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  • 1
    Online Resource
    Online Resource
    Spurious Autobiographical Memory of Psychosis: A Mechanistic Hypothesis for the Resolution, Persistence, and Recurrence of Positive Symptoms in Psychotic Disorders
    MDPI AG ; 2023
    In:  Brain Sciences Vol. 13, No. 7 ( 2023-07-13), p. 1069-
    Details
    In: Brain Sciences, MDPI AG, Vol. 13, No. 7 ( 2023-07-13), p. 1069-
    Abstract: Psychotic disorders are complex disorders with multiple etiologies. While increased dopamine synthesis capacity has been proposed to underlie psychotic episodes, dopamine-independent processes are also involved (less responsive to dopamine receptor-blocking medications). The underlying mechanism(s) of the reduction in antipsychotic responsiveness over time, especially after repeated relapses, remain unclear. Despite the consistent evidence of dopamine overactivity and hippocampal volume loss in schizophrenia, few accounts have been provided based on the interactive effect of dopamine on hippocampal synapse plasticity mediating autobiographical memory processes. The present hypothesis builds upon previous works showing the potential effects of dopamine overactivity on hippocampal-mediated neuroplasticity underlying autobiographical memory, alongside known patterns of autobiographical memory dysfunction in psychosis. We propose that spurious autobiographical memory of psychosis (SAMP) produced during active psychosis may be a key mechanism mediating relapses and treatment non-responsiveness. In a hyperdopaminergic state, SAMP is expected to be generated at an increased rate during active psychosis. Similar to other memories, it will undergo assimilation, accommodation, and extinction processes. However, if SAMP fails to integrate with existing memory, a discontinuity in autobiographical memory may result. Inadequate exposure to normalizing experiences and hyposalience due to overmedication or negative symptoms may also impede the resolution of SAMP. Residual SAMP is hypothesized to increase the propensity for relapse and treatment non-responsiveness. Based on recent findings on the role of dopamine in facilitating hippocampal synapse plasticity and autobiographical memory formation, the SAMP hypothesis is consistent with clinical observations of DUP effects, including the repetition of contents in psychotic relapses as well as the emergence of treatment non-responsiveness after repeated relapses. Clinical implications of the hypothesis highlight the importance of minimizing active psychosis, integrating psychosis memory, avoiding over-medication, and fostering normalizing experiences.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci13071069
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2651993-8
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  • 2
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    Rumination as a Transdiagnostic Phenomenon in the 21st Century: The Flow Model of Rumination
    MDPI AG ; 2023
    In:  Brain Sciences Vol. 13, No. 7 ( 2023-07-08), p. 1041-
    Details
    In: Brain Sciences, MDPI AG, Vol. 13, No. 7 ( 2023-07-08), p. 1041-
    Abstract: Rumination and its related mental phenomena share associated impairments in cognition, such as executive functions and attentional processes across different clinical conditions (e.g., in psychotic disorders). In recent decades, however, the notion of rumination has been increasingly narrowed to the “self-focused” type in depressive disorders. A closer review of the literature shows that rumination may be construed as a broader process characterized by repetitive thoughts about certain mental contents that interfere with one’s daily activities, not only limited to those related to “self”. A further examination of the construct of rumination beyond the narrowly focused depressive rumination would help expand intervention opportunities for mental disorders in today’s context. We first review the development of the clinical construct of rumination with regard to its historical roots and its roles in psychopathology. This builds the foundation for the introduction of the “Flow Model of Rumination (FMR)”, which conceptualizes rumination as a disruption of a smooth flow of mental contents in conscious experience that depends on the coordinated interactions between intention, memory, affect, and external events. The conceptual review concludes with a discussion of the impact of rapid technological advances (such as smartphones) on rumination. Particularly in contemporary societies today, a broader consideration of rumination not only from a cognition viewpoint, but also incorporating a human–device interaction perspective, is necessitated. The implications of the FMR in contemporary mental health practice are discussed.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci13071041
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2651993-8
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  • 3
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    Identification of Genetic Variations in the NAD-Related Pathways for Patients with Major Depressive Disorder: A Case-Control Study in Taiwan
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 13 ( 2022-06-23), p. 3622-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 13 ( 2022-06-23), p. 3622-
    Abstract: Background and Objectives: Nicotinamide adenine dinucleotide (NAD) is an important coenzyme in various physiological processes, including sirtuins (SIRTs) and kynurenine pathway (KP). Previous studies have shown that lower NAD levels can be indicative of increased risks of cancer and psychiatric disorders. However, there has been no prior study exploring the link between NAD homeostasis and psychiatric disorders from a genetic perspective. Therefore, we aimed to investigate the association of genetic polymorphism in the pathways of NAD biosynthesis with major depressive disorder (MDD). Methods: A total of 317 patients were included in the case group and were compared with sex-matched control group of 1268 participants (1:4 ratio) from Taiwan Biobank (TWB). All subjects in the control group were over 65 years old, which is well past the average age of onset of MDD. Genomic DNA extracted from patients’ blood buffy coat was analyzed using the Affymetrix TWB array. Full-model tests were conducted for the analysis of single nucleotide polymorphism (SNPs) in all candidate genes. We focused on genes within the NAD-related candidate pathways, including 15 in KP, 12 in nicotinate metabolism, 7 in SIRTs, and 19 in aldehyde dehydrogenases (ALDHs). A total of 508 SNPs were analyzed in this study. After significant SNPs were determined, 5000 genome-wide max(T) permutations were performed in Plink. Finally, we built a predictive model with logistic regression and assessed the interactions of SNPs with the haplotype association tests. Results: We found three SNPs that were significantly associated with MDD in our NAD-related candidate pathways, one within the KP (rs12622574 in ACMSD) and two within the nicotinate metabolism (rs28532698 in BST1 and rs3733593 in CD38). The observed association with MDD was significant in the dominant model of inheritance with marital status, education level, and body mass index (BMI) adjusted as covariates. Lastly, in haplotype analysis, the three associated SNPs consisted of one haploblock in ACMSD, four haploblocks in BST1, and two haploblocks in CD38. Conclusions: This study provides the first evidence that genetic variations involved in NAD homeostasis in the KP and nicotinate metabolism may be associated with the occurrence of MDD.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11133622
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 4
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    An Artificial Intelligence-Enabled ECG Algorithm for the Prediction and Localization of Angiography-Proven Coronary Artery Disease
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 2 ( 2022-02-07), p. 394-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 2 ( 2022-02-07), p. 394-
    Abstract: (1) Background: The role of using artificial intelligence (AI) with electrocardiograms (ECGs) for the diagnosis of significant coronary artery disease (CAD) is unknown. We first tested the hypothesis that using AI to read ECG could identify significant CAD and determine which vessel was obstructed. (2) Methods: We collected ECG data from a multi-center retrospective cohort with patients of significant CAD documented by invasive coronary angiography and control patients in Taiwan from 1 January 2018 to 31 December 2020. (3) Results: We trained convolutional neural networks (CNN) models to identify patients with significant CAD ( 〉 70% stenosis), using the 12,954 ECG from 2303 patients with CAD and 2090 ECG from 1053 patients without CAD. The Marco-average area under the ROC curve (AUC) for detecting CAD was 0.869 for image input CNN model. For detecting individual coronary artery obstruction, the AUC was 0.885 for left anterior descending artery, 0.776 for right coronary artery, and 0.816 for left circumflex artery obstruction, and 1.0 for no coronary artery obstruction. Marco-average AUC increased up to 0.973 if ECG had features of myocardial ischemia. (4) Conclusions: We for the first time show that using the AI-enhanced CNN model to read standard 12-lead ECG permits ECG to serve as a powerful screening tool to identify significant CAD and localize the coronary obstruction. It could be easily implemented in health check-ups with asymptomatic patients and identifying high-risk patients for future coronary events.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10020394
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 5
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    Online Resource
    Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 15 ( 2020-07-31), p. 5513-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 15 ( 2020-07-31), p. 5513-
    Abstract: The COVID-19 pandemic caused by the SARS-CoV-2 virus, overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined three independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cigs led to upregulation of pro-inflammatory cytokines and inflammasome-related genes. Specifically, chemokines including CCL20 and CXCL8 are upregulated in smokers, and CCL5 and CCR1 are upregulated in flavor/nicotine-containing e-cig users. We also found genes implicated in inflammasomes, such as CXCL1, CXCL2, NOD2, and ASC, to be upregulated in smokers and these e-cig users. Vaping flavor and nicotine-less e-cigs, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping may critically exacerbate COVID-19-related inflammation or increase susceptibility to COVID-19.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21155513
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
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    COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation
    MDPI AG ; 2021
    In:  Viruses Vol. 13, No. 6 ( 2021-05-28), p. 1018-
    Details
    In: Viruses, MDPI AG, Vol. 13, No. 6 ( 2021-05-28), p. 1018-
    Abstract: Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v13061018
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2516098-9
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  • 7
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    Online Resource
    Pulmonary Carcinoid Surface Receptor Modulation Using Histone Deacetylase Inhibitors
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 6 ( 2019-06-03), p. 767-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 6 ( 2019-06-03), p. 767-
    Abstract: Pulmonary carcinoids are a type of neuroendocrine tumor (NET) accounting for 1–2% of lung cancer cases. Currently, Positron Emission Tomography (PET)/CT based on the radiolabeled sugar analogue [18F]-FDG is used to diagnose and stage pulmonary carcinoids, but is suboptimal due to low metabolic activity in these tumors. A new techn ique for pulmonary carcinoid imaging, using PET/CT with radiolabeled somatostatin analogs that specifically target somatostatin receptor subtype 2 (SSTR2), is becoming more standard, as many tumors overexpress SSTR2. However, pulmonary carcinoid patients with diminished SSTR2 expression are not eligible for this imaging or any type of SSTR2-specific treatment. We have found that histone deacetylase (HDAC) inhibitors can upregulate the expression of SSTR2 in pulmonary carcinoid cell lines. In this study, we used a non-cytotoxic dose of HDAC inhibitors to induce pulmonary carcinoid SSTR2 expression in which we confirmed in vitro and in vivo. A non-cytotoxic dose of the HDAC inhibitors: thailandepsin A (TDP-A), romidepsin (FK228), suberoylanilide hydroxamic acid (SAHA), AB3, and valproic acid (VPA) were administered to promote SSTR2 expression in pulmonary carcinoid cell lines and xenografts. This SSTR2 upregulation technique using HDAC inhibitors could enhance radiolabeled somatostatin analog-based imaging and the development of potential targeted treatments for pulmonary carcinoid patients with marginal or diminished SSTR2 expression.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11060767
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 8
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    A Useful Combination of Quantitative Ultrashort Echo Time MR Imaging and a Probing Device for Biomechanical Evaluation of Articular Cartilage
    MDPI AG ; 2021
    In:  Biosensors Vol. 11, No. 2 ( 2021-02-17), p. 52-
    Details
    In: Biosensors, MDPI AG, Vol. 11, No. 2 ( 2021-02-17), p. 52-
    Abstract: In this study, we combined quantitative ultrashort echo time (UTE) magnetic resonance (MR) imaging and an investigation by a probing device with tri-axial force sensor to seek correlations with mechanical properties of human patellar cartilage for in situ evaluation of biomechanical properties. Cartilage blocks (15 × 20 × 5 mm3) were dissected from the patella of six donors; 5 mm square regions of interest from the cartilage blocks were imaged using UTE-MR imaging sequences (T2* and magnetization transfer ratio (MTR)), and mechanical properties were measured using a micro indentation device. Then, the vertical reaction force on the cartilage surface was measured while push-probing forward 3 mm with the probing device at a 30° tilt to the horizontal plane. The results showed a positive correlation between stiffness/elastic modulus and each predictor variable (UTE-T2* (r = 0.240 and 0.255, respectively, UTE-MTR (r = 0.378 and 0.379, respectively), and probing device force (r = 0.426 and 0.423, respectively). Furthermore, multiple linear regression analysis showed the combination of the three predictors had stronger correlation (adjusted r2 = 0.314 (stiffness), 0.323 (elastic), respectively). Our results demonstrate the potential for these non- and less- invasive methods for in situ evaluation of the mechanical properties of cartilage tissue.
    Type of Medium: Online Resource
    ISSN: 2079-6374
    URL: Article
    DOI: 10.3390/bios11020052
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662125-3
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  • 9
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    The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 11 ( 2020-11-18), p. 3425-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 11 ( 2020-11-18), p. 3425-
    Abstract: The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host–microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12113425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Synthesis and Biological Evaluation of Hydroxylated Monocarbonyl Curcumin Derivatives as Potential Inducers of Neprilysin Activity
    MDPI AG ; 2021
    In:  Biomedicines Vol. 9, No. 8 ( 2021-08-03), p. 955-
    Details
    In: Biomedicines, MDPI AG, Vol. 9, No. 8 ( 2021-08-03), p. 955-
    Abstract: Background: Alzheimer’s disease (AD) involves impairment of Aβ clearance. Neprilysin (NEP) is the most efficient Aβ peptidase. Enhancement of the activity or expression of NEP may provide a prominent therapeutic strategy against AD. Aims: Ten hydroxylated monocarbonyl curcumin derivatives were designed, synthesized and evaluated for their NEP upregulating potential using sensitive fluorescence-based Aβ digestion and inhibition assays. Results: Compound 4 was the most active one, resulting in a 50% increase in Aβ cleavage activity. Cyclohexanone-bearing derivatives exhibited higher activity enhancement compared to their acetone counterparts. Inhibition experiments with the NEP-specific inhibitor thiorphan resulted in dramatic cleavage reduction. Conclusion: The increased Aβ cleavage activity and the ease of synthesis of 4 renders it an extremely attractive lead compound.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines9080955
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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