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1.
Article in English | MEDLINE | ID: mdl-38718831

ABSTRACT

INTRODUCTION: Oridonin possesses remarkable anti-inflammatory, immunoregulatory properties. However, the renoprotective effects of Oridonin and the underlying molecular mechanisms have not been explored in Diabetic Nephropathy (DN). We hypothesized that Oridonin could ameliorate diabetes­induced renal fibrosis. METHODS: We used streptozocin (STZ)-induced diabetic rats combined high-fat diet to establish a type 2 diabetes mellitus (T2DM) animal model, and then treated with Oridonin (10,20mg/kg/day) for two weeks. Kidney function and renal fibrosis were assessed. We also treated high glucose-induced human renal proximal tubule epithelial cells (HK-2) with Oridonin. In addition, the expression of inflammatory factors and fibrotic markers were analyzed. RESULTS: Oridonin treatment preserved kidney function and markedly limited the renal fibrosis size in diabetic rats. The renal fibrotic markers were inhibited in the 10mg/kg/day group and 20mg/kg/day group compared to the T2DM group. Moreover, the expression levels of TXNIP/NLRP3 and NF­κB pathway were decreased and the level of PPARγ were increased in the Oridonin treatment group compared to non-treated group. In vitro, intervention of PPARγ could significantly regulate the effect of Oridonin on the high glucose-induced inflammatory changes in HK-2. CONCLUSION: Oridonin reduces renal fibrosis and preserves kidney function via the inhibition of TXNIP/NLRP3 and NF­κB pathway by activating PPARγ in T2DM rat model, which indicates potential therapeutic effect of Oridonin on DN.

2.
Int Immunopharmacol ; 135: 112223, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38772295

ABSTRACT

Although smoking is a significant risk factor for osteomyelitis, there is limited experimental evidence that nicotine, a key tobacco constituent, is associated with this condition, leaving its mechanistic implications uncharacterized. This study revealed that nicotine promotes Staphylococcus aureus-induced osteomyelitis by increasing Nrf2 and Slc7a11 expression in vivo and in vitro. Inhibition of Slc7a11 using Erastin augmented bacterial phagocytosis/killing capabilities and fortified antimicrobial responses in an osteomyelitis model. Moreover, untargeted metabolomic analysis demonstrated that Erastin mitigated the effects of nicotine on S. aureus-induced osteomyelitis by altering glutamate/glutathione metabolism. These findings suggest that nicotine aggravates S. aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling pathway and that Slc7a11 inhibition can counteract the detrimental health effects of nicotine.

3.
Article in English | MEDLINE | ID: mdl-38776891

ABSTRACT

Detecting cognitive decline early in the older adults is crucial for effective intervention. This study, part of the Ma'anshan Healthy Aging Cohort Study, examined 2,288 participants with normal cognitive function. Forty-two potential predictors, including demographics, chronic diseases, lifestyle factors, and baseline cognitive function, were selected. The dataset was divided into training, validation, and test sets (60%, 20%, and 20%, respectively). Recursive feature elimination (RFE) and six machine learning algorithms were used for model development. Model performance was assessed using area under the curve (AUC), specificity, sensitivity, and accuracy. SHapley Additive exPlanations (SHAP) was applied for interpretability, revealing the top ten influential features: baseline MMSE, education, economic status, social activities, PSQI, BMI, SBP, DBP, IADL, and age. The Naïve Bayes (NB) algorithm-based model achieved an AUC of 0.820 (95% CI 0.773-0.887) on the test set, outperforming other algorithms. This model can help primary healthcare staff in community settings identify individuals at higher risk of cognitive impairment within three years among older adults.

4.
FASEB J ; 38(10): e23698, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38780613

ABSTRACT

Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT-PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK-8 assay, flow cytometry, wound-healing assay, Transwell assay, and Co-IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.


Subject(s)
Epithelial-Mesenchymal Transition , Forkhead Transcription Factors , Gene Expression Regulation, Neoplastic , Phosphatidylinositol 3-Kinases , Prostatic Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Prostatic Neoplasms/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Male , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Focal Adhesion Kinase 1/metabolism , Focal Adhesion Kinase 1/genetics , Signal Transduction , Up-Regulation , Cell Movement , Cell Proliferation , Animals , Mice , Oncogenes , Prognosis , Mice, Nude
5.
ACS Appl Mater Interfaces ; 16(20): 25843-25855, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38717308

ABSTRACT

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.


Subject(s)
Calcium Phosphates , Nanofibers , Silicon Dioxide , Tissue Scaffolds , Wound Healing , Nanofibers/chemistry , Animals , Rabbits , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Wound Healing/drug effects , Tissue Scaffolds/chemistry , Skin/drug effects , Regeneration/drug effects , Mice , Gels/chemistry
6.
Front Immunol ; 15: 1361531, 2024.
Article in English | MEDLINE | ID: mdl-38698849

ABSTRACT

The whole-genome sequence of an African swine fever virus (ASFV) strain (HuB/HH/2019) isolated from Hubei, China, was highly similar to that of the Georgia 2007/1 strain ASFV. After infection with strong strains, domestic pigs show typical symptoms of infection, including fever, depression, reddening of the skin, hemorrhagic swelling of various tissues, and dysfunction. The earliest detoxification occurred in pharyngeal swabs at 4 days post-infection. The viral load in the blood was extremely high, and ASFV was detected in multiple tissues, with the highest viral loads in the spleen and lungs. An imbalance between pro- and anti-inflammatory factors in the serum leads to an excessive inflammatory response in the body. Immune factor expression is suppressed without effectively eliciting an immune defense. Antibodies against p30 were not detected in acutely dead domestic pigs. Sequencing of the peripheral blood mononuclear cell transcriptome revealed elevated transcription of genes associated with immunity, defense, and stress. The massive reduction in lymphocyte counts in the blood collapses the body's immune system. An excessive inflammatory response with a massive reduction in the lymphocyte count may be an important cause of mortality in domestic pigs. These two reasons have inspired researchers to reduce excessive inflammatory responses and stimulate effective immune responses for future vaccine development.


Subject(s)
African Swine Fever Virus , African Swine Fever , Animals , Swine , African Swine Fever/virology , African Swine Fever/immunology , African Swine Fever Virus/immunology , African Swine Fever Virus/genetics , Cytokines , Lymphocytes/immunology , Lymphocytes/metabolism , Genotype , Viral Load , Sus scrofa , Lymphocyte Count
7.
Life (Basel) ; 14(5)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38792597

ABSTRACT

(1) Background: Oxygen has exerted a great effect in shaping the environment and driving biological diversity in Earth's history. Green lineage has evolved primary and secondary carotenoid biosynthetic systems to adapt to Earth's oxygenation, e.g., Haematococcus lacustris, which accumulates the highest amount of secondary astaxanthin under stresses. The two systems are controlled by lycopene ε-cyclase (LCYE) and ß-cyclase (LCYB), which leave an important trace in Earth's oxygenation. (2) Objectives: This work intends to disclose the underlying molecular evolutionary mechanism of Earth's oxygenation in shaping green algal carotenogensis with a special focus on lycopene cyclases. (3) Methods: The two kinds of cyclases were analyzed by site-directed mutagenesis, phylogeny, divergence time and functional divergence. (4) Results: Green lineage LCYEs appeared at ~1.5 Ga after the first significant appearance and accumulation of atmospheric oxygen, the so-called Great Oxygenation Event (GOE), from which LCYBs diverged by gene duplication. Bacterial ß-bicyclases evolved from ß-monocyclase. Enhanced catalytic activity accompanied evolutionary transformation from ε-/ß-monocyclase to ß-bicyclase. Strong positive selection occurred in green lineage LCYEs after the GOE and in algal LCYBs during the second oxidation, the Neoproterozoic Oxygenation Event (NOE). Positively selected sites in the catalytic cavities of the enzymes controlled the mono-/bicyclase activity, respectively. Carotenoid profiling revealed that oxidative adaptation has been wildly preserved in evolution. (5) Conclusions: the functionalization of the two enzymes is a result of primary to secondary adaptations to Earth's oxygenation.

8.
Anal Sci ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795278

ABSTRACT

In this study, a reliable method for determining eugenol content in environmental water samples was established by combining magnetic solid-phase extraction with high-performance liquid chromatography. Magnetic molecular imprinted polymers MGO@MIPs were prepared through surface molecular imprinting technique with eugenol as the template molecule. The material displayed good superparamagnetic properties and magnetic responsiveness in favor of rapid separation. The adsorption properties of MGO@MIPs for eugenol were evaluated through adsorption kinetics and selectivity experiments. MGO@MIPs were found to have favorable reusability and obvious selectivity for eugenol. In addition, adsorption and elution conditions were investigated. Under optimal conditions, a linear relationship was obtained between the concentration of eugenol and its peak area in the range of 0.02-5 mg/L (R2 = 0.9998) and the limit of detection was 4.0 × 10-6 mg/mL. The performance of the established method was assessed with the average recovery of 96.59-102.20% and the relative standard deviation (RSD) below 3.5%. The application of this method provides a new perspective for the separation, enrichment and detection of eugenol in water environment.

9.
Genes (Basel) ; 15(5)2024 May 07.
Article in English | MEDLINE | ID: mdl-38790221

ABSTRACT

Early-onset breast cancer (EoBC), defined by a diagnosis <40 years of age, is associated with poor prognosis. This study investigated the mutational landscape of non-metastatic EoBC and the prognostic relevance of mutational signatures using 100 tumour samples from Alberta, Canada. The MutationalPatterns package in R/Bioconductor was used to extract de novo single-base substitution (SBS) and insertion-deletion (indel) mutational signatures and to fit COSMIC SBS and indel signatures. We assessed associations between these signatures and clinical characteristics of disease, in addition to recurrence-free (RFS) and overall survival (OS). Five SBS and two indel signatures were extracted. The SBS13-like signature had higher relative contributions in the HER2-enriched subtype. Patients with higher than median contribution tended to have better RFS after adjustment for other prognostic factors (HR = 0.29; 95% CI: 0.08-1.06). An unsupervised clustering algorithm based on absolute contribution revealed three clusters of fitted COSMIC SBS signatures, but cluster membership was not associated with clinical variables or survival outcomes. The results of this exploratory study reveal various SBS and indel signatures may be associated with clinical features of disease and prognosis. Future studies with larger samples are required to better understand the mechanistic underpinnings of disease progression and treatment response in EoBC.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Adult , Prognosis , Age of Onset , Mutation , INDEL Mutation , Biomarkers, Tumor/genetics , Alberta/epidemiology , Middle Aged
10.
J Agric Food Chem ; 72(21): 11900-11916, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38709250

ABSTRACT

Food quality and safety are related to the health and safety of people, and food hazards are important influencing factors affecting food safety. It is strongly necessary to develop food safety rapid detection technology to ensure food safety. As a new detection technology, artificial nanochannel-based electrochemical and other methods have the advantages of being real-time, simple, and sensitive and are widely used in the detection of food hazards. In this paper, we review artificial nanochannel sensors as a new detection technology in food safety for different types of food hazards: biological hazards (bacteria, toxins, viruses) and chemical hazards (heavy metals, organic pollutants, food additives). At the same time, we critically discuss the advantages and disadvantages of artificial nanochannel sensor detection, as well as the restrictions and solutions of detection, and finally look forward to the challenges and development prospects of food safety detection technology based on the limitations of artificial nanochannel detection. We expect to provide a theoretical basis and inspiration for the development of rapid real-time detection technology for food hazards and the production of portable detection equipment in the future.


Subject(s)
Biosensing Techniques , Food Contamination , Food Safety , Food Contamination/analysis , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Nanostructures/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation
11.
Talanta ; 275: 126196, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38705018

ABSTRACT

We have developed an innovative optical emission spectrometry imaging device integrating a diode laser for sample introduction and an atmospheric pressure plasma based on dielectric barrier discharge for atomization and excitation. By optimizing the device parameters and ensuring appropriate leaf moisture, we achieved effective imaging with a lateral resolution as low as 50 µm. This device allows for tracking the accumulation of Cd and related species such as K, Zn, and O2+∙, in plant leaves exposed to different Cd levels and culture times. The results obtained are comparable to established in-lab imaging and quantitative methods. With its features of compact construction, minimal sample preparation, ease of operation, and low limit of detection (0.04 µg/g for Cd), this novel methodology shows promise as an in-situ elemental imaging tool for interdisciplinary applications.


Subject(s)
Atmospheric Pressure , Cadmium , Plant Leaves , Cadmium/analysis , Cadmium/chemistry , Plant Leaves/chemistry , Plasma Gases/chemistry , Zinc/chemistry , Zinc/analysis , Spectrum Analysis/methods , Potassium/analysis , Potassium/blood , Potassium/chemistry
12.
Accid Anal Prev ; 203: 107605, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38743983

ABSTRACT

Safety is one of the most essential considerations when evaluating the performance of autonomous vehicles (AVs). Real-world AV data, including trajectory, detection, and crash data, are becoming increasingly popular as they provide possibilities for a realistic evaluation of AVs' performance. While substantial research was conducted to estimate general crash patterns utilizing structured AV crash data, a comprehensive exploration of AV crash narratives remains limited. These narratives contain latent information about AV crashes that can further the understanding of AV safety. Therefore, this study utilizes the Structural Topic Model (STM), a natural language processing technique, to extract latent topics from unstructured AV crash narratives while incorporating crash metadata (i.e., the severity and year of crashes). In total, 15 topics are identified and are further divided into behavior-related, party-related, location-related, and general topics. Using these topics, AV crashes can be systematically described and clustered. Results from the STM suggest that AVs' abilities to interact with vulnerable road users (VRUs) and react to lane-change behavior need to be further improved. Moreover, an XGBoost model is developed to investigate the relationships between the topics and crash severity. The model significantly outperforms existing studies in terms of accuracy, suggesting that the extracted topics are closely related to crash severity. Results from interpreting the model indicate that topics containing information about crash severity and VRUs have significant impacts on the model's output, which are suggested to be included in future AV crash reporting.

13.
Cancer Lett ; 593: 216875, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643837

ABSTRACT

Mesenchymal glioma stem cells (MES GSCs) are a subpopulation of cells in glioblastoma (GBM) that contribute to a worse prognosis owing to their highly aggressive nature and resistance to radiation therapy. Here, OCT4 is characterized as a critical factor in sustaining the stemness phenotype of MES GSC. We find that OCT4 is expressed intensively in MES GSC and is intimately associated with poor prognosis, moreover, OCT4 depletion leads to diminished invasive capacity and impairment of the stem phenotype in MES GSC. Subsequently, we demonstrated that USP5 is a deubiquitinating enzyme which directly interacts with OCT4 and preserves OCT4 stability through its deubiquitination. USP5 was additionally proven to be aberrantly over-expressed in MES GSCs, and its depletion resulted in a noticeable diminution of OCT4 and consequently a reduced self-renewal and tumorigenic capacity of MES GSCs, which can be substantially restored by ectopic expression of OCT4. In addition, we detected the dominant molecule that regulates USP5 transcription, E2F1, with dual luciferase reporter gene analysis. In combination, targeting the E2F1-USP5-OCT4 axis is a potentially emerging strategy for the therapy of GBM.

14.
J Intensive Med ; 4(2): 137-159, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38681796

ABSTRACT

The Chinese Society of Critical Care Medicine (CSCCM) has developed clinical practice guidelines for nutrition assessment and monitoring for patients in adult intensive care units (ICUs) in China. This guideline focuses on nutrition evaluation and metabolic monitoring to achieve optimal and personalized nutrition therapy for critically ill patients. This guideline was developed by experts in critical care medicine and evidence-based medicine methodology and was developed after a thorough review of the system and a summary of relevant trials or studies published from 2000 to July 2023. A total of 18 recommendations were formed and consensus was reached through discussions and reviews by expert groups in critical care medicine, parenteral and enteral nutrition, and surgery. The recommendations are based on currently available evidence and cover several key fields, including screening and assessment, evaluation and assessment of enteral feeding intolerance, metabolic and nutritional measurement and monitoring during nutrition therapy, and organ function evaluation related to nutrition supply. Each question was analyzed according to the Population, Intervention, Comparison, and Outcome (PICO) principle. In addition, interpretations were provided for four questions that did not reach a consensus but may have potential clinical and research value. The plan is to update this nutrition assessment and monitoring guideline using the international guideline update method within 3-5 years.

15.
Micromachines (Basel) ; 15(4)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38675253

ABSTRACT

To obtain precise positional information, in this study, we propose an adaptive expectation-maximization (EM)-based Kalman filter (KF)/finite impulse response (FIR) integrated filter for inertial navigation system (INS)-based posture capture of human upper limbs. Initially, a data fusion model for wrist and elbow position is developed. Subsequently, the Mahalanobis distance is utilized to evaluate the performance of the filter. The integrated filter employs the EM-based KF to enhance noise estimation accuracy when the performance of KF declines. Conversely, upon deterioration in the performance of the EM-based KF, which is evaluated using the Mahalanobis distance, the FIR filter is employed to maintain the effectiveness of the data fusion filter. This research utilizes the proposed EM-based KF/FIR integrated filter to ascertain wrist and elbow positions. The empirical results demonstrate the proficiency of the proposed approach in estimating these positions, thereby overcoming the challenge and highlighting its inherent effectiveness.

16.
Sci Rep ; 14(1): 8127, 2024 04 07.
Article in English | MEDLINE | ID: mdl-38584156

ABSTRACT

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.


Subject(s)
Learning , Problem-Based Learning , Humans , Problem-Based Learning/methods , Prospective Studies , Students , Educational Measurement
17.
Cancer Immunol Immunother ; 73(6): 111, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38668781

ABSTRACT

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.


Subject(s)
Lung Neoplasms , Mutation , Neoplasms, Multiple Primary , Receptors, Antigen, T-Cell , Humans , Lung Neoplasms/immunology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism , Neoplasms, Multiple Primary/immunology , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Male , Female , Middle Aged , Aged
18.
New Phytol ; 242(6): 2453-2463, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38567702

ABSTRACT

CO2 release in the light (RL) and its presumed source, oxidative pentose phosphate pathways, were found to be insensitive to CO2 concentration. The oxidative pentose phosphate pathways form glucose 6-phosphate (G6P) shunts that bypass the nonoxidative pentose phosphate reactions of the Calvin-Benson cycle. Using adenosine diphosphate glucose and uridine diphosphate glucose as proxies for labeling of G6P in the stroma and cytosol respectively, it was found that only the cytosolic shunt was active. Uridine diphosphate glucose, a proxy for cytosolic G6P, and 6-phosphogluconate (6PG) were significantly less labeled than Calvin-Benson cycle intermediates in the light. But ADP glucose, a proxy for stromal G6P, is labeled to the same degree as Calvin-Benson cycle intermediates and much greater than 6PG. A metabolically inert pool of sedoheptulose bisphosphate can slowly equilibrate keeping the label in sedoheptulose lower than in other stromal metabolites. Finally, phosphorylation of fructose 6-phosphate (F6P) in the cytosol can allow some unlabeled carbon in cytosolic F6P to dilute label in phosphenolpyruvate. The results clearly show that there is oxidative pentose phosphate pathway activity in the cytosol that provides a shunt around the nonoxidative pentose phosphate pathway reactions of the Calvin-Benson cycle and is not strongly CO2-sensitive.


Subject(s)
Carbon Dioxide , Oxidation-Reduction , Pentose Phosphate Pathway , Photosynthesis , Carbon Dioxide/metabolism , Glucose-6-Phosphate/metabolism , Cytosol/metabolism , Light , Arabidopsis/metabolism , Arabidopsis/physiology
19.
Zhen Ci Yan Jiu ; 49(4): 331-340, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38649200

ABSTRACT

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.


Subject(s)
Acupuncture Therapy , Arthritis, Experimental , Chemokine CXCL1 , Receptors, Interleukin-8B , Somatosensory Cortex , Animals , Humans , Male , Mice , Rats , Acupuncture Points , Arthritis, Experimental/therapy , Arthritis, Experimental/metabolism , Arthritis, Experimental/genetics , Chemokine CXCL1/metabolism , Chemokine CXCL1/genetics , Inflammation/therapy , Inflammation/metabolism , Inflammation/genetics , Mice, Inbred BALB C , Pain/metabolism , Pain/genetics , Pain Management , Rats, Wistar , Receptors, Interleukin-8B/metabolism , Receptors, Interleukin-8B/genetics , Signal Transduction , Somatosensory Cortex/metabolism
20.
Epilepsia ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38606600

ABSTRACT

OBJECTIVE: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. METHODS: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. RESULTS: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. SIGNIFICANCE: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.

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