ABSTRACT
Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol-based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu-FP successfully reduces the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod-like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu-FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu-FP in improving IVDD and provide novel insights for future research in IVDD treatments.
Subject(s)
Intervertebral Disc Degeneration , Nanoparticles , Humans , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis/physiology , Reactive Oxygen Species/metabolism , Intervertebral Disc Degeneration/drug therapy , Intervertebral Disc Degeneration/metabolism , Gasdermins , Inflammasomes/metabolism , Mitochondria/metabolism , Polyphenols/pharmacologyABSTRACT
BACKGROUND: PM2.5 can induce and aggravate the occurrence and development of cardiovascular diseases (CVDs). The objective of our study is to estimate the causal effect of PM2.5 on mortality rates associated with CVDs using the instrumental variables (IVs) method. METHODS: We extracted daily meteorological, PM2.5 and CVDs death data from 2016 to 2020 in Binzhou. Subsequently, we employed the general additive model (GAM), two-stage predictor substitution (2SPS), and control function (CFN) to analyze the association between PM2.5 and daily CVDs mortality. RESULTS: The 2SPS estimated the association between PM2.5 and daily CVDs mortality as 1.14% (95% CI: 1.04%, 1.14%) for every 10 µg/m3 increase in PM2.5. Meanwhile, the CFN estimated this association to be 1.05% (95% CI: 1.02%, 1.10%). The GAM estimated it as 0.85% (95% CI: 0.77%, 1.05%). PM2.5 also exhibited a statistically significant effect on the mortality rate of patients with ischaemic heart disease, myocardial infarction, or cerebrovascular accidents (P < 0.05). However, no significant association was observed between PM2.5 and hypertension. CONCLUSION: PM2.5 was significantly associated with daily CVDs deaths (excluding hypertension). The estimates from the IVs method were slightly higher than those from the GAM. Previous studies based on GAM may have underestimated the impact of PM2.5 on CVDs.
Subject(s)
Air Pollutants , Cardiovascular Diseases , Particulate Matter , Humans , Particulate Matter/adverse effects , Particulate Matter/analysis , Cardiovascular Diseases/mortality , China/epidemiology , Air Pollutants/adverse effects , Air Pollutants/analysis , Environmental Exposure/adverse effects , Male , Female , Air Pollution/adverse effects , Middle AgedABSTRACT
The pyramid wavefront sensor (PWS) presents numerous advantages, such as high energy utilization, exceptional spatial resolution, and adjustability. Precise calibration of the pupil's position and size in advance is essential for accurately extracting wavefront slope information from the captured pupil image by the PWS. What we believe to be a novel calibration method is proposed using a wavefront corrector to enhance the sharpness of the pupil images in the PWS. An experimental setup using a crystal spatial light modulator (SLM) is established to validate this method. Both physical experiments and simulated results demonstrate that our proposed method can achieve accurate calibration of the pupil image with an error within 4 pixels for pupil size and not exceeding 3 pixels for position, meeting practical application requirements. The proposed PWS calibration method exhibits excellent repeatability and robustness, making it directly applicable in astronomical adaptive optics systems.
ABSTRACT
Nanoparticle (NP) self-assembly from suspension evaporation has been a topic of interest in recent times to fabricate a solid-state structure with diverse functions. We present a simple and facile evaporation-induced strategy for the formation of NP arrays on a flat substrate utilizing a template-directed sandwich system. The lithographic features assist the assembly of the typical nanoparticles (NPs), including SiO2, QDs@PS FMs, and QDs, on the top into circle, stripe, triangle, or square geometries with a fixed width of 2 µm. Additionally, an anionic surfactant, sodium dodecyl sulfonate (SDS), is incorporated into a negatively charged, hydrophilic SiO2 dispersion to govern the aggregation and self-assembly of NPs, fine tuning the morphologies of the residual structures on the substrate. SDS is attributed to modify the nature of SiO2 NPs to be hydrophobic, increase the hydrophobic attraction, dominating particle-particle and particle-interface interactions, and strengthen the particle-particle repulsive electrostatic force that results in the reduction of SiO2 NPs trapped in the separated colloidal suspension drop. Thus, using the SDS surfactant with the concentration ranging from 0 to 1 wt %, the obtained well-ordered SiO2 NP pattern packing on the substrate varies from six layers to one layer.
ABSTRACT
We describe here a protocol for alkylation of quinazolinones with a series of primary or secondary alcohols under metal-free conditions. A class of quinazolinone derivatives were obtained in 31%-97% yield with good functional group tolerance. This protocol provides chemists a direct and effective way to obtain bioactive quinazolinone derivatives.
ABSTRACT
We report herein a protocol for an organocatalyzed asymmetric vinylogous Michael addition of aryl alkane nucleophiles with enals under base- and additive-free conditions. A series of allylic building blocks were obtained in 60%-93% yield and 88-99% ee with 20 mol % diphenylprolinol silyl ether as catalyst. This protocol has advantages such as excellent chemoselectivity and regioselectivity, good tolerance of functionalities, and simple reaction conditions.
ABSTRACT
This study aimed to examine change in tummy time patterns and preferences in the first 6 months of life, as well as dose-response relationships between tummy time duration and development at 2, 4, and 6 months. Participants were parents of infants from the Early Movers project in Edmonton, Canada (baseline: n = 411). At 2, 4, and 6 months, infant tummy time duration and preference (i.e., 1 = really likes to 5 = really dislikes) and development (i.e., Ages & Stages Questionnaire (ASQ-3) communication, fine motor, gross motor, problem-solving, personal-social) were measured by a parental questionnaire. In a subsample (n = 127), tummy time patterns (i.e., bout frequency, mean and median bout length) were measured using a 3-day time-use diary. Tummy time bout frequency, bout length, and preference significantly increased over time. Linear dose-response relationships between tummy time duration and development outcomes were observed at 4 (gross motor) and 6 months (all development outcomes). Moreover, at 2 months, 30-44 min/day of tummy time was associated with a higher total development score (vs. < 15 min/day; B = 11.14; 95%CI: 1.60, 20.68). At 6 months, 61-120 min/day (vs. < 30 min/day; B = 27.12; 95%CI: 11.93, 42.32) and > 120 min/day (vs. < 30 min/day; B = 33.80; 95%CI: 18.90, 48.70) of tummy time were associated with higher total development scores. Differences in threshold doses between some developmental outcomes were observed. Conclusion: In the first 6 months of life, increases were observed in tummy time preference as well as tummy time bout frequent and length. This finding may explain why the optimal amount of tummy time needed for more advanced development appeared to increase with age. What is Known: ⢠Tummy time is a type of physical activity in infancy. International and national guidelines recommend at least 30 minutes of tummy time per day for infants who are not yet mobile. What is New: ⢠In the first six months of life, preference for tummy time as well as tummy time bout frequency and length increased. ⢠Tummy time duration had dose-response associations with several development outcomes, and the optimal amount of tummy time needed for more advanced development appeared to increase with age.
Subject(s)
Child Development , Parents , Infant , Humans , Child Development/physiology , Exercise , Surveys and Questionnaires , CanadaABSTRACT
Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.
Subject(s)
Chondrocytes , Exosomes , Mesenchymal Stem Cells , MicroRNAs , Osteoarthritis , Animals , Rats , Chondrocytes/metabolism , Exosomes/metabolism , MicroRNAs/metabolism , Osteoarthritis/metabolism , TNF Receptor-Associated Factor 6/metabolism , TNF Receptor-Associated Factor 6/pharmacologyABSTRACT
BACKGROUND: Sleep is instrumental for growth and development in children, making it critical to establish healthy sleep habits from the earliest years of life. Many kindergarteners (3-6 years) in China have inadequate and poor sleep, necessitating targeted interventions. This research protocol details the "Healthy Sleep" intervention that was designed to promote healthy sleep among kindergarteners in China. METHODS: The "Healthy Sleep" intervention will be family-based and will support parents as change agents. The development of the intervention is based on evidence regarding correlates of sleep in young children and guided by Bandura's social cognitive theory. A 12-month randomised controlled trial will be conducted to examine the efficacy of the intervention for promoting healthy sleep in Chinese kindergarteners and the intervention's effects on child development outcomes. A targeted sample of 160 kindergarteners and their parents will be recruited through social media. The intervention group (n = 80) will receive monthly webinars for one year that include multiple intervention components - including educational training, goal setting and planning, as well as follow-up support sessions. The control group (n = 80) will receive videos of the recorded educational sessions after the study end. For primary outcomes, child sleep behaviours will be examined using the Child Sleep Health Questionnaire. For secondary outcomes, communication, fine motor, gross motor, personal-social, and problem-solving development will be examined using the Ages and Stages Questionnaire; executive functions will be examined using the Head, Toes, Knees, and Shoulders Revised tasks. Potential intervention mediators and covariates will be measured using a parental questionnaire. Mixed models will be conducted. DISCUSSION: This intervention targets sleep behaviours among kindergarteners in China. It has the potential to inform programs to support parents in helping their child establish healthy sleep habits from the earliest years of life. The study will provide high-quality experimental evidence on sleep behaviours in relation to development outcomes in kindergarteners. This evidence will inform family-based strategies to optimise early childhood development and inform national and international updates of the sleep recommendations for young children. TRIAL REGISTRATION: The trial was registered prospectively at Chinese Clinical Trial Registry (ID: ChiCTR2300072105) on 2 June 2023.
Subject(s)
East Asian People , Health Promotion , Sleep , Child , Child, Preschool , Humans , Child Development , Educational Status , Randomized Controlled Trials as Topic , ParentsABSTRACT
Cisplatin (Cis) is considered to be one of the most effective drugs for killing cancer cells and remains a first-line chemotherapeutic agent. However, Cis's multiple toxicities (especially nephrotoxicity) have limited its clinical use. Marsdenia tenacissima (Roxb.) Wight et Arn. (MT), a traditional Chinese medicine (TCM) employed extensively in China, not only enhances the antitumor effect in combination with Cis, but is also used for its detoxifying effect, as it reduces the toxic side effects of chemotherapy drugs. The aim of this study was to explore the therapeutic effect of MT on Cis-induced nephrotoxicity, along with its underlying mechanisms. In this study, liquid-mass spectrometry was performed to identify the complex composition of the extracts of MT. In addition, we measured the renal function, antioxidant enzymes, and inflammatory cytokines in mice with Cis-induced nephrotoxicity and conducted renal histology evaluations to assess renal injury. The expressions of the proteins related to antioxidant, anti-inflammatory, and apoptotic markers in renal tissues was detected by Western blotting (WB). MT treatment improved the renal function, decreased the mRNA expression of the inflammatory factors, and increased the antioxidant enzyme activity in mice. A better renal histology was observed after MT treatment. Further, MT inhibited the expression of the phospho-NFκB p65 protein/NFκB p65 protein (p-p65)/p65, phospho-inhibitor of nuclear factor kappa B kinase beta subunit/inhibitor of nuclear factor kappa B kinase beta subunit (p-IKKß/IKKß), Bcl-2-associated X (Bax), and Cleaved Caspase 3/Caspase 3 proteins, while the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Recombinant NADH Dehydrogenase, Quinone 1 (NQO1), and B-cell lymphoma-2 (Bcl-2) was increased. The present study showed that MT ameliorated renal injury, which mainly occurs through the regulation of the Nrf2 pathway, the NF-κB pathway, and the suppression of renal tissue apoptosis. It also suggests that MT can be used as an adjuvant to mitigate the nephrotoxicity of Cis chemotherapy.
Subject(s)
Cisplatin , Marsdenia , Mice , Animals , Cisplatin/adverse effects , Antioxidants/pharmacology , Antioxidants/metabolism , Caspase 3/metabolism , Marsdenia/metabolism , I-kappa B Kinase/metabolism , NF-E2-Related Factor 2/metabolism , Apoptosis , Oxidative Stress , NF-kappa B/metabolism , Inflammation/drug therapy , Inflammation/chemically induced , Proto-Oncogene Proteins c-bcl-2/metabolismABSTRACT
A microfluidic system was created to fabricate polydimethylsiloxane (PDMS) microspheres, whose shape, surface smoothness, and size were controlled. Resulting from their excellent optical properties and elasticity prepared by the apparatus, each PDMS microsphere could act as a microlens and separate imaging unit. The focal length of the microlens was simply tuned by the forces posed on the beads. For the microlens array (MLA) application, it was constructed simply through the assembly of the monodisperse PDMS beads.
Subject(s)
Dimethylpolysiloxanes , Microfluidics , MicrospheresABSTRACT
BACKGROUND: To examine: 1) longitudinal adherence to the Canadian 24-Hour Movement Guidelines in a sample of infants and 2) associations between adherence to the guidelines over time and development. METHODS: Participants were 250 parent-infant dyads from the Early Movers project in Edmonton, Alberta. At 2, 4, and 6 months of age, physical activity, sedentary behaviour, sleep, and development were measured with a parental questionnaire that included items from the Ages & Stages Questionnaire (ASQ-3). Parents also reported the dates six major gross motor milestones were acquired during the first 18 months of life according to World Health Organization criteria. In a sub-sample (n = 93), movement behaviours were also measured with a time-use diary at 2, 4, and 6 months and gross motor development was measured by a physiotherapist using the Alberta Infant Motor Scale (AIMS) at 6 months. Guideline adherence was defined as: 1) ≥ 30 min/day of tummy time, 2) no screen time, some reading time, no restrained bouts > 1 h (time-use diary only), and 3) 14-17 h (2 months) or 12-16 h (4 and 6 months) of sleep per 24-h period. Generalized estimating equations were conducted as well as linear mixed models and linear regression models that adjusted for demographic characteristics. RESULTS: Few infants met the guidelines at all time-points (questionnaire: 2%; time-use diary: 0%). Infants that met a recommendation at 2 months, compared to those that did not, were 1.8-8.2 times more likely to meet that recommendation at subsequent time-points. Meeting more recommendations across time-points, according to both measures, was associated with a higher mean ASQ-3 gross motor score. Each additional time-point of tummy time recommendation adherence (questionnaire-measured) was associated with a 5-11-day earlier acquisition of independent sitting, crawling, and independent standing milestones. In the sub-sample, each additional time-point of guideline adherence was associated with a 16% higher AIMS score at 6 months. CONCLUSIONS: Guideline adherence was low across the first 6 months of infancy. Overall, meeting more recommendations over this period appeared important for gross motor development. Parents and caregivers should be targeted as early as possible with guideline dissemination and activation strategies to promote healthy infant development.
Subject(s)
Exercise , Sedentary Behavior , Child , Infant , Humans , Longitudinal Studies , Exercise/physiology , Sleep/physiology , Guideline Adherence , AlbertaABSTRACT
BACKGROUND: This study aimed to address methodological limitations of the evidence that informed national and international movement behaviour guidelines for the early years. Specifically, the primary objective was to examine the longitudinal associations of infant physical activity (i.e., tummy time) and sedentary behaviour (i.e., back time, screen time, reading time, restrained time) with gross motor development. Secondary and tertiary objectives were to examine longitudinal associations of: (1) infant physical activity and sedentary behaviour with communication, fine motor, personal-social, and problem solving development, and (2) sleep time with primary and secondary outcomes. METHODS: Participants were 411 parents and their infants from the Early Movers project in Edmonton, Canada. Physical activity, sedentary behaviour, and sleep were measured with a parental questionnaire and the Ages & Stages Questionnaire (ASQ-3) developmental screening tool was administered at 2, 4, and 6 months. Parents reported the dates six major gross motor milestones (i.e., independent sitting, crawling, assisted standing, assisted walking, independent standing, independent walking) were acquired in the first 18 months of life according to World Health Organization criteria. In a subsample (n = 125), gross motor development was assessed using the Alberta Infant Motor Scale (AIMS) at 6 months. RESULTS: Higher tummy time across time points was significantly associated with higher ASQ-3 gross motor and personal-social development scores over time, higher total AIMS scores at 6 months, and earlier acquisition of all gross motor milestones. Higher reading time across time points was significantly associated with higher ASQ-3 fine motor, gross motor, personal-social, and total development scores over time. In contrast, higher back time across time points was significantly associated with lower total AIMS scores at 6 months and the later acquisition of assisted standing, assisted walking, and independent walking. Similarly, higher restrained time across time points was significantly associated with a later acquisition of supported walking. CONCLUSIONS: Tummy time was consistently longitudinally associated with more advanced gross motor development and reading with more advanced total development. Whereas, some detrimental associations were observed for back and restrained time. Findings support the promotion of tummy time and certain sedentary behaviours (i.e., reading) in young infants to enhance overall development.
Subject(s)
Screen Time , Sedentary Behavior , Alberta , Child Development , Exercise , Humans , Infant , SleepABSTRACT
BACKGROUND: In 2018, the Australian Government updated the Australian Physical Activity and Sedentary Behaviour Guidelines for Children and Young People. A requirement of this update was the incorporation of a 24-hour approach to movement, recognising the importance of adequate sleep. The purpose of this paper was to describe how the updated Australian 24-Hour Movement Guidelines for Children and Young People (5 to 17 years): an integration of physical activity, sedentary behaviour and sleep were developed and the outcomes from this process. METHODS: The GRADE-ADOLOPMENT approach was used to develop the guidelines. A Leadership Group was formed, who identified existing credible guidelines. The Canadian 24-Hour Movement Guidelines for Children and Youth best met the criteria established by the Leadership Group. These guidelines were evaluated based on the evidence in the GRADE tables, summaries of findings tables and recommendations from the Canadian Guidelines. We conducted updates to each of the Canadian systematic reviews. A Guideline Development Group reviewed, separately and in combination, the evidence for each behaviour. A choice was then made to adopt or adapt the Canadian recommendations for each behaviour or create de novo recommendations. We then conducted an online survey (n=237) along with three focus groups (n=11 in total) and 13 key informant interviews. Stakeholders used these to provide feedback on the draft guidelines. RESULTS: Based on the evidence from the Canadian systematic reviews and the updated systematic reviews in Australia, the Guideline Development Group agreed to adopt the Canadian recommendations and, apart from some minor changes to the wording of good practice statements, maintain the wording of the guidelines, preamble, and title of the Canadian Guidelines. The Australian Guidelines provide evidence-informed recommendations for a healthy day (24-hours), integrating physical activity, sedentary behaviour (including limits to screen time), and sleep for children (5-12 years) and young people (13-17 years). CONCLUSIONS: To our knowledge, this is only the second time the GRADE-ADOLOPMENT approach has been used to develop movement behaviour guidelines. The judgments of the Australian Guideline Development Group did not differ sufficiently to change the directions and strength of the recommendations and as such, the Canadian Guidelines were adopted with only very minor alterations. This allowed the Australian Guidelines to be developed in a shorter time frame and at a lower cost. We recommend the GRADE-ADOLOPMENT approach, especially if a credible set of guidelines that was developed using the GRADE approach is available with all supporting materials. Other countries may consider this approach when developing and/or revising national movement guidelines.
Subject(s)
Exercise , Sedentary Behavior , Adolescent , Australia , Canada , Child , Humans , SleepABSTRACT
BACKGROUND: A new physical activity and sedentary behaviour accreditation standard criterion for childcare settings was introduced by the provincial government in Alberta, Canada. The primary objective of this study was to examine if changes for in-care physical activity and sedentary time (ST) differed between centres in and around Edmonton, Alberta after implementing the new accreditation standards and non-accredited control centres in and around Ottawa, Ontario. Secondary objectives were to examine whether baseline age group (toddler, preschooler) or the childcare environment moderated any group differences in change of the primary outcomes. Furthermore, accreditation and control group differences in change of children's body mass index (BMI) Z-scores or cognitive development as well as educators' perceptions of the primary outcomes were explored. METHODS: Participants were 252 toddlers (19-35 months) and preschoolers (36-60 months) in childcare centres from Alberta (n = 11) and Ontario (n = 8) in the supporting Healthy physical AcTive CHildcare setting (HATCH) study. In-care ST, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were accelerometer-derived before and 6 months after the implementation of the new standards. At both time points, cognitive development (working memory, expressive vocabulary), heights, and weights were measured, and BMI Z-scores were calculated. Additionally, the childcare environment was observed using the Environment and Policy Assessment and Observation (EPAO) and Movement Environment Rating Scale (MOVERS) tools. Demographic characteristics were parent-reported and weather variables were derived from Environment Canada data. Mixed models were conducted. RESULTS: In adjusted models (n = 241), change in children's in-care ST (B = -0.07, 95%CI: - 1.43,1.29), LPA (B = 0.08, 95%CI: - 0.89,1.05), and log-transformed MVPA (B = 0.01, 95%CI: - 0.09,0.11) were not significantly different between accreditation and control groups. Age group and the childcare environment were not moderators. Significant increases in BMI Z-score (B = 0.19, 95%CI: 0.03,0.35) and high working memory (OR = 3.24, 95%CI: 1.32,7.97) were observed in the accreditation group and significant increases in expressive vocabulary (B = 3.18, 95%CI: 0.05,6.30) were observed in the control group. CONCLUSIONS: The new accreditation criterion may not significantly change physical activity or ST in childcare settings and therefore may not explain findings for BMI Z-scores and cognitive development. Additional training and resources may be needed.
Subject(s)
Child Care , Sedentary Behavior , Accreditation , Alberta , Child , Child Day Care Centers , Exercise , Government , HumansABSTRACT
Background: Helicobacter pylori (H. pylori) infection is closely associated with depression and development of neuroinflammation. The aim of this study is to explore the relationship between H. pylori, depression, and circulating levels of ghrelin. Methods: Mice were randomly divided into three groups: healthy control group (gavaged sterile saline and injected with saline, n = 8); H. pylori+saline group (gavaged H. pylori and injected with saline, n = 8); and H. pylori+rapa group (gavaged H. pylori and injected with rapamycin, n = 8). Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were used for anxiety and depressive behavior test. Western blotting was utilized to assess mTOR, p-mTOR, and GSMD expression, and serum ghrelin levels were estimated using ELISA. Results: In the OFT, the control mice moved more and exhibited a increase in crossing number relative to the H. pylori+saline mice (all P < 0.05). Increased quantity of fecal boli can be indicative of increased anxiety and emotionality of the subject animal. H. pylori+saline mice exhibited an increase in fecal boli when compared to control mice and H. pylori+rapa mice (P < 0.05). H. pylori infected mice decreasing the expression of ghrelin. The protein levels of p-mTOR/mTOR in the gastric antrum mTOR signaling activation and low-level ghrelin in H. pylori-infect mice compared to those in control mice (all P <0.001). Compared with single H. pylori infection, mTOR inhibitors increased the ghrelin secretion of H. pylori infection to a certain extent (P < 0.05). The protein levels of GSDMD expression significantly increase in hippocampus of H. pylori-infected mice (P < 0.001). Rapamycin treatment inhibited expression of GSDMD in H. pylori-infected mice (P < 0.05). Conclusions: H. pylori infection is associated with increased expression of mTOR and decreased circulating levels of ghrelin. Elevated pyroptosis in the brain and anxiety- and depressed-like behaviors occur when ghrelin levels are suppressed.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Animals , Anxiety/drug therapy , Ghrelin , Helicobacter Infections/complications , Helicobacter Infections/drug therapy , Mice , Sirolimus/pharmacology , TOR Serine-Threonine KinasesABSTRACT
Four new benzoylamide derivatives, lepidiumamide B-E (1-4), were isolated from the seeds of Lepidium apetalum Willd. The structures were determined by a combination of MS and NMR analyses. All compounds were evaluated for their protective effects against NRK-52e cell injury induced by lipopolysaccharide (LPS) in vitro. These compounds showed significantly protective activity and ameliorated LPS-induced NRK52e cells via the Nrf2/Keap1 pathway. The discovery of these active compounds is important for the prevention and treatment of renalinjury.
Subject(s)
Kelch-Like ECH-Associated Protein 1/metabolism , Kidney/drug effects , Lepidium/chemistry , Lipopolysaccharides/toxicity , NF-E2-Related Factor 2/metabolism , Phytochemicals/pharmacology , Seeds/chemistry , Animals , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Kelch-Like ECH-Associated Protein 1/genetics , Kidney/metabolism , Kidney/pathology , NF-E2-Related Factor 2/genetics , Plant Extracts/pharmacologyABSTRACT
Objectives: To examine the cross-sectional associations between screen time and cognitive development in preschoolers. Methods: Participants were 97 preschoolers (36 to 60 months) in Alberta and Ontario, Canada in the supporting Healthy physical AcTive Childcare setting (HATCH) study. The time that children spent watching television, videos or DVDs (television time) or playing video or computer games (video game time) on a television, computer, or portable device was assessed using a parental questionnaire. Television time and video game time were summed to calculate total screen time. Adherence to the screen time recommendation (≤1 hour/day) of the Canadian 24-Hour Movement Guidelines was calculated. Expressive vocabulary and working memory were assessed using the Early Years Toolbox. Due to the distribution of working memory, it was categorized as a binary variable based on the median score. The associations between screen time and cognitive development were examined using mixed models (expressive vocabulary) or generalized mixed models (working memory). Results: Screen time was not associated with expressive vocabulary. Preschoolers who had higher total screen time were less likely to have better working memory (OR=0.52; 95%CI:0.31, 0.88), despite the null associations for television time (P=0.155) and video game time (P=0.079). Preschoolers who met the screen time recommendation were more likely to have higher working memory capacity (OR=3.48; 95%CI:1.06, 11.47), compared to those who did not meet the recommendation. Conclusion: Limiting total screen time to no more than one hour per day may facilitate working memory development in preschoolers. Screen time may be unrelated to expressive language development in this age group.
ABSTRACT
OBJECTIVE: This systematic review aimed to summarize correlates of sleep duration in children under 5 years of age. METHODS: Six electronic databases (PubMed, PsycINFO, MEDLINE, CINAHL, SPORTDiscus, and Scopus) were searched from inception to May 2019. Observational studies and intervention studies reporting cross-sectional results from baseline data were considered. Data were extracted using a predesigned form and potential correlates were categorized following a sociological framework. RESULTS: One-hundred and sixteen studies, representing 329,166 children, met the inclusion criteria, with a high risk of bias in 62 included studies. A total of 83 correlates of sleep duration were identified. Among the associations studied four or more times, correlates of nap duration were child's age and nighttime sleep onset/bedtime; correlates of nighttime sleep duration were household income, parent marital status, parental adiposity level, nighttime sleep duration at younger age, nighttime sleep onset/bedtime, nighttime sleep wakeup time, and frequency of current bedtime routine; correlate of total sleep duration was screen time. CONCLUSIONS: Young children from low-income households, single families, or having overweight parents may be at risk for short sleep duration. Promoting healthy sleep duration from an early age appears essential. Effective practices may include encouraging an earlier bedtime, limiting screen time, and establishing a regular bedtime routine. The absence of consistent evidence in the psychological, cognitive, and emotional domain as well as the physical environmental domain warrants further research.
Subject(s)
Sleep , Child, Preschool , Cross-Sectional Studies , Humans , Infant , Observational Studies as Topic , Socioeconomic Factors , Time FactorsABSTRACT
Epidemiological data suggests that the genesis of cardiovascular disease occurs during childhood. Sedentary time (ST) is a main driver of high blood pressure (BP) in adolescents and adults. However, associations between ST and cardiovascular health in young children are uncertain. Prospective associations between ST and BP were assessed among 172 toddlers (88 boys), aged 19.5 ± 3.9 months at baseline, recruited from the GET-UP! Study, Australia and followed over a 12-month period. BP was measured with a digital monitor and z-scores were computed by age and sex for systolic and diastolic BP. Total ST was measured over 7 days using Actigraph accelerometers and expressed over a 24-h period. Multilevel linear regression models were used to assess regression coefficients and standard errors, predicting BP at follow-up from ST at baseline. Analyses controlled for socio-economic status, height, age, gender, group (intervention or control) and zWC at baseline. Adjusted analyses showed that total ST did not predict systolic or diastolic BP (ß = 0.0009, p = 0.368 and ß = 0.002, p = 0.05, respectively). Most likely, longer follow-up periods might be needed to confirm or rule out our results, as the effects of cumulative ST over time on BP values are prone to manifest later in life and track into adolescence and adulthood.