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1.
Technol Health Care ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38759033

ABSTRACT

BACKGROUND: Ever since the GALAD (gender-age-Lens culinaris agglutinin-reactive alpha-fetoprotein-alpha-fetoprotein-des-gamma-carboxy prothrombin) logistic regression model was established to diagnose hepatocellular carcinoma (HCC), there has been no high-level evidence that evaluates and summarizes it. OBJECTIVE: This meta-analysis was performed to assess the diagnostic ability of the GALAD model. METHODS: The following databases were systematically searched for original diagnostic studies on HCC: PubMed, Embase, Medline, the Web of Science, Cochrane Library, China National Knowledge Infrastructure Wanfang (China), Wiper and the Chinese BioMedical Literature Database. After screening the search results according to our criteria, the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to evaluate the methodologic qualities, and statistical software were used to output the statistics. RESULTS: Ultimately, 10 studies were included and analyzed. The results revealed the pooled sensitivity and specificity of the GALAD model to be 0.86 (95% confidence interval [CI]: 0.82, 0.90) and 0.90 (95% CI: 0.87, 0.92), respectively, for all-stage HCC. The area under the curve (AUC) was 0.94. For early-stage HCC, the pooled sensitivity and specificity of the GALAD model were 0.83 (95% CI: 0.78, 0.87) and 0.81 (95% CI: 0.78, 0.83), respectively. The AUC was 0.90. CONCLUSION: This meta-analysis confirmed that the GALAD model has excellent diagnostic performance for early-stage and all-stage HCC and can maintain high sensitivity and specificity in early-stage HCC. Therefore, the GALAD model is qualified for screening early-stage canceration from chronic liver disease.

2.
J Org Chem ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773694

ABSTRACT

Here, a novel iodine-catalyzed direct cyclization of o-nitrothiophenols with cyclohexanones to phenothiazines has been described without external oxidants and hydrogen acceptors. The nitro of o-nitrothiophenol works as both a hydrogen acceptor and a coupling group, and water is the only byproduct. The reaction involves the reduction of nitro groups, C-H bond thioetherification, and C-H bond dehydroaromatization. This scheme offers broad synthetic value for further elaborations, as exemplified by a 3-step total synthesis of antipsychotic chlorpromazine.

3.
Tree Physiol ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775231

ABSTRACT

Plant biomass is a highly promising renewable feedstock for the production of biofuels, chemicals, and materials. By enhancing the content of plant biomass through endophyte symbiosis, it can effectively reduce economic and technological barriers in industrial production. In this study, we found that symbiosis with the dark septate endophyte (DSE) Anteaglonium sp. T010 significantly promoted the growth of poplar trees and increased plant biomass, including cellulose, lignin and starch. To further investigate whether plant biomass was related to sucrose metabolism, we analyzed the levels of relevant sugars and enzyme activities. During the symbiosis of Anteaglonium sp. T010, sucrose, fructose and glucose levels in the stem of poplar decreased, while the content of intermediates such as glucose-6-phosphate (G6P), fructose-6-phosphate (F6P) and UDP-glucose (UDPG) and the activity of enzymes related to sucrose metabolism, including sucrose synthase (SUSY), cell wall invertase (CWINV), fructokinase (FRK) and hexokinase (HxK), increased. In addition, the contents of glucose, fructose, starch and their intermediates G6P, F6P and UDPG, as well as the enzyme activities of SUSY, CWINV, neutral invertase (NINV) and FRK in roots were increased, which ultimately led to the increase of root biomass. Besides that, during the symbiotic process of Anteaglonium sp. T010, there were significant changes in the expression levels of root-related hormones, which may promote changes in sucrose metabolism and consequently increase the plant biomass. Therefore, this study suggested that DSE fungi can increase the plant biomass synthesis capacity by regulating the carbohydrate allocation and sink strength in poplar.

4.
Nat Med ; 30(5): 1395-1405, 2024 May.
Article in English | MEDLINE | ID: mdl-38693247

ABSTRACT

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.


Subject(s)
Cerebral Palsy , DNA Copy Number Variations , Exome Sequencing , Genetic Heterogeneity , Humans , Cerebral Palsy/genetics , Female , Male , Child , Child, Preschool , DNA Copy Number Variations/genetics , Exome/genetics , Infant , Genetic Testing , Cohort Studies , Genetic Predisposition to Disease , Infant, Newborn
5.
PhytoKeys ; 241: 177-189, 2024.
Article in English | MEDLINE | ID: mdl-38721011

ABSTRACT

Angiopterisnodosipetiolata Ting Wang tris, H.F.Chen & Y.H.Yan, a new fern of Marattiaceae, is described and illustrated. Morphologically, A.nodosipetiolata is similar to A.chingii with more than one naked pulvinus on the stipe and numerous jointed hairs on the undersides of the mature pinnae. However, the pinnae of A.nodosipetiolata are lanceolate and can reach up to 4-6 pairs, whereas they are elliptic and occur in 2-3 pairs in A.chingii. Phylogenetic and genetic distance analysis, based on the plastid genomes, also indicates that A.nodosipetiolata is not closely related to A.chingii. Currently, there are ca. 500 mature individuals in Gulinqing Nature Reserve and we suggest A.nodosipetiolata should be categorised as an Endangered (EN) species according to the criteria of IUCN.

6.
Materials (Basel) ; 17(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38730813

ABSTRACT

We present a surface modification technique that turns CuNi foam films with a high contact angle and non-sticking property into a sticky surface. By decorating with mesh-like biaxially oriented polypropylene (BOPP) and adjusting the surface parameters, the surface exhibits water-retaining capability even when being held upside down. The wetting transition process of droplets falling on its surface were systematically studied using the finite element simulation method. It is found that the liquid filled the surface microstructure and curvy three-phase contact line. Moreover, we experimentally demonstrated that this surface can be further applied to capture underwater air bubbles.

7.
Materials (Basel) ; 17(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38730891

ABSTRACT

The simultaneous increase in strength and plasticity of aluminum and its alloys at cryogenic temperatures has been shown in previous research, but the deformation mechanism was still unclear. Therefore, the purpose of this investigation was to reveal the relationship between slip behavior and mechanical response at low temperatures. A quasi-in situ scanning electron microscope was used to observe the evolution of slip bands in the selected aluminum single crystals with two typical orientations at 25 °C, -100 °C, and -180 °C. The results showed that irrespective of orientation, the density of the slip plane was increased with the decline in temperature, which inhibited slip localization and significantly improved plasticity and work hardening. In detail, at RT, the slip bands were widening until the micro-cracks were generated, causing early failure during deformation. When the temperature was decreased to -180 °C, the slip plane density was increased, and the deformation was more homogenous. Moreover, the slip mode was influenced by orientation and temperature. In particular, a single slip system was activated in the sample with the [112] orientation at all the temperatures investigated. Multiple slip systems were found to activate at 25 °C and -100 °C, and only the primary slip system was activated in the sample with [114] orientation at -180 °C. These findings deepen the understanding of slip behavior at cryogenic temperatures, providing new insights into the deformation mechanism of aluminum and its alloys.

8.
IEEE Trans Cybern ; PP2024 May 07.
Article in English | MEDLINE | ID: mdl-38713576

ABSTRACT

This article is concerned with the prescribed performance tracking control problem for the strict-feedback systems with unknown nonlinearities and unmatched disturbances. The challenge lies in the realization of a complete performance specification for trajectory tracking in the sense of quantitatively regulating the peak value, overshoot, settling time, and accuracy while ensuring that the initial condition holds naturally. To this end, an error transformation, equipped with a shifting function, is introduced and incorporated with a new-type barrier function. Then, a class of performance functions is exploited to quantify the settling times and steady-state bounds of the intermediate errors. Moreover, to improve the flexibility of formulating performance specifications for the tracking error, a pair of asymmetric performance boundaries are further designed. With their combination, a novel robust prescribed performance control (PPC) approach is proposed in this article. It not only achieves the quantitative performance guarantees but also preserves the unique simplicity of PPC, evading the needs for function approximation, parameter identification, disturbance estimation, derivative calculation, or command filtering. The above theoretical findings are confirmed via three simulation studies.

9.
Int Immunopharmacol ; 134: 112141, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38733819

ABSTRACT

BACKGROUND: Novel coronaviruses constitute a significant health threat, prompting the adoption of vaccination as the primary preventive measure. However, current evaluations of immune response and vaccine efficacy are deemed inadequate. OBJECTIVES: The study sought to explore the evolving dynamics of immune response at various vaccination time points and during breakthrough infections. It aimed to elucidate the synergistic effects of epidemiological factors, humoral immunity, and cellular immunity. Additionally, regression curves were used to determine the correlation between the protective efficacy of the vaccine and the stimulated immune response. METHODS: Employing LASSO for high-dimensional data analysis, the study utilised four machine learning algorithms-logistical regression, random forest, LGBM classifier, and AdaBoost classifier-to comprehensively assess the immune response following booster vaccination. RESULTS: Neutralising antibody levels exhibited a rapid surge post-booster, escalating to 102.38 AU/mL at one week and peaking at 298.02 AU/mL at two weeks. Influential factors such as sex, age, disease history, and smoking status significantly impacted post-booster antibody levels. The study further constructed regression curves for neutralising antibodies, non-switched memory B cells, CD4+T cells, and CD8+T cells using LASSO combined with the random forest algorithm. CONCLUSION: The establishment of an artificial intelligence evaluation system emerges as pivotal for predicting breakthrough infection prognosis after the COVID-19 booster vaccination. This research underscores the intricate interplay between various components of immunity and external factors, elucidating key insights to enhance vaccine effectiveness. 3D modelling discerned distinctive interactions between humoral and cellular immunity within prognostic groups (Class 0-2). This underscores the critical role of the synergistic effect of humoral immunity, cellular immunity, and epidemiological factors in determining the protective efficacy of COVID-19 vaccines post-booster administration.

10.
Sensors (Basel) ; 24(9)2024 May 02.
Article in English | MEDLINE | ID: mdl-38733016

ABSTRACT

Within the context of a smart home, detecting the operating status of appliances in the environment plays a pivotal role, estimating power consumption, issuing overuse reminders, and identifying faults. The traditional contact-based approaches require equipment updates such as incorporating smart sockets or high-precision electric meters. Non-constant approaches involve the use of technologies like laser and Ultra-Wideband (UWB) radar. The former can only monitor one appliance at a time, and the latter is unable to detect appliances with extremely tiny vibrations and tends to be susceptible to interference from human activities. To address these challenges, we introduce HomeOSD, an advanced appliance status-detection system that uses mmWave radar. This innovative solution simultaneously tracks multiple appliances without human activity interference by measuring their extremely tiny vibrations. To reduce interference from other moving objects, like people, we introduce a Vibration-Intensity Metric based on periodic signal characteristics. We present the Adaptive Weighted Minimum Distance Classifier (AWMDC) to counteract appliance vibration fluctuations. Finally, we develop a system using a common mmWave radar and carry out real-world experiments to evaluate HomeOSD's performance. The detection accuracy is 95.58%, and the promising results demonstrate the feasibility and reliability of our proposed system.

11.
Mol Ecol ; : e17385, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38738821

ABSTRACT

Microbes are thought to be distributed and circulated around the world, but the connection between marine and terrestrial microbiomes remains largely unknown. We use Plantibacter, a representative genus associated with plants, as our research model to investigate the global distribution and adaptation of plant-related bacteria in plant-free environments, particularly in the remote Southern Ocean and the deep Atlantic Ocean. The marine isolates and their plant-associated relatives shared over 98% whole-genome average nucleotide identity (ANI), indicating recent divergence and ongoing speciation from plant-related niches to marine environments. Comparative genomics revealed that the marine strains acquired new genes via horizontal gene transfer from non-Plantibacter species and refined existing genes through positive selection to improve adaptation to new habitats. Meanwhile, marine strains retained the ability to interact with plants, such as modifying root system architecture and promoting germination. Furthermore, Plantibacter species were found to be widely distributed in marine environments, revealing an unrecognized phenomenon that plant-associated microbiomes have colonized the ocean, which could serve as a reservoir for plant growth-promoting microbes. This study demonstrates the presence of an active reservoir of terrestrial plant growth-promoting bacteria in remote marine systems and advances our understanding of the microbial connections between plant-associated and plant-free environments at the genome level.

12.
Nat Commun ; 15(1): 3946, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38729950

ABSTRACT

Disease modeling with isogenic Induced Pluripotent Stem Cell (iPSC)-differentiated organoids serves as a powerful technique for studying disease mechanisms. Multiplexed coculture is crucial to mitigate batch effects when studying the genetic effects of disease-causing variants in differentiated iPSCs or organoids, and demultiplexing at the single-cell level can be conveniently achieved by assessing natural genetic barcodes. Here, to enable cost-efficient time-series experimental designs via multiplexed bulk and single-cell RNA-seq of hybrids, we introduce a computational method in our Vireo Suite, Vireo-bulk, to effectively deconvolve pooled bulk RNA-seq data by genotype reference, and thereby quantify donor abundance over the course of differentiation and identify differentially expressed genes among donors. Furthermore, with multiplexed scRNA-seq and bulk RNA-seq, we demonstrate the usefulness and necessity of a pooled design to reveal donor iPSC line heterogeneity during macrophage cell differentiation and to model rare WT1 mutation-driven kidney disease with chimeric organoids. Our work provides an experimental and analytic pipeline for dissecting disease mechanisms with chimeric organoids.


Subject(s)
Cell Differentiation , Induced Pluripotent Stem Cells , Organoids , RNA-Seq , Single-Cell Analysis , Organoids/metabolism , Single-Cell Analysis/methods , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Humans , Cell Differentiation/genetics , RNA-Seq/methods , Sequence Analysis, RNA/methods , Macrophages/metabolism , Macrophages/cytology , Animals , Single-Cell Gene Expression Analysis
13.
Int J Mol Sci ; 25(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731915

ABSTRACT

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.


Subject(s)
Gonadotrophs , Pituitary Gland , Sexual Maturation , Single-Cell Analysis , Animals , Rats , Sexual Maturation/genetics , Pituitary Gland/metabolism , Gonadotrophs/metabolism , Single-Cell Analysis/methods , Male , Female , Biomarkers/metabolism , Transcriptome , Gene Expression Profiling , Follicle Stimulating Hormone/metabolism
14.
Heliyon ; 10(9): e30378, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707441

ABSTRACT

Objective: To explore the effects of propofol and ciprofol on patient euphoric reactions during sedation in patients undergoing gastroscopy and to investigate potential factors that may influence euphoric reactions in patients. Methods: A total of 217 patients were randomly divided into two groups: the propofol group (P group, n = 109) and the ciprofol group (C group, n = 108). The patients in the P group were given 2 mg/kg propofol, and those in the C group were given 0.5 mg/kg ciprofol. The patients were assessed using the Addiction Research Center Inventory-Chinese Version (ARCI-CV) to measure euphoric reactions at three time points: preexamination, 30 min after awakening, and 1 week after examination. Anxiety, depression, and sleep status were evaluated using appropriate scales at admission and 1 week after the examination. The dream rate, sedative effects, vital sign dynamics, and adverse reactions were documented during the sedation process. Results: After 30 min of awakening, the P group and C group showed no statistically significant differences in the mean morphine-benzedrine group (MBG) score (8.84 vs. 9.09, P > 0.05), dream rate (42.2 % vs. 40.7 %, P > 0.05), or MBG score one week after the examination (7.04 vs. 7.05, P > 0.05). The regression analysis revealed that sex, dream status, Alcohol Use Disorders Identification Test (AUDIT) score, and examination time had notable impacts on the MBG-30 min score. No statistically significant differences were observed in sedative effects, anxiety, depression, or sleep status between the two groups (P > 0.05). The incidence of injection pain and severe hypotension was significantly lower in the C group (P < 0.05), and hemodynamics and SpO2 were more stable during sedation (P < 0.05). Conclusion: There was no significant difference between propofol and ciprofol in terms of euphoria experienced by patients after sedation in patients undergoing gastroscopy. Ciprofol has demonstrated addictive potential similar to that of propofol, warranting careful attention to its addictive potential during clinical application.

15.
Int J Nanomedicine ; 19: 3773-3804, 2024.
Article in English | MEDLINE | ID: mdl-38708181

ABSTRACT

Geriatric diseases are a group of diseases with unique characteristics related to senility. With the rising trend of global aging, senile diseases now mainly include endocrine, cardiovascular, neurodegenerative, skeletal, and muscular diseases and cancer. Compared with younger populations, the structure and function of various cells, tissues and organs in the body of the elderly undergo a decline as they age, rendering them more susceptible to external factors and diseases, leading to serious tissue damage. Tissue damage presents a significant obstacle to the overall health and well-being of older adults, exerting a profound impact on their quality of life. Moreover, this phenomenon places an immense burden on families, society, and the healthcare system.In recent years, stem cell-derived exosomes have become a hot topic in tissue repair research. The combination of these exosomes with biomaterials allows for the preservation of their biological activity, leading to a significant improvement in their therapeutic efficacy. Among the numerous biomaterial options available, hydrogels stand out as promising candidates for loading exosomes, owing to their exceptional properties. Due to the lack of a comprehensive review on the subject matter, this review comprehensively summarizes the application and progress of combining stem cell-derived exosomes and hydrogels in promoting tissue damage repair in geriatric diseases. In addition, the challenges encountered in the field and potential prospects are presented for future advancements.


Subject(s)
Exosomes , Hydrogels , Stem Cells , Exosomes/chemistry , Humans , Hydrogels/chemistry , Aged , Aging/physiology , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Geriatrics
16.
Water Res ; 257: 121675, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38692258

ABSTRACT

Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) have aroused great concern owing to their widespread occurrence and toxic effects. However, their long-term trends and multimedia fate remain largely unknown. Here, we investigate the spatiotemporal characteristics and periodic oscillations of PFOS and PFOA in the Elbe River between 2010 and 2021. Anthropogenic emission inventories and multimedia fugacity model were developed to analyse their historical and future transport fates and quantify related human risks in each medium for the three age groups. The results show that average PFOS and PFOA concentrations in the Elbe River were 4.08 and 3.41 ng/L, declining at the annual rate of 7.36% and 4.98% during the study period, respectively. Periodic oscillations of their concentrations and mass fluxes were most pronounced at 40-60 and 20-40 months. The multimedia fugacity model revealed that higher concentrations occurred in fish (PFOS: 14.29, PFOA: 0.40 ng/g), while the soil was their dominant sink (PFOS: 179, PFOA: 95 tons). The exchange flux between water and sediment was the dominant pathway in multimedia transportation (397 kg/year). Although PFOS and PFOA concentrations are projected to decrease by 22.41% and 50.08%, respectively, from 2021 to 2050, the hazard quotient of PFOS in fish is a low hazard. This study provides information for the assessment of PFOS and PFOA pollution in global watersheds and the development of related mitigation policies, such as banning fish predation in polluted rivers, to mitigate their risks.

17.
Article in English | MEDLINE | ID: mdl-38709610

ABSTRACT

The Transformer has been successfully used in medical image segmentation due to its excellent long-range modeling capabilities. However, patch segmentation is necessary when building a Transformer class model. This process ignores the tissue structure features within patch, resulting in the loss of shallow representation information. In this study, we propose a Heterogeneous Swin Transformer with Multi-Receptive Field (HST-MRF) model that fuses patch information from different receptive fields to solve the problem of loss of feature information caused by patch segmentation. The heterogeneous Swin Transformer (HST) is the core module, which achieves the interaction of multi-receptive field patch information through heterogeneous attention and passes it to the next stage for progressive learning, thus complementing the patch structure information. We also designed a two-stage fusion module, multimodal bilinear pooling (MBP), to assist HST in further fusing multi-receptive field information and combining low-level and high-level semantic information for accurate localization of lesion regions. In addition, we developed adaptive patch embedding (APE) and soft channel attention (SCA) modules to retain more valuable information when acquiring patch embedding and filtering channel features, respectively, thereby improving model segmentation quality. We evaluated HST-MRF on multiple datasets for polyp, skin lesion and breast ultrasound segmentation tasks. Experimental results show that our proposed method outperforms state-of-the-art models and can achieve superior performance. Furthermore, we verified the effectiveness of each module and the benefits of multi-receptive field segmentation in reducing the loss of structural information through ablation experiments and qualitative analysis.

18.
Alzheimers Res Ther ; 16(1): 95, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693554

ABSTRACT

BACKGROUND: Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer's disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay. METHODS: 3×TG-AD transgenic mice were administered with chronic DMT (2 mg/kg) for 3 weeks and then performed water maze test. The Aß accumulation in the mice brain were determined. The Sig-1r level upon DMT treatment was tested. The effect of DMT on the ER-mitochondrial contacts site and multiple mitochondria-associated membrane (MAM)-associated proteins were examined. The effect of DMT on calcium transport between ER and mitochondria and the mitochondrial function were also evaluated. RESULTS: chronic DMT (2 mg/kg) markedly alleviated cognitive impairment of 3×TG-AD mice. In parallel, it largely diminished Aß accumulation in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of 3×TG-AD transgenic mice. The hallucinogen reinstated the expression of multiple MAM-associated proteins in the brain of 3×TG-AD mice. DMT also prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. DMT modulated oxidative phosphorylation (OXPHOS) and ATP synthase in the in vitro model of AD. CONCLUSION: The anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the activation of Sig-1r. DMT has the potential to serve as a novel preventive and therapeutic agent against AD.


Subject(s)
Alzheimer Disease , Endoplasmic Reticulum , Hallucinogens , Mice, Transgenic , Mitochondria , N,N-Dimethyltryptamine , Receptors, sigma , Sigma-1 Receptor , Animals , Receptors, sigma/metabolism , Receptors, sigma/agonists , Alzheimer Disease/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Mice , Hallucinogens/pharmacology , N,N-Dimethyltryptamine/pharmacology , Neurons/drug effects , Neurons/metabolism , Male
19.
J Cell Mol Med ; 28(9): e18350, 2024 May.
Article in English | MEDLINE | ID: mdl-38700030

ABSTRACT

Mechanical force induces hypoxia in the pulpal area by compressing the apical blood vessels of the pulp, triggering pulpal inflammation during orthodontic tooth movement. However, this inflammation tends to be restorable. Macrophages are recognized as pivotal immunoreactive cells in the dental pulp. Whether they are involved in the resolution of pulpal inflammation in orthodontic teeth remains unclear. In this study, we investigated macrophage polarization and its effects during orthodontic tooth movement. It was demonstrated that macrophages within the dental pulp polarized to M2 type and actively participated in the process of pulpal inflammation resolution. Inflammatory reactions were generated and vascularization occurred in the pulp during orthodontic tooth movement. Macrophages in orthodontic pulp show a tendency to polarize towards M2 type as a result of pulpal hypoxia. Furthermore, by blocking M2 polarization, we found that macrophage M2 polarization inhibits dental pulp-secreting inflammatory factors and enhances VEGF production. In conclusion, our findings suggest that macrophages promote pulpal inflammation resolution by enhancing M2 polarization and maintaining dental health during orthodontic tooth movement.


Subject(s)
Dental Pulp , Inflammation , Macrophages , Tooth Movement Techniques , Dental Pulp/metabolism , Dental Pulp/pathology , Animals , Macrophages/metabolism , Inflammation/pathology , Inflammation/metabolism , Mice , Cell Polarity , Male , Vascular Endothelial Growth Factor A/metabolism , Pulpitis/pathology , Pulpitis/metabolism , Macrophage Activation
20.
Behav Brain Res ; 469: 115006, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38692357

ABSTRACT

The nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway represents a crucial intrinsic protective system against oxidative stress and inflammation and plays a significant role in various neurological disorders. However, the effect of Nrf2 signalling on the regulation of cognitive impairment remains unknown. Dexmedetomidine (DEX) has neuroprotective effects and can ameliorate lipopolysaccharide (LPS)-induced cognitive dysfunction. Our objective was to observe whether Nrf2 knockout influences the efficacy of DEX in improving cognitive impairment and to attempt to understand its underlying mechanisms. An LPS-induced cognitive dysfunction model in wild-type and Nrf2 knockout mice (Institute of Cancer Research background; male; 8-12 weeks) was used to observe the impact of DEX on cognitive dysfunction. LPS was intraperitoneally injected, followed by novel object recognition and morris water maze experiments 24 h later. Hippocampal tissues were collected for histopathological and molecular analyses. Our research findings suggest that DEX enhances the expression of NQO1, HO-1, PSD95, and SYP proteins in hippocampal tissue, inhibits microglial proliferation, reduces pro-inflammatory cytokines IL-1ß and TNF-ɑ, increases anti-inflammatory cytokine IL-10, and improves dendritic spine density, thereby alleviating cognitive dysfunction induced by LPS. However, the knockout of the Nrf2 gene negated the aforementioned effects of DEX. In conclusion, DEX alleviates cognitive deficits induced by LPS through mechanisms of anti-oxidative stress and anti-inflammation, as well as by increasing synaptic protein expression and dendritic spine density. However, the knockout of the Nrf2 gene reversed the effects of DEX. The Nrf2 signaling pathway plays a crucial role in the mitigation of LPS-induced cognitive impairment by DEX.

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