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1.
J Cell Mol Med ; 28(7): e18190, 2024 04.
Article in English | MEDLINE | ID: mdl-38494844

ABSTRACT

Systemic lupus erythematosus (SLE), a multifactorial autoimmune disease, can affect the brain and cause neuropsychiatric dysfunction, also named neuropsychiatric lupus (NPSLE). Microglial activation is observed in NPSLE patients. However, the mechanisms regulating microglia-mediated neurotoxicity in NPSLE remain elusive. Here, we showed that M1-like proinflammatory cytokine levels were increased in the cerebrospinal fluid (CSF) of SLE patients, especially those with neuropsychiatric symptoms. We also demonstrated that MRL/lpr lupus mice developed anxiety-like behaviours and cognitive deficits in the early and active phases of lupus, respectively. An increase in microglial number was associated with upregulation of proinflammatory cytokines in the MRL/lpr mouse brain. RNA sequencing revealed that genes associated with phagocytosis and M1 polarization were upregulated in microglia from lupus mice. Functionally, activated microglia induced synaptic stripping in vivo and promoted neuronal death in vitro. Finally, tofacitinib ameliorated neuropsychiatric disorders in MRL/lpr mice, as evidenced by reductions in microglial number and synaptic/neuronal loss and alleviation of behavioural abnormalities. Thus, our results indicated that classically activated (M1) microglia play a crucial role in NPSLE pathogenesis. Minocycline and tofacitinib were found to alleviate NPSLE by inhibiting micrglial activation, providing a promising therapeutic strategy.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Vasculitis, Central Nervous System , Humans , Mice , Animals , Microglia , Depression/drug therapy , Mice, Inbred MRL lpr , Brain , Lupus Erythematosus, Systemic/genetics , Cytokines
2.
J Oral Pathol Med ; 53(2): 159-168, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38321252

ABSTRACT

BACKGROUND: The incidence and mortality of tongue squamous cell carcinoma have shown an alarming increase in recent years. This study aimed to investigate the potential of HHLA2 as an immune checkpoint in comparison to PD-L1. METHODS: We obtained RNA-seq data from TCGA to study HHLA2 and PD-L1 expression across various tissues. Using the CIBERSORT package, we estimated cell type abundances within mixed populations based on gene expression profiles. Immunohistochemistry was performed to analyze HHLA2 and PD-L1 expression in Tongue squamous cell carcinoma. Prognostic evaluation was carried out with Kaplan-Meier curves and the log-rank test. To explore factors affecting HHLA2, univariate and multivariate Cox regression analyses were conducted with the COX regression model. Additionally, we used single-cell RNA sequencing data from the GEO database for gene set enrichment analysis with genes strongly correlated with HHLA2. RESULTS: Our analysis of RNA-seq data unveiled a significant upregulation of HHLA2 and PD-L1 expression in primary tumors when compared with normal tissue. HHLA2 exhibited a positive expression rate of 36.9%, while PD-L1 had a positive expression rate of 24.6%. HHLA2 emerged as a noteworthy independent risk factor impacting the overall survival of Tongue squamous cell carcinoma patients. The analysis of scRNA-seq data shed light on the involvement of HHLA2 in key pathways related to cell cycle regulation and interferon alpha/beta signaling. CONCLUSIONS: This study suggests that in the context of Tongue squamous cell carcinoma, HHLA2 may represent a more promising target for immunotherapy when compared with PD-L1.


Subject(s)
Carcinoma, Squamous Cell , Tongue Neoplasms , Humans , Carcinoma, Squamous Cell/genetics , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Tongue Neoplasms/genetics , Biomarkers, Tumor/metabolism , Prognosis , Immunoglobulins/genetics , Immunoglobulins/metabolism
3.
Luminescence ; 39(3): e4715, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38506397

ABSTRACT

Short-chain fatty acids, such as butyrate, play pivotal roles in various physiological processes within the human body. Recent advances in understanding cell death pathways, specifically ferroptosis, have unveiled unique opportunities for therapeutic development. Ferroptosis is linked to iron accumulation and oxidative stress, whereas butyrate has emerged as a cellular protector against oxidative stress, potentially inhibiting ferroptosis. Hydrogen peroxide (H2 O2 ) is a key player in oxidative stress, and its monitoring has gained significance in disease mechanisms. We present an innovative fluorescent probe, HOP, capable of dynamically tracking intracellular H2 O2 levels, enabling spatial and temporal visualization. The probe exhibits high accuracy (limit of detection = 0.14 µM) and sensitivity, paving the way for disease diagnosis and treatment innovations. Importantly, HOP displayed minimal toxicity, making it suitable for cellular applications. Cellular imaging experiments demonstrated its ability to penetrate cells and monitor intracellular H2 O2 levels accurately. The HOP probe confirmed H2 O2 as a critical marker in ferroptosis. Our innovative HOP provides a powerful tool for tracking intracellular H2 O2 levels and offers insights into the modulation of ferroptosis, potentially opening new avenues for disease research and therapeutic interventions.


Subject(s)
Ferroptosis , Hydrogen Peroxide , Humans , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/metabolism , Fluorescent Dyes/pharmacology , Butyric Acid/pharmacology , Oxidative Stress
4.
J Proteome Res ; 22(10): 3332-3347, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37616386

ABSTRACT

Brown adipose tissue (BAT) thermogenesis confers beneficial effects on metabolic diseases such as obesity and type-2 diabetes. Nevertheless, the mechanism and lipid driving the process that evokes this response have not been investigated yet. Here, a multiomics approach of integrative transcriptomics and lipidomics is used to explore the mechanism of regulating thermogenesis in BAT and providing promising lipid biomarkers and biomarker genes for thermogenic activators as antiobesity drugs. Lipidomics analysis demonstrated that a high abundance of glycerophospholipids and sphingolipids was more significant in BAT than in WAT. Enrichment analysis of upregulated DEGs between WAT and BAT screened suggested that the differences were mainly involved in lipid metabolism. Besides, ß3-adrenergic agonist stimulation reduced the levels of TAG and DAG and increased the content of PC, PE, CL, and LPC and expression of genes involved in thermogenesis, fatty acid elongation, and glycerophospholipid metabolism in BAT. In this study, based on interpreting the inherent characterization of BAT as thermogenic tissue through comparison with WAT as fat storage tissue, adrenergic stimulation-induced BAT thermogenesis further identified specific lipid biomarkers (7 TAG species, 10 PC species, 1 LPC species, and 1 CL species) and Elovl3 and Crat gene biomarkers, which may provide targets for combating obesity by boosting BAT thermogenesis.

5.
J Environ Manage ; 345: 118916, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37690244

ABSTRACT

The commitment to waste management has gained increasing momentum as global waste generation continues to skyrocket and threaten the environment. However, detailed assessments and clear insights remain absent to address the global waste utilization conundrum. This study evaluated the impact-oriented energy, carbon, and water (ECW) footprints of three typical scenarios for a waste recycling activity (i.e., waste rubber recycling) from environmental and economic dimensions, and explored key factors, nexus characteristics, and optimization measures. Results indicated that the rubber powder as an asphalt modifier scenario had a 93% greater environmental impact and 87% higher economic cost compared with the pyrolysis and reclaimed rubber production scenarios. Key processes, such as direct processes, electricity generation, and transportation, were identified as the major contributors to the ECW footprints, with the internal costs of raw materials, equipment, and taxes coupled with the external costs of human health dominating the economic impact. The nexus analysis results highlighted the urgent need to optimize the energy system for waste rubber recycling. Greening the production process revealed the benefits, with natural additives mitigating 85% of the environmental burden and 97% of the external costs compared with conventional additives. Industrial green microgrids, clean energy generation, proximity waste management, and electrified transportation were explored to foster sustainable optimization of waste rubber recycling systems. Moreover, a joint tax-subsidy mechanism for rubber production-recycling systems can stimulate recycling-oriented product design and increase the motivation to recycle waste rubber.


Subject(s)
Carbon Footprint , Rubber , Humans , Taxes , Carbon , Electricity
6.
Int Heart J ; 64(4): 708-716, 2023 Jul 29.
Article in English | MEDLINE | ID: mdl-37460317

ABSTRACT

This study aimed to investigate the short-term predictors of aortic-related adverse events in patients with acute type B aortic intramural hematoma (IMH) initially treated with optimized medical therapy.A total of 157 patients with acute type B IMH were included in this study. These patients were divided into worsening group (n = 45) and stable group (n = 112) based on the incidence of aortic-related adverse events. The clinical data and imaging features of the two groups were compared. Multivariate logistic regression analysis of predictors of aortic-related adverse events in type B IMH was performed. Receiver operating characteristic (ROC) curve was applied to determine the optimal cutoff value for maximum descending aorta diameter (MDAD). Kaplan-Meier survival curve was used to analyze the incidence of aortic-related adverse events.Worsening and stable groups were statistically significant in diuretics, abnormal D-dimer level, observation endpoint systolic blood pressure (SBP), MDAD, aortic atherosclerosis, ulcer-like projection (ULP), and thickness of hematoma (P < 0.05). Multivariate logistic regression showed that abnormal D-dimer level (OR = 12.464, P = 0.025), MDAD (OR = 1.113, P = 0.030), and ULP (OR = 5.849, P = 0.022) were powerful independent risk factors for predicting aortic-related adverse events in type B IMH, and observation endpoint SBP within 100-120 mmHg (OR = 0.225, P = 0.014) was a protective factor for predicting aortic-related adverse events in type B IMH. The cutoff value of MDAD was 35.2 mm.Short-term imaging is recommended for type B IMH patients with abnormal D-dimer level, MDAD > 35.2 mm, and ULP. Blood pressure should also be strictly monitored and controlled during the acute phase of IMH.

7.
BMC Oral Health ; 22(1): 213, 2022 05 28.
Article in English | MEDLINE | ID: mdl-35643546

ABSTRACT

BACKGROUND: To assess the contributing risk factors for the progression of, and the postoperative poor prognosis associated with, osteoradionecrosis of jaw (ORNJ) following non-nasopharyngeal cancer treatment in head and neck. METHODS: A retrospective study of 124 non-nasopharyngeal carcinoma patients in head and neck treated at one institution between 2001 and 2020 was conducted. A cumulative meta-analysis was conducted according to PRISMA protocol and the electronic search was performed on the following search engines: PubMed, Embase, and Web of Science. After assessing surgery with jaw lesions as a risk factor for the occurrence of ORNJ, 124 cases were categorized into two groups according to the "BS" classification, after which jaw lesions, chemotherapy, flap reconstruction and onset time of ORNJ were analyzed through the chi-square test and t-test to demonstrate the potential association between them and the progression of ORNJ. Postoperative outcomes of wound healing, occlusal disorders, and nerve injury were statistically analyzed. RESULTS: With the statistically significant results of the meta-analysis (odds ratio = 3.07, 95% CI: 1.84-5.13, p < 0.0001), the chi-square test and t-test were used to validate our hypotheses and identified that surgery with jaw lesions could aggravate the progression and accelerate the appearance of ORNJ. Patients who underwent chemotherapy tended to suffer from severe-to-advanced osteonecrosis but did not shorten the onset time of ORNJ. Flap reconstruction presented obvious advantages in wound healing (p < 0.001) and disordered occlusion (p < 0.005). The mean onset time of ORNJ in non-nasopharyngeal cancer patients (4.5 years) was less than that in patients with nasopharyngeal cancer (NPC) (6.8 years). CONCLUSIONS: Iatrogenic jaw lesions are evaluated as a significant risk factor in the occurrence and progression of ORNJ in non-nasopharyngeal carcinoma patients who tend to have more severe and earlier osteonecrosis after radiotherapy than NPC patients. Flap reconstruction is a better choice for protecting the remaining bone tissue and reducing postoperative complications of ORNJ.


Subject(s)
Nasopharyngeal Neoplasms , Osteonecrosis , Osteoradionecrosis , Humans , Nasopharyngeal Carcinoma , Osteonecrosis/complications , Osteoradionecrosis/etiology , Postoperative Complications , Retrospective Studies
8.
Thromb J ; 19(1): 80, 2021 Nov 04.
Article in English | MEDLINE | ID: mdl-34736465

ABSTRACT

BACKGROUND: Lemierre syndrome (LS) is characterized by multisystemic infection beginning in the oropharynx, local thrombophlebitis (typically, of the internal jugular vein) and peripheral embolism. No evidence-based guidelines exist for the management of this disease, and the use of anticoagulation therapy remains particularly controversial. CASE PRESENTATION: A 61-year-old man presenting with left neck swelling, odynophagia, and dyspnea underwent emergency surgery and received intravenous antibiotics. The primary infection was controlled on hospital day 5, but on day 6 sudden leukocytosis and hypoxemia were observed. CT angiography revealed an intraluminal filling defect in the pulmonary artery on day 8. LS was diagnosed and anticoagulation therapy was initiated. The WBC count, which had maintained its peak values in the previous 2 days, decreased instantly after initiation, and follow-up controls showed thrombus resolution. CONCLUSIONS: Our case supports the notion that anticoagulation therapy may be a valid supplement to antimicrobial therapy in LS, especially in the presence of a possibly young thrombus as suggested by clinical worsening.

9.
Zhongguo Zhong Yao Za Zhi ; 42(24): 4744-4749, 2017 Dec.
Article in Zh | MEDLINE | ID: mdl-29493141

ABSTRACT

To further evaluate the safety of ginkgo diterpene lactone meglumine injection in the clinical use in ischemic stroke patients. Clinical safety study was conducted in 82 clinical units and 6 300 cases were completed and included from June 2013 to December 2014 by using multicenter, prospective, open and uncontrolled design methods for clinical research. A total of 29 cases of adverse reactions were observed in the experiment. Adverse reaction ratio (ADR) was 0.46%, and about 86.21% (25 cases) of them was mild with transient response which could be alleviated or disappeared without intervention; about 13.79% (4 cases) was moderate, including 2 cases of headache, 1 case of dizziness and 1 case of rash; no serious adverse reactions were found. The adverse reactions occurred in this study were pre-known adverse reactions or common adverse reactions of Chinese medicine injection. The overall incidence of adverse reactions was low, and the risk was controllable.


Subject(s)
Brain Ischemia/drug therapy , Diterpenes/pharmacology , Drugs, Chinese Herbal/pharmacology , Ginkgo biloba/chemistry , Lactones/pharmacology , Product Surveillance, Postmarketing , Stroke/drug therapy , Diterpenes/adverse effects , Drugs, Chinese Herbal/adverse effects , Ginkgo biloba/adverse effects , Humans , Lactones/adverse effects , Meglumine , Prospective Studies
10.
Anal Chem ; 88(21): 10411-10418, 2016 11 01.
Article in English | MEDLINE | ID: mdl-27690387

ABSTRACT

By complexing a nonionic G-quadruplex ligand with hybrid dual-emission quantum dots (QDs), a ratiometric fluorescent nanoprobe is developed for G-quadruplex detection in a sensitive and specific manner. The QDs nanohybrid comprised of a green-emission QD (gQD) and multiple red-emission QDs (rQDs) inside and outside of a silica shell, respectively, is utilized as the signal displaying unit. Only the presence of G-quadruplex can displace the ligand from QDs, breaking up the QDs-ligand complexation, and inducing the restoration of the rQDs fluorescence. Since the fluorescence of embedded gQD stays constant, variations of the dual-emission intensity ratios display continuous color changes from green to bright orange, which can be clearly observed by the naked eye. Furthermore, by utilizing competitive binding of a cationic ligand versus the nonionic ligand toward G-quadruplex, the nanoprobe is demonstrated to be applicable for assessing the affinity of a G-quadruplex-targeted anticancer drug candidate, exhibiting ratiometric fluorescence signals (reverse of that for G-quadruplex detection). By making use of the specificity of the ligand binding with G-quadruplex against a double helix, this nanoprobe is also demonstrated to be capable of sensitive detection of one-base mutation, exhibiting sequence-specific ratiometric fluorescence signals. By functionalizing with a nuclear localization peptide, the nanoprobe can be used for visualization of G-quadruplex in the nucleus of human cells.

11.
J Extracell Vesicles ; 13(7): e12490, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39051742

ABSTRACT

Extracellular vesicles (EVs) are emerging as promising carriers for the delivery of therapeutic biologics. Genetic engineering represents a robust strategy for loading proteins of interest into EVs. Identification of EV-enriched proteins facilitates protein cargo loading efficiency. Many EV-enriched proteins are sorted into EVs via an endosomal sorting complex required for transport (ESCRT)-dependent pathway. In parallel, viruses hijack this EV biosynthesis machinery via conserved late domain motifs to promote egress from host cells. Inspired by the similarity of biogenesis between EVs and viruses, we developed a synthetic, Late domain-based EV scaffold protein that enables the display of a set of single chain variable fragments (scFvs) on the EV surface. We named this scaffold the Late domain-based exosomal antibody surface display platform (LEAP). We applied the LEAP scaffold to reprogramme HEK293T cell-derived EVs to elicit T-cell anti-tumor immunity by simultaneously displaying αPD-L1 and αCD3 scFvs on the EV surface (denoted as αPD-L1×αCD3 bispecific T-cell engaging exosomes, BiTExos). We demonstrated that αPD-L1×αCD3 BiTExos actively redirected T cells to bind to PD-L1+ tumor cells, promoting T-cell activation, proliferation and tumoricidal cytokine production. Furthermore, the αPD-L1×αCD3 BiTExos promoted T-cell infiltration into the tumor microenvironment to mitigate the tumor burden in vivo. Our study suggested that the LEAP scaffold may serve as a platform for EV surface display and could be applied for a broad range of EV-based biomedical applications.


Subject(s)
B7-H1 Antigen , CD3 Complex , Extracellular Vesicles , Single-Chain Antibodies , T-Lymphocytes , Humans , Extracellular Vesicles/immunology , Extracellular Vesicles/metabolism , B7-H1 Antigen/metabolism , B7-H1 Antigen/immunology , Animals , CD3 Complex/immunology , CD3 Complex/metabolism , HEK293 Cells , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Mice , Single-Chain Antibodies/immunology , Exosomes/metabolism , Exosomes/immunology , Neoplasms/immunology , Neoplasms/therapy , Lymphocyte Activation/immunology
12.
Phytomedicine ; 128: 155375, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38507853

ABSTRACT

BACKGROUND: Osteoporosis (OP) is a prevalent chronic metabolic bone disease for which limited countermeasures are available. Cnidii Fructus (CF), primarily derived from Cnidium monnieri (L.) Cusson., has been tested in clinical trials of traditional Chinese medicine for the management of OP. Accumulating preclinical studies indicate that CF may be used against OP. MATERIALS AND METHODS: Comprehensive documentation and analysis were conducted to retrieve CF studies related to its main phytochemical components as well as its pharmacokinetics, safety and pharmacological properties. We also retrieved information on the mode of action of CF and, in particular, preclinical and clinical studies related to bone remodeling. This search was performed from the inception of databases up to the end of 2022 and included PubMed, China National Knowledge Infrastructure, the National Science and Technology Library, the China Science and Technology Journal Database, Weipu, Wanfang, the Web of Science and the China National Patent Database. RESULTS: CF contains a wide range of natural active compounds, including osthole, bergapten, imperatorin and xanthotoxin, which may underlie its beneficial effects on improving bone metabolism and quality. CF action appears to be mediated via multiple processes, including the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK), Wnt/ß-catenin and bone morphogenetic protein (BMP)/Smad signaling pathways. CONCLUSION: CF and its ingredients may provide novel compounds for developing anti-OP drugs.


Subject(s)
Cnidium , Drugs, Chinese Herbal , Fruit , Osteoporosis , Humans , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Osteoporosis/drug therapy , Cnidium/chemistry , Fruit/chemistry , Animals , Medicine, Chinese Traditional , Coumarins/pharmacology , Coumarins/therapeutic use , Phytochemicals/pharmacology , 5-Methoxypsoralen , Bone Remodeling/drug effects , Bone Density Conservation Agents/pharmacology , Bone Density Conservation Agents/therapeutic use , RANK Ligand
13.
Biomed Pharmacother ; 176: 116760, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38788595

ABSTRACT

With the increasing prevalence of metabolic disorders, hyperglycemia has become a common risk factor that endangers people's lives and the need for new drug solutions is burgeoning. Trans-2, 4-dimethoxystilbene (TDMS), a synthetic stilbene, has been found as a novel hypoglycemic small molecule from glucose consumption test. Normal C57BL/6 J mice, mouse models of type 1 diabetes mellitus and diet-induced obesity subjected to TDMS gavage were found with lower glycemic levels and better glycemic control. TDMS significantly improved the symptoms of polydipsia and wasting in type 1 diabetic mice, and could rise their body temperature at the same time. It was found that TDMS could promote the expression of key genes of glucose metabolism in HepG2, as do in TDMS-treated liver, while it could improve the intestinal flora and relieve intestinal metabolic dysbiosis in hyperglycemic models, which in turn affected its function in the liver, forming the gut-liver axis. We further fished PPARγ by virtual screening that could be promoted by TDMS both in-vitro and in-vivo, which was regulated by upstream signaling of AMPKα phosphorylation. As a novel hypoglycemic small molecule, TDMS was proven to be promising with its glycemic improvements and amelioration of diabetes symptoms. It promoted glucose absorption and utilization by the liver and improved the intestinal flora of diabetic mice. Therefore, TDMS is expected to become a new hypoglycemic drug that acts through gut-liver axis via AMPKα-PPARγ signaling pathway in improving glycemic metabolism, bringing new hope to patients with diabetes and glucose metabolism disorders.


Subject(s)
AMP-Activated Protein Kinases , Gastrointestinal Microbiome , Hypoglycemic Agents , Liver , Mice, Inbred C57BL , PPAR gamma , Signal Transduction , Stilbenes , Animals , Gastrointestinal Microbiome/drug effects , Hypoglycemic Agents/pharmacology , Liver/drug effects , Liver/metabolism , Humans , PPAR gamma/metabolism , AMP-Activated Protein Kinases/metabolism , Mice , Male , Stilbenes/pharmacology , Signal Transduction/drug effects , Hep G2 Cells , Diabetes Mellitus, Experimental/drug therapy , Blood Glucose/drug effects , Blood Glucose/metabolism
14.
Nutrients ; 16(10)2024 May 10.
Article in English | MEDLINE | ID: mdl-38794681

ABSTRACT

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant compound, on osteoporotic bone loss remains largely unknown. Here, we show that oral administration of LYC to OVX rats for 12 weeks reduced body weight gain, improved lipid metabolism, and preserved bone quality. In addition, LYC treatment inhibited ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon H2O2 stimulation, leading to inhibiting adipogenesis and promoting osteogenesis during bone remodeling. At the molecular level, LYC improved bone quality via an increase in the expressions of FoxO1 and Runx2 and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regulation of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for osteoporosis management.


Subject(s)
Adipogenesis , Lycopene , Mesenchymal Stem Cells , Osteogenesis , Ovariectomy , PPAR gamma , Rats, Sprague-Dawley , Signal Transduction , Animals , Osteogenesis/drug effects , Adipogenesis/drug effects , Lycopene/pharmacology , PPAR gamma/metabolism , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Female , Signal Transduction/drug effects , Rats , Osteoporosis/prevention & control , Oxidative Stress/drug effects , Forkhead Box Protein O1/metabolism , Antioxidants/pharmacology , Reactive Oxygen Species/metabolism
15.
JAMA Intern Med ; 184(7): 727-735, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38829648

ABSTRACT

Importance: Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin (HbA1c), and improve insulin resistance in people with type 2 diabetes. Objective: To evaluate the effect of long-term administration of JLD vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial (FOCUS) was conducted across 35 centers in 21 cities in China from June 2019 to February 2023. Individuals aged 18 to 70 years with IGT and multiple metabolic abnormalities were enrolled. Intervention: Participants were randomly allocated 1:1 to receive JLD or placebo (9 g, 3 times per day, orally). They continued this regimen until they developed diabetes, withdrew from the study, were lost to follow-up, or died. Main Outcomes and Measures: The primary outcome was the occurrence of diabetes, which was determined by 2 consecutive oral glucose tolerance tests. Secondary outcomes included waist circumference; fasting and 2-hour postprandial plasma glucose levels; HbA1c; fasting insulin level; homeostatic model assessment for insulin resistance (HOMA-IR); total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels; ankle-brachial index; and carotid intima-media thickness. Results: A total of 889 participants were randomized, of whom 885 were in the full analysis set (442 in the JLD group; 443 in the placebo group; mean [SD] age, 52.57 [10.33] years; 463 [52.32%] female). Following a median observation period of 2.20 years (IQR, 1.27-2.64 years), participants in the JLD group had a lower risk of developing diabetes compared with those in the placebo group (hazard ratio, 0.59; 95% CI, 0.46-0.74; P < .001). During the follow-up period, the JLD group had a between-group difference of 0.95 cm (95% CI, 0.36-1.55 cm) in waist circumference, 9.2 mg/dL (95% CI, 5.4-13.0 mg/dL) in 2-hour postprandial blood glucose level, 3.8 mg/dL (95% CI, 2.2-5.6 mg/dL) in fasting blood glucose level, 0.20% (95% CI, 0.13%-0.27%) in HbA1c, 6.6 mg/dL (95% CI, 1.9-11.2) in total cholesterol level, 4.3 mg/dL (95% CI, 0.8-7.7 mg/dL) in low-density lipoprotein cholesterol level, 25.7 mg/dL (95% CI, 15.9-35.4 mg/dL) in triglyceride levels, and 0.47 (95% CI, 0.12-0.83) in HOMA-IR compared with the placebo group. After 24 months of follow-up, the JLD group had a significant improvement in ankle-brachial index and waist circumference compared with the placebo group. Conclusions and Relevance: The findings suggest that JLD can reduce the risk of diabetes in participants with IGT and multiple metabolic abnormalities. Trial Registration: Chinese Clinical Trial Register: ChiCTR1900023241.


Subject(s)
Diabetes Mellitus, Type 2 , Drugs, Chinese Herbal , Glucose Intolerance , Humans , Middle Aged , Female , Male , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Double-Blind Method , Adult , Drugs, Chinese Herbal/therapeutic use , Blood Glucose/metabolism , Aged , China/epidemiology , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/analysis , Insulin Resistance , Glucose Tolerance Test
16.
Langmuir ; 29(23): 7102-10, 2013 Jun 11.
Article in English | MEDLINE | ID: mdl-23692027

ABSTRACT

Photothermal therapy using inorganic nanoparticles (NPs) is a promising technique for the selective treatment of tumor cells because of their capability to convert the absorbed radiation into heat energy. Although anisotropic gold (Au) NPs present an excellent photothermal effect, the poor structural stability during storage and/or upon laser irradiation still limits their practical application as efficient photothermal agents. With the aim of improving the stability, in this work we adopted biocompatible polypyrrole (PPy) as the shell material for coating urchinlike Au NPs. The experimental results indicate that a several nanometer PPy shell is enough to maintain the structural stability of NPs. In comparison to the bare NPs, PPy-coated NPs exhibit improved structural stability toward storage, heat, pH, and laser irradiation. In addition, the thin shell of PPy also enhances the photothermal transduction efficiency (η) of PPy-coated Au NPs, resulting from the absorption of PPy in the red and near-infrared (NIR) regions. For example, the PPy-coated Au NPs with an Au core diameter of 120 nm and a PPy shell of 6.0 nm exhibit an η of 24.0% at 808 nm, which is much higher than that of bare Au NPs (η = 11.0%). As a primary attempt at photothermal therapy, the PPy-coated Au NPs with a 6.0 nm PPy shell exhibit an 80% death rate of Hela cells under 808 nm NIR laser irradiation.


Subject(s)
Antineoplastic Agents/chemistry , Coated Materials, Biocompatible/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Polymers/chemistry , Pyrroles/chemistry , Temperature , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Coated Materials, Biocompatible/pharmacology , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Particle Size , Photochemical Processes , Structure-Activity Relationship , Surface Properties , Tumor Cells, Cultured
17.
Behav Sci (Basel) ; 13(5)2023 May 12.
Article in English | MEDLINE | ID: mdl-37232643

ABSTRACT

The emergence of artificial intelligence has made adaptive learning possible, but building an adaptive system requires a comprehensive understanding of students' cognition. The cognitive model provides a crucial theoretical framework to explore students' cognitive attributes, making it vital for learning assessment and adaptive learning. This study investigates 52 experts, including primary and secondary school teachers, mathematics education experts, and graduate students, based on the 16 cognitive attributes in the TIMSS 2015 assessment framework. Through an analysis of their attribute questionnaires, the Interpretive structural modeling (ISM) method is used to construct a five-level mathematical cognitive model. The model is then revised through oral reports and expert interviews, resulting in a final cognitive model ranging from "memorize" to "justify". The cognitive model describes the relationship between different attributes in detail, enabling the development of adaptive systems and aiding in the diagnosis of students' cognitive development and learning paths in mathematics.

18.
J Intell ; 11(12)2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38132840

ABSTRACT

Developing algebraic thinking in elementary school has gained consensus among mathematics educators. The objective of this study is to understand the developmental trajectory of early algebraic thinking in elementary school students so as to assist teachers and curriculum developers in implementing instruction that aligns with students' cognitive development. This study adopted a cross-sectional survey approach, involving 526 students from grades three to five in Shanghai, who were tested using a 12-item assessment that measured three aspects: "generalized arithmetic", "functional thinking", and "quantitative reasoning". Latent class analysis was used to analyze students' response strategies, and, in conjunction with individual interviews, this study identified potential developmental pathways in students' early algebraic thinking, progressing from "arithmetic thinking" to "concrete algebraic thinking", "generalized algebraic thinking", and finally to "symbolic algebraic thinking". As thinking levels advanced, significant differences in students' response strategies emerged, with notable improvements in "generalization abilities" and "symbolization abilities". This study suggests that educational practices should encompass content in elementary arithmetic curricula that fosters generalization abilities. Additionally, providing students with opportunities for diverse representations can effectively stimulate the development of early algebraic thinking.

19.
Sci Total Environ ; 863: 160970, 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36539091

ABSTRACT

Ecosystems provide benefits to human well-being, but highly concentrated human activities also cause environmental pressure. Previous studies focused only on one aspect: either ecosystem services (ESs) or ecosystem damage (ED). To provide comprehensive view of ecosystem status in the selected study area, an integrated ecosystem performance analytic framework was established based on the ED-ESs synergistic effect. This study quantitatively analyzed the dynamic variation in ecosystem status from both ED and ESs perspectives with a case study of Jinan City, China, from 2000 to 2020. The results showed that the environmental and economic impacts caused by pollution were 692.87 species.year and $15.58 × 108 in 2020, respectively, and they were mainly derived from energy consumption. Regarding ESs, three regulating services (water retention, soil retention, and carbon sequestration) increased from south to north, whereas material services presented the opposite trend. Ecosystem service value had declined after peaking in 2010 when material services contributed the most. Overall, the Jinan City suffered from ecosystem decline, with ecosystem performance on a downward trend from 2000 to 2020. Finally, the characterization factors of four ESs were appropriately incorporated into the life cycle impact assessment to drive the evolution in ecosystem performance calculations.


Subject(s)
Conservation of Natural Resources , Ecosystem , Humans , Conservation of Natural Resources/methods , Soil , Cities , China
20.
J Cardiothorac Surg ; 18(1): 180, 2023 May 11.
Article in English | MEDLINE | ID: mdl-37170323

ABSTRACT

BACKGROUNDS: Survival and aortic-related adverse events after thoracic endovascular aortic repair (TEVAR) for aortic intramural hematoma (IMH) and aortic dissection (AD) are controversial. We aimed to assess the preoperative characteristics and to evaluate TEVAR outcomes of acute type B IMH and AD. METHODS: Between June 2002 and May 2021, 83 patients with acute type B IMH and 755 patients with acute type B AD underwent TEVAR at the General Hospital of Northern Theater Command. We retrospectively analyzed data from these patients, including clinical characteristics and follow-up outcomes. RESULTS: The patients with IMH were significantly older than the ones with AD (P < 0.001). Diabetes mellitus (P = 0.035) and ischemic cerebrovascular disease (P = 0.017) were more common in the IMH group than in the AD group. The results demonstrated a less long-term aortic-related death-free survival rate in the IMH group than the AD group for all the patients (P = 0.014) and the matched patients (P = 0.027). It also presents a lower long-term overall survival rate (P = 0.047) and aortic-related event-free rate (P = 0.048) in the IMH group than in the matched patients. CONCLUSIONS: Compared with AD patients, patients with IMH who underwent TEVAR had a worse long-term outcome of aortic-related survival in all and matched patients.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Diseases , Aortic Dissection , Humans , Endovascular Aneurysm Repair , Retrospective Studies , Aortic Intramural Hematoma , Propensity Score , Aortic Diseases/surgery , Aortic Dissection/surgery , Hematoma/surgery , Aortic Aneurysm, Thoracic/surgery , Treatment Outcome
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