Environmental enrichment alleviates hyperalgesia by modulating central sensitization in a nitroglycerin-induced chronic migraine model of mice.

BACKGROUND: Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. METHODS: A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. RESULTS: Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. CONCLUSION: EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM.

Cohort Profile: Guangzhou Nutrition and Health Study (GNHS): A Population-Based Multi-Omics Study.

BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.

Effect of aqueous extract of seed of broccoli on inflammatory cytokines and Helicobacter pylori infection: a randomized, double-blind, controlled trial in patients without atrophic gastritis.

The purpose of this study was to investigate the anti-inflammatory effect of an aqueous extract of seed of broccoli (AESB) in Helicobacter pylori (HP)-infected patients without atrophic gastritis. This was a double-centre, randomized, double-blind, controlled study. A total of 110 HP-infected subjects were randomized to receive either AESB or placebo for 2 months. Inflammatory cytokine (IL-8, IFN-γ, TNF-α, CRP, IL-17A, IL-1ß, IL-18), pepsinogen I, II (PG I, PG II), and gastrin-17 (G-17) measurements and 13C-urea breath tests were performed at baseline and at 60 days. At 60 days, there was no significant difference in any of the inflammatory cytokines, pepsinogen or gastrin between the two groups. However, IL-8, IFN-γ, PG I, PG I/PG II ratio (PGR), and G-17 were reduced by 9.02 pg/mL, 5.08 pg/mL, 24.56 ng/mL, 1.75 and 0.3 pmol/L, respectively, in the AESB group compared with baseline (all P < 0.05). The HP eradication rates in the AESB group and placebo group were 11.11 and 3.70% at 60 days, respectively (P > 0.05). No treatment-related adverse events were reported. Thus, AESB may reduce the risk of gastric mucosal lesions and decrease the risk of gastric cancer by relieving inflammatory cytokines. The safety profile of AESB was satisfactory. This study is registered with the Chinese Clinical Trials Registry (Registration No. ChiCTR2100054249).

Dietary fruit and vegetable intake, gut microbiota, and type 2 diabetes: results from two large human cohort studies.

BACKGROUND: Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk. METHODS: This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008-2013). Fecal samples were collected at follow-up (2015-2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants. RESULTS: In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake (p < 0.001) and inversely associated with T2D risk (odds ratio (OR) 0.83, 95%CI 0.71-0.97). The FMI-fruit association (p = 0.003) and the FMI-T2D association (OR 0.90, 95%CI 0.84-0.97) were both successfully replicated in the independent cohort. The FMI-positive associated metabolite sebacic acid was inversely associated with T2D risk (OR 0.67, 95%CI 0.51-0.86). The FMI-negative associated metabolites cholic acid (OR 1.35, 95%CI 1.13-1.62), 3-dehydrocholic acid (OR 1.30, 95%CI 1.09-1.54), oleylcarnitine (OR 1.77, 95%CI 1.45-2.20), linoleylcarnitine (OR 1.66, 95%CI 1.37-2.05), palmitoylcarnitine (OR 1.62, 95%CI 1.33-2.02), and 2-hydroglutaric acid (OR 1.47, 95%CI 1.25-1.72) were positively associated with T2D risk. CONCLUSIONS: Higher fruit intake-associated gut microbiota and metabolic alteration were associated with a lower risk of T2D, supporting the public dietary recommendation of adopting high fruit intake for the T2D prevention.

Erythrocyte membrane n-3 polyunsaturated fatty acids are inversely associated with the presence and progression of nonalcoholic fatty liver disease in Chinese adults: a prospective study.

PURPOSE: Previous studies have shown that high-dose supplementation with n-3 polyunsaturated fatty acids (PUFAs) may benefit patients with nonalcoholic fatty liver disease (NAFLD), but the association of n-3 PUFAs with NAFLD among individuals with normal diets is only speculative. We investigated the cross-sectional and prospective associations between n-3 PUFAs and NAFLD in Chinese adults. METHODS: This community-based prospective study included 3049 men and women (40-75 years) in Guangzhou, China, whose participants completed an NAFLD ultrasound evaluation and erythrocyte PUFA tests. A total of 2660 participants underwent the second NAFLD evaluation approximately 3 years later. α-Linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes were measured by gas chromatography. RESULTS: After adjusting for potential confounders, we observed inverse associations between DHA, DHA + EPA, total n-3 PUFAs and the presence of NAFLD in the cross-sectional analysis. The adjusted odds ratios (95% confidence interval) of NAFLD for the highest (vs. lowest) tertile were 0.74 (0.61, 0.90) for DHA, 0.82 (0.67, 1.00) for EPA, 0.73 (0.60, 0.88) for DHA + EPA and 0.74 (0.61, 0.91) for total n-3 PUFAs  (all P values≤0.05). Over the average 3.12 years of follow-up, higher levels of DHA was associated with an improvement of NAFLD. The hazard ratio of improved NAFLD for the highest tertile was 1.18 (95% CI 1.09, 1.33) for DHA. Pathway analyses showed that favorable associations may be mediated by improvements in inflammatory markers (e.g., interleukin 1 beta and tumor necrosis factor alpha-like). CONCLUSIONS: Erythrocyte membrane n-3 PUFAs are inversely associated with the presence and progression of NAFLD in Chinese adults. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT03179657.

Alternate Mediterranean diet score is positively associated with skeletal muscle mass index in middle-aged adults.

Researches have suggested Mediterranean diet might lower the risk of chronic diseases, but data on skeletal muscle mass (SMM) are limited. This community-based cross-sectional study examined the association between the alternate Mediterranean diet score (aMDS) and SMM in 2230 females and 1059 males aged 40-75 years in Guangzhou, China. General information and habitual dietary information were assessed in face-to-face interviews conducted during 2008-2010 and 3 years later. The aMDS was calculated by summing the dichotomous points for the items of higher intakes of whole grain, vegetables, fruits, legumes, nuts, fish and ratio of MUFA:SFA, lower red meat and moderate ethanol consumption. The SMM of the whole body, limbs, arms and legs were measured using dual-energy X-ray absorptiometry during 2011-2013. After adjusting for potential covariates, higher aMDS was positively associated with skeletal muscle mass index (SMI, SMM/height2, kg/m2) at all of the studied sites in males (all P trend<0·05). The multiple covariate-adjusted SMI means were 2·70 % (whole body), 2·65 % (limbs), 2·50 % (arms) and 2·70 % (legs) higher in the high (v. low) category aMDS in males (all P<0·05). In females, the corresponding values were 1·35 % (P trend=0·03), 1·05, 0·52 and 1·20 %, (P trend>0·05). Age-stratified analyses showed that the favourable associations tended to be more pronounced in the younger subjects aged less than the medians of 59·2 and 62·2 years in females and males (P interaction>0·10). In conclusion, the aMDS shows protective associations with SMM in Chinese adults, particularly in male and younger subjects.

Diagnostic value of ultrasonographic combining biochemical markers for Down syndrome screening in first trimester: a meta-analysis.

OBJECTIVE: The meta-analysis was to determine the diagnostic value of the combining tests for Down syndrome and to evaluate their utilities in the Down syndrome screening. METHOD: Through comprehensive literature search, 24 studies met the inclusion criteria and were included in the databases (PubMed, Wed of knowledge, Chinese National Knowledge Infrastructure (CNKI)). Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The summary receiver operating characteristic curve was also undertaken. RESULTS: The overall sensitivity and specificity of the combination of NT and free ß-hCG and PAPP-A for Down syndrome were 0.86(95%CI 0.75-0.92) and 0.96(95%CI 0.95-0.97), respectively. The summary positive likelihood ratio and negative likelihood ratio were 23.3 (95%CI 16.7-32.5) and 0.15(95%CI 0.08-0.26), respectively. The pooled diagnostic odds ratio was 156 (95%CI 75-326). CONCLUSION: The meta-analysis shows the accumulative evidence for the clinician that the performance of the combined test of MA and NB and NT and PAPP-A and free ß-hCG is the most effective test in the four different combined tests, while, the combination of NT and PAPP-A and free ß-hCG is a cost-effective screening tool for Down syndrome.

Prevalence of human papillomavirus infection in Guangdong Province, China: a population-based survey of 78,355 women.

BACKGROUND: The prevalence of human papillomavirus (HPV) infection and the distribution of different HPV genotypes vary greatly within different geographical and ethnic populations, especially in Asia. The HPV infection data based on regional population are extremely important for researchers to develop new efficient HPV screening assays and estimate the effect of vaccines on preventing from cervical cancer. METHODS: A total of 78,355 women from Guangdong Province, China, whose ages were from 18 to 75 years were enrolled in this study. All epidemiological data were obtained by face-to-face interview. Cervical exfoliated cells were collected, and HPV-DNA test was conducted with the matrix-assisted laser desorption/ionization time-of flight mass spectrometry. RESULTS: The overall HPV infection prevalence in the study population was 7.3%. The top 6 HPV genotypes were HPV16 (1.5%), HPV52 (1.2%), HPV58 (1.0%), HPV18 (0.7%), HPV45 (0.5%), and HPV6 (0.5%), accounting for 69.7% of all detected HPV infection types. Two peaks of HPV infection were detected in the population of old age group (>50; 9.6%) and young group (<25; 8.2%). Infection with single genotype HPV (6.2% in all; 85.7% in HPV-positive women) was more frequent than infection with multiple HPV (1.0% and 14.3% respectively). Results of multivariate logistic regression revealed that sexual active years, numbers of sexual partner, and numbers of pregnancy were risk factors of HPV infection. CONCLUSIONS: This study provides useful epidemiological information on cervical HPV infection prevalence in general female population from Guangdong Province, China. In this population, HPV infection prevalence was 7.3%, and genotypes HPV16, HPV52, and HPV58 showed a relatively high prevalence.

HPV genotypes and associated cervical cytological abnormalities in women from the Pearl River Delta region of Guangdong province, China: a cross-sectional study.

BACKGROUND: It is important to understand the specific HPV genotype distribution in screen-detected lesions. HPV Genotype is helpful for separating HPV-positive women at greater risk of cancer from those who can regress spontaneously and for preventing cervical cancer at early stage. The aim of this study was to investigate the high-risk HPV genotype distribution among cervical cytology abnormality in Pearl River Delta Region, Southern China METHODS: 5585 HPV-infected women were screened from 77069 women in Pearl River Delta Region. Information was obtained from 3226 screened subjects through questionnaires and personal interviews. Exfoliated cervical cells were collected by doctors for HPV test with MassARRAY (Sequenom, Sandiego, CA) technique based on the matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF) mass spectrometry (MS). The ThinPrep cytology test was performed to screen for cervical cancer. Unconditional logistic was used to determine the most common HPV carcinogenic types. RESULTS: Of the 3226 HPV-positive samples tested, 1744 (54.1%) with normal cervical cytology, 1482 (45.9%) with abnormal cytology. The five most common HPV types in this study were HPV16 (20.2%), HPV52 (17.1%), HPV58 (13.2%), HPV18 (9.5%), HPV6 (7.6%). Overall, HPV16 (OR = 10.5, 95% CI: 3.7 ~ 29.6), HPV33 (OR = 9.1, 95% CI: 2.8 ~ 29.2), HPV58 (OR = 6.3, 95% CI: 2.1 ~ 18.6), HPV31 (OR = 4.5, 95% CI: 1.3 ~ 15.5), multiple genotype infection (OR = 3.0, 95% CI: 1.7 ~ 14.7), especially HPV16 and HPV33, increased the risk of cytology abnormalities. CONCLUSIONS: HPV16, HPV31, HPV33, HPV58, and multiple HPV genotype infection increased the risk of cytology abnormalities in Pearl River Delta Region and might be useful for the screening, preventing, treating, and monitoring of pre-cancer lesions in southern China.

Sex Differences in the Relationship Between Emotional Support and Self-rated Health among Chinese Elderly.

PURPOSE: This study aimed to explore sex differences in the association between emotional support and self-rated health among the elderly. DESIGN: This was a cross-sectional survey based on the sub-project of China's National Basic Public Health Service Project-Health Management Services for the Elderly. SETTING: Participants were recruited from ten rural townships in Jingyuan County, Gansu Province, Northwestern China. SUBJECTS: 1405 subjects aged 60 or above. METHODS: Emotional support (consisting of 5 items) and self-rated health (evaluated by EQ-VAS) were investigated in this study. Multiple linear regression was conducted to consider the potential relationship. RESULTS: The frequency of children visit and the number of providers of emotional support were positively associated with self-rated health among older women (ß = 1.13, 95%CI = 0.25-2.02; ß = 1.80, 95%CI = 1.01-2.58), whereas the number of close friends had a positive association with self-rated health among older men (ß = 1.11, 95%CI = 0.20-2.01). The number of close relatives and the frequency of seeking emotional support were not found to be associated with self-rated health among both older men and older women. CONCLUSION: The study has found that the relationship between emotional support and self-rated health was differed by sex, calling attention to the need for sex-specific interventions.

The Effect of Nattokinase-Monascus Supplements on Dyslipidemia: A Four-Month Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Dyslipidemia, a condition implying high cardiovascular risks, has been widely studied on its potential nutrition interventions, including functional foods. This study aims to examine the effect of nattokinase monascus supplements (NMSs) on cardiovascular biomarkers and carotid intima-media thickness (CIMT) in patients with dyslipidemia. A total of 113 eligible subjects were randomly assigned to receive either NMSs or a placebo (55 and 58, respectively). After a 120-day intervention, there were significant mean absolute changes in total cholesterol (TC), low-density cholesterol (LDL-C), non-high-density cholesterol (non-HDL-C), and low-density cholesterol to high-density cholesterol ratio (LDL-C to HDL-C ratio), with values of -0.52 (95% CI: -0.51 to -0.54) mmol/L, -0.43 (95% CI: -0.45 to -0.41) mmol/L, -0.52 (95% CI: -0.52 to -0.52) mmol/L, and -0.29 (95% CI: -0.30 to -0.28) mmol/L, respectively, between the two groups. However, no significant differences were found in triglycerides (TGs), high-density cholesterol (HDL-C), and CIMT. Furthermore, the results for lipids and CIMT remained essentially unchanged after adjusting for various confounding factors using the analysis of covariance model. There were no significant differences in coagulation, liver function, renal function, or other indicators. No intervention-related adverse events, such as mouth ulcers, drooling, and stomach pain, were reported. The study results demonstrate that NMSs can ameliorate lipid levels (TC, LDL-C, non-HDL-C, and the LDL-C to HDL-C ratio) without the occurrence of adverse events. However, it did not significantly affect serum TG, HDL-C, and CIMT.

Formula Milk Supplementation and Bone Acquisition in 4-6 Years Chinese Children: A 12-Month Cluster-Randomized Controlled Trial.

Dairy foods are crucial for adequate calcium intake in young children, but scarce data are available on the effects of formula milk on bone acquisition. This cluster-randomized controlled trial investigated the effects of the supplementation of formula milk on bone health in rural children accustomed to a low-calcium diet between September 2021 and September 2022. We recruited 196 healthy children aged 4-6 years from two kindergartens in Huining County, Northwest China. A class-based randomization was used to assign them to receive 60 g of formula milk powder containing 720 mg calcium and 4.5 µg vitamin D or 20-30 g of bread per day for 12 months, respectively. Bone mineral density (BMD) and bone mineral content (BMC) at the left forearm and calcaneus, bone biomarkers, bone-related hormones/growth factors, and body measures were determined at baseline, 6, and 12 months. A total of 174 children completed the trial and were included in the analysis. Compared with the control group, formula milk intervention showed significant extra increments in BMD (3.77% and 6.66%) and BMC (4.55% and 5.76%) at the left forearm at 6th and 12th months post-intervention (all p < 0.001), respectively. Similar trends were observed in BMD (2.83%) and BMC (2.38%) in the left calcaneus at 6 months (p < 0.05). The milk intervention (vs. control) also showed significant changes in the serum concentrations of osteocalcin level (-7.59%, p = 0.012), 25-hydroxy-vitamin-D (+5.54%, p = 0.001), parathyroid hormone concentration (-15.22%, p = 0.003), and insulin-like growth factor 1 (+8.36%, p = 0.014). The percentage increases in height were 0.34%, 0.45%, and 0.42% higher in the milk group than in the control group after 3-, 6-, and 9-month intervention, respectively (p < 0.05). In summary, formula milk supplementation enhances bone acquisition at the left forearm in young Chinese children.

Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility.

Identification of protein quantitative trait loci (pQTL) helps understand the underlying mechanisms of diseases and discover promising targets for pharmacological intervention. For most important class of drug targets, genetic evidence needs to be generalizable to diverse populations. Given that the majority of the previous studies were conducted in European ancestry populations, little is known about the protein-associated genetic variants in East Asians. Based on data-independent acquisition mass spectrometry technique, we conduct genome-wide association analyses for 304 unique proteins in 2,958 Han Chinese participants. We identify 195 genetic variant-protein associations. Colocalization and Mendelian randomization analyses highlight 60 gene-protein-phenotype associations, 45 of which (75%) have not been prioritized in Europeans previously. Further cross-ancestry analyses uncover key proteins that contributed to the differences in the obesity-induced diabetes and coronary artery disease susceptibility. These findings provide novel druggable proteins as well as a unique resource for the trans-ancestry evaluation of protein-targeted drug discovery.

High leukocyte-to-lymphocyte ratio is associated with acute relapse in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated chronic disease characterized by inflammatory demyelination in the central nervous system (CNS).As there is limited evidence on whether leukocyte-to-lymphocyte ratios (LLRs) are associated with MS, we carried out an investigation on the association between LLRs and MS as favorable markers and aimed to determine the cut-off LLR for the identification of early-stage MS patients. METHODS: A matched case-control study enrolled a total of 120 MS inpatients and 120 age- and sex-matched non-MS inpatients from January 2013 to June 2018. LLRs were tested from peripheral venous blood routinely during hospitalization. Conditional logistic regression analyses were used to explore differences in LLRs between cases and controls. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic ability of LLRs and determine the best cut-off value. Disease disability was assessed using the Expanded Disability Status Scale (EDSS). RESULTS: The LLR was significantly associated with MS in hospitalized patients (OR: 2.372, 95% CI: 1.282 to 4.387, p < 0.001) after adjusting for potential confounders. The area under the curve (AUC) value was 0.793 (95% CI: 0.736 to 0.851). The cut-off value for LLR was 3.18, with sensitivity and specificity values of 62.5% (95% CI: 53.2% to 71.2%) and 88.3% (95% CI: 81.2% to 93.5%), respectively. The EDSS scores of the higher LLR group were significantly higher than the lower group. CONCLUSION: Systemic inflammation measured using LLRs may be an inflammatory marker among MS inpatients. LLRs may serve as favorable inflammatory markers with which to discriminate MS among Chinese subjects.

The Association of Gut Microbiota With Osteoporosis Is Mediated by Amino Acid Metabolism: Multiomics in a Large Cohort.

CONTEXT: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. OBJECTIVE: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. METHODS: We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. CONCLUSION: This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

Serum Carotenoids Are Inversely Associated with RBP4 and Other Inflammatory Markers in Middle-Aged and Elderly Adults.

(1) Background: Carotenoids may be inversely associated with inflammatory markers (i.e., TNF-α, IL-6, IL-1ß). However, data are scarce on retinol binding protein 4 (RBP4) in humans. We examined the associations among serum carotenoids, RBP4 and several inflammatory markers in a Chinese population. (2) Methods: This community-based cross-sectional study included 3031 participants (68% males) aged 40-75 years in Guangzhou, China. Serum concentrations of carotenoids, RBP4, and inflammatory markers were measured. (3) Results: Generally, serum individual and total carotenoids were significantly and inversely associated with retinol-adjusted RBP4, RBP4, hsCRP, MCP1, and TNF-alpha levels. Age- and gender-adjusted partial correlation coefficients between total carotenoids and the above inflammatory markers were -0.129, -0.097, -0.159, -0.079, and -0.014 (all p < 0.01, except for TNF-alpha with p >0.05), respectively. The multivariate-adjusted values of partial correlation coefficients for these inflammation-related markers were -0.098, -0.079, -0.114, -0.090, and -0.079 (all p < 0.01), respectively. Among the individual carotenoids, those with the most predominant association were lutein-zeaxanthin and total carotenoids for retinol-adjusted RBP4 and RBP4, alpha- and beta-carotene for hsCRP, and alpha-carotene for MCP1 and TNF-alpha. No significant associations were observed for IL-6 and IL-1beta. (4) Conclusions: Serum carotenoids were inversely associated with RBP4, hsCRP, MCP1 and TNF-alpha among middle-aged and elderly Chinese adults.

Fat Mass Is Positively Associated with Estimated Hip Bone Strength among Chinese Men Aged 50 Years and above with Low Levels of Lean Mass.

This study investigated the relationships of fat mass (FM) and lean mass (LM) with estimated hip bone strength in Chinese men aged 50-80 years (median value: 62.0 years). A cross-sectional study including 889 men was conducted in Guangzhou, China. Body composition and hip bone parameters were generated by dual-energy X-ray absorptiometry (DXA). The relationships of the LM index (LMI) and the FM index (FMI) with bone phenotypes were detected by generalised additive models and multiple linear regression. The associations between the FMI and the bone variables in LMI tertiles were further analysed. The FMI possessed a linear relationship with greater estimated hip bone strength after adjustment for the potential confounders (p < 0.05). Linear relationships were also observed for the LMI with most bone phenotypes, except for the cross-sectional area (p < 0.05). The contribution of the LMI (4.0%-12.8%) was greater than that of the FMI (2.0%-5.7%). The associations between the FMI and bone phenotypes became weaker after controlling for LMI. Further analyses showed that estimated bone strength ascended with FMI in the lowest LMI tertile (p < 0.05), but not in the subgroups with a higher LMI. This study suggested that LM played a critical role in bone health in middle-aged and elderly Chinese men, and that the maintenance of adequate FM could help to promote bone acquisition in relatively thin men.

Interactions between polymorphisms in the 3'untranslated region of the cyclin dependent kinase 6 gene and the human papillomavirus infection, and risk of cervical precancerous lesions.

The human papillomavirus (HPV) infection is essential for the development of cervical cancer and its precursor lesions. However, only certain persistently infected individuals develop cervical cancer. Cyclin-dependent kinase 6 (CDK6) is a critical regulatory cancer-associated gene in the cell cycle and in tumorigenesis. Single nucleotide polymorphisms (SNPs) in microRNA sites in the 3'-untranslated region (UTR) of target genes may result in target gene expression level changes and susceptibility to diseases, including cancer. Therefore, the aim of the present study was to determine whether SNPs in the 3'UTR of the CDK6 gene may affect susceptibility to cervical precancerous lesions in a Chinese population. Five polymorphisms in the 3'UTR of the CDK6 gene were evaluated in 164 cervical precancerous lesion cases and 296 control subjects. Differences in environmental factors between cases and controls were evaluated using the χ2 test or unpaired t-test. Logistic regression was used to examine the association between the five polymorphisms and cervical precancerous lesions. The model-free multifactor dimensionality reduction (MDR) method was performed to evaluate the interaction effect of environment variables and gene polymorphisms. Interactions on the additive scale are calculated by using the relative excess risk due to interaction (RERI). After controlling for potential confounders, a significantly decreased risk of cervical precancerous lesions for the GA genotype, rs8179, and the AT genotype, rs42033 [GA vs. GA: odds ratio (OR)adjusted=0.17, 95% confidence interval (CI), 0.05-0.57; AT vs. AA: ORadjusted=0.18, 95% CI, 0.05-0.59, respectively] was identified. Furthermore, following MDR analysis, a significant three-locus interaction model was identified, which involved the HPV infection, the number of pregnancies and rs8179. Additionally, a significant antagonistic interaction between the HPV infection and rs8179 was identified on an additive scale. Haplotype AGTA was associated with a decreased risk of developing cervical precancerous lesions (ORadjusted=0.21; 95% CI, 0.06-0.75). Thus, the present results indicated that the rs8179 and rs42033 polymorphisms confer genetic susceptibility to cervical precancerous lesions. Furthermore, the interaction between the rs8179 polymorphism in CDK6 and the HPV infection and haplotype AGTA may be associated with cervical precancerous lesions.

Growth, Gastrointestinal Tolerance and Stool Characteristics of Healthy Term Infants Fed an Infant Formula Containing Hydrolyzed Whey Protein (63%) and Intact Casein (37%): A Randomized Clinical Trial.

To investigate whether healthy term infants, fed an infant formula containing hydrolyzed whey protein (HWP-F, hydrolyzed whey/intact casein =63/37), differ in growth, gastrointestinal tolerance and stool characteristics from those fed an infant formula containing intact whey protein (IWP-F, intact whey/intact casein =61/39) or breast milk. Healthy term infants, born within 14 days of the study's commencement, were randomly assigned to be fed IWP-F or HWP-F until 13 weeks of age, and breast-fed (BF) infants were enrolled as a reference group. Anthropometric measurements, gastrointestinal tolerance indexes and stool characteristics were assessed at baseline, and 7 and 13 weeks of age. There were no significant differences in any growth measurements and the occurrence of crying, spit-up and difficult defecation among the three feeding groups during the study period. However, daily feeding frequency was consistently lower in the formula-fed infants than in the BF group throughout the study (p < 0.05), and infants in the HWP-F group consumed more formula than those in the IWP-F group at 7 and 13 weeks of age (p ≤ 0.002). The HWP-F-fed infants had more similar stool characteristics to the breast-fed infants than infants in the IWP-F group at 13 weeks of age, regardless of frequency, volume, color or consistency of stool. This study demonstrates that the HWP-F could support the normal growth of healthy term infants, to a comparable extent to that of breast-fed infants during the first three months of life. Moreover, stool characteristics of HWP-F-fed infants are much closer to breast-fed infants than IWP-F-fed infants, but no significant gastrointestinal tolerance improvement was observed in HWP-F group.