Association between Whole Grain Intake and Chronic Kidney Disease.

BACKGROUND: The relationship between whole grain intake and chronic kidney disease (CKD) remains uncertain. OBJECTIVE: This study aimed to evaluate the association between whole grain intake and risk of CKD in Chinese adults. METHODS: The present cross-sectional study used data from the China Health and Nutrition Survey conducted in 2009. Whole grain intake was measured using 3 consecutive 24-h dietary recalls and a household food inventory. A multivariable logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of CKD. In addition, a restricted cubic spline was used to investigate the dose‒response relationship between whole grain and risk of CKD. RESULTS: A total of 6747 participants were included, 728 of whom had CKD. Compared with those in the lowest whole grain intake group, those in the higher grain intake group had an inverse association with risk of CKD (Q2: adjusted OR 0.70, 95% CI: 0.54, 0.89; Q3: adjusted OR 0.54, 95% CI: 0.42, 0.69; and Q4: adjusted OR 0.29, 95% CI: 0.21, 0.41). The association between whole grain intake and CKD seems to be stronger for individuals who were male (P for interaction = 0.008) or smokers (P for interaction = 0.013). In addition, the restricted cubic spline suggested an obvious L-shaped correlation. CONCLUSIONS: Increased whole grain intake was associated with a decreased risk of CKD in Chinese adults.

Associations between whole grains intake and new-onset hypertension: a prospective cohort study.

IMPORTANCE: Epidemiological evidences regarding the association between whole grain intake and the risk of new-onset hypertension are still controversial. OBJECTIVE: We aimed to investigate the relationship between whole grain intake and new-onset hypertension and examine possible effect modifiers in the general population. METHODS: A total of 10,973 participants without hypertension from the China Health and Nutrition Survey were enrolled, with follow-up beginning in 1997 and ending in 2015. Whole grain intake was assessed by 3 consecutive 24-h dietary recalls combined with a household food inventory. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression model after adjusting for potential risk factors. RESULTS: During a median follow-up of 7.0 years, 3,733 participants developed new-onset hypertension. The adjusted HRs (95% CIs) were as follows: for quartile 2 (HR: 0.52; 95% CI: 0.47-0.57), quartile 3 (HR: 0.46; 95% CI: 0.42-0.51), and quartile 4 (HR: 0.35; 95% CI: 0.31-0.38), compared with quartile 1. Different types of whole grain types, including wheat (adjusted HR, 0.35; 95% CI, 0.32-0.39), maize (adjusted HR, 0.50; 95% CI, 0.42-0.59), and millet (adjusted HR, 0.38; 95% CI, 0.30-0.48), showed significant associations with a reduced risk of hypertension. The association between whole grain intake and new-onset hypertension was stronger in individuals with older age (P for interaction < 0.001) and higher BMI (P for interaction < 0.001). CONCLUSION: Higher consumption of whole grains was significantly associated with a lower risk of new-onset hypertension. This study provides further evidence supporting the importance of increasing whole grain intake for hypertension prevention among Chinese adults.

[Application of Nice knot technique in wound closure of Gustilo type â ¢A and â ¢B open tibial fractures].

Objective: To explore the effectiveness of Nice knot technique for wound closure in Gustilo type ⅢA and ⅢB open tibial fractures. Methods: A retrospective study was performed on 22 patients with Gustilo type ⅢA and ⅢB open tibial fractures, who underwent wound closure using the Nice knot technique and were admitted between June 2021 and June 2022. There were 15 males and 7 females. The age ranged from 18 to 67 years, with an average of 41.9 years. The causes of injury included traffic accident in 11 cases, falling from height in 7 cases, and heavy object injuries in 4 cases. Fractures were located on the left side in 9 cases and on the right side in 13 cases. And 9 cases were type ⅢA fractures and 13 were type ⅢB fractures according to Gustilo classification. All patients had extensive soft tissue injuries, and no vascular or neurological damage was observed. The time from injury to debridement was 3-8 hours (mean, 6.5 hours). The sizes of wounds before operation and at 2 weeks after operation were measured and wound healing rate at 2 weeks after operation were calculated. The wound healing time and wound healing grading were recorded. The Vancouver Scar Scale (VSS) score was used to assess the wound scar after wound healed and the excellent and good rate was calculated. Results: The wound area was 21.0-180.0 cm 2 (mean, 57.82 cm 2) before operation, and it was 1.2-27.0 cm 2 (mean, 6.57 cm 2) at 2 weeks after operation. The wound healing rate at 2 weeks after operation was 76%-98% (mean, 88.6%). After operation, 2 cases needed to adjust Nice knot due to skin cutting and 1 case occurred soft tissue infection on the wound. The other patient's wounds healed. The average wound healing time was 27.8 days (range, 18-44 days). And the wound healing were grade A in 13 cases and grade B in 9 cases. VSS score was 2-9, with an average of 4.1; 10 cases were rated as excellent, 10 as good, and 2 as poor, with an excellent and good rate of 90.9%. All patients were followed up 9-24 months (mean, 14.6 months). During follow-up, no deep infection or osteomyelitis occurred. Two cases experienced fracture non-union, and were treated with compression fixation and bone grafting. The fractures of the other patients all healed, with a healing time of 85-190 days (mean, 148.2 days). Conclusion: Nice knot technique can be used in wound closure of Gustilo type ⅢA and ⅢB open tibial fractures effectively, which is easy to operate.

Causal Association between Circulating Metabolites and Dementia: A Mendelian Randomization Study.

The causal association of circulating metabolites with dementia remains uncertain. We assessed the causal association of circulating metabolites with dementia utilizing Mendelian randomization (MR) methods. We performed univariable MR analysis to evaluate the associations of 486 metabolites with dementia, Alzheimer's disease (AD), and vascular dementia (VaD) risk. For secondary validation, we replicated the analyses using an additional dataset with 123 metabolites. We observed 118 metabolites relevant to the risk of dementia, 59 of which were lipids, supporting the crucial role of lipids in dementia pathogenesis. After Bonferroni adjustment, we identified nine traits of HDL particles as potential causal mediators of dementia. Regarding dementia subtypes, protective effects were observed for epiandrosterone sulfate on AD (OR = 0.60, 95% CI: 0.48-0.75) and glycoproteins on VaD (OR = 0.89, 95% CI: 0.83-0.95). Bayesian model averaging MR (MR-BMA) analysis was further conducted to prioritize the predominant metabolites for dementia risk, which highlighted the mean diameter of HDL particles and the concentration of very large HDL particles as the predominant protective factors against dementia. Moreover, pathway analysis identified 17 significant and 2 shared metabolic pathways. These findings provide support for the identification of promising predictive biomarkers and therapeutic targets for dementia.

Associations of Regular Internet Usage with All-Cause and Cause-Specific Mortality: A Prospective Cohort Study.

OBJECTIVES: The impact of internet usage on mortality is not widely known. This study intended to investigate the associations between regular internet usage and the risks of all-cause and cause-specific mortality, while also ascertaining potential factors that may modify these correlations. DESIGN: A community-based prospective cohort study. SETTING AND PARTICIPANTS: The study included 21,481 individuals [mean (SD) age, 64.1 (11.0) years] from the Health and Retirement Study, with data collected between 2006 and 2020. METHODS: The Cox proportional hazards regression model was used to evaluate the associations between regular internet usage and the risks of all-cause and cause-specific mortality, adjusting for demographic factors, lifestyle behaviors, and other potential confounding factors. Moreover, we explored the association between daily hours of internet usage and the risk of outcomes. RESULTS: Regular internet usage was significantly associated with a lower risk of all-cause mortality (hazard ratio, 0.78; 95% CI, 0.74-0.83) and cardiovascular mortality (hazard ratio, 0.72; 95% CI, 0.64-0.82). No significant interaction effects were observed for age, sex, regular exercise, or current alcohol consumption (all P interactions > .05). Additionally, estimations for daily hours of usage indicated a U-shaped relationship with all-cause mortality. Adults who used 2.1 to 4 hours per day had the lowest risk; however, not all estimations showed their significance on account of the limited sample size. CONCLUSIONS AND IMPLICATIONS: Regular internet usage was associated with a lower risk of all-cause and cardiovascular mortality, which may prompt consideration of the beneficial impact of internet usage on lifespan.

Investigating Causal Associations between the Gut Microbiota and Dementia: A Mendelian Randomization Study.

Background: The causal association of specific gut microbiota with dementia remains incompletely understood. We aimed to access the causal relationships in which one or more gut microbiota account for dementia. Method: Using data from the MiBioGen and FinnGen consortia, we employed multiple Mendelian randomization (MR) approaches including two-sample MR (TSMR), multivariable MR (MVMR), and Bayesian model averaging MR to comprehensively evaluate the causal associations between 119 genera and dementia, and to prioritize the predominant bacterium. Result: We identified 21 genera that had causal effects on dementia and suggested Barnesiella (OR = 0.827, 95%CI = 0.722-0.948, marginal inclusion probability [MIP] = 0.464; model-averaged causal estimate [MACE] = -0.068) and Allisonella (OR = 0.770, 95%CI = 0.693-0.855, MIP = 0.898, MACE = -0.204) as the predominant genera for AD and all-cause dementia. Conclusions: These findings confirm the causal relationships between specific gut microbiota and dementia, highlighting the necessity of multiple MR approaches in gut microbiota analysis, and provides promising genera as potential novel biomarkers for dementia risk.

Corrigendum: A Novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fgene.2022.1068837.].

A novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive malignancies with increasing incidence worldwide. The oncogenic roles of transcription factors (TFs) were increasingly recognized in various cancers. This study aimed to develop a predicting signature based on TFs for the prognosis and treatment of HCC. Methods: Differentially expressed TFs were screened from data in the TCGA-LIHC and ICGC-LIRI-JP cohorts. Univariate and multivariate Cox regression analyses were applied to establish a TF-based prognostic signature. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the signature. Subsequently, correlations of the risk model with clinical features and treatment response in HCC were also analyzed. The TF target genes underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, followed by protein-protein-interaction (PPI) analysis. Results: A total of 25 differentially expressed TFs were screened, 16 of which were related to the prognosis of HCC in the TCGA-LIHC cohort. A 2-TF risk signature, comprising high mobility group AT-hook protein 1 (HMGA1) and MAF BZIP transcription factor G (MAFG), was constructed and validated to negatively related to the overall survival (OS) of HCC. The ROC curve showed good predictive efficiencies of the risk score regarding 1-year, 2-year and 3-year OS (mostly AUC >0.60). Additionally, the risk score independently predicted OS for HCC patients both in the training cohort of TCGA-LIHC dataset (HR = 2.498, p = 0.007) and in the testing cohort of ICGC-LIRI-JP dataset (HR = 5.411, p < 0.001). The risk score was also positively correlated to progressive characteristics regarding tumor grade, TNM stage and tumor invasion. Patients with a high-risk score were more resistant to transarterial chemoembolization (TACE) treatment and agents of lapatinib and erlotinib, but sensitive to chemotherapeutics. Further enrichment and PPI analyses demonstrated that the 2-TF signature distinguished tumors into 2 clusters with proliferative and metabolic features, with the hub genes belonging to the former cluster. Conclusion: Our study identified a 2-TF prognostic signature that indicated tumor heterogeneity with different clinical features and treatment preference, which help optimal therapeutic strategy and improved survival for HCC patients.

IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms.

Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.

Dietary Supplementation of n-3 LCPUFAs Prevents Salmonellosis in a Murine Model.

Salmonellosis is a world-wide epidemic, and n-3 long chain polyunsaturated fatty acids (LCPUFAs) possess various health benefits. This study is aimed to investigate the preventive effects of n-3 LCPUFAs against Salmonella infection. By pretreatment with n-3 LCPUFAs, but not n-6 LCPUFAs, the survival rate of the infected mice was increased. Further studies showed that n-3 LCPUFAs significantly increased the fecal contents of short-chain fatty acids (SCFAs). The cytokine expression in the liver and production in serum were both modulated by n-3 LCPUFAs into an anti-inflammatory profile against infection. Moreover, the changes in gut microbiota by n-3 LCPUFAs favored the host against pathogens, closely related to the modified SCFA production and immune responses. In conclusion, n-3 LCPUFAs prevented Salmonella infection through multiple mechanisms, especially by the interaction with gut microbiota and host immunology. Our results suggested great perspectives for n-3 LCPUFAs and their related products to control the prevalence of Salmonella, a most predominant food-borne pathogen.

Synergistic Effect of Eugenol and Probiotic Lactobacillus Plantarum Zs2058 Against Salmonella Infection in C57bl/6 Mice.

Previously, we showed the preventive effects of Lactobacillus plantarum ZS2058 (ZS2058) on Salmonella infection in murine models. In this work, we found that eugenol has a selective antibacterial effect, which inhibited Salmonella more than probiotics ZS2058 in vitro. It suggested a synergistic effect of them beyond their individual anti-Salmonella activity. We verified the conjecture in murine models. The results showed that the combination of ZS2058 and eugenol (CLPZE) significantly increased (p = 0.026) the survival rate of Salmonella-infected mice from 60% to 80% and the effect of CLPZE on preventing Salmonella-infection was 2-fold that of ZS2058 alone and 6-fold that of eugenol alone. CLPZE had a synergistic effect on inhibiting ST growth (the coefficient drug interaction ((CDI) = 0.829), reducing its invasiveness (CDI = 0.373) and downregulating virulence genes' expression in vitro. CLPZE helped the host form a healthier gut ecosystem. CLPZE also elicited a stronger and earlier immune response to systemic infection. In conclusion, these obtained results suggest that ZS2058 and eugenol have a synergistic effect on preventing Salmonella infection and open new perspectives in the strategies of controlling the prevalence of Salmonella by combination of probiotics and functional food components.

Multiple mechanisms applied by Lactobacillus pentosus AT6 to mute the lethal effects of Salmonella in a mouse model.

Probiotics are now prevalent world-wide, as functional food supplements with many benefits for humans and animals, such as protective effects against pathogenic infection. We showed that oral supplementation of Lactobacillus pentosus AT6 (AT6) decreased the mortality rate of mice with Salmonella infection. A series of experiments showed that the protective effects of AT6 on mice involved multiple mechanisms, including (1) the inhibition of Salmonella Typhimurium growth by AT6 or its cell-free culture supernatants (CFCSs); (2) the reduction of the bacterial loads of Salmonella Typhimurium in intestinal contents and internal organs, such as the liver and spleen; (3) the inhibition of adhesion and invasion of Salmonella Typhimurium into intestinal epithelial cells; and (4) the regulation of host immunities by modifying the production of a chain of cytokines. In conclusion, AT6 inhibited Salmonella infection via multiple mechanisms and therefore has great potential for the development of functional foods with anti-Salmonella activities.

Strain-specific properties of Lactobacillus plantarum for prevention of Salmonella infection.

Salmonella is a common food-borne pathogen; since lactobacilli show great potential for protecting against Salmonella infections, they are used as dietary supplements in functional foods. The aim of this study is to investigate the strain-specific properties and the involved mechanisms of action of Lactobacillus plantarum towards prevention of Salmonella infection. Mice were pretreated with mixed strains or single strain of Lactobacillus plantarum for 10 d prior to infection with Salmonella typhimurium SL1344, and the survival rates showed that lactobacilli exhibited strain-specific properties for preventing Salmonella infection. Then, in vitro and in vivo studies were carried out to investigate the involved mechanism of the strain-specific properties. The results showed that different Lactobacillus plantarum strains had different effects on inhibiting Salmonella growth, thus preventing adhesion to and invasion of epithelial cells by pathogens and enhancing immune responses. The present study demonstrated strain-specific properties of probiotics to prevent Salmonella infection and elucidated their underlying mechanisms.

Y-box binding protein-1 promotes hepatocellular carcinoma-initiating cell progression and tumorigenesis via Wnt/ß-catenin pathway.

Y-box binding protein-1 (YB-1) is a pleiotropic molecule that binds DNA to regulate genes on a transcriptional level in the nucleus and binds RNA to modulate gene translation in the cytoplasm. In our previous studies, YB-1 was also characterized as a fetal hepatic protein that regulates the maturation of hepatocytes and is upregulated during liver regeneration. Moreover, YB-1 has been shown to be expressed in human hepatocellular carcinoma (HCC). However, the role of YB-1 in HCC remains unclear. Here, we aimed to characterize the role of YB-1 in HCC. Based on the results of loss-of-function in HCC and gain-of-function in mice liver using hydrodynamic gene delivery, YB-1 promoted hepatic cells proliferation in vitro and in vivo. YB-1 was also involved in HCC cell proliferation, migration, and drug-resistance. The results of extreme limiting dilution sphere forming analysis and cancer initiating cell marker analysis were also shown that YB-1 maintained HCC initiating cells population. YB-1 also induced the epithelial-mesenchymal transition and stemness-related gene expression. Knockdown of YB-1 suppressed the expression of Wnt ligands and ß-catenin, impaired Wnt/ß-catenin signaling pathway and reduced the numbers of HCC initiating cells. Moreover, YB-1 displayed nuclear localization particularly in the HCC initiating cells, the EpCAM+ cells or sphere cells. Our findings suggested that YB-1 was a key factor in HCC tumorigenesis and maintained the HCC initiating cell population.

Carboxymethylcellulose with phenolic hydroxyl microcapsules enclosinggene-modified BMSCs for controlled BMP-2 release in vitro.

OBJECTIVES: The present study aimed to develop microparticles of phenolic hydroxyl derivative of carboxymethylcellulose (CMC-Ph) via Co-flow microfluidics technology and encapsulated gene-modified rat bone mesenchymal stem cells (BMSCs) for the detection of the growth factor release was controlled by Tet-on system. Meanwhile, we investigated the effect of the CMC-Ph microcapsules and Lentiviral transduction on osteogenesis of BMP2-BMSCs. METHODS: The middle size of CMC-Ph microcapsules was prepared by optimized co-flow microfluidics through ejecting fluid CMC-Ph suspension (mixed with HRP) into co-flowing liquid paraffin which blends H2O2 at priority. The Lentivirus-encoding hBMP-2 and Tet-On system were constructed and amplified by RT-PCR, then encapsulated in the microcapsules. The cellular viability of CMC-Ph microparticles was assessed by Live/dead staining and metabolic activity was estimated by colorimetric assay kit. In addition, BMP-2 secretion and kinetic studies were determined by ELISA, alkaline phosphatase (ALP) activity was evaluated using ALP assay kit, and ALP staining as well as mineral calcium deposition was detected by alizarin red S staining. KEY FINDINGS: The diameter of CMC-Ph microparticles was controlled between 100 and 150 µm by altering the flow speed of liquid paraffin and then encapsulated bone morphogenetic protein 2 (BMP-2) gene modified BMSCs transduced by a lentiviral vector. Moreover, the mitochondrial activity of the encapsulated cells was maintained at least 24 d and BMP-2 protein secretion into the supernatant sustained for 35 d without significant loss of efficiency under the induction of the doxycycline. Furthermore, mineral deposition staining and ALP activity detection showed that encapsulated lentiviral-BMP2 transduced BMSCs possess more osteogenic differentiation potential than normal cells. CONCLUSIONS: Co-flow microfluidics and phenolic hydroxyl derivative of carboxymethylcellulose (CMC-Ph) provide a promising strategy for cell-enclosed microcapsules in combination with BMP-2 gene and Tet-on system modified BMSCs and then controlled BMP-2 protein released effectively as well as promoted the osteogenic differentiation of BMSCs.