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1.
Phytomedicine ; 132: 155884, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39053245

ABSTRACT

BACKGROUND: QiJu-DiHuang Wan (QJDHW), a frequently employed Chinese herbal formula, is used to treat blurred vision. Even so, it is unclear how it works in treating age-related dry eyes. OBJECTIVE: The aim of this research is to explore the potential mechanisms of QJDHW in treating dry eye using UHPLC-QE-MS, metabolomics, and network pharmacology. METHODS: Six male SD rats were segregated into control and QJDHW groups. Following intervention, The primary active ingredients in QJDHW-containing serum were identified using UHPLC-QE-MS. Metabolomics and network pharmacology were utilized to investigate potential targets and pathways involved following QJDHW use. Primary lacrimal epithelial cells were used for validation. RESULTS: A total of 425 active ingredients of QJDHW were identified, along with 210 active ingredients in QJDHW-containing serum. A comparison of QJDHW-containing serum and control serum samples revealed 40 metabolic differentiators. A total of 24 metabolites were found in QJDHW and QJDHW-containing serum. Network pharmacology identified 3,144 targets for dry eye disease, and 102 metabolite action targets were found for QJDHW-entering components. KEGG Enrichment Analysis revealed significance of HIF-1, apoptosis, cell cycle and PI3K-Akt, among others. HIF-1 and PI3K-Akt were chosen for verification in the oxidative damage model of lacrimal epithelial cells. CONCLUSION: The main active ingredients of QJDHW and its containing serum were elucidated by UHPLC-QE-MS demonstrating that QJDHW treats age-associated dry eye by inhibiting HIF1α/NF-κB through ROS inhibition and PI3K/p-AKT activation.


Subject(s)
Drugs, Chinese Herbal , Dry Eye Syndromes , Metabolomics , Network Pharmacology , Rats, Sprague-Dawley , Animals , Drugs, Chinese Herbal/pharmacology , Male , Dry Eye Syndromes/drug therapy , Rats , Chromatography, High Pressure Liquid , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Lacrimal Apparatus/drug effects , Lacrimal Apparatus/metabolism , Signal Transduction/drug effects
2.
Semin Oncol Nurs ; 40(4): 151659, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38834450

ABSTRACT

OBJECTIVES: To examine the moderating effect of daylight exposure on physical activity and objective sleep quality, using wearable actigraph devices. METHODS: We recruited 324 patients with either gastric or esophageal cancer. Actigraphs were used to measure all objective data including daylight exposure, physical activity, and sleep quality. Pearson's correlation coefficients were used to examine the relationships among demographic data, disease attributes, physical activity, daylight exposure, and sleep. The Hayes PROCESS macro with the regression bootstrapping method was employed to analyze the moderating effect of daylight exposure on the relationship between physical activity and sleep. RESULTS: Sleep efficiency correlated positively with physical activity, while "wake after sleep onset" correlated negatively with physical activity and mean lux. Mean lux and light >500 lux significantly moderated the association between physical activity and sleep efficiency (P = .002 in both cases). Similarly, mean lux and light >500 lux significantly moderated the association between physical activity and "wake after sleep onset" (P = .002 and .001, respectively). CONCLUSION: Both average daylight exposure and time of exposure to >500 lux act as moderators of physical activity and objective sleep quality in patients with gastric or esophageal cancer. Healthcare practitioners should encourage patients with cancer to engage in daily outdoor physical activity. Further intervention studies are needed to verify the combined effect of daytime light exposure and physical activity on improving sleep quality. IMPLICATIONS FOR NURSING PRACTICE: Healthcare practitioners should encourage patients with cancer to engage in daily outdoor physical activity. Further intervention studies are needed to verify the combined effect of daytime light exposure and physical activity on improving sleep quality.


Subject(s)
Esophageal Neoplasms , Exercise , Humans , Male , Female , Middle Aged , Exercise/physiology , Aged , Esophageal Neoplasms/physiopathology , Sleep Quality , Adult , Actigraphy , Stomach Neoplasms/physiopathology , Sleep/physiology , Aged, 80 and over , Sunlight/adverse effects
3.
Open Biol ; 14(6): 240063, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38864245

ABSTRACT

Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in 'fresh' human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients' brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.


Subject(s)
Frontal Lobe , Mental Disorders , Psychotropic Drugs , Temporal Lobe , Humans , Psychotropic Drugs/pharmacology , Frontal Lobe/metabolism , Frontal Lobe/pathology , Temporal Lobe/metabolism , Temporal Lobe/pathology , Mental Disorders/genetics , Mental Disorders/metabolism , Neurons/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, N-Methyl-D-Aspartate/genetics , Genetic Predisposition to Disease , Gene Expression Profiling , Transcriptome , Gene Expression Regulation , Schizophrenia/genetics , Schizophrenia/metabolism , Bipolar Disorder/genetics , Bipolar Disorder/metabolism
4.
Front Cardiovasc Med ; 11: 1364332, 2024.
Article in English | MEDLINE | ID: mdl-38707890

ABSTRACT

Background: Postoperative acute kidney injury (PO-AKI) is a prevalent complication among patients with acute type A aortic dissection (aTAAD) for which unrecognized trajectories of renal function recovery, and their heterogeneity, may underpin poor success in identifying effective therapies. Methods: This was a retrospective, single-center cohort study in a regional Great Vessel Center including patients undergoing aortic dissection surgery. Estimated glomerular filtration rate (eGFR) recovery trajectories of PO-AKI were defined through the unsupervised latent class mixture modeling (LCMM), with an assessment of patient and procedural characteristics, complications, and early-term survival. Internal validation was performed by resampling. Results: A total of 1,295 aTAAD patients underwent surgery and 645 (49.8%) developed PO-AKI. Among the PO-AKI cohort, the LCMM identified two distinct eGFR trajectories: early recovery (ER-AKI, 51.8% of patients) and late or no recovery (LNR-AKI, 48.2% of patients). Binary logistic regression identified five critical determinants regarding poor renal recovery, including chronic kidney disease (CKD) history, renal hypoperfusion, circulation arrest time, intraoperative urine, and myoglobin. LNR-AKI was associated with increased mortality, continuous renal replacement therapies, mechanical ventilation, ICU stay, and hospital stay. The assessment of the predictive model was good, with an area under the curve (AUC) of 0.73 (95% CI: 0.69-0.76), sensitivity of 61.74%, and specificity of 75.15%. The internal validation derived a consistent average AUC of 0.73. The nomogram was constructed for clinicians' convenience. Conclusion: Our study explored the PO-AKI recovery patterns among surgical aTAAD patients and identified critical determinants that help to predict individuals at risk of poor recovery of renal function.

5.
Adv Mater ; 36(26): e2401821, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38567884

ABSTRACT

In the era of the Internet and the Internet of Things, display technology has evolved significantly toward full-scene display and realistic display. Incorporating "intelligence" into displays is a crucial technical approach to meet the demands of this development. Traditional display technology relies on distributed hardware systems to achieve intelligent displays but encounters challenges stemming from the physical separation of sensing, processing, and light-emitting modules. The high energy consumption and data transformation delays limited the development of intelligence display, breaking the physical separation is crucial to overcoming the bottlenecks of intelligence display technology. Inspired by the biological neural system, neuromorphic technology with all-in-one features is widely employed across various fields. It proves effective in reducing system power consumption, facilitating frequent data transformation, and enabling cross-scene integration. Neuromorphic technology shows great potential to overcome display technology bottlenecks, realizing the full-scene display and realistic display with high efficiency and low power consumption. This review offers a comprehensive summary of recent advancements in the application of neuromorphic technology in displays, with a focus on interoperability. This work delves into its state-of-the-art designs and potential future developments aimed at revolutionizing display technology.

6.
Int J Mol Sci ; 25(7)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38612639

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful technique for investigating biological heterogeneity at the single-cell level in human systems and model organisms. Recent advances in scRNA-seq have enabled the pooling of cells from multiple samples into single libraries, thereby increasing sample throughput while reducing technical batch effects, library preparation time, and the overall cost. However, a comparative analysis of scRNA-seq methods with and without sample multiplexing is lacking. In this study, we benchmarked methods from two representative platforms: Parse Biosciences (Parse; with sample multiplexing) and 10x Genomics (10x; without sample multiplexing). By using peripheral blood mononuclear cells (PBMCs) obtained from two healthy individuals, we demonstrate that demultiplexed scRNA-seq data obtained from Parse showed similar cell type frequencies compared to 10x data where samples were not multiplexed. Despite relatively lower cell capture affecting library preparation, Parse can detect rare cell types (e.g., plasmablasts and dendritic cells) which is likely due to its relatively higher sensitivity in gene detection. Moreover, a comparative analysis of transcript quantification between the two platforms revealed platform-specific distributions of gene length and GC content. These results offer guidance for researchers in designing high-throughput scRNA-seq studies.


Subject(s)
Benchmarking , Leukocytes, Mononuclear , Humans , Gene Library , Genomics , Sequence Analysis, RNA
8.
Gene ; 911: 148333, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38431233

ABSTRACT

BACKGROUND: The elevated metastasis rate of uveal melanoma (UM) is intricately correlated with patient prognosis, significantly affecting the quality of life. S100 calcium-binding protein A4 (S100A4) has tumorigenic properties; therefore, the present study investigated the impact of S100A4 on UM cell proliferation, apoptosis, migration, and invasion using bioinformatics and in vitro experiments. METHODS: Bioinformatic analysis was used to screen S100A4 as a hub gene and predict its possible mechanism in UM cells, and the S100A4 silencing cell line was constructed. The impact of S100A4 silencing on the proliferative ability of UM cells was detected using the Cell Counting Kit-8 and colony formation assays. Annexin V-FITC/PI double fluorescence and Hoechst 33342 staining were used to observe the effects of apoptosis on UM cells. The effect of S100A4 silencing on the migratory and invasive capabilities of UM cells was assessed using wound healing and Transwell assays. Western blotting was used to detect the expression of related proteins. RESULTS: The present study found that S100A4 is a biomarker of UM, and its high expression is related to poor prognosis. After constructing the S100A4 silencing cell line, cell viability, clone number, proliferating cell nuclear antigen, X-linked inhibitor of apoptosis protein, and survivin expression were decreased in UM cells. The cell apoptosis rate and relative fluorescence intensity increased, accompanied by increased levels of Bax and caspase-3 and decreased levels of Bcl-2. Additionally, a decrease in the cell migration index and relative invasion rate was observed with increased E-cadherin expression and decreased N-cadherin and vimentin protein expression. CONCLUSION: S100A4 silencing can inhibit the proliferation, migration, and invasion and synchronously induces apoptosis in UM cells.


Subject(s)
Melanoma , S100 Proteins , Uveal Neoplasms , Humans , Apoptosis/genetics , Carcinogenesis , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Melanoma/genetics , Melanoma/pathology , Quality of Life , S100 Calcium-Binding Protein A4/genetics , S100 Proteins/genetics , Uveal Neoplasms/genetics , Uveal Neoplasms/pathology
9.
Pharmacol Res Perspect ; 12(1): e1162, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38189160

ABSTRACT

Oxidative stress is an important mechanism of aging, and in turn, aging can also aggravate oxidative stress, which leads to a vicious cycle. In the process of the brain converting light into visual signals, the eye is stimulated by harmful blue-light radiation directly. Thus, the eye is especially vulnerable to oxidative stress and becomes one of the organs most seriously involved during the aging process. Cataracts, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and dry eye are inextricably linked to the aging process and oxidative stress. Chlorogenic acid (CGA) has been demonstrated to have antioxidant and anti-inflammatory activities, and its validity has been established experimentally in numerous fields, including cardiovascular disease, metabolic disorders, cancers, and other chronic diseases. There has previously been evidence of CGA's therapeutic effect in the field of ophthalmopathy. Considering that many ophthalmic drugs lead to systemic side effects, CGA may act as a natural exogenous antioxidant for patients to take regularly, controlling their condition while minimizing side effects. In this paper, in vitro and in vivo studies of CGA in the treatment of age-related eye diseases are reviewed, and the prospects of CGA's antioxidant application for the eye are discussed. The aim of this review is to summarize the relevant knowledge and provide theoretical support for future research.


Subject(s)
Diabetic Retinopathy , Eye Diseases , Humans , Antioxidants/pharmacology , Antioxidants/therapeutic use , Chlorogenic Acid/pharmacology , Chlorogenic Acid/therapeutic use , Eye Diseases/drug therapy , Oxidative Stress , Diabetic Retinopathy/drug therapy
10.
Cancer Nurs ; 47(2): 112-120, 2024.
Article in English | MEDLINE | ID: mdl-36728167

ABSTRACT

BACKGROUND: Although rest-activity circadian rhythm (RACR) disruption is associated with mortality in patients with cancer, few studies have examined the effect of RACR on patients with esophageal and gastric cancer. OBJECTIVE: The aim of this study was to identify the predictors of RACR. METHODS: This cross-sectional, single-site study included 276 patients with esophageal and gastric cancer recruited from chest-surgery and general-surgery outpatient departments. Actigraphy was used to assess objective physical activity (PA), daylight exposure, and RACR, and 3-day PA was used to indicate the subjective amount of PA. The parameter of objective PA was the up activity mean; the parameter of daylight exposure was >500 lx, and the parameters of RACR were the 24-hour correlation coefficient, in-bed less than out-of-bed dichotomy index, midline estimating statistic of rhythm, and amplitude. The subjective amount of PA was calculated as the sum of mild, moderate, and vigorous PA. RESULTS: The up activity mean predicted 24-hour correlation coefficient. The PA amount and up activity mean predicted in-bed less than out-of-bed dichotomy index. The up activity mean and >500-lx daylight exposure predicted midline estimating statistic of rhythm. Finally, the PA amount and up activity mean predicted the amplitude. CONCLUSIONS: Increased PA and daylight exposure may improve RACR. IMPLICATIONS FOR PRACTICE: Patients with esophageal and gastric cancer should be encouraged to engage in outdoor PA during the daytime as part of their regular lifestyle to maintain a robust circadian rhythm.


Subject(s)
Esophageal Neoplasms , Stomach Neoplasms , Humans , Cross-Sectional Studies , Circadian Rhythm , Exercise , Actigraphy , Sleep
11.
J Clin Invest ; 134(2)2024 Jan 16.
Article in English | MEDLINE | ID: mdl-37988169

ABSTRACT

Alzheimer's disease is characterized by the accumulation of amyloid-ß plaques, aggregation of hyperphosphorylated tau (pTau), and microglia activation. Galectin-3 (Gal3) is a ß-galactoside-binding protein that has been implicated in amyloid pathology. Its role in tauopathy remains enigmatic. Here, we showed that Gal3 was upregulated in the microglia of humans and mice with tauopathy. pTau triggered the release of Gal3 from human induced pluripotent stem cell-derived microglia in both its free and extracellular vesicular-associated (EV-associated) forms. Both forms of Gal3 increased the accumulation of pathogenic tau in recipient cells. Binding of Gal3 to pTau greatly enhanced tau fibrillation. Besides Gal3, pTau was sorted into EVs for transmission. Moreover, pTau markedly enhanced the number of EVs released by iMGL in a Gal3-dependent manner, suggesting a role of Gal3 in biogenesis of EVs. Single-cell RNA-Seq analysis of the hippocampus of a mouse model of tauopathy (THY-Tau22) revealed a group of pathogenic tau-evoked, Gal3-associated microglia with altered cellular machineries implicated in neurodegeneration, including enhanced immune and inflammatory responses. Genetic removal of Gal3 in THY-Tau22 mice suppressed microglia activation, reduced the level of pTau and synaptic loss in neurons, and rescued memory impairment. Collectively, Gal3 is a potential therapeutic target for tauopathy.


Subject(s)
Galectin 3 , Tauopathies , tau Proteins , Animals , Humans , Mice , Alzheimer Disease/pathology , Disease Models, Animal , Galectin 3/genetics , Galectin 3/metabolism , Induced Pluripotent Stem Cells/metabolism , Mice, Transgenic , Microglia/pathology , tau Proteins/genetics , tau Proteins/metabolism , Tauopathies/genetics , Tauopathies/metabolism
12.
Cancer Nurs ; 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38011048

ABSTRACT

BACKGROUND: Physical activity and daylight exposure predict rest-activity circadian rhythm (RACR) in patients with cancer. However, whether daylight exposure mediates the relationship between physical activity and RACR and the optimal amounts of physical activity and daylight that benefit RACR remain unclear. OBJECTIVES: This study investigated the mediating role of daylight exposure and determined the dose-response relationship among daylight exposure, physical activity, and RACR in patients with cancer. METHODS: This cross-sectional exploratory study recruited 319 patients with esophageal and gastric cancer from 2 surgery outpatient departments in Taiwan. Daylight exposure (>500 lux), physical activity (up activity mean), and RACR (midline estimating statistic of rhythm) were measured through actigraphy. Regression was performed, and the receiver operating characteristic curve was plotted. RESULTS: Daylight exposure (>500 lux) partially mediated the relationship between physical activity (up activity mean) and RACR (midline estimating statistic of rhythm). The optimal cutoffs for discriminating between satisfactory and poor RACR were 187.43 counts/min for physical activity (sensitivity, 90.3%; specificity, 84.4%) and 35.71 min/d for daylight exposure (sensitivity, 55.9%; specificity, 78.2%). CONCLUSIONS: Participants who engaged in physical activity were more likely to receive daylight exposure and experience improved RACR. The optimal level of daylight exposure and frequency of physical activity that can improve RACR in patients with esophageal and gastric cancer are 36 min/d and 187 counts/min, respectively. IMPLICATIONS FOR PRACTICE: Healthcare professionals should encourage patients to engage in exercise or physical activity during the daytime to improve their circadian rhythm.

13.
Trop Med Int Health ; 28(10): 797-805, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37641441

ABSTRACT

OBJECTIVES: Neisseria meningitidis is one of the major pathogens of meningitis in children worldwide and causes invasive meningococcal disease (IMD), which is a critical illness that mainly presents as meningitis and/or septicemia in children. Identification of N. meningitidis in cerebrospinal fluid (CSF) is the gold standard for the diagnosis of meningococcal meningitis, but antigen tests have advantages such as timely results, relatively low cost, and convenience. Yet, the diagnostic accuracy of antigen tests remains uncertain. Therefore, the aim of this meta-analysis was to evaluate the diagnostic accuracy of antigen tests for N. meningitidis in CSF. METHODS: We searched the PubMed, Embase, and Cochrane Library databases for studies evaluating the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We included studies that provided sufficient data to construct a 2 × 2 table on a per-sample basis. To determine the overall sensitivity and specificity of the antigen tests, we used polymerase chain reaction (PCR) as the reference standard and employed the hierarchical summary receiver operating characteristic model. RESULTS: Nine studies with 4533 CSF samples were included. The meta-analysis yielded a pooled sensitivity of 91.2% (95% confidence interval [CI]: 80.0%-100.0%) and a pooled specificity of 93.8% (95% CI: 83.9%-100.0%). A subgroup analysis of 2 studies that reported the outcomes of MeningoSpeed yielded a pooled sensitivity of 93.4% (95% CI: 90.0%-95.8%) and a pooled specificity of 91.9% (95% CI: 88.6%-94.4%). Antigen testing for the N. meningitidis serogroup X had a pooled sensitivity of 92.4% (95% CI: 85.2%-96.2%) and a pooled specificity of 99.2% (95% CI: 78.7%-100.0%). CONCLUSIONS: The studied antigen tests had high sensitivity and specificity for the diagnosis of meningococcal meningitis in CSF specimens. Antigen testing could serve as an accurate diagnostic method for assessing patients who have a suspected N. meningitidis infection.

14.
Adv Sci (Weinh) ; 10(5): e2206107, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36494096

ABSTRACT

Cobalt single atoms coordinated with planar four nitrogen atoms (Co1 N4 ) represent an efficient electrocatalyst for oxygen evolution reaction (OER), whereas the large energy barrier of CoOH dehydrogenation limits the OER activity. Herein, axial phosphate (PO4 ) coordination is incorporated in Co1 N4 single atoms of cobalt phthalocyanine@carbon nanotubes (P-CoPc@CNT), so as to boost the intrinsic OER performance through manipulating the reaction pathway. With a relative low mass loading of Co (2.7%), the P-CoPc@CNT shows remarkable alkaline OER activity with the overpotential of 300 mV and Tafel slope of 41.7 mV dec-1 , which dramatically outperforms the CoPc@CNT without axial PO4 coordination. Based on mechanistic analysis, the axial PO4 coordination directly participates in the OER cycle by the transformation of axial ligand. Specially, the CoOH dehydrogenation process is replaced by the dehydrogenation of HPO4 -Co1 N4 intermediate, which largely decreases the energy barrier and thus benefits the whole OER process.

15.
Toxins (Basel) ; 16(1)2023 12 20.
Article in English | MEDLINE | ID: mdl-38276530

ABSTRACT

The injudicious and excessive use of synthetic pesticides has deleterious effects on humans, ecosystems, and biodiversity. As an alternative to traditional crop-protection methods, botanical pesticides are gaining importance. In this research endeavor, we examined the contact toxicity, knockdown time, lethal time, and toxicity horizontal transmission of three natural pesticides from plants (azadirachtin, celangulin, and veratramine) on red imported fire ants (RIFA; Solenopsis invicta). Our research findings indicated that azadirachtin and celangulin exhibited relatively high toxicity, with median lethal dose (LD50) values of 0.200 and 0.046 ng/ant, respectively, whereas veratramine exhibited an LD50 value of 544.610 ng/ant for large workers of S. invicta at 24 h post-treatment. Upon treatment with 0.125 mg/L, the (median lethal time) LT50 values of azadirachtin and celangulin were determined to be 60.410 and 9.905 h, respectively. For veratramine, an LT50 value of 46.967 h was achieved after being tested with 200 mg/L. Remarkably, azadirachtin and celangulin were found to exhibit high horizontal transfer among RIFA, with high secondary mortality (100%) and tertiary mortalities (>61%) after 48 h of treatment with 250 mg/L, as well as with their dust formulations for 72 h. However, veratramine did not exhibit significant toxicity or horizontal transfer effects on RIFA, even at high concentrations. These findings suggest that azadirachtin and celangulin are likely to have a highly prominent potential in the management of S. invicta.


Subject(s)
Ants , Insecticides , Limonins , Pesticides , Veratrum Alkaloids , Animals , Humans , Fire Ants , Ecosystem , Insecticides/toxicity
16.
Sci Rep ; 12(1): 20977, 2022 12 05.
Article in English | MEDLINE | ID: mdl-36470908

ABSTRACT

Microbiota-gut-brain axis signaling plays a pivotal role in mood disorders. The communication between the host and the gut microbiota may involve complex regulatory networks. Previous evidence showed that host-fecal microRNAs (miRNAs) interactions partly shaped gut microbiota composition. We hypothesized that some miRNAs are correlated with specific bacteria in the fecal samples in patients with major depressive disorder (MDD), and these miRNAs would show enrichment in pathways associated with MDD. MDD patients and healthy controls were recruited to collect fecal samples. We performed 16S ribosome RNA sequence using the Illumina MiSeq sequencers and analysis of 798 fecal miRNAs using the nCounter Human-v2 miRNA Panel in 20 subjects. We calculated the Spearman correlation coefficient for bacteria abundance and miRNA expressions, and analyzed the predicted miRNA pathways by enrichment analysis with false-discovery correction (FDR). A total of 270 genera and 798 miRNAs were detected in the fecal samples. Seven genera (Anaerostipes, Bacteroides, Bifidobacterium, Clostridium, Collinsella, Dialister, and Roseburia) had fold changes greater than one and were present in over 90% of all fecal samples. In particular, Bacteroides and Dialister significantly differed between the MDD and control groups (p-value < 0.05). The correlation coefficients between the seven genera and miRNAs in patients with MDD showed 48 pairs of positive correlations and 36 negative correlations (p-value < 0.01). For miRNA predicted functions, there were 57 predicted pathways with a p-value < 0.001, including MDD-associated pathways, axon guidance, circadian rhythm, dopaminergic synapse, focal adhesion, long-term potentiation, and neurotrophin signaling pathway. In the current pilot study, our findings suggest specific genera highly correlated with the predicted miRNA functions, which might provide clues for the interaction between host factors and gut microbiota via the microbiota-gut-brain axis. Follow-up studies with larger sample sizes and refined experimental design are essential to dissect the roles between gut microbiota and miRNAs for depression.


Subject(s)
Depressive Disorder, Major , Gastrointestinal Microbiome , MicroRNAs , Humans , Gastrointestinal Microbiome/genetics , Depressive Disorder, Major/genetics , Depressive Disorder, Major/microbiology , MicroRNAs/genetics , Pilot Projects , Feces/microbiology , Bacteria/genetics , Bacteroides/genetics , Clostridiales/genetics , Veillonellaceae/genetics
17.
Nat Commun ; 13(1): 7375, 2022 11 30.
Article in English | MEDLINE | ID: mdl-36450710

ABSTRACT

Non-ischemic cardiomyopathy (NICM) can cause left ventricular dysfunction through interstitial fibrosis, which corresponds to the failure of cardiac tissue remodeling. Recent evidence implicates monocytes/macrophages in the etiopathology of cardiac fibrosis, but giving their heterogeneity and the antagonizing roles of macrophage subtypes in fibrosis, targeting these cells has been challenging. Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator of human and murine cardiac fibrosis, and show that myeloid specific deletion of WWP2 reduces cardiac fibrosis in hypertension-induced NICM. By using single cell RNA sequencing analysis of immune cells in the same model, we establish the functional heterogeneity of macrophages and define an early pro-fibrogenic phase of NICM that is driven by Ccl5-expressing Ly6chigh monocytes. Among cardiac macrophage subtypes, WWP2 dysfunction primarily affects Ly6chigh monocytes via modulating Ccl5, and consequentially macrophage infiltration and activation, which contributes to reduced myofibroblast trans-differentiation. WWP2 interacts with transcription factor IRF7, promoting its non-degradative mono-ubiquitination, nuclear translocation and transcriptional activity, leading to upregulation of Ccl5 at transcriptional level. We identify a pro-fibrogenic macrophage subtype in non-ischemic cardiomyopathy, and demonstrate that WWP2 is a key regulator of IRF7-mediated Ccl5/Ly6chigh monocyte axis in heart fibrosis.


Subject(s)
Cardiomyopathies , Myocardial Ischemia , Humans , Animals , Mice , Monocytes , Ubiquitin-Protein Ligases/genetics , Macrophages , Fibrosis , Cardiomyopathies/genetics
18.
J Alzheimers Dis ; 90(3): 1203-1213, 2022.
Article in English | MEDLINE | ID: mdl-36213992

ABSTRACT

BACKGROUND: The Mild Behavioral Impairment Checklist (MBI-C) has been developed to assess mild behavioral impairment (MBI). However, no study has validated the use of MBI-C using a promising translation method in Taiwan. Thus, consistency and discrepancy between informant-rated and self-rated scores have not been extensively researched. OBJECTIVE: This study validated and compared the informant- and self-rated versions of the MBI-C among community-dwelling people in Taiwan. METHOD: We recruited 202 pairs of individuals without dementia aged ≥50 years and their cohabitating informants. The participants completed the MBI-C (MBI-C-self), and the informants completed the MBI-C (MBI-C-informant) and the Neuropsychiatric Inventory Questionnaire (NPI-Q) independently. Internal consistency, inter-rater reliability, and convergent validity were examined. RESULTS: Both MBI-C-self and MBI-C-informant exhibited satisfactory Cronbach's α values (0.92 and 0.88, respectively). The MBI-C-informant total scorewas correlated with the NPI-Q total score (r = 0.83, p < 0.001). Inter-rater reliability between the two versions, as represented by the inter-rater correlation coefficient, was 0.57 (p < 0.001). The prevalence of MBI based on the MBI-C-informant scores was 1.5% higher than that based on the MBI-C-self scores according to the suggested cut-off score of 8.5. The affective dysregulation domain score of MBI-C-informant was significantly lower than that of MBI-C-self. CONCLUSION: MBI-C-informant exhibited both high reliability and validity. Discrepancies between MBI-C-informant and MBI-C-self related to the detection rates and affective dysregulation domain scores were noted. The level of consistency and discrepancy between these two versions provide implications for the use of MBI-C in clinical practice and future research.


Subject(s)
Cognitive Dysfunction , Humans , Neuropsychological Tests , Cognitive Dysfunction/psychology , Checklist , Reproducibility of Results , Translations
19.
Mov Disord ; 37(10): 2008-2020, 2022 10.
Article in English | MEDLINE | ID: mdl-35997316

ABSTRACT

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disease caused by CAG-repeat expansions (>36) in exon 1 of HTT, which dysregulates multiple cellular machineries. Translin-associated protein X (TRAX) is a scaffold protein with diverse functions, including suppressing the microRNA (miRNA)-mediated silencing by degrading pre-miRNA. To date, the role of TRAX in neurodegenerative diseases remains unknown. OBJECTIVES: We delineated the role of TRAX upregulation during HD progression. METHODS: Expression of TRAX in the brains of humans and three mouse models with HD were analyzed by immunohistochemistry staining, western blot, and quantitative reverse transcription-polymerase chain reaction. Adeno-associated viruses harboring TRAX short hairpin RNA were intrastriatally injected into HD mice to downregulate TRAX. HD-like symptoms were analyzed by behavioral and biochemical assessments. The miRNA-sequencing and RNA-sequencing analyses were used to identify the TRAX- regulated miRNA-messenger RNA (mRNA) axis during HD progression. The identified gene targets were validated biochemically in mouse and human striatal cells. RESULTS: We discovered that TRAX was upregulated in the brains of HD patients and three HD mouse models. Downregulation of TRAX enhanced 83 miRNAs (including miR-330-3p, miR-496a-3p) and subsequently changed the corresponding mRNA networks critical for HD pathogenesis (eg, DARPP-32 and brain-derived neurotrophic factor). Disruption of the TRAX-mediated miRNA-mRNA axis accelerated the progression of HD-like symptoms, including the degeneration of motor function, accumulation of mHTT aggregates, and shortened neurite outgrowth. CONCLUSIONS: We demonstrated that TRAX upregulation is authentic and protective in HD. Our study provides a novel layer of regulation for HD pathogenesis and may lead to the development of new therapeutic strategies for HD. © 2022 International Parkinson and Movement Disorder Society.


Subject(s)
Huntington Disease , MicroRNAs , Neurodegenerative Diseases , Animals , Humans , Mice , Brain-Derived Neurotrophic Factor , Disease Models, Animal , Huntingtin Protein/genetics , Huntington Disease/metabolism , MicroRNAs/genetics , Neuroprotection , RNA, Messenger , RNA, Small Interfering
20.
Pain Manag Nurs ; 23(6): 885-892, 2022 12.
Article in English | MEDLINE | ID: mdl-35922271

ABSTRACT

BACKGROUND: Up to 90% of patients still experience pain after abdominal surgery, which also affects their physical recovery and psychological anxiety. AIM: To evaluate the effects of guided imagery meditation on ameliorating anxiety, improving the quality of sleep, and relieving postoperative pain in patients after laparoscopic cholecystectomy surgery. METHOD: In the general surgical ward of a teaching hospital, patients were randomly assigned to usual care (n = 34) and guided imagery meditation intervention (n = 34) groups, using the method. The measuring outcomes included their anxiety score, quality of sleep, and pain control. RESULTS: In terms of the anxiety difference, the experimental group scored 0.42 (standard deviation [SD] = 0.97), while the control group scored 4.79 (SD = 7.56), which indicates a statistically significant difference (F = 8.04, p = .01, partial eta2 = 0.11). In terms of quality of sleep, the mean score of the experimental group was 2.67 (SD = 1.96), while the control group scored 7.55 (SD = 3.81), which indicates a significant difference (F = 39.99, p = .001, partial eta2 = 0.39). The mean of the degree of postoperative pain was 2.11 points (SD = 1.39), and the score of the control group was 4.00 points (SD = 1.62), which indicates a significant difference (p = .001). CONCLUSIONS: Guided imagery meditation is a simple, non-invasive, non-pharmacologic intervention measure. It can reduce anxiety and postoperative pain, and improve the quality of sleep. Thus, it should be promoted in clinical practice.


Subject(s)
Cholecystectomy, Laparoscopic , Meditation , Humans , Imagery, Psychotherapy/methods , Cholecystectomy, Laparoscopic/adverse effects , Anxiety/prevention & control , Anxiety/psychology , Pain, Postoperative/prevention & control
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