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Breast phyllodes tumor (PT) is a rare fibroepithelial neoplasm with potential malignant behavior. Long non-coding RNAs (lncRNAs) play multifaceted roles in various cancers, but their involvement in breast PT remains largely unexplored. In this study, microarray was leveraged for the first time to investigate the role of lncRNA in PT. We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT, and its overexpression endowed PT with high tumor grade and adverse prognosis. Furthermore, we elucidated that ZFPM2-AS1 promotes the proliferation, migration, and invasion of malignant PT in vitro. Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft (PDX) model could effectively inhibit tumor progression in vivo. Mechanistically, our findings showed that ZFPM2-AS1 is competitively bound to CDC42, inhibiting ACK1 and STAT1 activation, thereby launching the transcription of TNFRSF19. In conclusion, our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT, and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.

Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA, Cn-3, 22:6) are essential in improving cognitive function and protecting neurocytes. This study explored the effects of the combined intervention of MCTs and DHA on inhibiting neurocyte apoptosis of the brain and improving cognitive function in senescence-accelerated mouse-prone 8 (SAMP8). Four-month-old male SAMP8 mice were randomly divided into four treatment groups (12 mice/group): DHA, MCT, DHA + MCT, and control groups, which intervened for seven months. Twelve age-matched male senescence-accelerated mouse resistant 1 (SAMR1) was used as the natural aging group. TUNEL assay and HE staining were used to assess neurocyte apoptosis and damage in the brain of mice. Moreover, the cognitive function was analyzed using the Morris water maze (MWM) and open field (OF) tests. The results showed that the cognitive function of 11-month-old SAMP8 mice decreased with age, and further pathological examination revealed the damaged neurocyte structure, karyopyknosis, cell atrophy, and even apoptosis. MCTs combined with DHA supplementation could increase octanoic acid (C8:0), decanoic acid (C10:0), and DHA levels in the serum, inhibit neurocyte apoptosis, improve neurocyte damage, moreover delay age-related cognitive decline after seven-month treatment. Furthermore, combining MCTs and DHA was significantly more beneficial than MCTs or DHA alone. In conclusion, MCTs combined with DHA could delay cognitive decline by inhibiting neurocyte apoptosis of the brain in SAMP8 mice.

Introduction Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found.Methods/design The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35–45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases.Ethics and dissemination The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal.Trial registration number Chinese Clinical Trial Registry (ChiCTR2300072472).

IntroductionThe clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined. MethodsWe assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC in vitro using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and in vivo by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively.ResultsMUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells in vitro, in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. ConclusionThe MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.

The policies regarding the mandatory fortification of food with folic acid (FA) may impact the effectiveness of folate-based B vitamin treatment on cognitive function in older adults. We critically and systematically review the literature to assess whether food fortification policies affect folate-based B vitamin treatment efficacy on cognition function in older adults. Electronic databases, including PubMed, Web of Science, and CNKI, were searched for “Cognitive Function”, “Folate”, and “Older Adults”. The study had specific criteria for inclusion, which were as follows: (1) the studies should initially have randomized controlled trials that were conducted on older adults aged 60 or above; (2) the studies must assess the relationship between folate status and cognitive performance; and (3) the studies should clarify the policies regarding food fortification with FA. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Two reviewers independently extracted all the data, and any discrepancies were resolved by consensus. All the data collected were compiled, compared, and analyzed critically. Random effects models were used to assess the effects of interventions. The systematic review included fifty-one articles involving 42,768 participants. Of these, the 23 articles were included in the meta-analysis. The meta-analysis on the effects of folate-based B vitamin supplementation on cognitive function showed a significant overall impact (Z = 3.84; p = 0.0001; SMD, 0.18; 95% CI, 0.09, 0.28). Further analysis revealed that FA food fortification policies were not implemented in countries where folate-based B vitamin supplementation improved cognitive impairment in older adults (Z = 3.75; p = 0.0002; SMD, 0.27; 95% CI, 0.13, 0.40). However, the FA intervention did not have significant outcomes in areas where FA food fortification policies were mandatory (Z = 0.75; p = 0.45; SMD, 0.03; 95% CI, −0.06, 0.13). Supplementing with oral folic acid, alone or in combination, has been linked to improved cognitive performance in older adults. While mandatory FA fortification has the improved folic acid status, additional folate-based B vitamin supplements do not appear to influence cognitive function.

Objectives This study aimed to explore the influence of the interaction between parental myopia and lifestyle on myopia among school-age children.Design Cross-sectional study.Setting This study used data from the Tianjin Child and Adolescent Research of Eye between August and October 2022.Participants A total of 49 035 participants between 6 and 18 years of age were eligible for this study.Primary and secondary outcome measures The primary outcome was the interaction between eye-healthy lifestyle and parental myopia on myopia. Parental myopia and eye-healthy lifestyle were ascertained by a Child and Adolescent Behavior Questionnaire. The lifestyle risk score (LRS) of eye health was calculated based on beta-coefficient in the backward regression model. The interaction between LRS and parental myopia was analysed by multivariate logistic regression. The predictive value of different predicted models was estimated using receiver operating characteristic curves. Multiple linear regression was used to evaluate the associations of lifestyle risk factors and parental myopia with spherical equivalent refraction, which were defined as the secondary outcomes.Results A total of 31 839 participants aged 6–18 years were included, and the myopia prevalence was 55.46%. Eye-healthy lifestyle and parental myopia were significantly associated with myopia, as was interaction. The predictive value for LRS & parental myopia was 0.714 (95% CI: 0.709 to 0.720), which was higher than LRS (0.693, 95% CI: 0.687 to 0.699) and parental myopia (0.710, 95% CI: 0.704 to 0.716) separately.Conclusions High-risk lifestyles of myopia and parental myopia were significantly associated with a higher risk of myopia, and the combination had the strongest effect. For children, lifestyle adjustment should be prioritised in preventing myopia, especially for those with parental myopia.

Abstract Background Little is known on the association of types of grains with mortality and the moderating effect of lifestyle on this association. This study aims to evaluate the single or joint associations of types of grains and lifestyle with all-cause mortality among Chinese older adults. Methods Data were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018. Subjects aged ≥ 65 years were eligible. The types of grains included wheat, total rice, and coarse cereals. Lifestyle was derived using smoking, alcohol consumption, physical activity, and dietary pattern. All-cause mortality was the primary outcome. Results This study included 30275 participants with a mean age 87 ± 11 years and documented 19261 deaths during a mean follow-up of 4.8 years. Compared to wheat, in those with healthy and intermediate lifestyle, total rice was associated with a 13% (HR: 0.87, 95% CI 0.80, 0.93) and 6% (HR: 0.94, 95% CI 0.90, 1.00) lower risk of mortality, respectively, and coarse cereals were associated with a 14% (HR: 0.86, 95% CI 0.74, 1.00) and 12% (HR: 0.88, 95% CI 0.79, 0.97) lower risk of mortality, respectively. Meanwhile, an increase per SD in intakes of wheat and coarse cereals was associated with a 10% (HR: 1.10, 95% CI 1.03, 1.18) and 25% (HR: 1.25, 95% CI 1.08, 1.44) higher mortality rate in those with healthy lifestyle, and a 13% (HR: 1.13, 95% CI 1.08, 1.19) and 29% (HR: 1.29, 95% CI 1.17, 1.44) higher mortality in females but not males. In addition, a U-shaped association of intake of total grains with all- cause mortality was observed (P for non-linearity = 0.002), and a J-shaped association of intake of total rice with all- cause mortality was observed (P for non-linearity = 0.003). Conclusions Specific types of grains and lifestyle were separately or jointly associated with all-cause mortality. Compared to wheat, total rice and coarse cereals were advanced grains for participants with a relatively healthy lifestyle. Intake of total rice was related to all-cause mortality in a dose–response manner. Therefore, a combination of intermediate intake of total rice and healthy lifestyle should be encouraged in older adults.

Abstract Background Diet and chronic inflammation might play a major role in the pathogenesis of mild cognitive impairment (MCI). In addition, peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) might mediate the relationship between inflammation and MCI risk. The purpose of the present study is to evaluate whether inflammatory potential of diet assessed by dietary inflammatory index (DII), chronic inflammation, peripheral blood LTL, and mtDNAcn were associated with the risk of MCI. Results A population-based cohort study was conducted with a total of 2944 participants. During a median follow-up of 2 years, 438 (14.90%) individuals were new-onset MCI. After adjustment, a higher score of DII (hazard ratio [HR]: 1.056, 95% CI: 1.005, 1.109), a higher log systemic immune inflammation index (SII) (HR: 1.333, 95% CI: 1.089, 1.633) and log system inflammation response index (SIRI) (HR: 1.487, 95% CI: 1.024, 2.161) predicted elevated risk of MCI. An increased mtDNAcn (HR: 0.843, 95% CI: 0.712, 0.997), but not LTL, predicted a decreased risk of MCI. Negative associations of log SII with LTL (β:-0.359, 95% CI: -0.445, -0.273) and mtDNAcn (β:-0.048, 95% CI: -0.090, -0.006) were found. Additionally, negative associations of log SIRI with LTL (β: -0.035, 95% CI: -0.052, -0.017) and mtDNAcn (β:-0.136, 95% CI: -0.216, -0.056) were also found. Path analysis suggested that SIRI, LTL, and mtDNAcn, in series, have mediation roles in the association between DII score and MCI risk. Conclusions Higher DII, SII, and SIRI might predict a greater risk of MCI, while a longer LTL and an increased mtDNAcn were linked to a reduced risk of MCI among the older population. LTL and mtDNAcn could play mediation roles in the association between DII and MCI risk.

Objective: This cross-sectional study examined environmental correlates of sedentary behavior (SB) and physical activity (PA) in preschool children in the urban area of Tianjin, China. Methods: Data were collected from the Physical Activity and Health in Tianjin Chinese Children study, involving healthy children 3–6 years old and their families. In all children (n = 980), leisure-time SB (LTSB) and leisure-time PA (LTPA) were reported in min/day by parents. In a subgroup (n = 134), overall sedentary time, light PA, and moderate-to-vigorous PA (MVPA) were objectively measured using ActiGraph accelerometry (≥3 days, ≥10 h/day). Environmental correlates were collected using a questionnaire that included home and neighborhood characteristics (e.g., traffic safety, presence of physical activity facilities) and children's behaviors. Potential correlates were identified using linear regression analysis. Results: Multiple linear regression analysis showed that “having grandparents as primary caregivers” (βs and 95% confidence intervals (95%CIs) for overall sedentary time: 29.7 (2.1–57.2); LTSB (ln): 0.19 (0.11–0.28)) and “having a television (for LTSB (ln): 0.13 (0.00–0.25)) or computer (for LTSB (ln): 0.13 (0.03–0.23)) in the child's bedroom” were both associated with higher SB. Furthermore, “having grandparents as primary caregivers” was associated with less MVPA (β (95%CI): −7.6 (−14.1 to −1.2)), and “active commuting to school by walking” correlated with more MVPA (β (95%CI): 9.8 (2.2–17.4)). The path model showed that “more neighborhood PA facilities close to home” was indirectly related to higher LTPA (ln), which was partly mediated by “outdoor play” (path coefficients (95%CI): 0.005 (0.002–0.008)) and “going to these facilities more often” (path coefficients (95%CI): 0.013 (0.008–0.018)). Traffic safety was not a correlate. Conclusion: Family structure and media exposure in the home maybe important factors in shaping preschoolers’ PA patterns. Built environmental correlates could indirectly influence preschoolers’ LTPA through parental help with engaging in active behaviors.

The deterioration of brain glucose metabolism predates the clinical onset of Alzheimer’s disease (AD). Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA) positively improve brain glucose metabolism and decrease the expression of AD-related proteins. However, the effects of the combined intervention are unclear. The present study explored the effects of the supplementation of MCTs combined with DHA in improving brain glucose metabolism and decreasing AD-related protein expression levels in APP/PS1 mice. The mice were assigned into four dietary treatment groups: the control group, MCTs group, DHA group, and MCTs + DHA group. The corresponding diet of the respective groups was fed to mice from the age of 3 to 11 months. The results showed that the supplementation of MCTs combined with DHA could increase serum octanoic acid (C8:0), decanoic acid (C10:0), DHA, and β-hydroxybutyrate (β-HB) levels; improve glucose metabolism; and reduce nerve cell apoptosis in the brain. Moreover, it also aided with decreasing the expression levels of amyloid beta protein (Aβ), amyloid precursor protein (APP), β-site APP cleaving enzyme-1 (BACE1), and presenilin-1 (PS1) in the brain. Furthermore, the supplementation of MCTs + DHA was significantly more beneficial than that of MCTs or DHA alone. In conclusion, the supplementation of MCTs combined with DHA could improve energy metabolism in the brain of APP/PS1 mice, thus decreasing nerve cell apoptosis and inhibiting the expression of Aβ.

Research demonstrated that folate deficiency in either the mother or father could impact the biological functions of the offspring’s of neural cells. Folate deficiency can also impair the methionine cycle, thus contributing to the conversion of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), which could potentially cause damage to the central nervous system. The study focused on the effect of parental folate deficiency on neural cell apoptosis in offspring neonatal rats and whether it is mediated by the levels of SAM and SAH in brains. The experimental design was conducted by feeding female and male Sprague Dawley (SD) rats with either folate-deficient or folate-normal diets, sacrificing the offspring within 24 h and isolating their brain tissue. Rats were divided into four groups: the maternal-folate-deficient and paternal-folate-deficient (D-D) group; the maternal-folate-deficient and paternal-folate-normal (D-N) group; the maternal-folate-normal and paternal-folate-deficient (N-D) group; and the maternal-folate-normal and paternal-folate-normal (N-N) group. There was down-regulation of B-cell lymphoma 2 (Bcl-2) expression, up-regulation of Bcl-2-associated X protein (Bax) and Caspase-3 expression of neural cells, and pathological changes in the brain ultrastructure, as well as decreased SAM levels, increased SAH levels, and a decreased SAM/SAH ratio in the rat fetal brain via parental folate deficiency. In conclusion, parental folate deficiency could induce the apoptosis of neural cells in neonatal offspring rats, while biparental folate deficiency had the greatest effect on offspring, and the unilateral effect was greater in mothers than in fathers. This process may be mediated by the levels of SAM and SAH in the rat fetal brain.

Abstract Background Osteoporotic vertebral compression fracture (OVCF) is one of the most common fragile fractures, and percutaneous vertebroplasty provides considerable long-term benefits. At the same time, there are many reports of postoperative complications, among which fracture after percutaneous vertebroplasty is one of the complications after vertebroplasty (PVP). Although there are many reports on the risk factors of secondary fracture after PVP at home and abroad, there is no systematic analysis on the related factors of secondary fracture after PVP. Methods The databases, such as CNKI, Wan Fang Database and PubMed, were searched for documents on secondary fractures after percutaneous vertebroplasty published at home and abroad from January 2011 to March 2021. After strictly evaluating the quality of the included studies and extracting data, a meta-analysis was conducted by using Revman 5.3 software. Results A total of 9 articles were included, involving a total of 1882 patients, 340 of them diagnosed as secondary fractures after percutaneous vertebroplasty. Conclusion The additional history of fracture, age, bone mineral density (BMD), bone cement leakage, intravertebral fracture clefts and Cobb Angle might be risk factors related to secondary fractures after percutaneous vertebroplasty for osteoporotic vertebral compression fractures. The height of vertebral anterior and body mass index (BMI) were not correlated.

The effect of maternal folate status on the fetal central nervous system (CNS) is well recognized, while evidence is emerging that such an association also exists between fathers and offspring. The biological functions of telomeres and telomerase are also related to neural cell proliferation and apoptosis. The study aimed to investigate the effect of parental folate deficiency on the proliferation and apoptosis of neural stem cells (NSCs) in neonatal offspring and the role of telomeres in this effect. In this study, rats were divided into four groups: maternal folate-deficient and paternal folate-deficient diet (D-D) group; maternal folate-deficient and paternal folate-normal diet (D-N) group; maternal folate-normal and paternal folate-deficient diet (N-D) group; and the maternal folate-normal and paternal folate-normal diet (N-N) group. The offspring were sacrificed at postnatal day 0 (PND0), and NSCs were cultured from the hippocampus and striatum tissues of offspring for future assay. The results revealed that parental folate deficiency decreased folate levels, increased homocysteine (Hcy) levels of the offspring’s brain tissue, inhibited proliferation, increased apoptosis, shortened telomere length, and aggravated telomere attrition of offspring NSCs in vivo and in vitro. In vitro experiments further showed that offspring NSCs telomerase activity was inhibited due to parental folate deficiency. In conclusion, parental folate deficiency inhibited the proliferation and increased apoptosis of offspring NSCs, maternal folate deficiency had more adverse effects than paternal, and the mechanisms may involve the telomere attrition of NSCs.

BackgroundNowadays, immune checkpoint inhibitors (ICIs) have become one of the essential immunotherapies for cancer patients. However, the impact of antibiotic (ATB) use on cancer patients treated with ICIs remains controversial.MethodsOur research included retrospective studies and a randomized clinical trial (RCT) with cancer patients treated with ICIs and ATB, from the public database of PubMed, Web of Science, Embase, Cochrane, clinical trials, and JAMA. The survival outcomes included progression-free survival (PFS) and overall survival (OS). Meanwhile, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup analyses were performed to determine the concrete association between ATB use and the prognosis of cancer patients treated in ICIs.ResultsOur results revealed that ATB use was associated with poor survival outcomes, including OS (HR: 1.94, 95% CI: 1.68–2.25, p

A subset of CpG Island promoter genes are regulated by Polycomb-Repressive Complex 2 (PRC2+-CGI), which become DNA hypermethylated and silenced in cancer. Here, the authors investigate the transcriptomic and epigenomic characteristics of PRC2-occupied CGI and free CGI across pan-cancer types.

Abstract Background OPTION5 is a scale used to evaluate shared decision making (SDM) in health care from an observer’s perspective; however, to date, there is no simplified Chinese version of this scale. Objectives This study aims to produce a simplified Chinese version of the OPTION5 scale and to test its psychometric properties. Methods One rater observed and audio-recorded consultations between general practitioners (GPs) and chronically ill patients in a Beijing community health service center (CHSC) from May to June 2019. Meanwhile, demographic data of the patients and GPs were collected via information forms. Two raters assessed inter- and intra-rater reliability by calculating the intraclass correlation coefficient (ICC) and weighted Cohen’s Kappa values. Internal consistency was assessed using Cronbach’s α value. Concurrent was calculated by Spearman’s rank correlation coefficient. Results A total of 209 consultations were recorded and evaluated. As concerns inter-rater reliability, the ICC of the OPTION5 was 0.859 on the total score level, with Cohen’s weighted k ranging from 0.376 (item 5) to 0.649 (item 2) on the single item level. With regard to intra-rater reliability, the ICC was 0.945 on the total score level, with Cohen’s weighted k ranging from 0.469 (item 5) to 0.883 (item1) on the single item level. Cronbach’s α value of all 5 items amounted to 0.746. Spearman’s rank correlation coefficient between OPTION5 and OPTION12 for Chinese versions was 0.660. Conclusions The simplified Chinese version of the OPTION5 scale, developed using stringent translation procedures, demonstrated satisfactory psychometric characteristics. Specifically, inter- and intra-rater reliabilities were excellent, while criterion validity was moderate. The simplified Chinese version of the OPTION5 scale can be implemented in clinical settings to evaluate SDM of treatment during consultations between GPs and chronically ill patients.

Mesenchymal stem cells (MSCs) play an important role in developing bone tissue engineered constructs due to their osteogenic and chondrogenic differentiation potential. MSC-based tissue engineered constructs are generally considered a safe procedure, however, the long-term results obtained up to now are far from satisfactory. The main causes of these therapeutic limitations are inefficient homing, engraftment, and directional differentiation. Flavonoids are a secondary metabolite, widely existed in nature and have many biological activities. For a long time, researchers have confirmed the anti-osteoporosis effect of flavonoids through in vitro cell experiments, animal studies. In recent years the regulatory effects of flavonoids on mesenchymal stem cells (MSCs) differentiation have been received increasingly attention. Recent studies revealed flavonoids possess the ability to modulate self-renewal and differentiation potential of MSCs. In order to facilitate further research on MSCs osteogenic differentiation of flavonoids, we surveyed the literature published on the use of flavonoids in osteogenic differentiation of MSCs, and summarized their pharmacological activities as well as the underlying mechanisms, aimed to explore their promising therapeutic application in bone disorders and bone tissue engineered constructs.

A novel photonic sensor using a self-cross-linked imprinting close-packed opal (CPO) as a recognition element was developed for the detection of chloramphenicol (CAP). The self-cross-linked imprinting CPO film was consisted of monodisperse molecular imprinted – N-hydroxymethylacrylamide particles (MI-HAM particles) with self-assembling and self-crosslinking properties. A dilute dispersion of these particles was self-assembled to formation of the highly ordered CPO structure, and at the same time the neighboring particles reacted to form covalent bond to stabilize the CPO structure at the air/dispersion. Thus the obtained self-cross-linked imprinting CPO was characterized by a highly stable three-dimensional (3D) CPO structure without the interference of bulk hydrogel matrix, in which numerous CAP recognition sites were dispersed through the molecular imprinted process. The inherent high affinity of the recognition sites allowed the self-cross-linked imprinting CPO to recognize CAP with high specificity, and changes of the periodic structure enabled the self-cross-linked imprinting CPO to transfer the recognition events into readable optical signals. Then the self-cross-linked imprinting CPO film was packed into a reaction cell with an optical spectrometer to establish a novel photonic sensor. A linear relationship was found between the diffraction intensity decrease and CAP concentration in the range from 2 ng mL−1 to 512 ng mL−1, whereas there was no obvious optical change for CAP analogues, thus indicating that the sensor had selective and sensitive response to CAP molecules. Furthermore, the sensor was applied successfully to detect CAP in drinking water samples. As a result, the developed sensor might offer a potential alternative in routine supervision for residue due to its convenience, low cost, reusability, and high sensitivity as well as selectivity. Keywords: Photonic sensor, Molecular imprinting technique, Self-cross linking, Close-packed opal, N-hydroxymethylacrylamide, Chloramphenicol

Bone regeneration in osteoporosis and fragility fractures which are highly associated with age remains a great challenge in the orthopedic field, even though the bone is subjected to a continuous process of remodeling which persists throughout lifelong. Regulation of osteoblast and osteoclast differentiation is recognized as effective therapeutic targets to accelerate bone regeneration in osteopenic conditions. Anthocyanins (ACNs), a class of naturally occurring compounds obtained from colored plants, have received increasing attention recently because of their well-documented biological effects, such as antioxidant, anti-inflammation, and anti-apoptosis in chronic diseases, like osteoporosis. Here, we summarized the detailed research progress on ACNs on bone regeneration and their molecular mechanisms on promoting osteoblast differentiation as well as inhibiting osteoclast formation and differentiation to explore their promising therapeutic application in repressing bone loss and helping fragility fracture healing. Better understanding the role and mechanisms of ACNs on bone regeneration is helpful for the prevention or treatment of osteoporosis and also for the exploration of new bone regenerative medicine.

Geriatric depression, a chronic condition, has become a substantial burden in rural China. This study aimed to assess the association between dietary patterns and the risk of geriatric depression in rural China. Between March 2018 and June 2019, 3304 participants were recruited for this cross-sectional study in rural Tianjin, China. Principal component analysis was used to determine the major dietary patterns. The associations between dietary patterns and the risk of geriatric depression were assessed using a logistic regression model. Four dietary patterns were identified: vegetables-fruit, animal food, processed food, and milk-egg. The study found that vegetable-fruit (Q2 vs. Q1: OR = 0.62, 95% CI: 0.46–0.83; Q3 vs. Q1: OR = 0.54, 95% CI: 0.38–0.75; Q4 vs. Q1: OR = 0.39, 95% CI: 0.26–0.57) and animal food patterns (Q3 vs. Q1: OR = 0.69, 95% CI: 0.50–0.95; Q4 vs. Q1: OR = 0.58, 95% CI: 0.41–0.82) were associated with a decreased risk of depression, and inflammatory dietary pattern (Q2 vs. Q1: OR = 1.71, 95% CI: 1.23–2.38; Q3 vs. Q1: OR = 1.70, 95% CI: 1.22–2.36; Q4 vs. Q1: OR = 1.44, 95% CI: 1.03–2.03) was associated with an increased risk of depression. The present findings reinforce the importance of adopting an adequate diet consisting of vegetables, fruit and animal foods, while limiting the intake of pro-inflammatory foods, to decrease the risk of depression.

Abstract Background Several studies have indicated that inflammatory markers were associated with the risk of mild cognitive impairment (MCI) in type 2 diabetes (T2D). Serum folate was related to MCI as well as inflammation. However, no studies have investigated the association between inflammatory markers and MCI taking account of serum folate level in T2D patients. This study aimed to conduct a case-control study to evaluate the association between inflammatory markers and MCI taking account of serum folate level in Chinese patients with T2D. Methods This study consisted of 126 T2D patients (63 cases with MCI and 63 controls without MCI). Clinical parameters, serum folate, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were measured. Spearman correlation analysis and logistic regression analysis were used to analyze the association between the inflammatory markers and the risk of MCI in T2D patients. Results There were higher serum hs-CRP, IL-6 and TNF-α in T2D cases with MCI compared with the controls. Serum folate was negatively correlated with hs-CRP, TNF-α, and IL-6 (P

Early life stage folate status may influence neurodevelopment in offspring. The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from conception to 2 years) of life. This study aimed to evaluate the effect of early life stage folic acid deficiency on de novo telomere synthesis, neurobehavioral development, and the cognitive function of offspring rats. The rats were divided into three diet treatment groups: folate-deficient, folate-normal, and folate-supplemented. They were fed the corresponding diet from 5 weeks of age to the end of the lactation period. After weaning, the offspring rats were still fed with the corresponding diet for up to 100 days. Neurobehavioral tests, folic acid and homocysteine (Hcy) levels, relative telomere length in brain tissue, and uracil incorporation in telomere in offspring were measured at different time points. The results showed that folic acid deficiency decreased the level of folic acid, increased the level of Hcy of brain tissue in offspring, increased the wrong incorporation of uracil into telomeres, and hindered de novo telomere synthesis. However, folic acid supplementation increased the level of folic acid, reduced the level of Hcy of brain tissue in offspring, reduced the wrong incorporation of uracil into telomeres, and protected de novo telomere synthesis of offspring, which was beneficial to the development of early sensory-motor function, spatial learning, and memory in adolescence and adulthood. In conclusion, early life stage folic acid deficiency had long-term inhibiting effects on neurodevelopment and cognitive function in offspring.

Colorectal cancer (CRC) has two major subtypes, microsatellite instability (MSI) and microsatellite stability (MSS) based on the genomic instability. In this study, using computational programs, we identified 9 master transcription factors (TFs) based on epigenomic profiling in MSS CRC samples. Notably, unbiased gene set enrichment analysis (GSEA) showed that several master TFs were strongly associated with immune-related functions in TCGA MSS CRC tissues, such as interferon gamma (IFN-γ) and interferon alpha (IFN-α) responses. Focusing to the top candidate, ASCL2, we found that CD8+ T cell infiltration was low in ASCL2 overexpressed MSS CRC samples. Compared with other gastrointestinal (GI) cancers (gastric cancer, MSI CRC, and esophageal cancer), ASCL2 is specifically upregulated in MSS CRC. Moreover, we identified 28 candidate genes in IFN-γ and IFN-α response pathways which were negatively correlated with ASCL2. Together, these results link transcriptional dysregulation with the immune evasion in MSS CRC, which may advance the understanding of immune resistance and contribute to developing novel treatments of MSS CRC.

BackgroundMinimal data are available on the prevalence of mild cognitive impairment (MCI) in older Chinese adults. Moreover, the current information on MCI shows important geographical variations.ObjectiveWe aimed to assess the prevalence and risk factors for MCI by age and sex among older adults in a North Chinese population.MethodsIn this population-based cross-sectional study, we enrolled a random sample of 4,943 adults aged ≥ 60 years between March 2018 and June 2019 in Tianjin, China. Of these, 312 individuals were excluded due to a lack of data (e.g., fasting blood test). As a result, 4,631 subjects were assessed. Individuals with MCI were identified using neuropsychological assessments, including the Mini-Mental State Examination and Activities of Daily Living scale, based on a modified version of the Petersen’s criteria.ResultsThe mean (SD) age of the 4,631 participants was 67.6 (4.89) years, and 2,579 (55.7%) were female. The overall age- and sex-standardized prevalence of MCI in our study population was 10.7%. There were significant associations of MCI with age [65–69 vs. 60–64 years, OR = 0.74; 95% confidence interval (CI): 0.58, 0.96], physical activity (≥23.0 vs.

Endothelial cell injury and apoptosis play a primary role in the pathogenesis of atherosclerosis. Moreover, accumulating evidence indicates that oxidative injury is an important risk factor for endothelial cell damage. In addition, low folate levels are considered a contributing factor to promotion of vascular disease because of the deregulation of DNA methylation. We aimed to investigate the effects of folic acid on injuries induced by oxidative stress that occur via an epigenetic gene silencing mechanism in ApoE knockout mice fed a high-fat diet and in human umbilical vein endothelial cells treated with oxidized low-density lipoprotein (ox-LDL). We assessed how folic acid influenced the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG, an oxidative DNA damage marker) and cellular apoptosis in in vivo and in vitro models. Furthermore, we analyzed DNA methyltransferase (DNMT) activity, vascular peroxidase 1 (VPO1) expression, and promoter methylation in human umbilical vein endothelial cells. Our data showed that folic acid reduced 8-OHdG levels and decreased apoptosis in the aortic tissue of ApoE−/− mice. Likewise, our in vitro experiments showed that folic acid protects against endothelial dysfunction induced by ox-LDL by reducing reactive oxygen species (ROS)-derived oxidative injuries, 8-OHdG content, and the apoptosis ratio. Importantly, this effect was indirectly caused by increased DNMT activity and altered DNA methylation at VPO1 promoters, as well as changes in the abundance of VPO1 expression. Collectively, we conclude that folic acid supplementation may prevent oxidative stress-induced apoptosis and suppresses ROS levels through downregulating VPO1 as a consequence of changes in DNA methylation, which may contribute to beneficial effects on endothelial function. Keywords: Folic acid, DNA methylation, Vascular peroxidase 1, Apoptosis, Oxidative stress, Atherosclerosis

Abstract To enhance the lubricating and extreme pressure (EP) performance of base oils, two types of oil-soluble ionic liquids (ILs) with similar anion albeit dissimilar cations were synthesized. The physical properties of the prepared ILs were measured. The anticorrosion properties of ILs were assessed by conducting corrosion tests on steel discs and copper strips, which revealed the remarkable anticorrosion properties of the ILs in comparison with those of the commercial additive zinc dialkyldithiophosphate (ZDDP). The tribological properties of the two ILs as additives for poly-α-olefin-10 (PAO10) with various mass concentrations were investigated. The tribological test results indicate that these ILs as additives are capable of reducing friction and wear of sliding contacts remarkably as well as enhance the EP performance of blank PAO10. Under similar test conditions, these IL additives exhibit higher lubricating and anti-wear (AW) performances than those of ZDDP based additive package in PAO10. Subsequently, X-ray photoelectron spectroscopy (XPS) and energy dispersive spectrometer (EDS) were conducted to study the lubricating mechanism of the two ILs. The results indicate that the formation of tribochemical film plays the most crucial role in enhancing the lubricating and AW behavior of the mixture lubricants.

Abstract Background Elevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood. Methods The cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry. Results Elevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment. Conclusions STAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke.

Abstract Homocysteine (Hcy) has been shown to have a neurotoxic effect on ischemic brain cells; however, the underlying mechanisms remain incompletely understood. Here, we examined whether Hcy treatment influences mitochondria injury, oxidative stress, and mitochondrial STAT3 (mitoStat3) expression in rat ischemic brain. Our results demonstrated that Hcy treatment aggravated the damage of mitochondrial ultrastructure in the brain cortex and the dentate gyrus region of the hippocampus after focal cerebral ischemia. An elevated Hcy level was also accompanied by the significant inhibition of mitochondrial complex I–III enzymatic activities in addition to an increase in cytochrome c release. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) content and mitoStat3 protein phosphorylation level were increased in Hcy-treated animals, whereas AG490, a Jak2 inhibitor, inhibited mitoStat3 phosphorylation as well as 8-OHdG levels induced by Hcy. In vitro studies revealed that Hcy also markedly increased reactive oxygen species (ROS) and mitoStat3 levels. In addition, the inhibition of pSTAT3 reduced Hcy-mediated increase in ROS levels, whereas quenching ROS using the ROS inhibitor glutathione ethyl ester inhibited Hcy-mediated pSTAT3 overactivation in Neuro2a cells. These findings suggest that the development of therapies that interfere with the ROS/pSTAT3 pathway may be helpful for treating cerebral infarction-related diseases associated with Hcy.

Prehypertension is a public health epidemic associated with various adverse outcomes, but can be reversed by timely intervention. However, little attention has been paid to prehypertension. Complement C3 is a central hub of complement-related immune system. We examined the association between C3 and prehypertension in an adult population for the first time, aiming to investigate whether pro-inflammatory immune response is involved in the prehypertensive state. About 7820 Tianjin residents without hypertension were categorized into sex-specific quintiles based on their serum concentration of complement C3. Adjusted logistic regression models were used separately by gender to assess the association between C3 quintiles and the prevalence of prehypertension. After multiple adjustment, the odds ratios (95% confidence interval) for prehypertension across increasing quintiles of C3 were 1.00 (reference), 1.02 (0.84, 1.25), 1.15 (0.94, 1.42), 1.25 (1.01, 1.54), and 1.71 (1.35, 2.17) (p for trend < 0.0001) among men and were 1.00 (reference), 1.17 (0.92, 1.49), 1.13 (0.88, 1.44), 1.15 (0.89, 1.48), and 1.40 (1.07, 1.84) (p for trend = 0.03) among women. The findings suggested that elevated serum C3 levels are associated with prehypertension. Reducing inflammation may be a potential therapeutic strategy for prehypertension and hypertension that is worthy of further studies and discussion.

Alzheimer’s disease (AD) is a common neurodegenerative disease resulting in progressive dementia, and is a principal cause of dementia among older adults. Folate acts through one-carbon metabolism to support the methylation of multiple substrates. We hypothesized that folic acid supplementation modulates DNA methyltransferase (DNMT) activity and may alter amyloid β-peptide (Aβ) production in AD. Mouse Neuro-2a cells expressing human APP695 were incubated with folic acid (2.8–40 μmol/L), and with or without zebularine (the DNMT inhibitor). DNMT activity, cell viability, Aβ and DNMTs expression were then examined. The results showed that folic acid stimulated DNMT gene and protein expression, and DNMT activity. Furthermore, folic acid decreased Aβ protein production, whereas inhibition of DNMT activity by zebularine increased Aβ production. The results indicate that folic acid induces methylation potential-dependent DNMT enzymes, thereby attenuating Aβ production.

Few studies have examined the association between Asian dietary pattern and prediabetes, in particular, the Chinese diet. We conducted a cross-sectional study to identify dietary patterns associated with impaired fasting glucose (IFG) which considered a state of prediabetes in Chinese men. The study included 1495 Chinese men aged 20 to 75 years. Information about diet was obtained using an 81-item food frequency questionnaire (FFQ), and 21 predefined food groups were considered in a factor analysis. Three dietary patterns were generated by factor analysis: (1) a vegetables-fruits pattern; (2) an animal offal-dessert pattern; and (3) a white rice-red meat pattern. The multivariate-adjusted odds ratio (OR) of IFG for the highest tertile of the animal offal-dessert pattern in comparison with the lowest tertile was 3.15 (95% confidence intervals (CI): 1.87–5.30). The vegetables-fruits dietary pattern was negatively associated with the risk of IFG, but a significant association was observed only in the third tertile. There was no significant association between IFG and the white rice-red meat pattern. Our findings indicated that the vegetables-fruits dietary pattern was inversely associated with IFG, whereas the animal offal-dessert pattern was associated with an increased risk of IFG in Chinese men. Further prospective studies are needed to elucidate the diet-prediabetes relationships.

Background/Aims. Low serum folate levels can alter inflammatory reactions. Both phenomena have been linked to Alzheimer’s disease (AD), but the effect of folic acid on AD itself is unclear. We quantified folate supplementation’s effect on inflammation and cognitive function in patients with AD over the course of 6 months. Methods. Patients newly diagnosed with AD (age > 60 years; n=121; mild to severe; international criteria) and being treated with donepezil were randomly assigned into two groups with (intervention group) or without (control group) supplemental treatment with folic acid (1.25 mg/d) for 6 months. The Mini-Mental State Examination (MMSE) was administered to all patients at baseline and follow-up, and blood samples were taken before and after treatment. We quantified serum folate, amyloid beta (Aβ), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), plasma homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and the mRNA levels of presenilin (PS), IL-6, and TNFα in leukocytes. Data were analyzed using a repeated-measures mixed model. Results. The mean MMSE was slightly increased in the intervention group compared to that in the control group (P

Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function.

Postpartum depression (PPD), as a common complication of childbearing, could have adverse consequences on mothers, children, and families. This cohort study aimed to assess the association between duration of folic acid (FA) supplementation during pregnancy and the onset of PPD in Chinese women. A total of 1592 participants were recruited, and data collected between July 2015 and March 2017 in Tianjin, China. Participants’ baseline data were collected regarding socio-demographic and lifestyle characteristics, obstetric history, and FA supplementation during pregnancy. The Chinese version of the self-rating depression scale was used to assess depressive symptoms at 6–12 weeks postpartum, and the prevalence of PPD in participants was 29.4%. Pregnant women who took FA supplements for >6 months had a lower prevalence of PPD, compared to those who took FA for ≤6 months. After using the 1:1 ratio propensity score matching, 601 FA-users ≤ 6 months and 601 FA-users > 6 months were included in the further analyses; this also yielded similar results (P < 0.05). Logistic regression analysis showed that FA intake for >6 months was an independent determinant of PPD (odds ratio = 0.76; 95% confidence interval: 0.59–0.98; P < 0.05). Thus, prolonged FA supplementation during pregnancy was associated with a decreased risk of PPD in Chinese women.

To examine the trends in the prevalence of overweight and obesity among preschool children from 2006 to 2014.A total of 145,078 children aged 3-6 years from 46 kindergartens finished the annual health examination in Tianjin, China. Height, weight and other information were obtained using standardized methods. Z-scores for weight, height, and BMI were calculated based on the standards for the World Health Organization (WHO) child growth standards.From 2006 to 2014, mean values of height z-scores significantly increased from 0.34 to 0.54, mean values of weight z-scores kept constant, and mean values of BMI z-scores significantly decreased from 0.40 to 0.23. Mean values of height z-scores, weight z-scores, and BMI z-scores slightly decreased among children from 3 to 4 years old, and then increased among children from 4 to 6 years old. Between 2006 and 2014, there were no significant changes in prevalence of overweight (BMI z-scores >2 SD) and obesity (BMI z-scores >3 SD) among 3-4 years children. However, prevalence of obesity (BMI z-scores >2 SD) increased from 8.8% in 2006 to 10.1% in 2010, and then kept stable until 2014 among 5-6 years children. Boys had higher prevalence of obesity than girls.Mean values of BMI z-scores decreased from 2006 to 2014 among Chinese children aged 3-6 years old due to the significant increase of height z-scores. Prevalence of obesity increased from 2006 to 2010, and then kept stable until 2014 among children aged 5-6 years. The prevalence of obesity was higher in boys than in girls.

Homocysteine (Hcy) is a risk factor for brain atrophy, cognitive impairment, and dementia. Vitamin B12 and folate are cofactors necessary for the methylation of Hcy. However, there is some debate regarding the differing levels of plasma Hcy and serum folate and vitamin B12 among healthy controls, patients with mild cognitive impairment (MCI), and patients with Alzheimer’s disease (AD). This study aimed to evaluate how the levels of plasma Hcy and its biological determinants, folate and vitamin B12, are related to MCI and AD in older Chinese adults. This is a case-control study including 112 subjects with MCI, 89 AD patients and 115 healthy controls. Diagnosis of AD was made according to the NINCDS-ADRDA and MCI with modified Petersen’s criteria. Serum folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and plasma Hcy was assessed by a high-performance liquid chromatography-fluorescence method. Multivariate analysis of regression was used to examine the odds ratio (OR) of MCI or AD with Hcy or vitamin levels. Results have shown that serum folate and vitamin B12 levels were significantly lower, but the plasma Hcy level was higher, in patients with MCI and AD than in healthy controls. Multivariate regression analyses showed that subjects in the lowest folate tertile had significantly higher adjusted ORs for MCI (OR: 3.07; 95% confidence interval [CI]: 1.12, 8.07) and AD (3.42; 95% CI: 1.15, 8.34) compared to subjects in the highest tertile. The highest Hcy tertile was significantly associated with MCI (adjusted OR: 2.81; 95% CI: 1.15, 4.73) and AD (adjusted OR: 3.64; 95% CI: 1.13, 9.04) compared to the lowest tertile. No association existed between low vitamin B12 levels and AD or MCI (p > 0.05). Low blood levels of folate and vitamin B12 and elevated Hcy levels were associated with MCI and AD in older Chinese adults, and the association was stronger for AD.

High incidence rate of Alzheimer’s disease (AD) is observed in patients with type 2 diabetes. Aggregated β-amyloid (Aβ) and hyperphosphorylated tau are the hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as well as in diabetic patients. Folates mediate the transfer of one carbon unit, required in various biochemical reactions. The effect of folate on tau phosphorylation in diabetic models still remains unknown. In this study, we investigated the effect and mechanism of folic acid on hyperphosphorylation of tau in streptozotocin (STZ)-induced diabetic mice. Diabetic mice induced by STZ, at the age of 10 weeks, were administered with three levels of folic acid: folic acid-deficient diet, diet with normal folic acid content, and 120 μg/kg folic acid diet for 8 weeks. Levels of serum folate and blood glucose were monitored. Tau phosphorylation, protein phosphatase 2A (PP2A) methylation, and Glycogen synthase kinase 3β (GSK-3β) phosphorylation were detected using Western blot. The S-adenosyl methionine:S-adenosyl homocysteine ratio (SAM:SAH) in brain tissues was also determined. DNA methyltransferase (DNMT) mRNA expression levels were detected using real-time PCR. Folic acid reduced tau hyperphosphorylation at Ser396 in the brain of diabetes mellitus (DM) mice. In addition, PP2A methylation and DNMT1 mRNA expression were significantly increased in DM mice post folic acid treatment. GSK-3β phosphorylation was not regulated by folic acid administration. Folic acid can reduce tau phosphorylation by regulating PP2A methylation in diabetic mice. These results support that folic acid can serve as a multitarget neuronal therapeutic agent for treating diabetes-associated cognitive dysfunction.

Lung cancer is one of the leading malignancies worldwide, but the regulatory mechanism of its growth and metastasis is still poorly understood. We investigated the possible expression of immunoglobulin G (IgG) genes in squamous cell carcinomas and adenocarcinomas of the lung and related cancer cell lines. Abundant mRNA of IgG and essential enzymes for IgG synthesis, recombination activation genes 1, 2 (RAG1, 2) and activation-induced cytidine deaminase (AID) were detected in the cancer cells but not in adjacent normal lung tissue or normal lung epithelial cell line. The extents of IgG expression in 86 lung cancers were found to associate with clinical stage, pathological grade and lymph node metastasis. We found that knockdown of IgG with siRNA resulted in decreases of cellular proliferation, migration and attachment for cultured lung cancer cells. Metastasis-associated gene 1 (MTA1) appeared to be co-expressed with IgG in lung cancer cells. Statistical analysis showed that the rate of IgG expression was significantly correlated to that of MTA1 and to lymph node metastases. Inhibition of MTA1 gene expression with siRNA also led to decreases of cellular migration and attachment for cultured lung cancer cells. These evidences suggested that inhibition of cancer migration and attachment induced by IgG down-regulation might be achieved through MTA1 regulatory pathway. Our findings suggest that lung cancer-produced IgG is likely to play an important role in cancer growth and metastasis with significant clinical implications.

Older adults can experience glucose metabolism dysfunction, and although manganese may help regulate glucose metabolism, there is little information regarding this association among older people. This cross-sectional study included 2402 Chinese adults who were ≥60 years old in 2013 (Tianjin, China), and evaluated the associations of serum manganese with prediabetes and diabetes. Serum manganese levels were measured using inductively coupled plasma mass spectrometry. Multivariable logistic regression models were used to evaluate the sex-specific associations of manganese levels with diabetes and prediabetes after adjusting for confounding factors (age, sex, life style factors, and health status). Based on the WHO criteria, prediabetes was observed in 15.1% of men and 13.4% of women, while diabetes was observed in 30.0% of men and 34.4% of women. In the final model, the odds ratios (95% confidence interval) for prediabetes according to manganese quartile were 1.000, 0.463 (0.269–0.798), 0.639 (0.383–1.065), and 0.614 (0.365–1.031) among men and 1.000, 0.773 (0.498–1.200), 0.602 (0.382–0.947), and 0.603 (0.381–0.953) among women (p for trend = 0.134 and 0.015, respectively). The lowest prevalence of diabetes among men occurred at a moderate range of serum manganese (p < 0.05). Therefore, appropriate serum manganese levels may help prevent and control prediabetes and diabetes.

Elevated homocysteine (Hcy) levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. The level and localization of autophagy were detected by transmission electron microscopy, western blot and immunofluorescence double labeling. The oxidative DNA damage was revealed by immunofluorescence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG). Hcy treatment aggravated neuronal cell death, significantly increased the formation of autophagosomes and the expression of LC3B and Beclin-1 in the brain cortex after middle cerebral artery occlusion-reperfusion (MCAO). Immunofluorescence analysis of LC3B and Beclin-1 distribution indicated that their expression occurred mainly in neurons (NeuN-positive) and hardly in astrocytes (GFAP-positive). 8-OHdG expression was also increased in the ischemic cortex of Hcy-treated animals. Conversely, LC3B and Beclin-1 overexpression and autophagosome accumulation caused by Hcy were partially blocked by the autophagy inhibitor 3-methyladenine (3-MA). Hcy administration enhanced neuronal autophagy, which contributes to cell death following cerebral ischemia. The oxidative damage-mediated autophagy may be a molecular mechanism underlying neuronal cell toxicity of elevated Hcy level.

In China, the rates of chronic diseases characteristic of countries in nutritional transition have been increasing. However, few studies have examined diet changes in recent decades. We analyzed dietary changes in Tianjin, China. The data in this descriptive, population-based study in ≥18-year-old adults were collected from three surveys from 1986 to 2011. Food consumption and nutrient intake were compared among the three surveys separately for urban and rural areas. Differences in food consumption between urban and rural areas in different periods were also shown. The consumption of cereals, vegetables, and oils decreased, and that of fruits and beans increased in both urban and rural areas. Moreover, the total consumption of animal foods, especially milk, increased (0.01% in 1986–1988; 1.72% in 2008–2011) in rural areas. Although milk consumption also increased in urban areas, consumption of other animal foods decreased (19.33% in 1986–1988; 13.74% in 2008–2011). Meanwhile, cereals consumption rebounded from 22.63% in 2000–2004 to 29.75% in 2008–2011. Moreover, the lack of dairy products and some nutrients, e.g., retinol, calcium, and dietary fiber (

Surfactant protein A2 (SP-A2) plays an essential role in surfactant metabolism and lung host defense. SP-A2 mutations in the carbohydrate recognition domain have been related to familial pulmonary fibrosis and can lead to a recombinant protein secretion deficiency in vitro. In this study, we explored the molecular mechanism of protein secretion deficiency and the subsequent biological effects in CHO-K1 cells expressing both wild-type and several different mutant forms of SP-A2. We demonstrate that the SP-A2 G231V and F198S mutants impair the formation of dimmer/trimer SP-A2 which contributes to the protein secretion defect. A deficiency in sialylation, but not N-linked glycosylation, is critical to the observed dimmer/trimer impairment-induced secretion defect. Furthermore, both mutant forms accumulate in the ER and form NP-40-insoluble aggregates. In addition, the soluble mutant SP-A2 could be partially degraded through the proteasome pathway but not the lysosome or autophagy pathway. Intriguingly, 4-phenylbutyrate acid (4-PBA), a chemical chaperone, alleviates aggregate formation and partially rescued the protein secretion of SP-A2 mutants. In conclusion, SP-A2 G231V and F198S mutants impair the dimmer/trimer assembly, which contributes to the protein sialylation and secretion deficiency. The intracellular protein mutants could be partially degraded through the proteasome pathway and also formed aggregates. The treatment of the cells with 4-PBA resulted in reduced aggregation and rescued the secretion of mutant SP-A2.

It has long been accepted that immunoglobulins (Igs) were produced by B lymphoid cells only. Recently Igs have been found to be expressed in various human cancer cells and promote tumor growth. Recombination activating gene 1 (RAG1) and RAG2, which are essential enzymes for initiating variable-diversity-joining segment recombination, have also been found to be expressed in cancer cells. However, the mechanism of RAG activation in these cancer cells has not been elucidated. Here, we investigated the regulatory mechanism of RAG expression in four human cancer cell lines by analyzing transcription factors that induce RAG activation in B cells. By RT-PCR, Western blot and immunofluorescence, we found that transcription factors E2A, FOXO1 and FOXP1 were expressed and localized to the nuclei of these cancer cells. Over-expression of E2A, FOXO1 or Foxp1 increased RAG expression, while RNA interference of E2A, FOXO1 or FOXP1 decreased RAG expression in the cancer cells. Chromatin immunoprecipitation experiments showed acetylation of RAG enhancer (Erag) and E2A, FOXO1 or FOXP1 were bound to Erag in vivo. These results indicate that in these cancer cells the transcription factors E2A, FOXO1 and FOXP1 regulate RAG expression, which initiates Ig gene rearrangement much in the way similar to B lymphocytes.

Recently immunoglobulins (Igs) have been found to be expressed by cells other than B lymphocytes, including various human carcinoma cells. Sarcomas are derived from mesenchyme, and the knowledge about the occurrence of Ig production in sarcoma cells is very limited. Here we investigated the phenomenon of immunoglobulin G (IgG) expression and its molecular basis in 3 sarcoma cell lines. The mRNA transcripts of IgG heavy chain and kappa light chain were detected by RT-PCR. In addition, the expression of IgG proteins was confirmed by Western blot and immunofluorescence. Immuno-electron microscopy localized IgG to the cell membrane and rough endoplasmic reticulum. The essential enzymes required for gene rearrangement and class switch recombination, and IgG germ-line transcripts were also identified in these sarcoma cells. Chromatin immunoprecipitation results demonstrated histone H3 acetylation of both the recombination activating gene and Ig heavy chain regulatory elements. Collectively, these results confirmed IgG expression in sarcoma cells, the mechanism of which is very similar to that regulating IgG expression in B lymphocytes.

Objective: To examine the mental health status and related factors in children and adolescents, and to assess age groups and sexes differences in factors influencing mental health. Methods: This cross-sectional study was performed on Chinese children aged 6-18 years from November 2021 to January 2022. Mental health difficulties were accessed by the Strengths and Difficulties Questionnaire. Multivariate logistic regression was used to analyze factors associated with mental health status. Multiple linear regression was used to evaluate factors associated with the scores of the Strengths and Difficulties Questionnaire. Results: The prevalence of mental health difficulties was 12.98% (n =1348). Age (OR, 0.909, [95%CI, 0.830-0.996]), sex (OR, 1.424, [95%CI, 1.033-1.963]) and screen time on weekdays ("-2" h/d vs "< 1" h/d: OR, 2.001, [95%CI, 1.300-3.080]) were related factors for mental health difficulties. For children (year - 12), the strongest related factor for mental health difficulties was screen time on weekdays ("- 2" h/d vs "< 1" h/d: OR, 1.821 [95%CI, 1.203-2.755]). The risk of mental health difficulties in females with - 2 h/d screen time on weekends was 3.420 times higher than those with < 1 h/d (OR, 3.420, [95%CI, 1.923-6.081]). Conclusion: The prevalence of mental health difficulties among children and adolescents was relatively high. The lower age, female sex and excessive screen time were associated with a higher risk of mental health difficulties. The factors influencing mental health varied by different age groups and sexes. Thus, specific measures for different age groups and sexes should be adopted to mitigate the impact. [ABSTRACT FROM AUTHOR]