Causal relationship of genetically predicted gut microbiota with thyroid cancer: a bidirectional two-sample mendelian randomization study.

Background: Previous investigations have demonstrated a correlation between the composition of gut microbiota and the development of thyroid cancer (TC). Nonetheless, there was no consensus on the causal effect of gut microbiota composition on TC risk. Therefore, the present study aimed to perform a bidirectional two-sample Mendelian randomization (MR) analysis to explore potential causal associations between gut microbiota and TC risk. Methods: Utilizing data from the MiBioGen consortium's genome-wide association studies (GWAS) meta-analysis involving a sample size of 18,340, we identified instrumental variables for 211 gut microbiota taxa. The summary statistics for TC was from relevant large-scale GWAS conducted by the FinnGen consortium. In the first stage, the Inverse-variance weighted (IVW) method was used as the primary estimate method, and the stability of estimations was tested by a battery of sensitivity analyses. In the second stage, a reverse MR analysis was applied to determine whether reverse causality existed. Results: According to the IVW method, we identified 9 genetically predicted gut microbiota that were causally correlated with TC risk. Among them, we observed a positive causal effect of Family Christensenellaceae (OR = 1.664, 95% CI: 1.103-2.511, P = 0.015), Family Victivallaceae (OR = 1.268, 95% CI: 1.009-1.594, P = 0.042), Genus Methanobrevibacter (OR = 1.505, 95% CI: 1.049-2.159, P = 0.027), Genus Ruminococcus2 (OR = 1.846, 95% CI: 1.261-2.704, P = 0.002), Genus Subdoligranulum (OR = 1.907, 95% CI: 1.165-3.121, P = 0.010), Phylum Verrucomicrobia (OR = 1.309, 95% CI: 1.027-1.668, P = 0.029) on TC risk, while Class Betaproteobacteria (OR = 0.522, 95% CI: 0.310-0.879, P = 0.015), Family Family XI (OR = 0.753, 95% CI: 0.577-0.983, P = 0.037), Genus Sutterella (OR = 0.596, 95% CI: 0.381-0.933, P = 0.024) might be correlated with a decreased risk of TC. Subsequently, various sensitivity analyses indicated no heterogeneity, directional pleiotropy or outliers. In addition, reverse analysis demonstrated a negative causal effect of TC risk on the abundance of the gut microbiota (Genus Ruminococcus2, OR = 0.947, 95% CI: 0.907-0.989, P = 0.014). Conclusion: Genetic evidence suggested that bidirectional causal associations of specific bacteria taxa and the risk of TC, highlighting the association of the "gut-thyroid" axis. Further exploration of the potential microbiota-related mechanisms might have profound implications for public health in terms of the early prevention and treatment of TC.

Association between the dietary inflammatory index and all-cause mortality in the U.S. cancer survivors: A prospective cohort study using the National Health and Nutrition Examination Survey database.

Background: Cancer remains one of the leading causes of mortality worldwide. Diet can impact inflammation and consequently affect cancer outcomes. The Dietary Inflammatory Index (DII) can serve as a tool to assess the inflammatory potential of cancer survivors' diets and further predict their survival. Objectives: To investigate the relationship between the DII and the survival of cancer survivors in National Health and Nutrition Examination Survey (NHANES). Methods: An overall sample of 2359 U.S. cancer survivors from the 2005-2014 cohorts of the NHANES were studied. The DII scores were calculated using 28 dietary components and the mortality status was ascertained until December 31, 2015. Based on the multiple analyses, the relationship between DII and all-cause mortality was examined. Results: The weighted mean age at baseline was 65.17 ± 14.46 years, 53.16 % were female and 71.30 % were non-Hispanic white. The average DII was 1.51 ± 1.97. After accounting for multiple covariates, positive associations were observed (P < 0.01). Based on Kaplan-Meier survival curves, their significant relationship remains same and the survival probability was decreased among the groups of anti-inflammatory diets (DII < 0) versus pro-inflammatory diets (DII ≥ 0) significantly (Log rank test; P = 0.03). Further analyses were conducted on subgroups and the results are still robust. Conclusions: An elevated DII was associated with a rising mortality rate among cancer survivors. DII might serve as a potential inflammatory predictor of cancer mortality prognosis, as well as guide nutritional care and even clinical treatment of cancer survivors.

Association between inflammatory markers and bone mineral density: a cross-sectional study from NHANES 2007-2010.

PURPOSE: Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) are acknowledged as novel inflammatory markers. However, studies investigating the correlation between inflammatory markers and osteoporosis (OP) remain scarce. We aimed to investigate the relationship between NLR, MLR, PLR and bone mineral density (BMD). METHODS: A total of 9054 participants from the National Health and Nutrition Examination Survey were included in the study. MLR, NLR and PLR were calculated for each patient based on routine blood tests. Given the complex study design and sample weights, the relationship between inflammatory markers and BMD was evaluated through weighted multivariable-adjusted logistic regression and smooth curve fittings. In addition, several subgroup analyses were conducted to assess the robustness of the outcomes. RESULTS: This study observed no significant relationship between MLR and lumbar spine BMD (P = 0.604). However, NLR was positively correlated with lumbar spine BMD (ß = 0.004, 95% CI: 0.001 to 0.006, P = 0.001) and PLR was negatively linked to lumbar spine BMD (ß = - 0.001, 95% CI: - 0.001 to - 0.000, P = 0.002) after accounting for covariates. When bone density measurements were changed to the total femur and femoral neck, PLR was still significantly positively correlated with total femur (ß = - 0.001, 95% CI: - 0.001, - 0.000, P = 0.001) and femoral neck BMD (ß = - 0.001, 95% CI: - 0.002, - 0.001, P < 0.001). After converting PLR to a categorical variable (quartiles), participants in the highest PLR quartile had a 0.011/cm2 lower BMD than those in the lowest PLR quartile (ß = - 0.011, 95% CI: - 0.019, - 0.004, P = 0.005). According to subgroup analyses stratified by gender and age, the negative correlation with PLR and lumbar spine BMD remained in males and age < 18 groups, but not in female and other age groups. CONCLUSIONS: NLR and PLR were positively and negatively correlated with lumbar BMD, respectively. And PLR might serve as a potential inflammatory predictor of osteoporosis outperforming MLR and NLR. The complex correlation between the inflammation markers and bone metabolism requires further evaluation in large prospective studies.

S100P promotes trophoblast syncytialization during early placenta development by regulating YAP1.

Recurrent pregnancy loss (RPL) is a severe complication of pregnancy that is caused by genetic abnormalities, immune dysfunction, aberrant cell biology, and tissue structure destruction. Among which, placental dysfunction is crucial in the pathogenetic progression of RPL. Although some regulatory factors associated with RPL have been reported, the placental changes correlated with RPL still need to be elucidated. Here, we found that a portion of RPL patients presented with low serum and placental S100P expression. Using a human trophoblast stem cell model, we demonstrated that S100P was exclusively expressed in syncytiotrophoblast (ST)-like syncytia (ST(2D)-TSCT) and that loss of S100P expression in ST(2D)-TSCT cells impaired ß-hCG secretion, leading to syncytialization failure during early placental development. Moreover, we found that S100P is involved in regulating trophoblast syncytialization by downregulating the protein level of Yes-associated protein 1 (YAP1), which plays a pivotal role in maintaining trophoblast stemness. Together, our findings suggest that S100P plays an essential role in regulating trophoblast syncytialization during early placental development in humans via YAP1. Additionally, lower serum S100P levels may predict poor pregnancy outcomes and represent a potentially useful marker for evaluating placental biological function during early pregnancy.

Icariin, an Up-and-Coming Bioactive Compound Against Neurological Diseases: Network Pharmacology-Based Study and Literature Review.

Icariin is a biologically active substance in Epimedii herba that is used for the treatment of neurologic disorders. However, a comprehensive analysis of the molecular mechanisms of icariin is lacking. In this review, we present a brief history of the use of icariin for medicinal purposes; describe the active chemical components of Epimedii herba; and examine the evidence from experimental studies that have uncovered molecular targets of icariin in different diseases. We also constructed a protein-protein interaction network and carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses to predict the therapeutic actions of icariin in nervous system diseases including Alzheimer disease, Parkinson disease, ischemic stroke, depressive disorder, multiple sclerosis, glioblastoma, and hereditary spastic paraplegias. The results of our analyses can guide future studies on the application of icariin to the treatment of neurologic disorders.

Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin-avidin-specific binding.

Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin-avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM-1 s-1) was observed compared to Magnevist® (4.9 mM-1 s-1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor.