Atramacrolodes A-D (1-4), Four Undescribed Eudesmane-type Sesquiterpenes from the Rhizome of Atractylodes macrocephala.

Four undescribed sesquiterpenes, atramacrolodes A-D (1-4), along with six known compounds 5-10 were isolated from the rhizome of Atractylodes macrocephala. Compound 3 possessed a new skeleton based on an unprecedented carton-carton connection. Their structures were determined by UV, IR, HRESIMS, NMR spectra, 13C NMR calculation with DP4+ analysis, and the comparison of experimental and calculated ECD spectra. Compounds 5 and 8 showed protective effects against paracetamol-induced liver cell injury.

Deciphering spatial domains from spatially resolved transcriptomics with Siamese graph autoencoder.

BACKGROUND: Cell clustering is a pivotal aspect of spatial transcriptomics (ST) data analysis as it forms the foundation for subsequent data mining. Recent advances in spatial domain identification have leveraged graph neural network (GNN) approaches in conjunction with spatial transcriptomics data. However, such GNN-based methods suffer from representation collapse, wherein all spatial spots are projected onto a singular representation. Consequently, the discriminative capability of individual representation feature is limited, leading to suboptimal clustering performance. RESULTS: To address this issue, we proposed SGAE, a novel framework for spatial domain identification, incorporating the power of the Siamese graph autoencoder. SGAE mitigates the information correlation at both sample and feature levels, thus improving the representation discrimination. We adapted this framework to ST analysis by constructing a graph based on both gene expression and spatial information. SGAE outperformed alternative methods by its effectiveness in capturing spatial patterns and generating high-quality clusters, as evaluated by the Adjusted Rand Index, Normalized Mutual Information, and Fowlkes-Mallows Index. Moreover, the clustering results derived from SGAE can be further utilized in the identification of 3-dimensional (3D) Drosophila embryonic structure with enhanced accuracy. CONCLUSIONS: Benchmarking results from various ST datasets generated by diverse platforms demonstrate compelling evidence for the effectiveness of SGAE against other ST clustering methods. Specifically, SGAE exhibits potential for extension and application on multislice 3D reconstruction and tissue structure investigation. The source code and a collection of spatial clustering results can be accessed at https://github.com/STOmics/SGAE/.

Identification of Key Genes for Pyroptosis-Induced Salivary Gland Inflammation in Sjogren's Syndrome Based on Microarray Data and Immunohistochemistry Analysis.

Purpose: Sjogren's Syndrome (SS) is a systemic autoimmune disease primarily characterized by dysfunction of the exocrine glands. Research into the etiology and pathogenesis of salivary glands (SG) inflammation of SS is very limited. The aim of this study was to identify potential pyroptosis-related genes in SG inflammation through bioinformatics analysis and validation of the SG in SS. Methods: GSE157159 dataset and GSE159574 dataset were downloaded from Gene Expression Omnibus (GEO). Differentially Expressed Genes (DEGs) analysis was used to screen DEGs from SS and non-SS SG samples. Pyroptosis-related genes were obtained from GeneCards. After intersecting DEGs with pyroptosis-related genes, the pyroptosis-related DEGs in SS were obtained. Subsequently, ClueGO enrichment analysis, Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis, Protein-protein Interaction (PPI), and identification and co-expression analysis of hub genes were performed. Subsequently, we collected SG samples from 17 SS patients and 17 non-SS patients and validated the expression of two hub genes (GZMA, GBP1) and characteristic genes (GSDMD) of pyroptosis through immunohistochemistry. The accuracy of hub genes as biomarkers for predicting SS was evaluated by receiver operating characteristic (ROC) curve. Results: 834 DEGs were selected from the GSE157159 dataset, and a total of 39 pyroptosis-related DEGs were obtained. Functional analysis showed that these DEGs were significantly enriched in some inflammatory signaling pathways. Through the intersection of seven algorithms proposed by CytoHubba and validation using the GSE159574 dataset, 11 hub genes were identified, including IL18, AIM2, CCL5, CD274, GBP1, GBP5, GZMA, GZMB, TLR8, TNFS13B, and ICAM1. Finally, the results of immunohistochemistry showed that GSDMD, GZMA and GBP1 were all significantly highly expressed in SG from SS. And ROC analysis showed a high combined diagnostic value of the 3 genes (AUC=0.8858). Conclusion: Our study revealed enhanced levels of pyroptosis in the SS. GZMA and GBP1 were identified as candidate genes for pyroptosis-induced inflammation of the SG in SS, which may be used as biomarkers or potential therapeutic targets for SS.

Network pharmacology identifies the inhibitory effect of Yiqiyangyinquyu prescription on salivary gland inflammation in Sjögren's syndrome.

This study aimed to explore the mode of action of Yiqiyangyinquyu prescription (YP) against Sjögren's syndrome (SS) by combining network pharmacology with molecular docking techniques. YP's active components and target proteins were identified using the BATMAN-traditional Chinese medicine database. Concurrently, targets associated with SS were extracted from databases, including Genecards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The standard targets were then imported into the STRING database to construct a protein-protein interaction network. We then conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, which were succeeded by molecular docking studies to validate core active components and key targets. Finally, in vitro experiments and molecular dynamics simulation were conducted to substantiate the therapeutic efficacy of YP in treating SS. A total of 206 intersection targets and 46 active compounds were identified. Gene ontology analysis unveiled that YP targets were primarily enriched in cellular responses to chemical stress, inflammation, and cell proliferation. Key enriched signaling pathways encompassed the interleukin 17, hypoxia-inducible factor-1, tumor necrosis factor (TNF-α), and advanced glycation end products-receptor for AGEs (AGE-RAGE) signaling pathways. Molecular docking results demonstrated high-affinity between neotanshinone C, tanshiquinone B, miltionone I, TNF-α, interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). Noteworthy, TNF-α, considered the most important gene in YP against SS, binds to YP most stably, which was further validated by molecular dynamics simulation. In vitro experiments confirmed YP's capacity to reduce TNF-α, IL-1ß, and IL-6 expression, effectively alleviating SS-related inflammation. YP demonstrated a significant anti-inflammatory effect by suppressing inflammatory cytokines (TNF-α, IL-6, and IL-1ß), providing experimental evidence for its clinical application in treating SS.

Associations of 10 trace element levels in the whole blood with risk of three types of obesity in the elderly.

BACKGROUND: Currently, over 2 billion people worldwide suffer from obesity, which poses a serious health risk. More and more attention is being given to the effects of trace elements on obesity in recent years. Synergistic or antagonistic interactions among these elements can adversely or positively impact human health. However, epidemiological evidence on the relationship between trace element exposure levels and obesity has been inconclusive. METHODS: Baseline data of 994 participants from the Cohort of Elderly Health and Environment Controllable Factors were used in the present study. ICP-MS was used to measure the concentrations of 10 trace elements in the whole blood of the older population. Binary logistic regression, restricted cubic splines (RCS) models, and Bayesian kernel machine regression (BKMR) models were employed to assess single, nonlinear, and mixed relationships between 10 trace element levels and three types of obesity based on body mass index (BMI), waist circumference (WC), and body fat percentage (BFP) in the elderly. RESULTS: Based on BMI, WC and BFP, 51.8% of the included old population were defined as general overweight/obesity, 67.1% as abdominal obesity, and 36.2% as having slightly high/high BFP. After multivariable adjustment, compared with the lowest tertile, the highest tertile of blood selenium (Se) concentration was associated with an increased risk of all three types of obesity. Additionally, compared with the lowest tertile, higher tertiles of strontium (Sr) concentrations were associated with a lower risk of general overweight/obesity and having slightly high/high BFP, and the highest tertile of barium (Ba) was associated with a lower risk of having slightly high BFP, while higher tertiles of arsenic (As) concentrations were associated with an increased risk of having slightly high/high BFP, and the highest tertile of manganese (Mn) was associated with a higher risk of abdominal obesity. BKMR analyses showed a strong linear positive association between Se and three types of obesity. Higher blood levels of trace element mixture were associated with increased obesity risks in a dose-response pattern, with Se having the highest value of the posterior inclusion probability (PIP) within the mixture. CONCLUSIONS: In this study, we found higher Se levels were associated with an elevated risk of obesity and high levels of Ba, Pb and Cr were associated with a decreased risk of obesity. Studies with larger samples are needed to confirm these findings.

Integrated Analysis Identifies Upregulated SAMD9L as a Potential Biomarker Correlating with the Severity of Primary Sjögren's Syndrome.

Background: Primary Sjögren's syndrome (pSS) is an autoimmune disease with lymphocytic infiltration of the salivary and lachrymal glands, whose present disease-specific objective indicators are few and have shortcomings that should be addressed. An integrated analysis of sequencing data from different cohorts has the potential to unveil novel biomarkers in pSS. Methods: We identified 3 GEO datasets, including gene expression data from minor salivary gland (MSG) biopsy samples of 49 patients with pSS and 31 non-pSS and whole blood cells of 30 pSS patients and 30 healthy controls (HCs). Differentially expressed genes (DEGs) involved in pSS were identified from these datasets. Function Enrichment Analyses of common upregulated DEGs and PPI (protein-protein interaction) networks were performed. Furthermore, we have carried out further analysis of these DEGs to explore their potential clinical significance and diagnostic efficacy as a biomarker for pSS. Sterile Alpha Motif Domain Containing 9 Like (SAMD9L), one of the DEGs, has been identified as a promising candidate biomarker that correlates with the severity of pSS. This has been validated by analyzing local clinical samples from 30 pSS and non-pSS patients' MSG biopsies, as well as serum samples of 18 pSS and HC individuals. Finally, we performed correlation analysis to understand the relationship between SAMD9L and infiltrated immune cells. Results: We identified 10 common highly expressed DEGs in pSS of different tissues. These genes were mainly involved in virus infection-related pathways and inferno-related pathways. GEO data and our clinical data showed that SAMD9L increases with disease severity. Public and local cohorts showed that SAMD9L has high diagnostic performance (AUC=0.845-0.867) as a biomarker, and its AUC was comparable to the Focus score when combined with RF or SSA. Conclusion: Up-regulated SAMD9L may serve as a promising novel pSS diagnostic biomarker and have potential value for evaluating the severity of pSS.

Genome-wide DNA methylation sequencing reveals epigenetic features and potential biomarkers of Sjögren syndrome.

AIM: Sjögren syndrome (SS) is a slowly progressive, inflammatory, autoimmune disease. The aim of this study was to construct the DNA methylation profiles of whole blood of SS patients and healthy controls (HC), and to explore the role of differentially methylated genes in the pathogenesis of the disease. METHODS: Whole-genome bisulfite sequencing was performed on three SS patients and four HC. The biological function of genes associated with differentially methylated regions (DMRs) was investigated using Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, using network-based key driver analysis (KDA) to find KDA genes. In clinical samples of SS patients and controls, the expression levels of KDA genes were validated by quantitative real-time polymerase chain reaction and immunohistochemical analysis. Moreover, the diagnostic value of KDA genes for SS was confirmed using receiver operating characteristic curves. RESULTS: We identified 322 DMRs, annotated as 162 associated genes. Six genes were selected via the number of networks of KDA genes. Differential expression of genes such as human leukocyte antigen (HLA) class I, ADAR, and OAS2 was observed in patients' peripheral blood mononuclear cells and the minor salivary glands, which can be used as potential diagnostic biomarkers for SS. CONCLUSION: Clinical sample validation suggested that HLA class I, ADAR, and OAS2 might play a role in the development of SS. Our study shows epigenetic regulatory mechanisms and potential disease markers associated with SS, which in turn will enable us to identify new therapeutic targets.

Identification of key genes in salivary gland in Sjögren's syndrome complicated with Hashimoto thyroiditis: Common pathogenesis and potential diagnostic markers.

The coexistence of Sjögren's syndrome (SS) and Hashimoto thyroiditis (HT) has been confirmed, but the common mechanism of its co-occurrence remains unknown. This study aims to further explore the underlying mechanism and biomarkers for the co-occurrence of SS and HT. The Gene Expression Omnibus databases were used to obtain gene expression profiles for SS (GSE127952 and GSE23117) and HT (GSE29315 and GSE138198). Following identifying SS and HT's shared differentially expressed genes, functional annotation, protein-protein interaction network creation, and module assembly were performed to discover hub genes. H&E staining and immunohistochemistry were performed to validate the expression of the hub genes in salivary glands. Finally, the receiver operating characteristic (ROC) curve was utilized to assess the discrimination of the hub genes as biomarkers in predicting SS, this study applied CIBERSORTx to analyze the immune infiltration in SS and HT in addition. A total of 48 common differentially expressed genes (48 upregulated genes and 0 downregulated genes) were chosen for further investigation. We analyzed the expression and function of PTPRC, CD69, IKZF1, and lymphocyte cytosolic protein 2 via H&E, immunohistochemistry, and ROC analysis. The 4 hub genes were mainly enriched in the T-cell receptor signaling pathway. We then evaluated and verified the diagnosis value of 4 hub genes in clinical minor labial gland biopsy of SS with HT, SS without HT, and non-SS. ROC analysis revealed that the 4 hub genes had a strong diagnostic value. Our study showed the common pathogenesis of SS and HT. These hub genes and diagnostic models may put forward some new insights for diagnosing and treating SS complicated with HT.

Serum Metabolomics Analysis of Skin-Involved Systemic Lupus Erythematosus: Association of Anti-SSA Antibodies with Photosensitivity.

Purpose: Systemic lupus erythematosus is a heterogeneous autoimmune disease in which skin involvement is a common manifestation. It is currently thought that the photosensitivity of SLE skin involvement is associated with anti-SSA antibodies. This study aimed to expand the current state of knowledge surrounding the molecular pathophysiology of SLE skin photosensitivity through Serum metabolomics analysis. Patients and Methods: The serum metabolites of 23 cases of skin-involved SLE (SI) group, 14 cases of no SI (NSI) group, and 30 cases of healthy controls (HC) were analyzed by using UPLC-MS/MS technology, and subgroup analysis was performed according to the expression of anti-SSA antibodies in SI. MetaboAnalyst 5.0 was used for enrichment analysis and ROC curve construction, identifying serum metabolic markers of skin-involved SLE associated with anti-SSA antibodies. Results: We identified several metabolites and metabolic pathways associated with SLE photosensitivity. Two metabolites, SM (d18:1/24:0) and gamma-CEHC can distinguish between anti-SSA antibody-positive and negative SI, with AUC of 0.829 and 0.806. These two photosensitization-related substances may be potential markers of skin involvement in SLE associated with anti-SSA antibody. Conclusion: This study provides new insights into the pathogenesis of SI patients, and provides a new molecular biological basis for the association between anti-SSA antibodies and skin photoallergic manifestations of SLE.

Whole-genome bisulfite sequencing identified the key role of the Src family tyrosine kinases and related genes in systemic lupus erythematosus.

BACKGROUND: As a multisystemic autoimmune illness, the basic mechanisms behind the pathophysiology of systemic lupus erythematosus (SLE) remain poorly understood. OBJECTIVE: We aimed to investigate the possible significance of SLE's DNA methylation and gain further insight into potential SLE-related biomarkers and therapeutic targets. METHODS: We used whole genome bisulfite sequencing (WGBS) method to analyze DNA methylation in 4 SLE patients and 4 healthy people. RESULTS: 702 differentially methylated regions (DMRs) were identified, and 480 DMR-associated genes were annotated. We found the majority of the DMR-associated elements were enriched in repeat and gene bodies. The top 10 hub genes identified were LCK, FYB, PTK2B, LYN, CTNNB1, MAPK1, GNAQ, PRKCA, ABL1, and CD247. Compared to the control group, LCK and PTK2B had considerably decreased levels of mRNA expression in the SLE group. Receiver operating characteristic (ROC) curve suggested that LCK and PTK2B may be potential candidate biomarkers to predict SLE. CONCLUSIONS: Our study improved comprehension of the DNA methylation patterns of SLE and identified potential biomarkers and therapeutic targets for SLE.

Lipidomics Changes in a Murine Model of Neuropsychiatric Lupus.

Purpose: Neuropsychiatric lupus (NPSLE) is one of the important manifestations of systemic lupus erythematosus. Previous studies mainly focused on the disruption of the blood-brain barrier and the production of brain-reactive autoantibodies, However, there is no comprehensive lipidomic analysis in NPSLE. Therefore, this research evaluated the lipidomic analysis in the hippocampus and liver of NPSLE mice with mood disorders, to explore the influence of the liver-brain axis on this disease. Methods: MRL/lpr mice and MRL/mpj mice were respectively used as NPSLE and control groups. Behavioral tests and systemic disease characteristics of mice were assessed at the age of 18 weeks. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) was used for lipid metabolite determination. Multivariate statistical analysis was used to identify lipid metabolites that were differentially expressed in two groups. Results: Our results showed that 355 and 405 lipid metabolites were differentially expressed between the NPSLE and control groups in the hippocampus and liver. According to the pathway enrichment analysis, several pathways were affected, and the glycerophospholipid metabolism pathway was most relevant to the mouse's depressive behavior. Conclusion: Based on UPLC-MS/MS, the results provide evidence for how the liver-brain axis affects NPSLE and improve the understanding of NPSLE pathogenesis.

Trends in Research of Prenatal Stress From 2011 to 2021: A Bibliometric Study.

Background: Maternal stress during pregnancy can raise the risk of mental disorders in offspring. The continuous emergence of clinical concepts and the introduction of new technologies are great challenges. In this study, through bibliometric analysis, the research trends and hotspots on prenatal stress (PS) were explored to comprehend clinical treatments and recommend future scientific research directions. Methods: Studies on PS published on the Web of Science Core Collection (WoSCC) database between 2011 and 2021 were reviewed. Bibliometric analysis was conducted according to the number of publications, keywords, journals, citations, affiliations, and countries. With the data collected from the WoSCC, visualization of geographic distribution; clustering analysis of keywords, affiliations, and authors; and descriptive analysis and review of PS were carried out. Results: A total of 7,087 articles published in 2011-2021 were retrieved. During this period, the number of publications increased. Psychoneuroendocrinology is the leading journal on PS. The largest contributor was the United States. The University of California system was leading among institutions conducting relevant research. Wang H, King S, and Tain YL were scholars with significant contributions. Hotspots were classified into four clusters, namely, pregnancy, prenatal stress, oxidative stress, and growth. Conclusion: The number of studies on PS increased. Journals, countries, institutions, researchers with the most contributions, and most cited articles worldwide were extracted. Studies have mostly concentrated on treating diseases, the application of new technologies, and the analysis of epidemiological characteristics. Multidisciplinary integration is becoming the focus of current development. Epigenetics is increasingly used in studies on PS. Thus, it constitutes a solid foundation for future clinical medical and scientific research.

Effects of RhoA on depression-like behavior in prenatally stressed offspring rats.

Depression is a common mental disease that can lead to suicide when severe. Exposure to prenatal stress (PS) can lead to depression-like behavior in offspring, but the mechanism is unclear. RhoA (Ras homology family member A) plays an important role in stress-induced changes in synaptic plasticity, participating in the development of depression by activating the downstream effector ROCK (Rho-associated protein kinase). This study explored the influence in the expression of RhoA and downstream molecules ROCK1/2 in prenatally stressed rats, and the effect of RhoA inhibitor simvastatin on depression-like behavior induced by PS. Depression-like behavior in offspring was detected by sucrose preference test, forced swimming test, and open-field test. The mRNA and protein expression of RhoA and ROCK1/2 in the hippocampus and prefrontal cortex of offspring rats were detected by qRT-PCR and western blotting, respectively. Our results showed that PS causes depression-like behavior in offspring rats, associated with elevated expression of RhoA, ROCK1/2 in the hippocampus and prefrontal cortex. After administration of simvastatin to PS rats, the expression of RhoA and ROCK2 was significantly reduced, alleviating depression-like behavior. Our study demonstrated that RhoA participates in the depression-like behavior in prenatally stressed offspring rats, which may be a potential target for antidepressant therapy.

Application of Smart Healthcare in LTCI, Outpatient Mutual-Aid Guarantee Mechanism, and Sustainability of Medical Insurance Fund for Urban Employees.

With the aggravation of population aging and the increase of life expectancy, long-term care insurance (LTCI) system has been established to meet the medical and long-term care needs of the increasing elderly population. In China, LTCI system is currently not a stand-alone insurance, but it is attached to the national basic medical insurance fund for urban employees (MIUE). As a result, the expenditure of LTCI is a part of the expenditure of the MIUE, which has an impact on the sustainability of the MIUE. By modeling the income and expenditure of MIUE, especially including the expenditure of LTCI, this study optimized an LTCI system with a higher individual out-of-pocket payment ratio of LTCI and implementation of the outpatient mutual-aid guarantee mechanism (OMAGM), which could improve the sustainability of the MIUE. The study also reveals the following: (i) solely increasing individual out-of-pocket payment ratio of LTCI to 20%-50% can only postpone the deficit on Social Pooling Accounts (SPAs) by 1 or 2 years, and the effect is very limited. (ii) Besides a higher individual out-of-pocket payment ratio, further implementation of a partial OMAGM from 2022 will postpone the deficit on SPAs by 7-9 years, and the implementation of a complete OMAGM from 2022 will postpone the deficit by 14-18 years. Accordingly, China should implement OMAGM as soon as possible to enhance the solvency of MIUE fund, and, in the long run, an independent LTCI scheme should be established to ensure the stability and sustainability of the LTCI fund and the MIUE fund.

Cross-fostering alleviates depression-like behavior mediated by EAAT2 and SNARE complex in prenatal stress offspring rat.

Previous studies have shown that prenatal stress (PS) can potentially contribute to depression-like behavior in offspring and that this effect may be moderated by cross-fostering. However, the underlying mechanism of this effect remains to be determined. This study aimed to determine the effect of cross-fostering on the expression of EAAT2 and the SNARE complex in the hippocampus and the prefrontal cortex of PS offspring rats and to demonstrate functional effects on depression-like behavior. The impacts of cross-fostering were functionally assessed using the sucrose preference test (SPT), the forced swimming test (FST) and the elevated plus maze (EPM). Quantitative real-time PCR was used to determine changes in the expression of EAAT2 and SNAREs mRNA in the hippocampus and the prefrontal cortex of offspring rats. PS offspring rats showed significantly decreased sucrose preference and prolonged immobility time, while cross-fostering effectively increased sucrose preference and shorten the time of immobility. The expression of EAAT2 mRNA in PS offspring rats was markedly reduced, whilst the core mRNA expression of the SNARE complex increased. Our results provide strong evidence demonstrating that cross-fostering can alleviate depression-like behavior and regulate the abnormal expression levels of EAAT2 mRNA and SNARE complex in the hippocampus and the prefrontal cortex of PS offspring rats. Our findings contribute to further understanding of the pathogenesis of PS-induced depression and may help to inform the future development of novel treatment approaches.

Molecular mechanism of Epicedium treatment for depression based on network pharmacology and molecular docking technology.

BACKGROUND: Increasing attention has been paid to the effect of Epimedium on the nervous system, particularly anti-depression function. In the present study, we applied network pharmacology to introduce a testable hypothesis on the multi-target mechanisms of Epicedium against depression. METHODS: By reconstructing the network of protein-protein interaction and drug-component-target, we predicted the key protein targets of Epicedium for the treatment of depression. Then, through molecular docking, the interaction of the main active components of Epicedium and predicted candidate targets were verified. RESULTS: Nineteen active compounds were selected from Epicedium. There were 200 targets associated with Epicedium and 537 targets related to depression. The key targets of Epicedium for treating depression were IL6, VEGFA, AKT1, and EGF. According to gene ontology functional enrichment analysis, 22 items of biological process (BP), 13 items of cell composition (CC) and 9 items of molecular function (MF) were obtained. A total of 56 signaling pathways (P < 0.05) were identified by Kyoto Encyclopedia of Genes and Genomes analysis, mainly involving depression-related pathways such as dopaminergic synapse, TNF signaling pathway, and prolactin signaling pathway. The results of molecular docking showed that the most important activity components, including luteoklin, quercetin and kaempferol, were well combined with the key targets. CONCLUSIONS: Luteoklin, quercetin, kaempferol and other active compounds in Epicedium can regulate multiple signaling pathways and targets such as IL6, AKT1, and EGF, therefore playing therapeutic roles in depression.

CRTC1 signaling involvement in depression-like behavior of prenatally stressed offspring rat.

A large body of literature has demonstrated that prenatal stress (PS) can induce depression-like behavior in the offspring. However, the underlying mechanism remains largely unknown. CREB-regulated transcriptional coactivator 1(CRTC1) has recently been shown to involve in mood regulation. This research aims to investigate whether CRTC1 signaling was involved in the depression-like behavior of prenatally stressed offspring rats. Sucrose preference test (SPT), forced swimming test (FST) and open field test (OFT) were adopted to test the depression-like behavior in the male offspring rats, and CRTC1 signaling was measured. The results showed that there were significantly reduced sucrose intake in SPT and prolonged immobility time in FST in PS-exposure offspring rats. It was also found decreased levels of total CRTC1, nuclear CRTC1, calcineurin, brain-derived neurotrophic factor (BDNF) and c-fos, but increased cytoplasmic p-CRTC1 in the hippocampus (HIP) and prefrontal cortex (PFC) of the offspring rats. Furthermore, the mRNA level of CRTC1, calcineurin, BDNF, c-fos were down-regulated. Abnormal expression of CRTC1 signaling could be alleviated by fluoxetine treatment. In conclusion, our research indicated that the aberration of CRTC1 expression and/or phosphorylation activity might play a vital role in PS-induced depression-like behavior of offspring rats.

Effect of borneol as a penetration enhancer on brain targeting of nanoliposomes: facilitate direct delivery to neurons.

AIM: This study is aimed to evaluate borneol as a penetration enhancer to improve brain target of nanoliposome. MATERIALS & METHODS: Effects of borneol on pharmacokinetics, targeting efficiency, brain subareas distribution and neuron-targeting level and pathway were studied by fluorescence spectrophotometry and immunofluorescence. RESULTS: Borneol did not influence physicochemical property of doxorubicin hydrochloride nanoliposome (Dox-nanoLips). Co-administration of Dox-nanoLips with borneol elevated brain-target efficiency due to selective distribution increase in the cerebral cortex and hippocampus without difference in contralateral hemisphere. Borneol improved neuronal-targeting level of Dox-nanoLips in the cortex, CA3 and dentate gyrus regions via opening tight junctions of blood-brain barrier and then bypassing astrocyte. CONCLUSION: Borneol is potential to be a promising penetration enhancer for nanocarrier to target neurons.