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1.
Article in English | MEDLINE | ID: mdl-38949258

ABSTRACT

BACKGROUND: Non-suicidal self-injury (NSSI) in early adolescence has been amply documented. However, there has been little research on the progression of NSSI over time. Most studies have focused on the risk factors for NSSI, with less attention devoted to understanding the role of protective factors. This paper aimed to expand existing knowledge about the development of NSSI, with an emphasis on the impacts of protective factors such as social support and socioeconomic status (SES). METHODS: A total of 436 adolescents completed self-report surveys that addressed social support including friend, family, and teacher support, objective and subjective SES, and NSSI at three different points in time for 2 years. RESULTS: Latent growth curve analyses revealed that NSSI increased across early adolescence to mid-adolescence. Support from friends and family negatively predicted adolescents' initial NSSI level. Furthermore, subjective SES negatively predicted the rate of NSSI. CONCLUSIONS: These findings contribute to an understanding of the influences of both social support and SES on NSSI over time. NSSI interventions and education should include considerations of both the value of support from friends and family as well as subjective SES.

2.
Article in English | MEDLINE | ID: mdl-38955781

ABSTRACT

Accurate detection of heterogeneous circulating tumor cells (CTCs) is critical as they can make tumor cells more aggressive, drug-resistant, and metastasizing. Although the leukocyte membrane coating strategy is promising in meeting the challenge of detecting heterogeneous CTCs due to its inherent antiadhesive properties, it is still limited by the reduction or loss of expression of known markers. Bioorthogonal glycol-metabolic engineering is expected to break down this barrier by feeding the cells with sugar derivatives with a unique functional group to establish artificial targets on the surface of tumor cells. Herein, an engineered leukocyte biomimetic colorimetric sensor was accordingly fabricated for high-efficient detection of heterogeneous CTCs. Compared with conventional leukocyte membrane coating, the sensor could covalently bound to the heterogeneous CTCs models fed with Ac4ManNAz in vitro through the synergy of bioorthogonal chemistry and metabolic glycoengineering, ignoring the phenotypic changes of heterogeneous CTCs. Meanwhile, a sandwich structure composed of leukocyte biomimetic layer/CTCs/MoS2 nanosheet was formed for visual detection of HeLa cells as low as 10 cells mL-1. Overall, this approach can overcome the dependence of conventional cell membrane biomimetic technology on specific cell phenotypes and provide a new viewpoint to highly efficiently detect heterogeneous CTCs.

3.
Org Lett ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958587

ABSTRACT

The integration of umpolung and carbon isotope exchange for accessing isotopically labeled α-keto acids through photoredox catalysis is elucidated. This process involves the carbonyl umpolung of C(sp2)-α-keto acids to yield C(sp3)-α-thioketal acids, followed by the carbon isotope exchange of C(sp3)-α-thioketal acids, and ultimately, deprotection to generate carbon-labeled α-keto acids.

4.
J Youth Adolesc ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926214

ABSTRACT

Non-suicidal self-injury (NSSI) is considered a strong risk factor for suicide. Although NSSI is prevalent among adolescents and varies by gender, few studies have examined the gender-specific trajectory of NSSI and its predictors. This study examined the trajectory of NSSI among Chinese adolescent boys and girls separately, and the roles of distal (i.e., childhood maltreatment and its specific subtypes) and proximal risk factors (i.e., emotional dysregulation, peer victimization) on their trajectories. A total of 3290 Chinese adolescents (Mage = 13.08; SD = 0.84; 57.6% boys) participated in assessments at three time points. Latent class growth models identified three trajectories for boys: Low stable (92.5%), moderate increasing (5.0%) and high decreasing (2.5%). Four trajectories were identified for girls: Low stable (87.9%), moderate increasing (7.6%), high decreasing (3.0%) and high stable (1.5%). Multinomial logistic regression analyses revealed that both emotional dysregulation and emotional abuse predicted the trajectories of moderate increasing, high decreasing and high stable for girls, as well as predicted moderate increasing and high decreasing trajectories for boys. Peer victimization served as a significant risk factor predicting the moderate increasing and high decreasing trajectories only for girls, while overall childhood maltreatment was a remarkable predictor for the moderate increasing and high decreasing trajectories of boys. The findings highlighted the importance of gender differences in understanding the progression of NSSI and the key predictors, informing effective strategies for prevention and intervention.

5.
Nutrients ; 16(12)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38931321

ABSTRACT

Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.


Subject(s)
Apoptosis , Reactive Oxygen Species , STAT3 Transcription Factor , Selenomethionine , Signal Transduction , Humans , Selenomethionine/pharmacology , Apoptosis/drug effects , Signal Transduction/drug effects , Reactive Oxygen Species/metabolism , STAT3 Transcription Factor/metabolism , Janus Kinases/metabolism , Antiviral Agents/pharmacology , Membrane Potential, Mitochondrial/drug effects , A549 Cells
6.
Front Public Health ; 12: 1298612, 2024.
Article in English | MEDLINE | ID: mdl-38939566

ABSTRACT

Cardiovascular disease remains the leading cause of mortality on a global scale. Individuals who possess risk factors for cardiovascular disease, such as high blood pressure (BP) and obesity, face an elevated risk of experiencing organ-specific pathophysiological changes. This damage includes pathophysiological changes in the heart and peripheral vascular systems, such as ventricular hypertrophy, arterial stiffening, and vascular narrowing and stenosis. Consequently, these damages are associated with an increased risk of developing severe cardiovascular outcomes including stroke, myocardial infarction, heart failure, and coronary heart disease. Among all the risk factors associated with cardiovascular disease, high blood pressure emerges as the most prominent. However, conventional resting BP measurement methods such as auscultatory or oscillometric methods may fail to identify many individuals with asymptomatic high BP. Recently, exercise BP has emerged as a valuable diagnostic tool for identifying real (high) blood pressure levels and assessing underlying cardiovascular risk, in addition to resting BP measurements in adults. Furthermore, numerous established factors, such as low cardiorespiratory fitness and high body fatness, have been confirmed to contribute to exercise BP and the associated cardiovascular risk. Modifying these factors may help reduce high exercise BP and, consequently, alleviate the burden of cardiovascular disease. A significant body of evidence has demonstrated cardiovascular disease in later life have their origins in early life. Children and adolescents with these cardiovascular risk factors also possess a greater propensity to develop cardiovascular diseases later in life. Nevertheless, the majority of previous studies on the clinical utility of exercise BP have been conducted in middle-to-older aged populations, often with pre-existing clinical conditions. Therefore, there is a need to investigate further of the factors influencing exercise BP in adolescence and its association with cardiovascular risk in early life. Our previously published work showed that exercise BP is a potential useful method to detect adolescents with increased cardiovascular risk. Children and adolescents with cardiovascular risk factors are more likely to develop cardiovascular diseases later in life. However, previous studies on the clinical utility of exercise BP have largely focused on middle-to-older aged populations with pre-existing clinical conditions. Therefore, there is a need to investigate further the factors influencing exercise BP in adolescence and its association with future cardiovascular risk. Our previous studies, which focused on exercise BP measured at submaximal intensity, have shown that exercise BP is a potentially useful method for identifying adolescents at increased cardiovascular risk. Our previous findings suggest that improving cardio-respiratory fitness and reducing body fatness may help to reduce the risk of developing cardiovascular disease and improve overall cardiovascular health. These findings have important implications for the development of effective prevention and early detection strategies, which can contribute to improved public health outcomes.


Subject(s)
Blood Pressure , Cardiorespiratory Fitness , Cardiovascular Diseases , Exercise , Humans , Child , Adolescent , Cardiorespiratory Fitness/physiology , Blood Pressure/physiology , Risk Factors , Male , Heart Disease Risk Factors , Female
7.
Adv Sci (Weinh) ; : e2400480, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38881515

ABSTRACT

Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short-term memory loss and reduced amyloid-beta (Aß) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aß plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy-lysosome pathway in astrocytes, thereby mediating Aß clearance and alleviating AD pathology. ECM remodeling also promoted Aß plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy-lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease.

8.
NPJ Biofilms Microbiomes ; 10(1): 48, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898104

ABSTRACT

As the central members of the microbiome networks, viruses regulate the composition of microbial communities and drive the nutrient cycles of ecosystems by lysing host cells. Therefore, uncovering the dynamic patterns and the underlying ecological mechanisms mediating the tiniest viral communities across space and through time in natural ecosystems is of crucial importance for better understanding the complex microbial world. Here, the temporal dynamics of intertidal viral communities were investigated via a time-series sampling effort. A total of 1911 viral operational taxonomic units were recovered from 36 bimonthly collected shotgun metagenomes. Functionally important auxiliary metabolic genes involved in carbohydrate, sulfur, and phosphorus metabolism were detected, some of which (e.g., cysH gene) were stably present within viral genomes over time. Over the sampling period, strong and comparable temporal turnovers were observed for intertidal viromes and their host microbes. Winter was determined as the pivotal point for the shifts in viral diversity patterns. Notably, the viral micro-diversity covaried with the macro-diversity, following similar temporal patterns. The relative abundances of viral taxa also covaried with their host prokaryotes. Meanwhile, the virus-host relationships at the whole community level were relatively stable. Further statistical analyses demonstrated that the dynamic patterns of viral communities were highly deterministic, for which temperature was the major driver. This study provided valuable mechanistic insights into the temporal turnover of viral communities in complex ecosystems such as intertidal wetlands.


Subject(s)
Biodiversity , Metagenome , Viruses , Wetlands , Viruses/genetics , Viruses/classification , Viruses/isolation & purification , Seasons , Microbiota , Genome, Viral , Metagenomics/methods , Virome/genetics , Phylogeny
9.
Food Chem ; 457: 140083, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38905843

ABSTRACT

A highly sensitive Surface Plasmon Resonance (SPR) sensor coupled magnetic molecularly imprinted polymers nanoparticles (MMIPs NPs) was developed and validated for the determination of 6-benzylaminopurine (6-BA) in vegetables. MMIPs NPs were synthesized using methacrylic acid (MAA) and sodium p-styrene sulfonate (SSS) as functional monomers. The SPR exhibited a linear dependence on 6-BA concentration in the range 5-300 pg/mL with a low limit of detection (3.02 pg/mL) and limit of quantitation (10.08 pg/mL). The SPR signal of 6-BA-captured MAA/SSS-MMIPs NPs is higher than those of the structural analogues (6-KT and 2-IP: 1.72 and 2.12 times) and the non-structural analogues (2, 4-D and NAA: 2.31 and 2.57 times), indicating the SPR sensor has good selectivity for 6-BA. The recovery of the established method was between 93.8% and 108.6% with a coefficient of variation less than 9.2% in four vegetables. This SPR sensor shows great potential in detecting 6-BA in more vegetables.

10.
ISA Trans ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38853110

ABSTRACT

This article studies the passive tracking problem of a wearable exoskeleton for lower limb rehabilitation therapy in the face of unmodeled dynamics, interactive friction, disturbance, prescribed performance constraints, and actuator faults. Adaptive neural networks and a smooth performance function are incorporated to establish a novel fault-tolerant tracking scheme, which can not only compensate for the nonlinear uncertainties and disturbance, but also handle the actuator fault with guaranteed tracking performance. A state feedback controller is presented by using the full state information and an output feedback controller is developed when the angular velocity is unavailable. The differential explosion issue of the backstepping technique is resolved by constructing a first-order filter and the unmeasurable velocity is estimated by a nonlinear observer. Semiglobal uniform boundedness stabilities of the exoskeleton system are proved via the Lyapunov direct method. The tracking performances of the designed control approaches are tested by comparative simulations.

11.
J Cell Mol Med ; 28(11): e18443, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38837873

ABSTRACT

The human auricle has a complex structure, and microtia is a congenital malformation characterized by decreased size and loss of elaborate structure in the affected ear with a high incidence. Our previous studies suggest that inadequate cell migration is the primary cytological basis for the pathogenesis of microtia, however, the underlying mechanism is unclear. Here, we further demonstrate that microtia chondrocytes show a decreased directional persistence during cell migration. Directional persistence can define a leading edge associated with oriented movement, and any mistakes would affect cell function and tissue morphology. By the screening of motility-related genes and subsequent confirmations, active Rac1 (Rac1-GTP) is identified to be critical for the impaired directional persistence of microtia chondrocytes migration. Moreover, Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) are detected, and overexpression of Tiam1 significantly upregulates the level of Rac1-GTP and improves directional migration in microtia chondrocytes. Consistently, decreased expression patterns of Tiam1 and active Rac1 are found in microtia mouse models, Bmp5se/J and Prkralear-3J/GrsrJ. Collectively, our results provide new insights into microtia development and therapeutic strategies of tissue engineering for microtia patients.


Subject(s)
Cell Movement , Chondrocytes , Congenital Microtia , T-Lymphoma Invasion and Metastasis-inducing Protein 1 , rac1 GTP-Binding Protein , Animals , Female , Humans , Male , Mice , Chondrocytes/metabolism , Chondrocytes/cytology , Congenital Microtia/metabolism , Congenital Microtia/genetics , Congenital Microtia/pathology , Disease Models, Animal , rac1 GTP-Binding Protein/metabolism , T-Lymphoma Invasion and Metastasis-inducing Protein 1/metabolism , T-Lymphoma Invasion and Metastasis-inducing Protein 1/genetics
12.
Bioorg Med Chem Lett ; 109: 129818, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823726

ABSTRACT

Despite the availability of various 11C-labeled positron emission tomography (PET) tracers for assessing P-glycoprotein (P-gp) function, there are still limitations related to complex metabolism, high lipophilicity, and low baseline uptake. This study aimed to address these issues by exploring a series of customized dihydropyridines (DHPs) with enhanced stability and reduced lipophilicity as alternative PET tracers for P-gp dysfunction. Compared with verapamil and the rest DHPs, dimethyl 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1) exhibited superior cellular uptake differences between the human gastric cancer cell line SGC7901 and its drug-resistant counterpart. [18F]1 is successfully synthesized using a novel "hot-Hantzsch" approach in 22.1 ± 0.1 % radiochemical yields. MicroPET/CT imaging demonstrated that the uptake of [18F]1 in the brains of P-gp blocked mice increased by > 3 times compared to the control group. Additionally, [18F]1 displayed favorable lipophilicity (log D = 2.3) and excellent clearance characteristics, making it a promising tracer candidate with low background noise and high contrast.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1 , Dihydropyridines , Fluorine Radioisotopes , Positron-Emission Tomography , Dihydropyridines/chemistry , Dihydropyridines/chemical synthesis , Dihydropyridines/pharmacology , Humans , Animals , Fluorine Radioisotopes/chemistry , Mice , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Cell Line, Tumor , Molecular Structure , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacology , Structure-Activity Relationship , Tissue Distribution
13.
Int Immunopharmacol ; 138: 112473, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38943977

ABSTRACT

As the resident immune cells in the central nervous system, microglia exhibit a 'sensitized' or 'primed' phenotype with dystrophic morphology and dysregulated functions in aged brains. Although studies have demonstrated the inflammatory profile of aged microglia in several neurological diseases, this issue is largely uncertain in stroke. Consequently, this study investigated the effects of primed and repopulated microglia on post-ischemic brain injury in aged mice. We replaced primed microglia with newly repopulated microglia through pharmacological administration and withdrawal of the colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX3397. Further, we performed a series of behavioral tests and flow cytometry in mouse models of middle cerebral artery occlusion (MCAO) to study the effects of microglial replacement on ischemic injury in the aged brain. With depletion and subsequent repopulation of microglia in MCAO mice, microglial replacement in aged mice improved neurological function and decreased brain infarction. This protective effect was accompanied by the reduction of peripheral immune cells infiltrating into brains. We showed that the repopulated microglia expressed elevated neuroprotective factors (including Cluster of Differentiation 206, transforming growth factor-ß, and interleukin-10) and diminished expression of inflammatory markers (including Cluster of Differentiation 86, interleukin-6, and tumor necrosis factor α). Moreover, microglial replacement protected the blood-brain barrier and relieved neuronal death in aged mice subjected to 60 min of MCAO. These results imply that the replacement of microglia in the aged brain may alleviate brain damage and neuroinflammation, and therefore, ischemic brain damage. Thus, targeting microglia could be a promising therapeutic strategy for ischemic stroke.

14.
Int J Biol Macromol ; 275(Pt 1): 133424, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945330

ABSTRACT

The absence of effective therapeutic targets poses considerable obstacles to the treatment of triple-negative breast cancer (TNBC). This study aimed to explore the function and mechanism of polysaccharides derived from the aerial parts of Tetrastigma hemsleyanum (THP) for the treatment of TNBC. THP exerts notable anti-TNBC effects when used alone, and its combination with Doxorubicin (DOX) effectively augments the sensitivity of TNBC cells to DOX. Through RNA sequencing, Fe2+ assays, western blotting, and transmission electron microscopy, THP was identified as a natural inducer of ferroptosis and ferritinophagy through the xCT/GSH/GPX4 and Nrf2/NCOA4/FTH1 pathways. Further research revealed that the THP branched-chain hexose directly binds to the xCT protein to inhibit its expression and promotes ferroptosis. In vivo experiments confirmed the role of THP in inducing ferroptosis and showed that THP improves the tumor microenvironment and immune function by increasing the ratio of CD4+ and CD8+ T cells to regulatory T cells and modulating cytokine levels. As demonstrated by electrocardiography, blood chemistry, and histological analyses, THP alleviates organ toxicity caused by DOX. Overall, these results suggest that THP has significant clinical potential as a natural macromolecular drug and may provide a safe and effective treatment strategy for TNBC when combined with DOX.

15.
Environ Monit Assess ; 196(7): 628, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888677

ABSTRACT

Pit lakes are currently being investigated as a way to store and reclaim waste materials in the Alberta Oil Sands (AOS) region, Canada. Lake Miwasin (LM) is a pilot-scale pit lake consisting of treated fine tailings overlayed with oil sands process-affected water (OSPW) blended with fresh surface water. In October 2021, the surface water contained a mean concentration of 1.33 ± 0.04 µg/L dissolved selenium (Se), slightly above the Canadian Council of Ministers of Environment water quality guideline for long-term protection of aquatic life (1 µg Se/L). This study assessed the bioaccumulation of Se by the cladoceran Daphnia pulex under laboratory conditions through both aqueous and dietary exposure routes for comparison to field-collected specimens. In 12-day semi-static tests, lab-cultured D.pulex were exposed to water, and algae grown in media spiked with selenate. Results showed that Se bioaccumulation by lab-cultured D. pulex increased in all exposure treatments from days 5 to 12, with maximum Se concentrations of 3.08-3.47 µg/g dry weight (dw) observed within the exposure range tested. Interestingly, lower Se bioaccumulation concentrations (1.26-1.58 µg/g dw) were observed in the highest dissolved Se and dietary Se treatments, suggesting potential internal regulatory mechanisms. In addition, native D. pulex (LM) collected from Lake Miwasin and cultured in-house were exposed in 8-day semi-static tests to Lake Miwasin surface water and algae cultured in Lake Miwasin surface water. Selenium bioaccumulation in native D. pulex (LM) ranged from 2.00 to 2.04 µg/g dw at day 8 and was not significantly different (p > 0.05) compared to Se concentrations in D. pulex collected from Lake Miwasin (2.15 ± 0.28 µg/g) in summer 2022.


Subject(s)
Bioaccumulation , Daphnia , Dietary Exposure , Environmental Monitoring , Lakes , Selenium , Water Pollutants, Chemical , Animals , Daphnia/metabolism , Selenium/metabolism , Selenium/analysis , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/analysis , Lakes/chemistry , Alberta , Daphnia pulex
16.
Ultrason Sonochem ; 107: 106936, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38834000

ABSTRACT

This study focuses on developing a water-in-oil-in-water (W1/O/W2) double emulsion system using high-intensity ultrasound (HIU)-treated pea protein isolate (HIU-PPI) and pectin to encapsulate Lactobacillus plantarum (L. plantarum). The effects of ultrasound treatment on pea protein isolate (PPI) characteristics such as solubility, particle size, emulsification, surface hydrophobicity, and surface free sulfhydryl group were examined, determining optimal HIU processing conditions was 400 W for 10 min. The developed W1/O/W2 double emulsion system based on HIU-PPI demonstrated effective encapsulation and protection of L. plantarum, especially at the HIU-PPI concentration of 4 %, achieving an encapsulation efficiency of 52.65 %. Incorporating both HIU-PPI and pectin as emulsifiers increased the particle size and significantly enhanced the emulsion's viscosity. The highest bacterial encapsulation efficiency of the emulsion, 59.94 %, was attained at a HIU to pectin concentration ratio of 3:1. These emulsions effectively encapsulate and protect L. plantarum, with the concentration of HIU-PPI being a critical factor in enhancing probiotic survival under simulated gastrointestinal digestion. However, the concurrent utilization of pectin and HIU-PPI as emulsifiers did not provide a notable advantage compared to the exclusive use of HIU-PPI in enhancing probiotic viability during in vitro simulated digestion. This research offers valuable perspectives for the food industry on harnessing environmentally friendly, plant-based proteins as emulsifiers in probiotic delivery systems. It underscores the potential of HIU-modified pea protein and pectin in developing functional food products that promote the health benefits of probiotics.


Subject(s)
Emulsions , Lactobacillus plantarum , Pea Proteins , Pectins , Pea Proteins/chemistry , Pectins/chemistry , Particle Size , Water/chemistry , Ultrasonic Waves , Sonication , Solubility , Probiotics/chemistry , Oils/chemistry , Hydrophobic and Hydrophilic Interactions
18.
Gut Microbes ; 16(1): 2363020, 2024.
Article in English | MEDLINE | ID: mdl-38841892

ABSTRACT

CD4+ T cells play a critical role in regulating autoimmune diseases, and intestinal microbial metabolites control various immune responses. Granzyme B (GzmB)-producing CD4+ T cells have been recently reported to participate in the pathogenesis of autoimmune diseases. Here, we found that GzmbB-deficient CD4+ T cells induced more severe colitis in Rag1-/- mice than wild-type (WT) CD4+ T cells. Germ-free (GF) mice exhibited a lower expression of GzmB in intestinal CD4+ T cells compared to specific pathogen-free (SPF) mice. Intestinal microbial metabolite butyrate increased GzmB expression in CD4+ T cells, especially in IL-10-producing Th1 cells, through HDAC inhibition and GPR43, but not GPR41 and GPR109a. Butyrate-treated GzmB-deficient CD4+ T cells demonstrated more severe colitis compared to butyrate-treated WT CD4+ T cells in the T cell transfer model. Butyrate altered intestinal microbiota composition, but altered microbiota did not mediate butyrate induction of intestinal CD4+ T cell expression of GzmB in mice. Blimp1 was involved in the butyrate induction of GzmB in IL-10-producing Th1 cells. Glucose metabolism, including glycolysis and pyruvate oxidation, mediated butyrate induction of GzmB in Th1 cells. In addition, we found that IKZF3 and NR2F6 regulated GzmB expression induced by butyrate. Together, our studies underscored the critical role of GzmB in mediating gut bacterial metabolite butyrate regulation of T cell tolerance at the mucosal surface.


Subject(s)
Butyrates , Colitis , Gastrointestinal Microbiome , Granzymes , Interleukin-10 , Mice, Inbred C57BL , Th1 Cells , Animals , Interleukin-10/metabolism , Interleukin-10/genetics , Interleukin-10/immunology , Th1 Cells/immunology , Mice , Gastrointestinal Microbiome/drug effects , Butyrates/metabolism , Butyrates/pharmacology , Granzymes/metabolism , Colitis/immunology , Colitis/microbiology , Colitis/metabolism , Mice, Knockout , Positive Regulatory Domain I-Binding Factor 1/metabolism , Positive Regulatory Domain I-Binding Factor 1/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Immune Tolerance , Homeodomain Proteins
19.
Front Med (Lausanne) ; 11: 1396254, 2024.
Article in English | MEDLINE | ID: mdl-38835803

ABSTRACT

Objectives: The association between vitamin D and blood pressure in elderly patients with hypertension complicated by osteoporosis remains unclear. The objective of this study is to explore whether vitamin D deficiency contributes to elevated blood pressure in elderly individuals with both hypertension and osteoporosis. Methods: This study represents a single-center retrospective observational investigation carried out at the Zhongshan Hospital Affiliated to Xiamen University. Ambulatory blood pressure, bone density, vitamin D levels, and additional laboratory parameters were collected upon admission. The association between vitamin D and ambulatory blood pressure outcomes was assessed using Spearman correlation tests and partial correlation analyses. The relationship between vitamin D and changes in blood pressure was analyzed through Generalized Additive Models, and threshold analysis was conducted to explore potential thresholds. Results: 139 patients with newly diagnosed osteoporosis were consecutively included (mean age 73 years, 84.9% female). There is a negative correlation between 25-(OH) D3 and 24 h mean systolic blood pressure (mSBP), diurnal mSBP, nocturnal mSBP, maximum SBP, respectively. The results of the generalized additive model analysis show that there is a nonlinear relationship between 25-(OH) D3 and 24 h mSBP, diurnal mSBP, nocturnal mSBP, respectively. After determining the critical point of 25-(OH) D3 as 42 nmol/L, a segmented linear regression model was used to calculate the effect size and 95% confidence interval on both sides of the critical point. When 25-(OH) D3 is ≤42 nmol/L, it significantly negatively correlates with 24 h, diurnal, and nocturnal mean SBP. Conversely, when 25-(OH) D3 exceeds 42 nmol/L, there is no statistically significant association with 24 h, diurnal, or nocturnal mSBP. Conclusion: There was a significant negative correlation between vitamin D levels and blood pressure levels in elderly patients with hypertension and osteoporosis.

20.
Fa Yi Xue Za Zhi ; 40(2): 149-153, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38847029

ABSTRACT

OBJECTIVES: To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China, and to explore the feasibility of applying this method to determine whether an individual is 18 years or older. METHODS: A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population, and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method, and the age distribution of the samples at each stage was analyzed using descriptive statistics. RESULTS: Stages 0, 1, 2 and 3 first appeared in 16.88, 19.18, 21.91 and 25.44 years for males and in 17.47, 20.91, 22.01 and 26.01 years for females. In all samples, individuals at stages 1 to 3 were over 18 years old. CONCLUSIONS: It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.


Subject(s)
Age Determination by Teeth , Dental Pulp , Molar, Third , Radiography, Panoramic , Tooth Root , Humans , Molar, Third/diagnostic imaging , Male , Adolescent , Female , Adult , Young Adult , China , Tooth Root/diagnostic imaging , Age Determination by Teeth/methods , Dental Pulp/diagnostic imaging , Mandible/diagnostic imaging , Forensic Dentistry/methods , Age Factors
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