Association between standing height and physical disability among U.S. adults aged 60 years and older: findings from NHANES 2015-2018.

BACKGROUND: Physical disability is an important cause of affecting the quality of life in the elderly. The association between standing height and physical disability is less studied. PURPOSE: The purpose of this study is to investigate the possible link between standing height and physical disability among U.S. adults aged 60 years and older. METHODS: The cross-sectional data were obtained from the US National Health and Nutrition Examination Survey (NHANES) 2015-2018. Physical disability was assessed by six questions: "Have serious difficulty hearing (SDH)?", "Have serious difficulty seeing (SDS)?", "Have serious difficulty concentrating (SDC)?", "Have serious difficulty walking (SDW)?", "Have difficulty dressing or bathing (DDB)?" and "Have difficulty doing errands alone (DDEA)?". Responses to these questions were "yes" or "no". Answer yes to one of the above six questions was identified as physical disability. Standing height (cm) was measured with an altimeter. Multivariate logistic regression was performed to examine the possible link between standing height and physical disability after adjustment for all covariates. RESULTS: A total of 2624 participants aged ≥ 60 years were included in our study, including 1279 (48.7%) females and 1345 (51.3%) males. The mean age of participants was 69.41 ± 6.82 years. After adjusting for all potential confounders, the inverse relationship between standing height and all physical disability (APD) was statistically significant (OR = 0.976, 95%CI:0.957-0.995). In addition, among six types of physical disability (SDH, SDS, SDC, SDW, DDB, DDEA), standing height was also a protective factor for SDW (OR = 0.961, 95%CI:0.939-0.983) and DDEA (OR = 0.944, 95%CI:0.915-0.975) in the full-adjusted model. CONCLUSION: The cross-sectional population based study demonstrates that standing height is a protective factor for physical disability among U.S. adults aged 60 years and older.

Effects of Different Surface Functionalizations of Silica Nanoparticles on Mesenchymal Stem Cells.

Physicochemical properties of nanoparticles, such as particle size, surface charge, and particle shape, have a significant impact on cell activities. However, the effects of surface functionalization of nanoparticles with small chemical groups on stem cell behavior and function remain understudied. Herein, we incorporated different chemical functional groups (amino, DETA, hydroxyl, phosphate, and sulfonate with charges of +9.5, + 21.7, -14.1, -25.6, and -37.7, respectively) to the surface of inorganic silica nanoparticles. To trace their effects on mesenchymal stem cells (MSCs) of rat bone marrow, these functionalized silica nanoparticles were used to encapsulate Rhodamine B fluorophore dye. We found that surface functionalization with positively charged and short-chain chemical groups facilitates cell internalization and retention of nanoparticles in MSCs. The endocytic pathway differed among functionalized nanoparticles when tested with ion-channel inhibitors. Negatively charged nanoparticles mainly use lysosomal exocytosis to exit cells, while positively charged nanoparticles can undergo endosomal escape to avoid scavenging. The cytotoxic profiles of these functionalized silica nanoparticles are still within acceptable limits and tolerable. They exerted subtle effects on the actin cytoskeleton and migration ability. Last, phosphate-functionalized nanoparticles upregulate osteogenesis-related genes and induce osteoblast-like morphology, implying that it can direct MSCs lineage specification for bone tissue engineering. Our study provides insights into the rational design of biomaterials for effective drug delivery and regenerative medicine.

Bayesian network analysis of factors influencing type 2 diabetes, coronary heart disease, and their comorbidities.

OBJECTIVE: Bayesian network (BN) models were developed to explore the specific relationships between influencing factors and type 2 diabetes mellitus (T2DM), coronary heart disease (CAD), and their comorbidities. The aim was to predict disease occurrence and diagnose etiology using these models, thereby informing the development of effective prevention and control strategies for T2DM, CAD, and their comorbidities. METHOD: Employing a case-control design, the study compared individuals with T2DM, CAD, and their comorbidities (case group) with healthy counterparts (control group). Univariate and multivariate Logistic regression analyses were conducted to identify disease-influencing factors. The BN structure was learned using the Tabu search algorithm, with parameter estimation achieved through maximum likelihood estimation. The predictive performance of the BN model was assessed using the confusion matrix, and Netica software was utilized for visual prediction and diagnosis. RESULT: The study involved 3,824 participants, including 1,175 controls, 1,163 T2DM cases, 982 CAD cases, and 504 comorbidity cases. The BN model unveiled factors directly and indirectly impacting T2DM, such as age, region, education level, and family history (FH). Variables like exercise, LDL-C, TC, fruit, and sweet food intake exhibited direct effects, while smoking, alcohol consumption, occupation, heart rate, HDL-C, meat, and staple food intake had indirect effects. Similarly, for CAD, factors with direct and indirect effects included age, smoking, SBP, exercise, meat, and fruit intake, while sleeping time and heart rate showed direct effects. Regarding T2DM and CAD comorbidities, age, FBG, SBP, fruit, and sweet intake demonstrated both direct and indirect effects, whereas exercise and HDL-C exhibited direct effects, and region, education level, DBP, and TC showed indirect effects. CONCLUSION: The BN model constructed using the Tabu search algorithm showcased robust predictive performance, reliability, and applicability in forecasting disease probabilities for T2DM, CAD, and their comorbidities. These findings offer valuable insights for enhancing prevention and control strategies and exploring the application of BN in predicting and diagnosing chronic diseases.

Association between vitamin C in serum and trouble sleeping based on NHANES 2017-2018.

Vitamin C is an important micronutrient for human. Association between vitamin C and trouble sleeping was less studied. Therefore, the purpose of this study was to investigate the possible link between vitamin C in serum and trouble sleeping. The cross-sectional data was derived from the National Health and Nutrition Examination Survey (NHANES, 2017-2018). Trouble sleeping was measured by asking participants: "Have you ever told doctor had trouble sleeping". Responses to this question was "yes" or "no". vitamin C in serum was obtained by measuring the serum samples. We used multivariable binary logistic regressions to examine the possible link between vitamin C in serum and trouble sleeping, and then a subgroup analysis was performed. Moreover, the non-linear relationship between vitamin C in serum and trouble sleeping was further detected using a restricted cubic spline (RCS) model. A total of 3227 participants were included in the study. After adjusting all potential confounders, the results of multivariable logistic regression showed the significant negative association between vitamin C in serum and trouble sleeping(OR = 0.816; 95% CI:0.669 ~ 0.995). The significant inverse association was also found in female(OR = 0.713; 95% CI:0.546 ~ 0.931), age ≤ 65 years(OR = 0.773; 95% CI:0.600 ~ 0.996), and in participants with high cholesterol level(OR = 0.738; 95% CI:0.548 ~ 0.994). In addition, the RCS model demonstrated the significant non-linear relationship between vitamin C in serum and trouble sleeping (P value of nonlinear = 0.010). Our study demonstrates the significant negative association between vitamin C in serum and trouble sleeping.

Role of remnant cholesterol in the relationship between physical activity and diabetes mellitus: an intermediary analysis.

Objective: The purpose of this investigation was to evaluate the potential link between physical activity (PA) and the heightened susceptibility to diabetes mellitus (DM), by examining whether remnant cholesterol (RC) might act as a mediator in this correlation. Methods: The research utilized data from the National Health and Nutrition Examination Survey, spanning from 2005 to 2018. Various statistical analyses were conducted for continuous and categorical variables, including the t-test, ANOVA, and χ2 test. Logistic regression was employed to analyze the association between PA and DM across three distinct models. Mediation analysis was also conducted to assess the potential mediation effects of RC. Results: The study encompassed a total of 9,149 participants, and it was observed that individuals with DM exhibited lower levels of PA. Furthermore, PA levels were found to be associated with all participant characteristics except poverty income ratio, fasting blood glucose, and HOMA-IR (p < 0.05). After adjusting for covariates (Model 3), individuals with high PA levels demonstrated a decreased likelihood of developing DM compared to those in the low PA group (OR: 0.73, 95%CI: 0.54-0.99). A significant dose-response relationship was identified (p < 0.05). No interaction between PA and RC in relation to DM risk was detected, and RC was found to serve as a mediator in the connection between PA and DM. After considering covariates, the mediating effect of RC between PA and DM weakens. Discussion: Our findings suggest that higher levels of PA are linked to a reduced risk of DM in U.S. adults, with RC likely playing a mediating role.

Associations between dietary inflammatory index and stroke risk: based on NHANES 2005-2018.

The dietary inflammatory index (DII) is a measure of the inflammatory potential of the diet and is closely associated with insulin resistance (IR) and stroke. And IR may play an important role in the development of stroke. Therefore, this study aimed to evaluate the relationship between DII and stroke risk while delving into the potential role of IR in this association. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, performing weighted univariate analyses, logistic regression, and mediation analyses. At baseline, 3.89% of participants developed stroke, and we observed stroke patients exhibited higher DII scores. After adjusting for covariates, compared to participants in the first quartile of DII scores, those in the third quartile and fourth quartile had increased odds of experiencing a stroke (OR: 1.78, 95% CI: 1.18-2.68) and (OR: 1.70, 95% CI: 1.16-2.50), respectively. Moreover, a significant dose-response relationship was observed (P-trend < 0.05). However, there was no observed interaction between DII and homeostatic model assessment-IR (HOMA-IR) concerning stroke risk, and HOMA-IR did not mediate the association between DII and stroke. In summary, our study elucidated the significant association between DII and stroke risk, independent of IR. This insight suggests that an anti-inflammatory diet may serve as an effective strategy for stroke prevention.

A meta-analysis of the accuracy of Xpert MTB/RIF in diagnosing intestinal tuberculosis.

OBJECTIVE: A detection method with high efficiency and accuracy is urgently needed in clinical work. The purpose of our study was to determine the diagnostic accuracy of the Xpert MTB/RIF assay for intestinal tuberculosis (ITB). METHODS: We searched PubMed and 4 other databases from their establishment to July 19, 2022, for published essays of diagnostic performance in which Xpert MTB/RIF was used to test patients with clinically suspected ITB. An assessment of the quality of the selected literature was conducted using QUADAS-2. We built forest plots by MetaDiSc software. RESULTS: The pooled Xpert MTB/RIF sensitivity was 48%, and the specificity was 99%. Moreover, the positive likelihood ratio for ITB diagnosis was 21.61. The negative likelihood ratio was 0.54. There were substantial variations between the study estimates of sensitivity (I2 = 87.6%) and specificity (I2 = 82.4%). CONCLUSION: Intestinal TB is detected with limited diagnostic sensitivity by Xpert MTB/RIF but with high specificity. An Xpert-positive result may facilitate the rapid identification of ITB cases. Nevertheless, a negative result has less certainty in excluding the disease.

[Effect of vitamin D binding protein gene polymorphism on susceptibility and prognosis of severe acute pancreatitis].

OBJECTIVE: To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP). METHODS: A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence. RESULTS: The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (µg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (µg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05). CONCLUSIONS: The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.

The association between dietary inflammation index and depression.

Objective: We aimed to evaluate whether depression is associated with increased risk of dietary inflammatory index (DII) or energy-adjusted DII (E-DII) and whether the association is partly explained by insulin resistance (IR). Methods: Base on the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Univariate analyses of continuous and categorical variables were performed using t-test, ANOVA, and χ 2 test, respectively. Logistic regression was used to analyze the relationship between DII or E-DII and depression in three different models. Mediation analysis was used to assess the potential mediation effects of homeostatic model assessment-IR (HOMA-IR). Results: A total of 70,190 participants were included, and the DII score was higher in the depressed group. DII score was related to all participant characteristics except age (p < 0.05). After being included in covariates (Model 3), participants in the highest quartile of DII score have increased odds of depression (OR: 1.82, 95% CI: 1.28-2.58) compared with those in the first quartile of DII score. And, a significant dose-response relationship was found (p-trend <0.05). No interaction between DII and HOMA-IR was observed in terms of the risk of depression, and HOMA-IR did not find to play a mediating role in the association between DII and depression. Similar results were obtained for the association between E-DII and depression. Conclusion: Our results suggest that a higher pro-inflammatory diet increases the risk of depression in U.S. adults, while there was no evidence of a multiplicative effect of DII or E-DII and HOMA-IR on disease risk, nor of a mediating effect of HOMA-IR.

Study on the role of calcium channel protein TRPV4 in the inflammatory pathway of type 2 diabetic adipose tissue based on gene databases.

BACKGROUND: Chronic inflammation of adipose tissue may be one of the key factors contributing to the development of insulin resistance in T2DM adipose tissue. Transient receptor potential vanilloid type 4 (TRPV4) can be involved in a variety of cellular inflammatory responses. In this study, we evaluated the role of TRPV4 channelin in the T2DM adipose tissue inflammatory pathway. METHODS: Based on the gene expression profiling data of the public database, bioinformatics methods were used to screen the target gene population of the TRPV4 channel protein involved in the regulation of T2DM fat cells. A mature adipocyte model was constructed to verify the expression level of target genes and to evaluate the regulatory effect of TRPV4 channel inhibition on target genes of inflammation-related pathways. RESULTS: In shTRPV4 adipocytes, 144 genes with downregulation expression were screened, a PPI network was constructed and a core module containing 15 genes was screened out, and the core genes were mainly enriched in the Toll-like receptor signaling pathway through enrichment analysis. Constructing a mature adipocyte model found that the TRPV4 inhibitor HC067047 inhibited the effect of upregulation of the expression level of the relevant gene in the signaling pathway. CONCLUSIONS: Our findings suggest that the expression of highly expressed pro-inflammatory cytokines and chemokines in T2DM adipose tissue decreases after inhibiting the expression of TRPV4 in adipocytes, suggesting that TRPV4 may become a potential drug target for the treatment of T2DM.

Genetically predicted lifestyle factors, socioeconomic status and risk of coronary artery disease in individuals with diabetes: a Mendelian randomization study.

Background: This study explores the causal links between genetically predicted lifestyle factors, socioeconomic status, and coronary artery disease (CAD) risk in individuals with diabetes using a bidirectional Mendelian-randomization approach. Methods: This study explored the potential causal relationships of lifestyle factors and socioeconomic status with the risk of CAD in diabetes patients by a bidirectional, two-sample Mendelian-randomization (MR) analysis. Results: Genetically predicted smoking initiation (p = 0.005, 95% CI: 1.08-1.55) and insomnia (p = 0.001, 95% CI: 1.06-1.29) were associated with a higher risk of CAD in individuals with diabetes, whereas educational attainment (p = 0.0001, 95% CI: 0.47-0.78) was associated with a lower risk of CAD. The lifetime smoking index (p = 0.016, 95% CI: 1.12-3.03) was suggestively associated with a higher risk of CAD, while household income before taxes (p = 0.048, 95% CI: 0.41-1.00) was suggestively associated with a lower risk of CAD. In addition, we observed a suggestive negative association between the genetically predicted risk of CAD and the lifetime smoking index (p = 0.016, 95% CI: 0.98-0.99) and a significant causal relationship between the risk of CAD and household income before taxes (p = 0.006, 95% CI: 0.97-0.99). Conclusion: The results of this study provide evidence that smoking initiation, lifetime smoking index and insomnia are associated with an increased risk of CAD in individuals with diabetes, educational attainment and household income before taxes are associated with a reduced risk of CAD in individuals with diabetes, and the possible role of lifetime smoking index and household income before taxes on the risk of CAD in individuals with diabetes. It provides an opportunity for the prevention and management of CAD in individuals with diabetes.

Association between systemic immune-inflammatory index and diabetes mellitus: mediation analysis involving obesity indicators in the NHANES.

Background: Inflammation and obesity have been widely recognized to play a key role in Diabetes mellitus (DM), and there exists a complex interplay between them. We aimed to clarify the relationship between inflammation and DM, as well as the mediating role of obesity in the relationship. Methods: Based on the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Univariate analyses of continuous and categorical variables were performed using t-test, linear regression, and χ2 test, respectively. Logistic regression was used to analyze the relationship between Systemic Immune-Inflammatory Index (SII) or natural logarithm (Ln)-SII and DM in three different models. Mediation analysis was used to determine whether four obesity indicators, including body mass index (BMI), waist circumference (WC), visceral adiposity index (VAI) and lipid accumulation product index (LAP), mediated the relationship between SII and DM. Results: A total of 9,301 participants were included, and the levels of SII and obesity indicators (BMI, WC, LAP, and VAI) were higher in individuals with DM (p < 0.001). In all three models, SII and Ln-SII demonstrated a positive correlation with the risk of DM and a significant dose-response relationship was found (p-trend <0.05). Furthermore, BMI and WC were associated with SII and the risk of DM in all three models (p < 0.001). Mediation analysis showed that BMI and WC mediated the relationship between SII with DM, as well as Ln-SII and DM, with respective mediation proportions of 9.34% and 12.14% for SII and 10.23% and 13.67% for Ln-SII (p < 0.001). Conclusion: Our findings suggest that increased SII levels were associated with a higher risk of DM, and BMI and WC played a critical mediating role in the relationship between SII and DM.

ATL I, Acts as a SIRT6 Activator to Alleviate Hepatic Steatosis in Mice via Suppression of NLRP3 Inflammasome Formation.

Accumulating evidence has highlighted that sirtuin-6 (SIRT6) plays an important role in hepatic gluconeogenesis and lipogenesis. We aim to investigate the underlying mechanisms and pharmacological interventions of SIRT6 on hepatic steatosis treatment. Herein, our results showed that atractylenolide I (ATL I) activated the deacetylase activity of SIRT6 to promote peroxisome proliferator-activated receptor alpha (PPARα) transcription and translation, while suppressing nuclear factor NF-kappa-B (NFκB)-induced NACHT, LRR, and PYD domains containing protein 3 (NLRP3) inflammasome formation. Together, these decreased the infiltration of F4/80 and CD11B positive macrophages, accompanied by decreased mRNA expression and serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL6), and interleukin-1 beta (IL1ß). Additionally, these changes decreased sterol regulatory element-binding protein-1c (SREBP-1c) expression, while restoring carnitine O-palmitoyltransferase 1a (Cpt1a) expression, to decrease the size of adipocytes and adipose deposition, which, in turn, reversed high-fat diet (HFD)-induced liver weight and body weight accumulation in C57 mice. SIRT6 knockout or hepatic SIRT6 knockout in C57 mice largely abolished the effect of ATL I on ameliorating hepatic steatosis. Taken together, our results suggest that ATL I acts as a promising compound that activates SIRT6/PPARα signaling and attenuates the NLRP3 inflammasome to ameliorate hepatic inflammation and steatosis.

Application of back propagation neural network model optimized by particle swarm algorithm in predicting the risk of hypertension.

The structure of a back propagation neural network was optimized by a particle swarm optimization (PSO) algorithm, and a back propagation neural network model based on a PSO algorithm was constructed. By comparison with a general back propagation neural network and logistic regression, the fitting performance and prediction performance of the PSO algorithm is discussed. Furthermore, based on the back propagation neural network optimized by the PSO algorithm, the risk factors related to hypertension were further explored through the mean influence value algorithm to construct a risk prediction model. In the evaluation of the fitting effect, the root mean square error and coefficient of determination of the back propagation neural network based on the PSO algorithm were 0.09 and 0.29, respectively. In the comparison of prediction performance, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the back propagation neural network based on PSO algorithm were 85.38%, 43.90%, 96.66%, and 0.86, respectively. The results showed that the backpropagation neural network optimized by PSO had the best fitting effect and prediction performance. Meanwhile, the mean impact value algorithm could screen out the risk factors related to hypertension and build a disease prediction model, which can provide clues for exploring the pathogenesis of hypertension and preventing hypertension.

Ginsenoside Rc attenuates DSS-induced ulcerative colitis, intestinal inflammatory, and barrier function by activating the farnesoid X receptor.

Objectives: Farnesoid X receptor (FXR) activation is involved in ameliorating inflammatory bowel disease (IBD), such as ulcerative colitis (UC), and inflammatory regulation may be involved in its mechanism. Ginsenoside Rc (Rc) is a major component of Panax ginseng, and it plays an excellent role in the anti-inflammatory processes. Our aim is to explore the alleviative effect of Rc on dextran sulfate sodium (DSS)-induced inflammation and deficiencies in barrier function based on FXR signaling. Materials and Methods: In vitro, we treated human intestinal epithelial cell lines (LS174T) with LPS to explore the anti-inflammatory effect of Rc supplementation. In vivo, a DSS-induced IBD mice model was established, and the changes in inflammatory and barrier function in colons after Rc treatment were measured using the disease activity index (DAI), hematoxylin and eosin (H&E) staining, immunofluorescence, ELISA, and qPCR. Molecular docking analysis, luciferase reporter gene assay, and qPCR were then used to analyze the binding targets of Rc. DSS-induced FXR-knockout (FXR-/-) mice were used for further validation. Results: Rc significantly recovered the abnormal levels of inflammation indexes (TNF-α, IL-6, IL-1ß, and NF-KB) induced by LPS in LS174T. DSS-induced C57BL/6 mice exhibited a significantly decreased body weight and elevated DAI, as well as a decrease in colon weight and length. Increased inflammatory markers (TNF-α, IL-6, IL-1ß, ICAM1, NF-KB, F4/80, and CD11b displayed an increased expression) and damaged barrier function (Claudin-1, occludin, and ZO-1 displayed a decreased expression) were observed in DSS-induced C57BL/6 mice. Nevertheless, supplementation with Rc mitigated the increased inflammatory and damaged barrier function associated with DSS. Further evaluation revealed an activation of FXR signaling in Rc-treated LS174T, with FXR, BSEP, and SHP found to be upregulated. Furthermore, molecular docking indicated that there is a clear interaction between Rc and FXR, while Rc activated transcriptional expression of FXR in luciferase reporter gene assay. However, these reversal abilities of Rc were not observed in DSS-induced FXR-/- mice. Conclusion: Our findings suggest that Rc may ameliorate inflammation and barrier function in the intestine, which in turn leads to the attenuation of DSS-induced UC, in which Rc may potentially activate FXR signaling to protect the intestines from DSS-induced injury.

Chemokines in progression, chemoresistance, diagnosis, and prognosis of colorectal cancer.

Plenty of factors affect the oncogenesis and progression of colorectal cancer in the tumor microenvironment, including various immune cells, stromal cells, cytokines, and other factors. Chemokine is a member of the cytokine superfamily. It is an indispensable component in the tumor microenvironment. Chemokines play an antitumor or pro-tumor role by recruitment or polarization of recruiting immune cells. Meanwhile, chemokines, as signal molecules, participate in the formation of a cross talk among signaling pathways and non-coding RNAs, which may be involved in promoting tumor progression. In addition, they also function in immune escape. Chemokines are related to drug resistance of tumor cells and may even provide reference for the diagnosis, therapy, and prognosis of patients with colorectal cancer.

Molecular recognition of the interaction between ApoE and the TREM2 protein.

Alzheimer's disease (AD) is the most common type of dementia. The ε4 allele of the apolipoprotein E (ApoE) gene is the strongest known genetic risk factor for late-onset AD. Triggering receptor expressed on myeloid cells 2 (TREM2) is another important risk factor affecting the AD process after ApoE. Emerging evidence has identified TREM2 as a putative receptor for ApoE, raising the possibility that interactions between ApoE and TREM2 modulate the pathogenesis of AD. In this study, we performed molecular docking and molecular dynamics (MD) analyses to characterize the ApoE-TREM2 interaction and further investigated the effect of the major TREM2 disease-associated mutation (R47H) on the affinity of TREM2 for ApoE. The results indicate that the binding energy between ApoE and TREM2 occurs in an isoform-dependent manner with the following potency rank order: ApoE4 > ApoE3 > ApoE2. In addition, the R47H mutant reduced the interaction between ApoE and TREM2 protein, which may be attributed to decreased hydrogen-bonding interactions, hydrophobic interactions, and electrostatic forces between ApoE and TREM2. Our study analyzed the molecular pattern of the interactions between ApoE and TREM2 and how the variants affect these interactions based on in silico modeling, and the results might help to elucidate the interaction mechanism between ApoE and TREM2. Additional experimental studies will be needed to verify and explore the current findings.

Impact of Older Age Adiposity on Incident Diabetes: A Community-Based Cohort Study in China.

BACKGROUND: Obesity classifications vary globally and the impact of older age adiposity on incident diabetes has not been well-studied. METHODS: We examined a random sample of 2,809 participants aged ≥60 years in China, who were free of diabetes at baseline and were followed up for up to 10 years to document diabetes (n=178). The incidence of diabetes was assessed in relation to different cut-off points of body mass index (BMI) and waist circumference (WC) in multiple adjusted Cox regression models. RESULTS: The diabetic risk in the cohort increased linearly with the continuous and quartile variables of BMI and WC. The BMI-World Health Organization (WHO) and BMI-China criteria analysis did not show such a linear relationship, however, the BMI-Asian/Hong Kong criteria did; adjusted hazards ratio (HR) was 0.42 (95% confidence interval [CI], 0.20 to 0.90) in BMI <20 kg/m2, 1.46 (95% CI, 0.99 to 2.14) in 23-≤26 kg/m2, and 1.63 (95% CI, 1.09 to 2.45) in ≥26 kg/m2. The WC-China criteria revealed a slightly better prediction of diabetes (adjusted HRs were 1.79 [95% CI, 1.21 to 2.66] and 1.87 [95% CI, 1.22 to 2.88] in central obese action levels 1 and 2) than the WC-WHO. The combination of the BMI-Asian/Hong Kong with WC-China demonstrated the strongest prediction. There were no gender differences in the impact of adiposity on diabetes. CONCLUSION: In older Chinese, BMI-Asian/Hong Kong criteria is a better predictor of diabetes than other BMI criterion. Its combination with WC-China improved the prediction of adiposity to diabetes, which would help manage bodyweight in older age to reduce the risk of diabetes.

Association analysis of SOCS3, JAK2 and STAT3 gene polymorphisms and genetic susceptibility to type 2 diabetes mellitus in Chinese population.

AIM: The association of polymorphisms in the three genes of SOCS3, JAK2 and STAT3 with genetic susceptibility to type 2 diabetes mellitus (T2DM) was explored, and its interaction with environmental factors such as hypertension and triglycerides was analyzed. METHODS: The Hardy-Weinberg balance test was used to analyze the random balance of genes in the population. The analysis of the association of SNPs with T2DM was performed using Pearson's chi-square test. Haplotype frequency distribution, SNPs-SNPs interaction and environmental factors were analyzed by chi-square test and logistic regression. RESULTS: The genotype distribution of SNPs rs2280148 of the SOCS3 gene was statistically significant. The allele frequency distribution of SNPs (rs4969168/rs2280148) was statistically different. After covariate correction, the SOCS3 gene locus (rs4969168) showed an association with T2DM in additive model, while the rs2280148 locus showed an association with T2DM in all three models. The locus (rs10974914/rs10815157) allele and genotype frequency distribution of JAK2 were statistically significant. After covariate correction, two SNPs in the gene showed association with T2DM in both additive and recessive models. The distribution of genotype frequencies of SNPs rs1053005 locus in gene STAT3 was statistically significant between the two groups. In recessive genetic models, rs1053005 locus polymorphisms was associated with T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene as well as haplotype J2 (A G)/J 3 (G C) of the JAK2 gene were closely associated with T2DM. There was an interaction between SNPs rs4969168 and SNPs rs2280148 in the SOCS3 gene. There was an interaction between the SOCS3, JAK2 and STAT3 genes and hypertension/triglycerides. CONCLUSION: The SOCS3 and JAK2 genes may be associated with T2DM in the Chinese population, in which SNPs carrying the A allele (rs4969168)/G allele (rs2280148)/C allele (rs10815157) have a reduced risk of T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene and haplotype J2 (A G)/J 3 (G C) of the JAK2 gene may be influencing factor for T2DM. The interaction between SNPs rs4969168 and SNPs rs2280148 increases the risk of T2DM. Hypertension and triglycerides may interact with SNPs of T2DM susceptibility genes.

Polymorphisms analysis for association between ADIPO signaling pathway and genetic susceptibility to T2DM in Chinese han population.

The aim of the present study is to explored the relationship between ADIPO signalling pathway and T2DM, to provide clues for further study of the pathogenesis of T2DM and to determine the possible drug targets. This study employed a case-control study design. Twenty-three single nucleotide polymorphisms (SNPs) of 13 genes in the selected ADIPO signalling pathway were genotyped by SNPscanTM kit. All statistical analysis was performed by SPSS 25.0, PLINK 1.07, R 2.14.2, Haploview 4.2, SNPstats, and other statistical software packages. In the association analysis based on a single SNPs, rs1044471 had statistical significance in the overdominant model without adjusting covariates. Rs1042531 had statistical significance in the overdominant model. Rs12718444 had statistical significance in the recessive model. There was a linkage disequilibrium between the loci within 9 genes, and the two loci in RXRA gene did not form blocks. Four kernel functions were used for SNPs set analysis based on ADIPO signalling pathway showed that there was no statistical significance whether covariates were added or not, P>0.05.According to our research results, it is found that some single nucleotide polymorphisms (ADIPOR2 rs1044471, PCK1 rs1042531, GLUT1 rs12718444) in the adiponectin signalling pathway may be associated with T2DM.