system is set up to simulate hemodynamic abnormalities of PH in different etiologies and pathogenesis. Four typical cases are considered, which are distal pulmonary artery stenosis, left ventricular diastolic dysfunction, ventricular septal defect, and mitral stenosis. The authors propose regulation laws for chambers and vessels to adapt the abnormal hemodynamic conditions for each PH case. The occurrence and development of each PH case are simulated over time using the lumped-parameter circuit platform. The blood pressure, blood flow, pressure-volume relations for chambers and vessels are numerically calculated for each case of PH progression. The model results could be a quite helpful to understand the hemodynamic mechanism of typical PHs. Graphical Abstract.

Positive hepatitis B surface antibody is associated with reduced risk of diabetes mellitus in retired female Chinese workers.

BACKGROUND: To study the relationship between positivity for hepatitis B surface antibody (HBsAb) and the risk of diabetes mellitus in the retired Chinese population. METHODS: A cross-sectional analysis was conducted in 900 retired Chinese workers attending a health check-up program. HBsAb, hepatitis B surface antigen, oral glucose tolerance test (OGTT), fasting plasma glucose (FBG), 2-h plasma glucose 2hBG, and insulin levels were collected. RESULTS: Participants positive for HBsAb were younger, with lower blood pressure, lower FBG and 2hBG serum uric acid, and glutamic pyruvic transaminase than those who were HbsAb negative. There were 306 subjects with impaired glucose tolerance and 121 with type 2 diabetes (T2D) in the present cohort. Using Chi-squared analysis to assess the risk of diabetes, women positive for HBsAb had a lower prevalence of T2D than those negative for HBsAb (15.7% vs 26.5%, respectively; P < 0.01). Multivariate analysis revealed family history of diabetes, age, and waist circumference were independently associated with a higher prevalence of diabetes, and that HBsAb positivity was independently associated with a lower prevalence of diabetes (odds ratio 0.579; 95% confidence interval 0.388-0.918) when adjusted for sex, family history of hypertension and dyslipidemia, and body mass index. CONCLUSIONS: An HBsAb-positive status is associated with a low rate of diabetes and better metabolic status. A prospective study of patients with known vaccination records is needed to investigate whether hepatitis B virus vaccination could protect against the development of diabetes.