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1.
Alpha Psychiatry ; 25(1): 9-14, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38799487

ABSTRACT

Schizophrenia is a severe mental disorder with a neurodevelopmental origin. Although schizophrenia results from changes in the brain, the underlying biological mechanisms are unknown. Transcriptomics studies quantitative expression changes or qualitative changes of all genes and isoforms, providing a more meaningful biological insight. Magnetic resonance imaging (MRI) techniques play roles in revealing brain structure and function. We give a narrative focused review on the current transcriptome combined with MRI studies related to schizophrenia and summarize the research methodology and content of these studies to identify the research commonalities as well as the implications for future research, in an attempt to provide new insights into the mechanism, clinical diagnosis, and treatments of schizophrenia.

2.
Nat Commun ; 15(1): 2038, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38448448

ABSTRACT

Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.


Subject(s)
Cicatrix, Hypertrophic , Humans , Animals , Female , Mice , Rabbits , Cicatrix, Hypertrophic/drug therapy , Reactive Oxygen Species , Biological Availability , Cell Differentiation , Matrix Metalloproteinases
3.
J Colloid Interface Sci ; 663: 1074-1086, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38331692

ABSTRACT

Drug-resistant biofilm infection is an extremely serious clinical problem, that easily leads to failure of antibiotic treatment. Although gold nanoparticles (AuNPs) as photothermal agents have been widely used in biofilm eradication, there are still challenges to be addressed, such as insignificantly redshifted absorption and slow assembly process of aggregated AuNPs. Herein, we developed an acidity-activated dispersion-to-aggregation transition to enhance the accumulation of self-complementary zwitterionic peptide-decorated AuNPs for photothermal eradication of drug-resistant biofilm infections. AuNPs were decorated with self-complementary zwitterionic peptides (ZP1 and ZP2) coupled with pH-sensitive anhydride (DMA) and pH-insensitive anhydride (SA), respectively. ZP2-decorated AuNPs with DMA modification (AuNP@ZP2(DMA)) exhibited prolonged blood circulation and enhanced accumulation in acidic biofilm microenvironment. Moreover, the electrostatic attraction between self-complementary ligands drove AuNPs to form closely packed aggregates with strong near-infrared absorption, leading to in vivo photoacoustic imaging ability and photothermal effect against drug-resistant bacteria and fungus, as well as microbial biofilms. AuNP@ZP2(DMA) with longer charge domains and a polyethylene glycol oligomer spacer showed greater photothermal antimicrobial and biofilm resistance in vitro and in vivo. This study develops an innovative acidity-activated AuNP photothermal agent, which provides an effective approach for treatment of biofilm infections.


Subject(s)
Gold , Metal Nanoparticles , Gold/pharmacology , Gold/chemistry , Metal Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Biofilms , Anhydrides/pharmacology
4.
Heliyon ; 10(4): e25915, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38404811

ABSTRACT

Cognitive impairments in schizophrenia are pivotal clinical issues that need to be solved urgently. However, the mechanism remains unknown. It has been suggested that cognitive impairments in schizophrenia are associated with connectome damage, and are especially relevant to the disrupted hub nodes in the frontal and parietal lobes. Activating the dorsolateral prefrontal cortex (DLPFC) via repetitive transcranial magnetic stimulation (rTMS) could result in improved cognition. Based on several previous magnetic resonance imaging (MRI) studies on schizophrenia, we found that the first-episode patients showed connectome damage, as well as abnormal activation and connectivity of the DLPFC and inferior parietal lobule (IPL). Accordingly, we proposed that DLPFC-IPL pathway destruction might mediate connectome damage of cognitive impairments in schizophrenia. In the meantime, with the help of multimodal MRI and noninvasive neuromodulation tool, we may not only validate the hypothesis, but also find IPL as the potential intervention target for cognitive impairments in schizophrenia.

5.
BMC Med ; 21(1): 250, 2023 07 10.
Article in English | MEDLINE | ID: mdl-37424013

ABSTRACT

BACKGROUND: Inflammation has been implicated in the pathology of schizophrenia and may cause neuronal cell death and dendrite loss. Neuroimaging studies have highlighted longitudinal brain structural changes in patients with schizophrenia, yet it is unclear whether this is related to inflammation. We aim to address this question, by relating brain structural changes with the transcriptional profile of inflammation markers in the early stage of schizophrenia. METHODS: Thirty-eight patients with first-episode schizophrenia and 51 healthy controls were included. High-resolution T1-weighted magnetic resonance imaging (MRI) and clinical assessments were performed at baseline and 2 ~ 6 months follow-up for all subjects. Changes in the brain structure were analyzed using surface-based morphological analysis and correlated with the expression of immune cells-related gene sets of interest reported by previous reviews. Transcriptional data were retrieved from the Allen Human Brain Atlas. Furthermore, we examined the brain structural changes and peripheral inflammation markers in association with behavioral symptoms and cognitive functioning in patients. RESULTS: Patients exhibited accelerated cortical thickness decrease in the left frontal cortices, less decrease or an increase in the superior parietal lobule and right lateral occipital lobe, and increased volume in the bilateral pallidum, compared with controls. Changes in cortical thickness correlated with the transcriptional level of monocyte across cortical regions in patients (r = 0.54, p < 0.01), but not in controls (r = - 0.05, p = 0.76). In addition, cortical thickness change in the left superior parietal lobule positively correlated with changes in digital span-backward test scores in patients. CONCLUSIONS: Patients with schizophrenia exhibit regional-specific cortical thickness changes in the prefrontal and parietooccipital cortices, which is related to their cognitive impairment. Inflammation may be an important factor contributing to cortical thinning in first-episode schizophrenia. Our findings suggest that the immunity-brain-behavior association may play a crucial role in the pathogenesis of schizophrenia.


Subject(s)
Schizophrenia , Humans , Schizophrenia/diagnostic imaging , Schizophrenia/genetics , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/pathology , Cognition , Cerebral Cortex/pathology
6.
BMC Psychiatry ; 23(1): 526, 2023 07 21.
Article in English | MEDLINE | ID: mdl-37479996

ABSTRACT

BACKGROUND: Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. METHODS: 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects' cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. RESULTS: Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = - 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. CONCLUSION: Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.


Subject(s)
Cognitive Dysfunction , Schizophrenia , Adult , Humans , Cognitive Dysfunction/complications , Cross-Sectional Studies , Diacylglycerol Kinase , Parietal Lobe , Schizophrenia/complications
7.
Front Psychiatry ; 14: 1185471, 2023.
Article in English | MEDLINE | ID: mdl-37383618

ABSTRACT

Major psychiatric disorders create a significant public health burden, and mental disorders such as major depressive disorder, bipolar disorder, and schizophrenia are major contributors to the national disease burden. The search for biomarkers has been a leading endeavor in the field of biological psychiatry in recent decades. And the application of cross-scale and multi-omics approaches combining genes and imaging in major psychiatric studies has facilitated the elucidation of gene-related pathogenesis and the exploration of potential biomarkers. In this article, we summarize the results of using combined transcriptomics and magnetic resonance imaging to understand structural and functional brain changes associated with major psychiatric disorders in the last decade, demonstrating the neurobiological mechanisms of genetically related structural and functional brain alterations in multiple directions, and providing new avenues for the development of quantifiable objective biomarkers, as well as clinical diagnostic and prognostic indicators.

8.
Psychoradiology ; 3: kkad019, 2023.
Article in English | MEDLINE | ID: mdl-38666113

ABSTRACT

Catatonia is a psychomotor syndrome that can occur in a broad spectrum of brain disorders, including schizophrenia. Current findings suggest that the neurobiological process underlying catatonia symptoms in schizophrenia is poorly understood. However, emerging neuroimaging studies in catatonia patients have indicated that a disruption in anatomical connectivity of the cortico-striatal-cerebellar system is part of the neurobiology of catatonia, which could serve as a target of neurostimulation such as electroconvulsive therapy and repetitive transcranial magnetic stimulation.

10.
J Integr Neurosci ; 21(5): 139, 2022 Jul 27.
Article in English | MEDLINE | ID: mdl-36137953

ABSTRACT

As a non-invasive detection method and an advanced imaging method, magnetic resonance imaging (MRI) has been widely used in the research of schizophrenia. Although a large number of neuroimaging studies have confirmed that MRI can display abnormal brain phenotypes in patients with schizophrenia, no valid uniform standard has been established for its clinical application. On the basis of previous evidence, we argue that MRI is an important tool throughout the whole clinical course of schizophrenia. The purpose of this commentary is to systematically describe the role of MRI in schizophrenia and to provide references for its clinical application.


Subject(s)
Schizophrenia , Brain/diagnostic imaging , Brain/pathology , Humans , Magnetic Resonance Imaging/methods , Neuroimaging/methods , Schizophrenia/diagnostic imaging
11.
Front Neurosci ; 16: 912665, 2022.
Article in English | MEDLINE | ID: mdl-35615271

ABSTRACT

Background and Purpose: The proportion of patients with somatic diseases associated with anxiety is increasing each year, and pulmonary nodules have become a non-negligible cause of anxiety, the mechanism of which is unclear. The study focus on the cerebral blood flow (CBF) of anxiety in patients with pulmonary nodules to explore the cerebral perfusion pattern of anxiety associated with pulmonary nodules, blood perfusion status and mode of pulmonary nodule induced anxiety state. Materials and Methods: Patients with unconfirmed pulmonary nodules were evaluated by Hamilton Anxiety Scale (HAMA). The total score > 14 was defined as anxiety group, and the total score ≤ 14 points was defined as non-anxiety group. A total of 38 patients were enrolled, of which 19 patients were the anxiety group and 19 were the non-anxiety group. All subjects underwent arterial spin labeling imaging using a 3.0 T MRI. A two-sample t-test was performed to compare the CBF between the two groups. The CBF was extracted in brain regions with difference, and Spearman correlation was used to analyze the correlation between CBF and HAMA scores; ROC was used to analyze the performance of CBF to distinguish between the anxiety group and the non-anxiety group. Results: The CBF in the right insula/Heschl's cortex of the anxiety group decreased (cluster = 109, peak t = 4.124, and P < 0.001), and the CBF in the right postcentral gyrus increased (cluster = 53, peak t = -3.912, and P < 0.001) in the anxiety group. But there was no correlation between CBF and HAMA score. The ROC analysis of the CBF of the right insula/Heschl's cortex showed that the AUC was 0.856 (95%CI, 0.729, 0.983; P < 0.001), the optimal cutoff value of the CBF was 50.899, with the sensitivity of 0.895, and specificity of 0.789. The ROC analysis of CBF in the right postcentral gyrus showed that the AUC was 0.845 (95%CI, 0.718, 0.972; P < 0.001), the optimal cutoff value of CBF was 43.595, with the sensitivity of 0.737, and specificity of 0.842. Conclusion: The CBF of the right insula/Heschl's cortex decreased and the CBF of the right postcentral gyrus increased in patients with pulmonary nodules under anxiety state, and the CBF of the aforementioned brain regions can accurately distinguish the anxiety group from the non-anxiety group.

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