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1.
Liver Int ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847599

ABSTRACT

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the foremost cause of chronic liver disease, yet its underlying mechanisms remain elusive. Our group previously discovered a novel long non-coding RNA (lncRNA) in rats, termed lncHC and its human counterpart, LNCHC. This study aimed to explore the role of LNCHC in the progression of MASLD. METHODS: RNA-binding proteins bound to LNCHC were searched by mass spectrometry. The target genes of LNCHC and Y-Box binding protein 1 (YBX1) were identified by RNA-seq. MASLD animal models were utilised to examine the roles of LNCHC, YBX1 and patatin-like phospholipase domain containing 3 (PNPLA3) in MASLD progression. RESULTS: Here, we identified LNCHC as a native restrainer during MASLD development. Notably, LNCHC directly binds YBX1 and prevents protein ubiquitination. Up-regulation of YBX1 then stabilises PNPLA3 mRNA to alleviate lipid accumulation in hepatocytes. Furthermore, both cell and animal studies demonstrate that LNCHC, YBX1 and PNPLA3 function to improve hepatocyte lipid accumulation and exacerbate metabolic dysfunction-associated steatohepatitis development. CONCLUSIONS: In summary, our findings unveil a novel LNCHC functionality in regulating YBX1 and PNPLA3 mRNA stability during MASLD development, providing new avenues in MASLD treatment.

2.
Immunotargets Ther ; 13: 287-304, 2024.
Article in English | MEDLINE | ID: mdl-38881647

ABSTRACT

Alzheimer's disease (AD) is a fatal neurodegenerative disease with a subtle and progressive onset and is the most common type of dementia. However, its etiology and pathogenesis have not yet been fully elucidated. The common pathological manifestations of AD include extraneuronal ß-amyloid deposition (Aß), intraneuronal tau protein phosphorylation leading to the formation of 'neurofibrillary tangles' (NFTs), neuroinflammation, progressive loss of brain neurons/synapses, and glucose metabolism disorders. Current treatment approaches for AD primarily focus on the 'Aß cascade hypothesis and abnormal aggregation of hyperphosphorylation of tau proteins', but have shown limited efficacy. Therefore, there is an ongoing need to identify more effective treatment targets for AD. The central nervous system (CNS) inflammatory response plays a key role in the occurrence and development of AD. Neuroinflammation is an immune response activated by glial cells in the CNS that usually occurs in response to stimuli such as nerve injury, infection and toxins or in response to autoimmunity. Neuroinflammation ranks as the third most prominent pathological feature in AD, following Aß and NFTs. In recent years, the focus on the role of neuroinflammation and microglia in AD has increased due to the advancements in genome-wide association studies (GWAS) and sequencing technology. Furthermore, research has validated the pivotal role of microglia-mediated neuroinflammation in the progression of AD. Therefore, this article reviews the latest research progress on the role of neuroinflammation triggered by microglia in AD in recent years, aiming to provide a new theoretical basis for further exploring the role of neuroinflammation in the process of AD occurrence and development.

3.
Sci Rep ; 14(1): 14231, 2024 06 20.
Article in English | MEDLINE | ID: mdl-38902260

ABSTRACT

Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of butorphanol on ALI and investigated its underlying mechanisms. We established a "two-hit" rat model and "two-hit" cell model to prove our hypothesis. Rats were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 mg/kg and 8 mg/kg) (OA + LPS + B1 and OA + LPS + B2)]. RPMVE cells were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 µM and 8 µM) (OA + LPS + 4 µM and OA + LPS + 8 µM)]. Inflammatory injury was assessed by the histopathology and W/D ratio, inflammatory cytokines, and arterial blood gas analysis. Apoptosis was assessed by Western blotting and flow cytometry. The effect of NF-κB p65 was detected by ELISA. Butorphanol could relieve the "two-hit" induced lung injury, the expression of TNF, IL-1ß, IL-6, and improve lung ventilation. In addition, butorphanol decreased Bax and cleaved caspase-3, increased an antiapoptotic protein (Bcl-2), and inhibited the "two-hit" cell apoptosis ratio. Moreover, butorphanol suppressed NF-κB p65 activity in rat lung injury. Our research showed that butorphanol may attenuate "two-hit"-induced lung injury by regulating the activity of NF-κB p65, which may supply more evidence for ALI treatment.


Subject(s)
Acute Lung Injury , Apoptosis , Butorphanol , Inflammation , Animals , Butorphanol/pharmacology , Apoptosis/drug effects , Rats , Male , Acute Lung Injury/chemically induced , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Acute Lung Injury/drug therapy , Acute Lung Injury/prevention & control , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Transcription Factor RelA/metabolism , Lipopolysaccharides , Rats, Sprague-Dawley , Lung Injury/chemically induced , Lung Injury/drug therapy , Lung Injury/metabolism , Lung Injury/pathology , Lung Injury/prevention & control , Disease Models, Animal , Cytokines/metabolism , Lung/pathology , Lung/drug effects , Lung/metabolism
4.
ACS Sens ; 9(6): 3075-3084, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38807573

ABSTRACT

Cardiac hypertrophy characterized by abnormal cardiomyocyte viscosity is a typical sign of heart failure (HF) with vital importance for early diagnosis. However, current biochemical and imaging diagnostic methods are unable to detect this subclinical manifestation. In this work, we developed a series of NIR-I fluorescence probes for detecting myocardial viscosity based on the pyridazinone scaffold. The probes showed weak fluorescence due to free intramolecular rotation under low-viscosity conditions, while they displayed strong fluorescence with limited intramolecular rotation in response to a high-viscosity environment. Among them, CarVis2 exhibited higher stability and photobleaching resistance than commercial dyes. Its specific response to viscosity was not influenced by the pH and biological species. Furthermore, CarVis2 showed rapid and accurate responses to the viscosity of isoproterenol (ISO)-treated H9C2 cardiomyocytes with good biocompatibility. More importantly, CarVis2 demonstrated excellent sensitivity in monitoring myocardial viscosity variation in HF mice in vivo, potentially enabling earlier noninvasive identification of myocardial abnormalities compared to traditional clinical imaging and biomarkers. These findings revealed that CarVis2 can serve as a powerful tool to monitor myocardial viscosity, providing the potential to advance insights into a pathophysiological mechanism and offering a new reference strategy for early visual diagnosis of HF.


Subject(s)
Fluorescent Dyes , Heart Failure , Fluorescent Dyes/chemistry , Heart Failure/diagnostic imaging , Animals , Mice , Viscosity , Myocytes, Cardiac , Early Diagnosis , Rats , Cell Line , Isoproterenol , Humans , Optical Imaging , Infrared Rays , Male
5.
BMC Psychol ; 12(1): 290, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38790020

ABSTRACT

BACKGROUND: Experiential avoidance represents the tendency to avoid negative internal experiences, which is a key concept in Acceptance and Commitment Therapy. However, existing measures of experiential avoidance (i.e., Acceptance and Action Questionnaire-II, AAQ-II) have some limitations. This study aims to assess the psychometric properties of the Chinese version of Multidimensional Experiential Avoidance Questionnaire-30 (MEAQ-30) and provide evidence for the reliability and validity of this new instrument. METHODS: Two questionnaire surveys were conducted. The first sample (N = 546) was analyzed using classical test theory (CTT), and the second sample (N = 511) was analyzed using multidimensional item response theory (MIRT). RESULTS: CTT supported the six-factor structure of MEAQ-30, indicating good internal consistency and measurement invariance across genders. Furthermore, the Chinese version of MEAQ-30 showed satisfactory convergent and discriminant validity. The incremental validity test showed that after controlling for the effects of neuroticism and AAQ-II, the Chinese version of MEAQ-30 could still significantly predict depression, anxiety, and stress. MIRT indicated that 30 items had good discrimination and difficulty, and the six subscales were sufficiently reliable across the continuum of experiential avoidance. CONCLUSION: The Chinese version of MEAQ-30 has good reliability and validity and is suitable for assessing experiential avoidance among Chinese populations.


Subject(s)
Psychometrics , Humans , Psychometrics/instrumentation , Male , Female , Surveys and Questionnaires/standards , Reproducibility of Results , Adult , Young Adult , China , Avoidance Learning , Middle Aged , Adolescent , Anxiety/psychology , Depression/psychology , Depression/diagnosis
6.
J Evid Based Med ; 17(2): 341-350, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38651546

ABSTRACT

OBJECTIVE: This meta-analysis aimed to comprehensively explore the risk factors for inadequate bowel preparation (IBP). METHODS: We searched the Embase, PubMed, Web of Science, and The Cochrane Library databases up to August 24, 2023, to identify observational studies and randomized controlled trials (RCTs) that examined risk factors for IBP. A random effects model was used to pool the adjusted odds ratios and 95% confidence intervals. RESULTS: A total of 125 studies (91 observational studies, 34 RCTs) were included. Meta-analyses of observational studies revealed that three preparation-related factors, namely, characteristics of last stool (solid or brown liquid), incomplete preparation intake, and incorrect diet restriction, were strong predictors of IBP. The other factors were moderately correlated with IBP incidence, including demographic variables (age, body mass index, male sex, Medicaid insurance, and current smoking), comorbidities (diabetes, liver cirrhosis, psychiatric disease, Parkinson's disease, previous IBP, poor mobility, inpatient, and Bristol stool form 1/2), medications (tricyclic antidepressants, opioids, antidepressants, narcotics, antipsychotics, and calcium channel blockers), and preparation-related factors (preparation-to-colonoscopy interval not within 3 to 5/6 h, nonsplit preparation, and preparation instructions not followed). No colonoscopy indications were found to be related to IBP. Meta-analyses of RCTs showed that education, constipation, stroke/dementia, and discomfort during preparation were also moderately associated with IBP. Most of the other findings were consistent with the pooled results of observational studies. However, primarily due to imprecision and inconsistency, the certainty of evidence for most factors was very low to moderate. CONCLUSIONS: We summarized five categories of risk factors for IBP. Compared to demographic variables, comorbidities, medications, and colonoscopy indications, preparation-related elements were more strongly associated with IBP. These findings may help clinicians identify high-risk individuals and provide guidance for IBP prevention.


Subject(s)
Cathartics , Colonoscopy , Humans , Risk Factors , Colonoscopy/methods , Cathartics/administration & dosage
7.
Dalton Trans ; 53(10): 4598-4606, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38349531

ABSTRACT

From paddle-wheel starting material Na3Ru2(CO3)4·6H2O, a family of edge-sharing bi-octahedral (ESBO) diruthenium(IV,IV) compounds formulated as Ru2O2(CO3)2(H2O)2L2·nH2O [L = piperazine (1) or 2-methylpiperazine (2), n = 4, and L = 2,2-dimethylpiperazine (3), n = 12] and Ru2O2(CO3)2(OH)4{M(H2O)4}2·nH2O [M = Mg (4), n = 4, and Ni (5), n = 2] were prepared and structurally characterized. The Ru28+ dimer is chelated and bridged by two CO32- and two µ-O in a trans manner, and the Ru-Ru distances fall in the range 2.3808(6)-2.4001(4) Å. Compound 2 shows the shortest Ru-Ru distance for all known ESBO Ru2 compounds reported thus far. Increasing -CH3 groups of terminal piperazine ligands coordinated to the Ru(µ-O)2(µ-O3C)2Ru core, and according to Raman spectra experiments combined with theoretical calculations, the intense bands of compounds 1-3 appearing at ∼360 cm-1 can be assigned to the stretching of Ru-Ru bonds.

8.
Neurochem Res ; 49(3): 660-669, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38010603

ABSTRACT

Hexavalent chromium (Cr (VI)), one of the most detrimental pollutants, has been ubiquitously present in the environment and causes serious toxicity to humans, such as hepatotoxicity, nephrotoxicity, pulmonary toxicity, and cardiotoxicity. However, Cr (VI)-induced neurotoxicity in primary neuron level has not been well explored yet. Herein, potassium dichromate (K2Cr2O7) was employed to examine the neurotoxicity of Cr (VI) in rat primary hippocampal neurons. MTT test was used to examine the neural viability. Mitochondrial dysfunction was assessed by the JC-1 probe and Mito-Tracker probe. DCFH-DA and Mito-SOX Red were utilized to evaluate the oxidative status. Bcl-2 family and MAPKs expression were investigated using Western blotting. The results demonstrated that Cr (VI) treatment dose- and time-dependently inhibited neural viability. Mechanism investigation found that Cr (VI) treatment causes mitochondrial dysfunction by affecting Bcl-2 family expression. Moreover, Cr (VI) treatment also induces intracellular reactive oxygen species (ROS) generation, DNA damage, and MAPKs activation in neurons. However, inhibition of ROS by glutathione (GSH) effectually balanced Bcl-2 family expression, attenuated DNA damage and the MAPKs activation, and eventually improved neural viability neurons. Collectively, these above results above suggest that Cr (VI) causes significant neurotoxicity by triggering mitochondrial dysfunction, ROS-mediated oxidative damage and MAKPs activation.


Subject(s)
Mitochondrial Diseases , Oxidative Stress , Humans , Rats , Animals , Reactive Oxygen Species/metabolism , Chromium/toxicity , Glutathione/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism
9.
Metab Brain Dis ; 39(2): 263-282, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38019374

ABSTRACT

Most scholars believe that amyloid-beta (Aß) has the potential to induce apoptosis, stimulate an inflammatory cascade, promote oxidative stress and exacerbate the pathological progression of Alzheimer's disease (AD). Therefore, it is crucial to investigate the deposition of Aß in AD. At approximately 6 months of age, APP/PS1 double transgenic mice gradually exhibit the development of plaques, as well as spatial and learning impairment. Notably, the hippocampus is specifically affected in the course of AD. Herein, 6-month-old APP/PS1 double transgenic mice were utilized, and the differentially expressed (DE) proteins in the hippocampus were identified and analyzed using 4D label-free quantitative proteomics technology and parallel reaction monitoring (PRM). Compared to wild-type mice, 29 proteins were upregulated and 25 proteins were downregulated in the AD group. Gene Ontology (GO) enrichment analysis of biological processes (BP) indicated that the DE proteins were mainly involved in 'ribosomal large subunit biogenesis'. Molecular function (MF) analysis results were primarily associated with '5.8S rRNA binding' and 'structural constituent of ribosome'. In terms of cellular components (CC), the DE proteins were mainly found in 'polysomal ribosome', 'cytosolic large ribosomal subunit', 'cytosolic ribosome', and 'large ribosomal subunit', among others. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the results were mainly enriched in the 'Ribosome signaling pathway'. The key target proteins identified were ribosomal protein (Rp)l18, Rpl17, Rpl19, Rpl24, Rpl35, and Rpl6. The PRM verification results were consistent with the findings of the 4D label-free quantitative proteomics analysis. Overall, these findings suggest that Rpl18, Rpl17, Rpl19, Rpl24, Rpl35, and Rpl6 may have potential therapeutic value for the treatment of AD by targeting Aß.


Subject(s)
Alzheimer Disease , Mice , Animals , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Proteomics , Mice, Transgenic , Ribosomal Proteins/genetics , Ribosomes , Disease Models, Animal , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism
10.
Neural Regen Res ; 19(8): 1741-1750, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38103240

ABSTRACT

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms. This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms. Ferroptosis is a classic regulatory mode of cell death. Extensive studies of regulatory cell death in Alzheimer's disease have yielded increasing evidence that ferroptosis is closely related to the occurrence, development, and prognosis of Alzheimer's disease. This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferroptosis in Alzheimer's disease. Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer's disease.

11.
Drug Des Devel Ther ; 17: 3295-3323, 2023.
Article in English | MEDLINE | ID: mdl-38024535

ABSTRACT

Alzheimer's disease is a prevalent form of dementia among elderly individuals and is characterized by irreversible neurodegeneration. Despite extensive research, the exact causes of this complex disease remain unclear. Currently available drugs for Alzheimer's disease treatment are limited in their effectiveness, often targeting a single aspect of the disease and causing significant adverse effects. Moreover, these medications are expensive, placing a heavy burden on patients' families and society as a whole. Natural compounds and extracts offer several advantages, including the ability to target multiple pathways and exhibit high efficiency with minimal toxicity. These attributes make them promising candidates for the prevention and treatment of Alzheimer's disease. In this paper, we provide a summary of the common natural products used in Chinese medicine for different pathogeneses of AD. Our aim is to offer new insights and ideas for the further development of natural products in Chinese medicine and the treatment of AD.


Subject(s)
Alzheimer Disease , Biological Products , Humans , Aged , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , tau Proteins/metabolism , Medicine, Chinese Traditional , Biological Products/pharmacology , Biological Products/therapeutic use , Amyloid beta-Peptides/metabolism
12.
Clin Res Hepatol Gastroenterol ; 47(10): 102233, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37879535

ABSTRACT

BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , Anti-Bacterial Agents/therapeutic use , Cross-Sectional Studies , Proton Pump Inhibitors/therapeutic use , Drug Therapy, Combination , Helicobacter Infections/drug therapy , Bismuth/therapeutic use , Amoxicillin/therapeutic use , Treatment Outcome
13.
ACS Chem Neurosci ; 14(19): 3564-3587, 2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37703318

ABSTRACT

Alzheimer's disease (AD), the most common type of dementia, is a neurodegenerative disorder characterized by progressive cognitive dysfunction. Epidemiological investigation has demonstrated that, after cardiovascular and cerebrovascular diseases, tumors, and other causes, AD has become a major health issue affecting elderly individuals, with its mortality rate acutely increasing each year. Regulatory cell death is the active and orderly death of genetically determined cells, which is ubiquitous in the development of living organisms and is crucial to the regulation of life homeostasis. With extensive research on regulatory cell death in AD, increasing evidence has revealed that ferroptosis, pyroptosis, and cuproptosis are closely related to the occurrence, development, and prognosis of AD. This paper will review the molecular mechanisms of ferroptosis, pyroptosis, and cuproptosis and their regulatory roles in AD to explore potential therapeutic targets for the treatment of AD.

14.
Front Med (Lausanne) ; 10: 1252346, 2023.
Article in English | MEDLINE | ID: mdl-37727758

ABSTRACT

Background: Contradictory evidence suggested gastric xanthelasma (GX) was associated with some upper gastrointestinal (GI) diseases. Additionally, no research has been performed on the relationship between esophageal/duodenal xanthelasma and upper GI diseases. Methods: Individuals who underwent esophagogastroduodenoscopy at Tongji Hospital, Tongji Medical College, participated in this retrospective study. This study evaluated whether the risk of GX or esophageal/duodenal xanthelasma was influenced by the following gastroesophageal diseases: superficial gastritis, gastric polyp, bile reflux, peptic ulcer, reflux esophagitis, Barrett's esophagus, esophageal cancer, atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia, gastric cancer, and Helicobacter pylori (H. pylori) infection. Furthermore, subgroup analysis was conducted to establish the relationship between the number of GX and upper GI diseases. Results: Of the 69,071 subjects reviewed, 1,220 (1.77%) had GX, and 54 (0.08%) had esophageal/duodenal xanthelasma. There was no difference in the prevalence of upper GI diseases between patients with and without esophageal/duodenal xanthelasma. Nevertheless, compared with non-xanthelasma patients, GX patients had a greater proportion of AG, IM, dysplasia, gastric cancer, and H. pylori infection and a lower incidence of superficial gastritis (p < 0.05). The multivariate logistic regression analysis indicated AG (OR = 1.83, 95%CI: 1.56-2.16), IM (OR = 2.42, 95%CI: 2.41-2.85), and H. pylori infection (OR = 1.32, 95%CI: 1.17-1.50) were independent risk factors for GX. In addition, patients with multiple GXs had a higher rate of AG and IM than those with single GX. Conclusion: Esophageal/duodenal xanthelasma may not be associated with upper GI diseases, and further research is needed to support this hypothesis. Notably, GX, especially multiple GXs, may be a more easily detected warning sign of AG, IM, or H. pylori infection.

15.
Curr Med Imaging ; 2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37691202

ABSTRACT

AIMS: This study aimed to develop a method for predicting short-term outcomes of lung cancer patients treated with intensity-modulated radiotherapy (IMRT) using radiomic features detected through computed tomography images. METHOD: A prediction model was developed based on a dataset of radiomic features obtained from 132 patients with lung cancer receiving IMRT. Dimension reduction was performed for the features using the maximum-relevance and minimum-redundancy (mRMR) algorithm, and the least absolute shrinkage and selection operator (LASSO) regression model was utilized to optimize feature selection for the IMRT-sensitivity prediction model. The model was constructed using binary logistic regression analysis and was evaluated using the concordance index (C-index), calibration plots, receiver operating characteristic curve, and decision curve analysis. RESULTS: Fifty features were selected from 1348 radiomic features using the mRMR method. Of these, three radiomic features were selected by LASSO logistic regression to construct the radiomics nomogram. The C-index of the model was 0.776 (95% confidence interval: 0.689-0.862) and 0.791 (95% confidence interval: 0.607-0.974) in the training and validation cohorts, respectively. Decision curve analysis showed that the radiomics nomogram was clinically useful. CONCLUSION: Radiomic features have the potential to be applied to predict the short-term efficacy of IMRT in patients with inoperable lung cancer.

16.
CNS Neurosci Ther ; 29(12): 3725-3740, 2023 12.
Article in English | MEDLINE | ID: mdl-37551863

ABSTRACT

Stroke has been associated with devastating clinical outcomes, with current treatment strategies proving largely ineffective. Therefore, there is a need to explore alternative treatment options for addressing post-stroke functional deficits. Gene therapy utilizing adeno-associated viruses (AAVs) as a critical gene vector delivering genes to the central nervous system (CNS) gene delivery has emerged as a promising approach for treating various CNS diseases. This review aims to provide an overview of the biological characteristics of AAV vectors and the therapeutic advancements observed in preclinical models of ischemic stroke. The study further investigates the potential of manipulating AAV vectors in preclinical applications, emphasizing the challenges and prospects in the selection of viral vectors, drug delivery strategies, immune reactions, and clinical translation.


Subject(s)
Ischemic Stroke , Stroke , Humans , Dependovirus/genetics , Genetic Therapy , Gene Transfer Techniques , Genetic Vectors , Stroke/genetics , Stroke/therapy
17.
Metab Brain Dis ; 38(7): 2315-2325, 2023 10.
Article in English | MEDLINE | ID: mdl-37556042

ABSTRACT

The incidence of mild cognitive impairment (MCI) and diabetes mellitus (DM) is increasing year by year. Clinical findings show that Banxia Xiexin Decoction (BXD) can be combined to treat MCI and DM. However, the principle and mechanism of BXD in treating MCI and DM remain unclear. In this study, to explore the common mechanism of BXD in treating MCI and DM by using the method of network pharmacology. Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was used to screen the main active components of BXD, as well as to predict and screen its potential targets. Using Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), DisGeNET, GeneCards to select the target proteins of two diseases, and intersecting the drug target and the disease target to obtain the common target of drug diseases, which is imported into cytoscape software to draw the network diagram of "drug components-target diseases" and the interaction network diagram between the common target proteins. According to the Database for Annotation, Visualization and Integrated Discovery (DAVID) database, we analyzed the common targets using two methods, gene ontology Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway enrichment analysis and Gene Ontology (GO) function enrichment analysis, as well as studied the interaction mechanism of the two diseases, with the results validated using molecular docking. A total of 267 main active components of BXD were screened, together with the two diseases shared 233 common targets. The top five key targets identified by the topological analysis were TP53, AKT1, STAT3, TNF, and MAPK3. Go enrichment results indicated that it was primarily related to response to drug, extracellular space, enzyme binding, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding. t KEGG enrichment pathway analysis identified 20 significant pathways, the majority of which are AGE-RAGE signaling pathways in diabetic complications, lipid and atherosclerosis, fluid shear stress and atherosclerosis, IL-17 signaling pathway, TNF signaling pathway, and so on. The results of molecular docking revealed that the key components of BXD, baicalein, licochalcone a, quercetin, and naringenin, had strong binding ability with core targets TP53, AKT1, STAT3, TNF, MAPK3. BXD can treat MCI and DM by multi-targets and multi-channels,and plays a role of "homotherapy for heteropathy" mainly through response to drug, positive regulation of gene expression, extracellular space and enzyme binding and other ways.


Subject(s)
Atherosclerosis , Cognitive Dysfunction , Diabetes Mellitus , Humans , Network Pharmacology , Molecular Docking Simulation , Cognitive Dysfunction/drug therapy
18.
Crit Rev Oncol Hematol ; 189: 104070, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37468083

ABSTRACT

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer and has an increasing incidence worldwide. The management of HCC still has many restrictions, despite the fact that there are now numerous treatment options, including liver transplantation/resection, locoregional treatments (LRT), and systemic medication. As a turning point in the history of cancer treatment, the discovery of the immune checkpoints and the development of their inhibitors provide new hope for HCC patients. However, limited objective response rate and insignificant overall survival improvement are still urgent problems to be solved for immune checkpoint inhibitors (ICIs). Combination therapies are considered a solution for improving the effectiveness and response rate of ICIs, and several forms of combination treatments are currently being actively researched. In this review, we summarize the mainstream combination strategies, explain their theoretical basis, introduce several important and ongoing clinical trials, and suggest some potential future paths in this area at the conclusion of the review. AVAILABILITY OF DATA AND MATERIALS: Not applicable.

19.
Front Psychol ; 14: 1098506, 2023.
Article in English | MEDLINE | ID: mdl-37333578

ABSTRACT

Introduction: An effective assessment of preschoolers' approaches to learning (ATL) requires multiple-reporter co-evaluation, such as teachers and parents. Based on extant research on children's ATL combined with Chinese cultural background and educational policies, this study aims to develop an ATL scale suitable for Chinese teachers and parents to co-evaluate preschoolers' ATL. Methods: Exploratory and confirmatory factor analysis (CFA) of the data collected from teachers (n=833) and parents (n=856) demonstrates the four-factor structure of the ATL: creativity, learning strategy, competence motivation, and attention/persistence, wherein creativity is a new dimension uncovered in the Chinese context. Results: Psychometric analysis demonstrates that the scale has good reliability and validity. Multi-group CFA further shows that the measurement model is robust and independent from reporter identity. Discussion: The current study contributes a novel and easy-to-use measurement instrument with 20 items for educational practitioners and for scholars who are interested in cross-cultural comparison or longitudinal development of Chinese children's ATL.

20.
Angew Chem Int Ed Engl ; 62(33): e202307776, 2023 08 14.
Article in English | MEDLINE | ID: mdl-37358791

ABSTRACT

The low oxygen dependence of type I photosensitizers (PSs) has made them a popular choice for treating solid tumors. However, the drawbacks of poor water solubility, short emission wavelength, poor stability, and inability to distinguish cancer cells from normal cells limit the application of most type I PSs in clinical therapy. Thereby, developing novel type I PSs for overcoming these problems is an urgent but challenging task. Herein, by utilizing the distinctive structural characteristics of anion-π+ interactions, a highly water-soluble type I PS (DPBC-Br) with aggregation-induced emission (AIE) characteristic and near-infrared (NIR) emission is fabricated for the first time. DPBC-Br displays remarkable water solubility (7.3 mM) and outstanding photobleaching resistance, enabling efficient and precise differentiation between tumor cells and normal cells in a wash-free and long-term tracking manner via NIR-I imaging. Additionally, the superior type I reactive oxygen species (ROS) produced by DPBC-Br provide both specific killing of cancer cells in vitro and inhibition of tumor growth in vivo, with negligible systemic toxicity. This study rationally constructs a highly water-soluble type I PS, which has higher reliability and controllability compared with conventional nanoparticle formulating procedures, offering great potential for clinical cancer treatment.


Subject(s)
Neoplasms , Photochemotherapy , Humans , Water , Reproducibility of Results , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/chemistry , Diagnostic Imaging , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Reactive Oxygen Species
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