Health Control Group Research Articles

Potential different immune phenotypes of macrophages in oral lichen planus by integrating immunofluorescence double staining and single-cell RNA sequencing

Background/purposeOral lichen planus (OLP) is a chronic inflammatory disease with obscure etiopathogenesis. Macrophages play an important role in interaction between innate and adaptive immunity. This study aimed to investigate the macrophage phenotypes and obtain more comprehensive gene characteristics of macrophages in OLP. Materials and methodsDouble cluster of differentiation (CD) 68/CD86 and CD68/CD206 immunofluorescence staining was conducted in 11 biopsy-proven OLP tissue samples and 5 health control (HC) to represent M1 and M2 macrophages, respectively. The number of positively stained cells was manually counted, and the density was calculated. Furtherly, OLP single-cell dataset GSE211630 was downloaded from Gene Expression Omnibus. Gene characteristics and functional analysis of the macrophages were elucidated. ResultsIn the OLP group, the densities of M1 (P < 0.001), M2 macrophages (P < 0.001) and M1/M2 ratio (P = 0.001) were significantly higher than those in HC group. Single-cell RNA sequencing revealed that proportions of CXCL10 macrophages (P = 0.003), IL1B/MMP19 macrophages (P < 0.001) were increased in OLP tissues compared with those in HC. Macrophages in OLP tissues had a stronger ability to cell chemotaxis, positive regulation of cell adhesion and antigen processing and presentation. Functional analysis revealed macrophages in OLP tissues could interact with multiple immune cells, and multiple signaling pathways were associated with macrophages in OLP. ConclusionA pro-inflammatory status of macrophages with different gene characteristics was found in the microenvironment of OLP by integrating immunofluorescence double staining and single-cell RNA sequencing, which provided a potential target for clinical treatment of OLP.

In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures from HBV-Associated Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC), being ranked as the top fifth most prevalent cancer globally, poses a significant health challenge, with a considerable mortality rate. Hepatitis B virus (HBV) infection stands as the primary factor contributing to HCC, presenting substantial challenges in its treatment. This study aimed to identify lactic acid bacteria (LAB) with anti-HBV properties and evaluate their impact on the intestinal flora in HBV-associated HCC. Initially, two LAB strains, Levilactobacillus brevis SR52-2 (L. brevis SR52-2) and LeviLactobacillus delbrueckii subsp. bulgaicus Q80 (L. delbrueckii Q80), exhibiting anti-HBV effects, were screened in vitro from a pool of 498 LAB strains through cell experiments, with extracellular expression levels of 0.58 ± 0.05 and 0.65 ± 0.03, respectively. These strains exhibited the capability of inhibiting the expression of HBeAg and HBsAg. Subsequent in vitro fermentation, conducted under simulated anaerobic conditions mimicking the colon environment, revealed a decrease in pH levels in both the health control (HC) and HCC groups influenced by LAB, with a more pronounced effect observed in the HC group. Additionally, the density of total short-chain fatty acids (SCFAs) significantly increased (p < 0.05) in the HCC group. Analysis of 16S rRNA highlighted differences in the gut microbiota (GM) community structure in cultures treated with L. brevis SR52-2 and L. delbrueckii Q80. Fecal microflora in normal samples exhibited greater diversity compared to HBV-HCC samples. The HCC group treated with LAB showed a significant increase in the abundance of the phyla Firmicutes, Bacteroidetes and Actinobacteria, while Proteobacteria significantly decreased compared to the untreated HCC group after 48 h. In conclusion, the findings indicate that LAB, specifically L. brevis SR52-2 and L. delbrueckii Q80, possessing antiviral properties, contribute to an improvement in gastrointestinal health.

Galectin-9 in synergy with NF-κB inhibition restores immune regulatory capability in dendritic cells of subjects with food allergy.

The pathogenesis of immune tolerance disruption is not fully understood. Galectin-9 (Gal9) has immune regulatory functions. The objective of the present study is to assess the role of Gal9 in maintaining immune tolerance. Blood and intestinal biopsies were taken from patients with food allergy (FA). The status of tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cells) in the samples was evaluated and used as representative parameters of immune tolerance. An FA mouse model was established to assess the role of Gal9 in maintaining immune tolerance. We found that peripheral CD11c+ CD5+ CD1d+ tDC frequency was significantly lower in FA patients as compared to health control (HC) subjects. There was no significant change in CD11c+ DC frequency between the FA group and the HC group. The expression of IL-10 in peripheral tDCs was lower in the FA group than that in the HC group. A positive correlation was detected between the serum levels of IL-10 and Gal9. The expression of Gal9 was observed in intestinal biopsies, which was positively correlated with the serum levels of Gal9 as well as serum IL-10 levels. Peripheral Tr1 cells had lower frequencies in the FA group than in the non-FA (Con) group. tDCs demonstrated the ability to generate Tr1 cells, which was weaker in the FA group as compared with the Con group. Exposure of FA tDCs to Gal9 in culture restored the ability to generate Tr1 cells. In summary, the lower frequency of tDC and Tr1 cell of FA patients was associated with the levels of Gal9. The presence of Gal9 restored the capacity of tDC to generate Tr1 cells.

The different damage patterns of short-, middle- and long-range connections between patients with relapse-remitting multiple sclerosis and neuromyelitis optica spectrum disorder.

To investigate the differences in short-, middle- and long-range connections between patients with relapse-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD), and their correlation with brain tissue volume, structural and functional network parameters. A total of 51 RRMS, 42 NMOSD and 56 health controls (HC) were recruited. Of these 25 RRMS (median: 1.37 years) and 20 NMOSD (median: 1.25 years) patients were also studied at follow-up. The whole-brain fiber connection was divided into three groups according to the trisected lengths of the tract in HC group, including short-, middle- and long-range connections. The brain tissue features (including total brain tissue and deep grey matter volumes) and parameters of DTI and functional networks (including the shortest path, clustering coefficient, local efficiency and global efficiency) were calculated. The differences in fiber number (FN) and average fractional anisotropy (FA) were compared between RRMS and NMOSD by the One-way ANOVA and post hoc tests. The correlation between the FN or FA and the brain tissue volume, DTI and functional network parameters were further analyzed by Pearson analysis. Compared to HC and NMOSD, the total number of fibers in RRMS was decreased, including the reduced FN of middle- and long-range connections, but increased FN of short-range connections. Compared to HC, the FA of three fibers in RRMS and NMOSD were reduced significantly, and the decrease of FA in RRMS was greater than in NMOSD. There were correlations between the FN of short-, and long-range connections and the atrophy of whole brain tissue in two diseases and structural network topological parameters in RRMS. Additionally, there was no significant difference of FN and FA in short-, middle- and long-range connections between the baseline and follow-up in two diseases. RRMS and NMOSD patients have different patterns of fiber connection damage. The FN of different lengths in RRMS and NMOSD patients may be associated with brain atrophy. The FN and FA of different lengths may explain the decreased efficiency of the structural network in RRMS patients. In the short-term follow-up, neither has worsened damage of different fibers in two diseases.

The diagnostic and prognostic value of serum exosome-derived carbamoyl phosphate synthase 1 in HEV-related acute liver failure patients.

Early diagnosis and prognosis evaluation are of great significance to hepatitis E virus(HEV)-related acute liver failure (HEV-ALF) patients. We collected serum samples from 200 health controls (HCs), 200 patients with acute hepatitis E (AHE), and 200 HEV-ALF patients to evaluate serum exosome-derived carbamoyl phosphate synthase 1 (CPS1) levels and determine its diagnostic and prognostic value. The exosome-derived CPS1 levels in the HEV-ALF group were significantly higher than those in the AHE and HCs groups. The AUC of exosome-derived CPS1 to predict the occurrence of HEV-ALF was 0.850 (0.811-0.883). Both logistical regression and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that exosome-derived CPS1 is an independent risk factor for HEV-ALF. The exosome-derived CPS1 levels were positively correlated with organ failureand the outcomes in HEV-ALF patients. The exosome-derived CPS1 levels in the worsening group were significantly higher than those in the fluctuating and the improving groups. The AUC of serum exosome-derived CPS1 to predict 30-day mortality was 0.829 (0.770-0.879), which was significantly greater than that of the Child-Pugh, KCH, and MELD models. The level of serum exosome-derived CPS1 might serve as a promising diagnostic and prognostic biomarker for HEV-ALF patients, which may provide better guidance for the diagnosis, prognosis, and treatment of HEV-ALF patients.

EEG Oscillatory Networks in Peri-Ictal Period of Absence Epilepsy.

ObjectiveTo investigate the dynamical brain network changes before and after an absence seizure episode in absence epilepsy (AE).Methods21 AE patients with a current high frequency of seizures and 21 sex- and age-matched health control (HC) who reported no history of neurological or psychiatric disorders and visited the hospital for routine physical examinations were included. Each included subject underwent a 2-h and 19-channel video EEG examination. For AE patients, five epochs of 10-s EEG data in inter-ictal, pre-ictal, and post-ictal states were collected. For the HC group, five 10-s resting-state EEG epochs were extracted. Functional independent components analysis (ICA) was carried out using the LORETA KEY tool.ResultsCompared with the resting-state EEG data of the HC group, the EEG data from AE patients during inter-ictal periods showed decreased alpha oscillations in regions involving the superior frontal gyrus (SFG) (BA11). From inter-ictal to pre-ictal, SFG (BA10) showed maximum decreased delta oscillations. Additionally, from pre-ictal to post-ictal, superior temporal gyrus (STG) (BA 22) presented maximum increased neural activity in the alpha band. Moreover, compared with inter-ictal EEG, post-ictal EEG showed significantly decreased theta activity in SFG (BA8).ConclusionThe changes in SFG alpha oscillations are the key brain network differences between inter-ictal EEG of AE patients and resting-state EEG of HCs. The brain networks of EEG oscillatory during peri-ictal episodes are mainly involving SFG and STG. Our study suggests that altered EEG brain networks dynamics exist between inter-ictal EEG of AE patients and resting-state EEG of HCs and between pre- and post-ictal EEG in AE patients.

Transcutaneous Auricular Vagus Nerve Stimulation Modulates the Prefrontal Cortex in Chronic Insomnia Patients: fMRI Study in the First Session

ObjectivesTranscutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective for chronic insomnia (CI). However, the appropriate population for taVNS to treat insomnia is unclear.MethodsTotal twenty-four patients with CI and eighteen health controls (HC) were recruited. Rest-state functional magnetic resonance imaging (Rs-fMRI) was performed before and after 30 min' taVNS at baseline. The activated and deactivated brain regions were revealed by different voxel-based analyses, then the seed-voxel functional connectivity analysis was calculated. In the CI group, 30 min of taVNS were applied twice daily for 4 weeks. Pittsburgh Sleep Quality Index (PSQI) and Flinders Fatigue Scale (FFS) were also assessed before and after 4 weeks of treatment in the CI group. The HC group did not receive any treatment. The correlations were estimated between the clinical scales' score and the brain changes.ResultsThe scores of PSQI (p < 0.01) and FFS (p < 0.05) decreased after 4 weeks in the CI group. Compared to the HC group, the first taVNS session up-regulated left dorsolateral prefrontal cortex (dlPFC) and decreased the functional connectivity (FCs) between dlPFC and bilateral medial prefrontal cortex in the CI group. The CI groups' baseline voxel wised fMRI value in the dlPFC were negatively correlated to the PSQI and the FFS score after 4 weeks treatment.ConclusionsIt manifests that taVNS has a modulatory effect on the prefrontal cortex in patients with CI. The initial state of dlPFC may predict the efficacy for taVNS on CI.

Association between IL-18, IFN-γ and TB susceptibility: a systematic review and meta-analysis.

This study sought to evaluate the relationship between interleukin 18 (IL-18), interferon-gamma (IFN-γ), and susceptibility to tuberculosis (TB). We searched multiple databases, such as PubMed, Embase, Cochrane and China National Knowledge Database, for full-text articles on IL-18, IFN-γ, and TB. Bias risk tool in Review Manager 5.2 was used to evaluate the seven kinds of bias. We used Review Manager 5.2 to evaluate the effects of the results in the selected articles, analyzed the heterogeneity of the included articles to make a forest map, and undertook a sensitivity analysis and publication bias analysis. Ultimately, 10 studies met the inclusion criteria, and were subjected to a data analysis. IL-18 was higher in the TB group than the health control (HC) group [mean difference (MD) =248.11, 95% confidence interval CI: 197.25, 298.98, P<0.0001; I2=63%]. The meta-analysis also showed that IFN-γ was higher in the TB group than the HC group (MD =38.74, 95% CI: 14.84, 62.64, P=0.001; I2=100%). Sensitivity analysis proved the robustness of this research and limited publication bias was observed in this study. This study showed that IL-18 and IF-γ had a relationship with TB and might be used to help diagnose TB, which might be helpful in the clinical diagnosis about TB.

Effect of GLP-1/GLP-1R on the Polarization of Macrophages in the Occurrence and Development of Atherosclerosis.

Aims To investigate the effect of GLP-1/GLP-1R on the polarization of macrophages in the occurrence and development of atherosclerosis. Methods Totally, 49 patients with coronary heart disease (CHD) and 52 cases of health control (HC) were recruited, all subjects accept coronary angiography gold standard inspection. One or more major coronary arteries (LM, LAD, LCx, and RCA) stenosis degree in 50% of patients as CHD group; the rest of the stenosis less than 50% or not seen obvious stenosis are assigned to the HC group. Flow cytometry were used to detect the percentage of (CD14+) M macrophages, (CD14+CD80+) M1 macrophages, (CD14+CD206+) M2 macrophages, and their surface GLP-1R expression differences in the two groups, using BD cytokine kit to detect the levels of IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70. Results GLP-1R expression on the surface of total macrophages and M2 macrophages was different between the CHD group and the HC group (P < 0.05). There was no difference in the percentage of total, M1 or M2 macrophages (P > 0.05). Concentration of IL-8 in the HC group was higher than that in the CHD group (P < 0.05). There is no significant difference in the cytokine IL-1β, IL-6, IL-10, TNF, and IL-12p70 in the two groups (P > 0.05). After controlling for potential confounders including age, gender, smoking status (S.S.), drinking status (D.S.), HR, SBP, DBP, PP, TC, TG, HDL-C, LDL-C, GHbA1c, M, M1, M2, GLP-1R_M, GLP-1R_M1, GLP-1R_M2, IL-8, IL-1β, IL-6, IL-10, TNF, and IL-12p70 by multiple linear regression, decreasing Gensini Score was significantly associated with increased percentage of M1 macrophage. Conclusion GLP-1R agonist is independent of the hypoglycemic effect of T2DM and has protective effect on cardiovascular system. GLP-1R may regulate the polarization of macrophages toward M2, thus playing a protective role in the progression of coronary atherosclerosis.

Classification of Alzheimer's Disease and Mild Cognitive Impairment Based on Cortical and Subcortical Features from MRI T1 Brain Images Utilizing Four Different Types of Datasets.

Alzheimer's disease (AD) is one of the most common neurodegenerative illnesses (dementia) among the elderly. Recently, researchers have developed a new method for the instinctive analysis of AD based on machine learning and its subfield, deep learning. Recent state-of-the-art techniques consider multimodal diagnosis, which has been shown to achieve high accuracy compared to a unimodal prognosis. Furthermore, many studies have used structural magnetic resonance imaging (MRI) to measure brain volumes and the volume of subregions, as well as to search for diffuse changes in white/gray matter in the brain. In this study, T1-weighted structural MRI was used for the early classification of AD. MRI results in high-intensity visible features, making preprocessing and segmentation easy. To use this image modality, we acquired four types of datasets from each dataset's server. In this work, we downloaded 326 subjects from the National Research Center for Dementia homepage, 123 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) homepage, 121 subjects from the Alzheimer's Disease Repository Without Borders homepage, and 131 subjects from the National Alzheimer's Coordinating Center homepage. In our experiment, we used the multiatlas label propagation with expectation–maximization-based refinement segmentation method. We segmented the images into 138 anatomical morphometry images (in which 40 features belonged to subcortical volumes and the remaining 98 features belonged to cortical thickness). The entire dataset was split into a 70 : 30 (training and testing) ratio before classifying the data. A principal component analysis was used for dimensionality reduction. Then, the support vector machine radial basis function classifier was used for classification between two groups—AD versus health control (HC) and early mild cognitive impairment (MCI) (EMCI) versus late MCI (LMCI). The proposed method performed very well for all four types of dataset. For instance, for the AD versus HC group, the classifier achieved an area under curve (AUC) of more than 89% for each dataset. For the EMCI versus LMCI group, the classifier achieved an AUC of more than 80% for every dataset. Moreover, we also calculated Cohen kappa and Jaccard index statistical values for all datasets to evaluate the classification reliability. Finally, we compared our results with those of recently published state-of-the-art methods.

Serum Granulysin in Differentiation of Stevens-Johnson Syndrome/toxic Epidermal Necrolysis and Erythema Multiforme

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute, life-threatening drug reactions, which lead to massive epidermal necrolysis. Granulysin plays an important role as a key mediator for keratinocyte apoptosis in these conditions. Erythema multiforme (EM) may have skin manifestation similar to SJS/TEN.&#x0D; AIMS: The aim of the study was to compare serum granulysin levels in patients with SJS/TEN and EM as well as to investigate a possible association between serum granulysin levels and the severity of SJS/TEN.&#x0D; METHODS: In total, 48 patients with SJS/TEN, 43 patients with EM, and 20 health controls (HCs) were enrolled. We measured serum granulysin levels using enzyme-linked immunosorbent assay.&#x0D; RESULTS: The average level of serum granulysin in the SJS/TEN patients was 23.0 ng/ml (range 1.2–144.6 ng/ml), significantly higher than that of EM group (20.1 ng/ml; range 8.5–121 ng/ml, p &lt; 0.05) and HCs group (20.8 ng/ml; range 10.1–46.7 ng/ml, p &lt; 0.05). Of 48 SJS/TEN patients, the 25 samples collected &lt;6 days after onset showed higher level of serum granulysin (27.7 ng/ml; range 2.5–144.6 ng/ml) than those collected ≥6 days after onset (17.9 ng/ml; range 1.2–59 ng/ml; p &gt; 0.05). No significant correlation was found between serum granulysin levels and the body surface area affected and the modified-SCORTEN. At the day of re-epithelialization, serum granulysin levels were not different compared with those at the day of hospitalization.&#x0D; CONCLUSIONS: Serum granulysin levels are significantly higher in SJS/TEN group than in EM group. After the onset, serum granulysin levels in patients with SJS/TEN are not a good biomarker to evaluate the severity of the diseases.

A Systematic Review of Neurocognitive Functioning in Behçet's Disease.

Behçet's disease (BD) is a vascular, inflammatory multisystem disorder with neuro-Behçet's (NBD) diagnosed in a subset of patients with neurological manifestations. The objective of this review was to determine whether neurocognitive dysfunction is observed in BD, in which neurocognitive domains, and whether there are differences in rates of dysfunction observed between BD and NBD groups. Studies of any methodology were included that reported results from standardized neurocognitive assessment measures in participants with BD or NBD. Twelve group comparison studies met the criteria for inclusion in the review (totalling 284 BD and 157 NBD participants), as well as 17 case study/series papers (11 BD, 35 NBD). Issues with blinding, incomplete data reporting and selective reporting bias were found across the group and case study/series papers, as well as inadequate statistical adjustment for multiple comparisons in the group studies, and the lack of the use of appropriate norms or adjustment for premorbid ability in the case series/studies papers. These quality issues impacted on the conclusions that could be drawn from the current literature. Neurocognitive dysfunction was found in NBD compared to health controls (HC) in a higher proportion of results across studies, than in comparisons between BD and HC groups. The domains in which neurocognitive attenuation was most often reported were visual spatial ability, working memory and acquired knowledge, with more than 25% of these results showing significantly lower functioning in both the BD and NBD groups compared to HC. More than 25% of the processing speed and long-term memory encoding and retrieval results were also lower for the NBD group, compared to HC. Group comparisons between NBD and multiple sclerosis participants indicated few significant differences in neurocognitive test results. The majority of case study/series participants were found to have some degree of attenuated neurocognitive functioning, as defined by case study/series authors.

Severity of irritable bowel syndrome in patients with temporomandibular disorders: A case-control study.

BackgroundTo assess the risk and severity of IBS in a population of TMD patients.Material and MethodsSubjects for the study group were recruited from patients attending the Dental Clinic. Health controls (HC) were recruited among patients’ friends and clinic staff. All subjects filled in the RDC/TMD questionnaire and the ROME III questionnaire for the diagnosis of IBS. The IBS Severity Scoring System (IBS-SSS) was used to evaluate the severity of each case of IBS. Categorical variables were compared through the Chi square test. The risk of having abdominal pain was analysed using logistic regression.ResultsTwenty-two (46.8%) cases of IBS were diagnosed among TMD patients, whereas only 4 (11.4%) were in the HC group. This difference was statistically significant (χ2(1)=11.6; p<.01). The differences in the distribution of IBS-SSS were statistically significant (χ2(3)=12.49; p<.05). The regression model resulted statistically significant (χ2(5)=24.08; p<.001, R2=.37): abdominal pain was significantly related to nonspecific physical symptoms independent of the other variables.ConclusionsTMD patients had a greater risk of having IBS compared to HC. TMD patients presented also more severe form of IBS than HC. Key words:Temporomandibular disorders, irritable bowel syndrome, facial pain, case-control study.

Impaired Executive Functioning of Sexual Assault Survivors with Acute Stress Disorder.

This study aimed to examine the executive functioning of survivors exposed to recent sexual assaults. Twenty-seven female rape survivors who met the criterion for acute stress disorder (ASD) were enrolled and completed the assessment within 4 weeks after the traumatic experience. Additionally, 25 age-matched female health controls (HC) never exposed to such a traumatic event were enrolled. The assessments evaluated psychiatric symptoms including post-traumatic stress symptoms, depression, anxiety, and trait and state anger; general intelligence indexed by intellectual quotient (IQ); and executive functioning including set-shift/attention, planning, spatial working memory, and inhibition using the Cambridge Neuropsychological Test Automated Battery. The ASD group showed higher levels of depression, anxiety, and state anger, and lower IQ than the HC group. The ASD group also showed global impairment of executive functioning for set-shifting, attention, planning, and response inhibition compared to the HC group. Rather than being associated with low IQ and education levels, these results could be from trauma-related effects in survivors with ASD. Additionally, the state anger level was related to survivors’ deficient executive functioning. The findings indicate the importance of providing assessment and intervention efforts to sexual assault survivors soon after the trauma occurs.

Study on the expressions of NLRP3 gene transcript variants in peripheral blood monocytes of primary gout patients.

It is well-known that NLRP3 is closely related to the onset of primary gout (PG). However, the relation between NLRP3 gene transcript variants and the occurrence of PG remains unclear. This study was undertaken to evaluate whether NLRP3 gene transcript variants are involved in the occurrence of PG. A total of 44 acute phase PG (APPG), 52 non-acute phase PG (NAPPG) male patients, and 30 male health control (HC) were involved in this study. We measured NLRP3 and its transcript variants 2, 3, 4, 5, and 1 + 6 expressions in the PBMCs, together with the level of IL-1β in the serum. Further, PBMCs of HC were stimulated with MSU crystals. The levels of NLRP3, NLRP3 gene transcript variants 2, 3, 4 mRNA, and protein expressions were significantly lower in the APPG and NAPPG groups than in the HC group (P < 0.05, respectively), and IL-1β expression was significantly higher in the APPG group than in the HC and NAPPG groups (P < 0.05, respectively). Levels of IL-1β and NLRP3-4 mRNA expressions were negatively correlated with APPG group (r = - 0.2828, P = 0.0252). After stimulating PBMCs of HC with MSU crystals, levels of NLRP3, NLRP3-4 mRNA, and NLRP3 protein expressions were reduced significantly (P < 0.05, respectively), and the level of IL-1β in MSU group was increased significantly (P < 0.05). Here, we show that NLRP3-4 transcript variant may be closely related to the occurrence of PG. Thus, NLRP3-4 gene transcript variant may provide a novel target for the diagnosis and therapy of PG.

Gut microbiome and magnetic resonance spectroscopy study of subjects at ultra-high risk for psychosis may support the membrane hypothesis

BackgroundThe microbiota-gut-brain axis and membrane dysfunction in the brain has attracted increasing attention in the field of psychiatric research. However, the possible interactive role of gut microbiota and brain function in the prodromal stage of schizophrenia has not been studied yet. MethodsTo explore this, we collected fecal samples and performed Magnetic Resonance Spectroscopy (MRS) scans in 81 high risk (HR) subjects, 19 ultra-high risk (UHR) subjects and 69 health controls (HC). Then we analyzed the differences in gut microbiota and choline concentrations in the anterior cingulate cortex (ACC). ResultsPresences of the orders Clostridiales, Lactobacillales and Bacteroidales were observed at increase levels in fecal samples of UHR subjects compared to the other two groups. The composition changes of gut microbiota indicate the increased production of Short Chain Fatty Acids (SCFAs), which could activate microglia and then disrupt membrane metabolism. Furthermore, this was confirmed by an increase of choline levels, a brain imaging marker of membrane dysfunction, which is also significantly elevated in UHR subjects compared to the HR and HC groups. ConclusionBoth gut microbiome and imaging studies of UHR subjects suggest the membrane dysfunction in the brain and hence might support the membrane hypothesis of schizophrenia.

The circular RNA of peripheral blood mononuclear cells: Hsa_circ_0005836 as a new diagnostic biomarker and therapeutic target of active pulmonary tuberculosis

It has been reported that circular RNA (circRNA) is associated with human cancer. However, few studies have been reported in active pulmonary tuberculosis (APTB). The global circRNA expression was detected in the peripheral blood mononuclear cells (PBMCs) of APTB patients (n=5) and health controls (HC) (n=5) by using high-throughput sequencing. According to the systematical bioinformatics analysis, the basic content of circRNAs and their fold changes in the two groups were calculated. We selected 6 significant differentially expressed circRNAs, hsa_circ_0005836, hsa_circ_0009128, hsa_circ_0003519, hsa_circ_0023956, hsa_circ_0078768, and hsa_circ_0088452 and validated the expression in PBMCs from APTB (n=10) and HC (n=10) by real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs). Further, the verification of these specific circRNAs (hsa_circ_0005836 and hsa_circ_0009128) between APTB (n=34) and HC (n=30) in PBMCs was also conducted by qRT-PCRs. The RNA-seq data showed the significant differential expression of the 523 circRNAs between the APTB and HC groups (199 circRNAs were significantly up-regulated and 324 circRNAs were down-regulated). Hsa_circ_0005836 and hsa_circ_0009128 expression was significantly down-regulated in the PBMCs of APTB (P<0.05) in the samples of APTB compared to HC in our study. The gene ontology based enrichment analysis of the circRNA-miRNA-mRNAs network showed that cellular catabolic process (P=7.10E-08), regulation of metabolic process (P=2.10E-06), catalytic activity (P=3.67E-08), protein binding (P=1.71E-07), cell part (P=3.46E-06), intracellular part (P=1.71E-07), and intracellular (P=3.67E-08) were recognized in the comparisons between APTB and HC. Based on KEGG analysis, HTLV-I infection, regulation of actin cytoskeleton, neurotrophin signaling pathway and mTOR signaling pathway were relevant during tuberculosis bacillus infection. We found for the first time that hsa_circ_0005836 and hsa_circ_0009128 were significantly down-regulated in the PBMCs of APTB compared with HC. Our findings indicate hsa_circ_0005836 might serve as a novel potential biomarker for TB infection.

IL-37 inhibits the production of pro-inflammatory cytokines in MSU crystal-induced inflammatory response.

Acute gouty arthritis (AGA) is an auto-inflammatory disease characterized by resolving spontaneously, which suggests that negative feedback loops control inflammatory and immunological responses to monosodium urate (MSU) crystals. By now, the molecular mechanism for spontaneous resolution of acute GA remains unclear; this study was undertaken to evaluate whether IL-37 is involved in spontaneous resolution of AGA. A total of 45 acute GA (AGA),29 non-acute GA (NAGA) male patients and 82 male health control (HC) were involved in this study, we measured IL-7 expression in the peripheral blood mononuclear cells (PBMCs), together with levels of IL-1β, IL-6, IL-10, TNF-α and TGF-β1 in the serum. Further, we either inhibited IL-37 expression in human PBMCs with siRNA or over-expressed the cytokine in human macrophages. Pro-inflammatory cytokine IL-1β, IL-6, and TNF-α expressions were significantly higher in the AGA group than in the NAGA or HC group (P < 0.05, respectively). However, anti-inflammatory IL-37, TGF-β1, and IL-10 were greater in the NAGA group than in the AGA and HC groups (P < 0.05, respectively). Expression of IL-37 in MSU crystal-treated macrophages inhibited the expression of pro-inflammatory cytokines, whereas the abundance of these cytokines increased with silencing of endogenous IL-37 in human blood cells. However, anti-inflammatory TGF-β1 and IL-10 expressions in these supernatants were unaffected by over-expression or knockdown of IL-37. Our study indicates that IL-37 is an important anti-inflammatory cytokine in AGA by suppressing the production of pro-inflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of GA.

Resting-state functional connectivity of dentate nucleus is associated with tremor in Parkinson's disease.

Cerebello-thalamo-cortical circuit has been indicated important for tremor in Parkinson's disease (PD), but the role of dentate nucleus (DN) in parkinsonian tremor remains unclear. To investigate whether DN plays a role in PD tremor, we recruited 50 PD and 29 age-matched health controls (HC). The patients were divided into tremor-dominant (TD) and non-tremor-dominant (NTD) groups. We collected resting-state fMRIs data for each subject. The bilateral DN was then chosen as the region of interest to examine PD tremor-related network changes, as well as its correlation with tremor severity. Voxel-wise functional connectivity analysis revealed that the bilateral DN had higher connectivity with the bilateral cerebellar anterior lobe, and had lower connectivity with the bilateral prefrontal cortex in TD compared to the HC and NTD groups. Functional connectivity of the bilateral DN with the bilateral cerebellar posterior lobe was also higher in TD than NTD group. Functional connectivity between the bilateral DN and the bilateral cerebellar posterior lobe showed positive correlation with tremor severity, while that between the bilateral DN and the bilateral prefrontal cortex displayed negative correlation. Our study demonstrates higher dentato-cerebellar connectivity and lower dentato-prefrontal connectivity in TD patients, which might be involved in the pathogenesis of PD tremor. And we conclude that DN might be associated with the pathogenesis of PD tremor.

A clinical control study of error monitoring in the patients with schizophrenia

Objective To investigate the error monitoring function damages on the patients with schizophrenia (SCH). Methods A total of 32 patients with schizophrenia were compared with matched 34 health controls (HC) on the error monitoring tasks which were compiled by E-Prime. Results The comparison between SCH group ((713.22±174.52)ms, ( 491.14±170.29) ms, ( 1060.31±130.84) ms, (8.28±12.55)time, ( 8.00±7.53)time respectively) and HC group ((560.73±156.94) ms, (395.62±188.03) ms, (989.85±104.33) ms, (2.97±4.13) times, (3.12±6.50) times) on the reaction time of choice, assessment, incongruent condition, the numbers of uncertain and the numbers of dropout were significant (t=-3.737, P=0.000; t=-2.159, P=0.035; t=-2.426, P=0.018; t=-2.282, P=0.022; t=-2.824, P=0.006). The SCH group and HC group did not significantly difference in Full Correct((124.72±23.74)/(131.74±21.96)times), Full Error((15.69±17.64)/(13.35±18.63)times), Part Correct((6.83±10.40)/(4.21±7.03)times), Part Error((2.91±10.91)/(0.62±1.10)times) and Accuracy((0.831±0.161)/(0.874±0.159))(P>0.05). There was no significantly correlation among the course of disease, HAMA, HAMD and the error monitoring. Conclusion These results demonstrate that the error monitoring function damages on the patient with SCH may be involved in the dysfunction of anterior cingulate cortex. Key words: Schizophrenia; Error monitoring; Anterior cingulate cortex