Effects of dietary phytosterols or phytosterol esters supplementation on growth performance, biochemical blood indices and intestinal flora of C57BL/6 mice.

This study was conducted to evaluate the effects of phytosterols (PS) and phytosterol esters (PSE) on C57BL/6 mice. Three groups of 34 six-week-old C57BL/6 mice of specific pathogen free (SPF) grade, with an average initial body weight (IBW) of 17.7g, were fed for 24 days either natural-ingredient diets without supplements or diets supplemented with 89 mg/kg PS or diets supplemented with 400 mg/kg PSE. Growth performance, blood biochemistry, liver and colon morphology as well as intestinal flora status were evaluated. Both PS and PSE exhibited growth promotion and feed digestibility in mice. In blood biochemistry, the addition of both PS and PSE to the diet resulted in a significant decrease in Total Cholesterol (TC) and Triglyceride (TG) levels and an increase in Superoxide Dismutase (SOD) activity. No significant changes in liver and intestinal morphology were observed. Both increased the level of Akkermansia in the intestinal tract of mice. There was no significant difference between the effects of PS and PSE. It was concluded that dietary PS and PSE supplementation could improve growth performance, immune performance and gut microbiome structure in mice, providing insights into its application as a potential feed additive in animals production.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Causal associations between genetically determined common psychiatric disorders and the risk of falls: evidence from Mendelian randomization.

BACKGROUND: The causal associations between psychiatric disorders and falls risk remains uncertain. Consequently, this study aimed to explore the causal relationship between genetically determined three common psychiatric disorders and the risk of falls based on Mendelian randomization (MR). METHODS: The genome-wide association study (GWAS) data for schizophrenia (SCZ) (N = 320,404), major depressive disorder (MDD) (N = 480,359), and Alzheimer's disease (AD) (N = 63,926) were obtained as exposures. The GWAS data for falls risk (N = 451,179) was obtained as outcome. Univariate Mendelian randomization (UVMR) was used to evaluate the direct causal relationship between SCZ, MDD, AD, and risk of falls. Inverse variance weighting (IVW) was used as the primary analysis method. Sensitivity analysis was performed to assess the validity of the casualty. Multivariate Mendelian randomization (MVMR) analysis was conducted after adjusting body mass index and smoking initiation. Mediating MR was conducted to calculate the mediating effects of potential intermediaries. RESULTS: UVMR analysis showed that SCZ (OR 1.02, 95% CI 1.01-1.04, p = 8.03E-03) and MDD (OR 1.15, 95% CI 1.08-1.22, p = 1.38E-05) were positively associated with the risk of falls. Sensitivity analysis results were reliable and robust. MVMR results indicated that the relationship between MDD and SCZ and falls risk remained significant. Mediating MR results demonstrated that smoking initiation mediated partial causal effect of SCZ (0.65%, P = 0.03) and MDD (14.82%, P = 2.02E-03) on risk of falls. CONCLUSIONS: This study provides genetic evidence for a causal relationship of individuals with SCZ and MDD on an increased risk of falls. Healthcare providers should be aware of the risk of falls in MDD and SCZ patients and develop strategies accordingly.

Management of Intraductal Papilloma of the Breast Diagnosed on Core Needle Biopsy: Latest Controversies.

Intraductal papillomas (IDPs), including central papilloma and peripheral papilloma, are common in the female population. Due to the lack of specific clinical manifestations of IDPs, it is easy to misdiagnose or miss diagnose. The difficulty of differential diagnosis using imaging techniques also contributes to these conditions. Histopathology is the gold standard for the diagnosis of IDPs while the possibility of under sample exists in the percutaneous biopsy. There have been some debates about how to treat asymptomatic IDPs without atypia diagnosed on core needle biopsy (CNB), especially when the upgrade rate to carcinoma is considered. This article concludes that further surgery is recommended for IDPs without atypia diagnosed on CNB who have high-risk factors, while appropriate imaging follow-up may be suitable for those without risk factors.

Effects of obesity with reduced 25(OH)D levels on bone health in elderly Chinese people: a nationwide cross-sectional study.

Background: Obesity is often accompanied by lower 25(OH)D levels, whereas these two parameters exhibit opposite effects on bone health. It is uncertain what are the effects of lower 25(OH)D levels in obesity on bone health in elderly Chinese people. Methods: A nationally representative cross-sectional analysis of China Community-based Cohort of Osteoporosis (CCCO) was performed from 2016 to 2021, which consisted of 22,081 participants. Demographic data, disease history, Body mass index (BMI), bone mineral density (BMD), the levels of the biomarkers of vitamin D status and those of bone metabolism markers were measured for all participants (N = 22,081). The genes (rs12785878, rs10741657, rs4588, rs7041, rs2282679 and rs6013897) related to 25(OH)D transportation and metabolism were performed in a selected subgroup (N = 6008). Results: Obese subjects exhibited lower 25(OH)D levels (p < 0.05) and higher BMD (p < 0.001) compared with those of normal subjects following adjustment. The genotypes and allele frequency of rs12785878, rs10741657, rs6013897, rs2282679, rs4588 and rs7041 indicated no significant differences among three BMI groups following correction by the Bonferroni's method (p > 0.05). The levels of total 25(OH)D (ToVD) were significantly different among the GC1F, GC1S and GC2 haplotype groups (p < 0.05). Correlation analysis indicated that ToVD levels were significantly correlated with parathyroid hormone levels, BMD, risk of osteoporosis (OP) and the concentration levels of other bone metabolism markers (p < 0.05). Generalized varying coefficient models demonstrated that the increasing BMI, ToVD levels and their interactions were positively associated with BMD outcomes (p < 0.001), whereas the reduced levels of ToVD and BMI increased the risk of OP, which was noted notably for the subjects with reduced ToVD levels (less than 20.69 ng/ml) combined with decreased BMI (less than 24.05 kg/m2). Conclusion: There was a non-linear interaction of BMI and 25(OH)D. And higher BMI accompanied by decreased 25(OH)D levels is associated with increased BMD and decreased incidence of OP, optimal ranges exist for BMI and 25(OH)D levels. The cutoff value of BMI at approximately 24.05 kg/m2 combined with an approximate value of 25(OH)D at 20.69 ng/ml are beneficial for Chinese elderly subjects.

Integrated Analysis of Gut Microbiome and Liver Metabolome to Evaluate the Effects of Fecal Microbiota Transplantation on Lipopolysaccharide/D-galactosamine-Induced Acute Liver Injury in Mice.

Acute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.

Correlation between the non-use of cooking oil fume extractors and bone mineral density in population aged 45 years and older in China: a cross-sectional study.

Introduction: The correlation between the non-use of cooking oil fumes (COFs) extractors and bone mineral density (BMD) have not been clarified. Consequently, this study attempted to explore the impact of non-use COFs extractors on BMD in population aged 45 years and older based on a cross-sectional study. Methods: This study was a cross-sectional study within the framework of an ongoing prospective population-based cohort study in China. The multivariate linear regression models were used to evaluate the correlation between the non-use of fume extractors in family cooking and total lumbar spine (LS), femoral neck (FN), total hip BMD and levels of bone metabolism markers. Results: A total of 3433 participants were included in the final analyses, of which 2607 (75.93%) participants used fume extractors. The results of models indicated that there were significant correlations of the non-use of fume extractors on total LS BMD (ß = -0.024, 95% CI, -0.036, -0.012, p < 0.001), PINP (ß = 4.363, 95% CI, 2.371, 6.356, p < 0.001) and ALP (ß = 4.555, 95% CI, 2.593, 6.517, p < 0.001) levels. Conclusions: This study verified that the use of fume extractors is an efficacious measure to prevent LS bone loss. For the sake of public bone health, people should install a fume extractor in the kitchen and use it routinely when cooking.

Effects of Dietary Multienzyme Complex Supplementation on Growth Performance, Digestive Capacity, Histomorphology, Blood Metabolites and Hepatic Glycometabolism in Snakehead (Channa argus).

The present study evaluated the impact of dietary multienzyme complex (MEC) supplementation on growth performance, digestive enzyme activity, histomorphology, serum metabolism and hepatopancreas glycometabolism in snakeheads (Channa argus). A total of 600 fish (initial weight, 69.70 ± 0.30 g) were randomly divided into four groups. Four diets were formulated: (1) control (basic diet); (2) E1 (400 U kg-1 amylase, 150 U kg-1 acid protease, 1900 U kg-1 neutral protease and basic diet); (3) E2 (800 U kg-1 amylase, 300 U kg-1 acid protease, 3800 U kg-1 neutral protease and basic diet); and (4) E3 (1200 U kg-1 amylase, 450 U kg-1 acid protease, 5700 U kg-1 neutral protease and basic diet). The results show that the E2 group increased the specific growth rate, weight gain rate and the final body weight, as well as decreasing the blood urea nitrogen, alanine aminotransferase and triglyceride. The mRNA levels and activities of digestive enzymes and key glucose metabolism enzymes in the hepatopancreas were enhanced in snakeheads fed the MEC. Meanwhile, moderate MEC diet (E2 groups) supplementation improved digestive tract morphology, increased the glycogen in the hepatopancreas and the lipids in the dorsal muscle. Moreover, plasma metabolomics revealed differential metabolites mainly involved in amino acid metabolism. These findings suggest that dietary supplementation with the MEC improved growth performance, digestive tract morphology, gene expression and the activity of digestive enzymes, enhanced the glycolysis-gluconeogenesis and amino acid metabolism of snakeheads, and the optimal composition of the MEC was group E2.

Chinese Medicine Phenomics (Chinmedphenomics): Personalized, Precise and Promising.

The systematicness of phenomics and Traditional Chinese Medicine (TCM) enable these two disciplines to interlink with each other. This article discussed the similarity in theory and application between TCM and phenomics and illustrates their respective advantages in diagnosis and treatment of diseases, forming a new discipline eventually. Chinese medicine phenomics (Chinmedphenomics) is built on classic TCM, combined with phenomics technology, and the development of which needs the mega cohort with TCM syndrome and the characteristics of precision medicine as well as multi-disciplinary cooperation, which is personalized, precise and promising, providing unique scientific insights into understanding human health.

Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice.

Introduction: Campylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host's innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a central role in resistance to C. jejuni infection have not been explored. Methods: We treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques. Results: We first investigated the therapeutic effect of FMT on C. jejuni infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of C.jejuni into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that C.jejuni induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of C. jejuni and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by C. jejuni, with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by C. jejuni. Discussion: This is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by C. jejuni and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens.