Analyzing the topological properties of resting-state brain function network connectivity based on graph theoretical methods in patients with high myopia.

AIM: Recent imaging studies have found significant abnormalities in the brain's functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. METHODS: We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. RESULTS: In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P < 0.001, Bonferroni-corrected). Notably, there is an increase in functional connectivity (FC) between the saliency network (SN) and Sensorimotor Network (SMN) in the HM group, while the strength of FC between the basal ganglia is relatively weaker (P < 0.01). CONCLUSION: HM Patients exhibit reduced small-world characteristics in their brain networks, with significant drops in γ and σ values indicating weakened global interregional information transfer ability. Not only that, the topological properties of the amygdala nodes in HM patients significantly decline, indicating dysfunction within the brain network. In addition, there are abnormalities in the FC between the SN, SMN, and basal ganglia networks in HM patients, which is related to attention regulation, motor impairment, emotions, and cognitive performance. These findings may provide a new mechanism for central pathology in HM patients.

Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis.

Platelet homeostasis is essential for vascular integrity and immune defence1,2. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear3,4. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet homeostasis at steady state and under stress. pDCs are best known for their ability to function as vigilant detectors of viral infection5. We show that virus-induced activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis. Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis. Together, we identify a pDC-dependent homeostatic circuit that involves innate immune sensing and demand-adapted release of inflammatory mediators to maintain homeostasis of the megakaryocytic lineage.

Investigation on the Therapeutic Mechanism of Danbie Capsules for Endometriosis: A Network Pharmacology Approach.

Objective: To explore the active substances and targets of Danbie Capsules in Endometriosis therapy. Methods: This study was conducted through TCMSP and published literature screened and obtained 183 active substances of Danbie Capsules, combined and intersected with Endometriosis target genes collected and screened in the GEO database, obtained 24 target genes for Endometriosis treatment, and mapped the target network map of Danbie Capsules active substances against Endometriosis. The network was analyzed with the aid of Cytoscape version 3.9.1. With the aid of the platform of the STRING data analysis, PPI network analysis was conducted on 24 anti-Endometriosis targets of the Danbie Capsules. Results: The research results obtained three critical active substances, namely, Quercetin, ß-sitosterol, and Luteolin. Seven critical targets were identified, and two representative genes (TP53 and AKT1) have been verified in Macromolecular docking and immunohistochemical verification. Conclusion: The active substances of Danbie Capsules in the treatment of Endometriosis are Quercetin, ß-sitosterol and Luteolin, and the main targets are TP53 and AKT1.

Microglia Caspase11 non-canonical inflammasome drives fever.

AIM: Animals exhibit physiological changes designed to eliminate the perceived danger, provoking similar symptoms of fever. However, a high-grade fever indicates poor clinical outcomes. Caspase11 (Casp11) is involved in many inflammatory diseases. Whether Casp11 leads to fever remains unclear. In this study, we investigate the role of the preoptic area of the hypothalamus (PO/AH) microglia Casp11 in fever. METHODS: We perform experiments using a rat model of LPS-induced fever. We measure body temperature and explore the functions of peripheral macrophages and PO/AH microglia in fever signaling by ELISA, immunohistochemistry, immunofluorescence, flow cytometry, macrophage depletion, protein blotting, and RNA-seq. Then, the effects of macrophages on microglia in a hyperthermic environment are observed in vitro. Finally, adeno-associated viruses are used to knockdown or overexpress microglia Casp11 in PO/AH to determine the role of Casp11 in fever. RESULTS: We find peripheral macrophages and PO/AH microglia play important roles in the process of fever, which is proved by macrophage and microglia depletion. By RNA-seq analysis, we find Casp11 expression in PO/AH is significantly increased during fever. Co-culture and conditioned-culture simulate the induction of microglia Casp11 activation by macrophages in a non-contact manner. Microglia Casp11 knockdown decreases body temperature, pyrogenic factors, and inflammasome, and vice versa. CONCLUSION: We report that Casp11 drives fever. Mechanistically, peripheral macrophages transmit immune signals via cytokines to microglia in PO/AH, which activate the Casp11 non-canonical inflammasome. Our findings identify a novel player, the microglia Casp11, in the control of fever, providing an explanation for the transmission and amplification of fever immune signaling.

Exploration of Hippocampal Functional Connectivity Alterations in Patients with High Myopia via Seed-Based Functional Connectivity Analysis.

Aim: The objective of this study was to examine changes in functional connectivity (FC) in the hippocampus among patients with high myopia (HM) compared to healthy controls (HCs) through the utilization of seed-based functional connectivity (FC) analysis. Methods: Resting-state functional magnetic resonance imaging (fMRI) was conducted on a sample of 82 patients diagnosed with high myopia (HM) and 59 HCs. The two groups were matched based on age, weight and other relevant variables. Using seed-based FC analysis to detect alterations in hippocampal FC patterns in HM patients and HCs. Furthermore, a correlation analysis was performed to examine the associations between the mean functional connectivity (FC) signals in various brain regions of patients with HM and their corresponding clinical manifestations. Results: The FC values in the left temporal pole-temporal gyrus (L-TPOsup), right hippocampus (R-HIP), left medial temporal gyrus (L-MTG) and left hippocampus in HM patients were significantly lower than those of healthy subjects. In the left temporal pole-superior temporal gyrus (L-TPOsup), right orbital part of middle frontal gyrus (RO-MFG), left fusiform gyrus (L-FG), left cerebellum superior (L-Cbe6), left middle temporal gyrus (L-MTG), right thalamus (R-THA), and right hippocampus, FC values were also significantly lower. Conclusion: Brain dysfunction was observed in various regions of the HM patients, suggesting the existence of neurobiological alterations that could lead to impairments in visual cognition, movement, emotional processing, and visual memory.

Machine learning analysis reveals aberrant dynamic changes in amplitude of low-frequency fluctuations among patients with retinal detachment.

Background: There is increasing evidence that patients with retinal detachment (RD) have aberrant brain activity. However, neuroimaging investigations remain focused on static changes in brain activity among RD patients. There is limited knowledge regarding the characteristics of dynamic brain activity in RD patients. Aim: This study evaluated changes in dynamic brain activity among RD patients, using a dynamic amplitude of low-frequency fluctuation (dALFF), k-means clustering method and support vector machine (SVM) classification approach. Methods: We investigated inter-group disparities of dALFF indices under three different time window sizes using resting-state functional magnetic resonance imaging (rs-fMRI) data from 23 RD patients and 24 demographically matched healthy controls (HCs). The k-means clustering method was performed to analyze specific dALFF states and related temporal properties. Additionally, we selected altered dALFF values under three distinct conditions as classification features for distinguishing RD patients from HCs using an SVM classifier. Results: RD patients exhibited dynamic changes in local intrinsic indicators of brain activity. Compared with HCs, RD patients displayed increased dALFF in the bilateral middle frontal gyrus, left putamen (Putamen_L), left superior occipital gyrus (Occipital_Sup_L), left middle occipital gyrus (Occipital_Mid_L), right calcarine (Calcarine_R), right middle temporal gyrus (Temporal_Mid_R), and right inferior frontal gyrus (Frontal_Inf_Tri_R). Additionally, RD patients showed significantly decreased dALFF values in the right superior parietal gyrus (Parietal_Sup_R) and right paracentral lobule (Paracentral_Lobule_R) [two-tailed, voxel-level p < 0.05, Gaussian random field (GRF) correction, cluster-level p < 0.05]. For dALFF, we derived 3 or 4 states of ALFF that occurred repeatedly. There were differences in state distribution and state properties between RD and HC groups. The number of transitions between the dALFF states was higher in the RD group than in the HC group. Based on dALFF values in various brain regions, the overall accuracies of SVM classification were 97.87, 100, and 93.62% under three different time windows; area under the curve values were 0.99, 1.00, and 0.95, respectively. No correlation was found between hamilton anxiety (HAMA) scores and regional dALFF. Conclusion: Our findings offer important insights concerning the neuropathology that underlies RD and provide robust evidence that dALFF, a local indicator of brain activity, may be useful for clinical diagnosis.

Corrigendum: Comparison of peripheral blood regulatory T cells and functional subsets between ocular and generalized myasthenia gravis.

[This corrects the article DOI: 10.3389/fmed.2022.851808.].

Changes and significance of vascular endothelial injury markers in patients with diabetes mellitus and pulmonary thromboembolism.

BACKGROUND: To investigate the changes and clinical significance of vascular endothelial injury markers in type 2 diabetes mellitus (T2DM) complicated with pulmonary embolism (PE). METHODS: This prospective study enrolled patients with T2DM hospitalized in one hospital from January 2021 to June 2022. Soluble thrombomodulin (sTM) (ELISA), von Willebrand factor (vWF) (ELISA), and circulating endothelial cells (CECs) (flow cytometry) were measured. PE was diagnosed by computed tomography pulmonary angiography (CTPA). RESULTS: Thirty participants were enrolled in each group. The plasma levels of sTM (151.22 ± 120.57 vs. 532.93 ± 243.82 vs. 1016.51 ± 218.00 pg/mL, P < 0.001) and vWF (9.63 ± 2.73 vs. 11.50 ± 2.17 vs. 18.02 ± 3.40 ng/mL, P < 0.001) and the percentage of CECs (0.17 ± 0.46 vs. 0.30 ± 0.08 vs. 0.56 ± 0.18%, P < 0.001) gradually increased from the control group to the T2DM group to the T2DM + PE group. sTM (OR = 1.002, 95%CI: 1.002-1.025, P = 0.022) and vWF (OR = 1.168, 95%CI: 1.168-2.916, P = 0.009) were associated with T2DM + PE. sTM > 676.68 pg/mL for the diagnosis of T2DM + PE achieved an AUC of 0.973, while vWF > 13.75 ng/mL achieved an AUC of 0.954. The combination of sTM and vWF above their cutoff points achieved an AUC of 0.993, with 100% sensitivity and 96.7% specificity. CONCLUSIONS: Patients with T2DM show endothelial injury and dysfunction, which were worse in patients with T2DM and PE. High sTM and vWF levels have certain clinical predictive values for screening T2DM accompanied by PE.

Exploration of static functional connectivity and dynamic functional connectivity alterations in the primary visual cortex among patients with high myopia via seed-based functional connectivity analysis.

Aim: This study was conducted to explore differences in static functional connectivity (sFC) and dynamic functional connectivity (dFC) alteration patterns in the primary visual area (V1) among high myopia (HM) patients and healthy controls (HCs) via seed-based functional connectivity (FC) analysis. Methods: Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 82 HM patients and 59 HCs who were closely matched for age, sex, and weight. Seed-based FC analysis was performed to identify alterations in the sFC and dFC patterns of the V1 in HM patients and HCs. Associations between mean sFC and dFC signal values and clinical symptoms in distinct brain areas among HM patients were identified via correlation analysis. Static and dynamic changes in brain activity in HM patients were investigated by assessments of sFC and dFC via calculation of the total time series mean and sliding-window analysis. Results: In the left anterior cingulate gyrus (L-ACG)/left superior parietal gyrus (L-SPG) and left V1, sFC values were significantly greater in HM patients than in HCs. In the L-ACG and right V1, sFC values were also significantly greater in HM patients than in HCs [two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05]. In the left calcarine cortex (L-CAL) and left V1, dFC values were significantly lower in HM patients than in HCs. In the right lingual gyrus (R-LING) and right V1, dFC values were also significantly lower in HM patients than in HCs (two-tailed, voxel-level P < 0.01, GRF correction, cluster-level P < 0.05). Conclusion: Patients with HM exhibited significantly disturbed FC between the V1 and various brain regions, including L-ACG, L-SPG, L-CAL, and R-LING. This disturbance suggests that patients with HM could exhibit impaired cognitive and emotional processing functions, top-down control of visual attention, and visual information processing functions. HM patients and HCs could be distinguished from each other with high accuracy using sFC and dFC variabilities. These findings may help to identify the neural mechanism of decreased visual performance in HM patients.

Ginsenoside Rc Alleviates Myocardial Ischemia-Reperfusion Injury by Reducing Mitochondrial Oxidative Stress and Apoptosis: Role of SIRT1 Activation.

Myocardial ischemia-reperfusion (MI/R) injury occurs when coronary blood supply is impaired and then re-established, leading to additional injury to the myocardial tissue, including mitochondria oxidative stress and apoptosis. Ginsenoside Rc is one of the main protopanaxadiol-type saponins, and there has been relatively little research on it. Despite research confirming that ginsenoside Rc regulates mitochondrial functions, its potential benefits against MI/R injury have not been explored. In this study, we examined the protective effects of ginsenoside Rc in MI/R injury, along with its underlying mechanisms, using an in vitro H9c2 cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) and an in vivo rat model of MI/R injury. Prior to this, the H9c2 cells or rats were exposed to ginsenoside Rc with or without SIRT1 small interfering RNA (siRNA) or the selective SIRT1 inhibitor EX527. The results showed that after MI/R (or OGD/R) injury, ginsenoside Rc had a cardioprotective effect; improved cardiac function (or cell survival); reduced myocardial infarct size; decreased levels of creatine kinase-MB, cardiac troponin I, and lactate dehydrogenase (LDH) in the serum (or LDH release into culture medium); reduced cardiomyocyte apoptosis; and attenuated mitochondrial oxidative damage. Ginsenoside Rc pre-treatment also upregulated the anti-apoptotic protein Bcl-2 while downregulating the pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the cardioprotective effect of ginsenoside Rc was concomitant with upregulated SIRT1 expression and downregulated Ac-FOXO1 expression. SIRT1 siRNA or SIRT1 inhibitor EX527 abolished the cardioprotective effects of ginsenoside Rc by inhibiting the SIRT1 signaling pathway. In conclusion, our findings demonstrate that ginsenoside Rc ameliorated MI/R injury by reducing mitochondrial oxidative stress and apoptosis, at least in part, by activating SIRT1.

Ginsenoside Rd Inhibited Ferroptosis to Alleviate CCl4-Induced Acute Liver Injury in Mice via cGAS/STING Pathway.

Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd is considered an active ingredient of ginseng. Evidence suggests that ginsenoside Rd may improve ischaemic stroke, nerve damage, cancer and other diseases involving apoptosis, inflammation, oxidative stress, mitochondrial injury and autophagy. However, the effects of ginsenoside Rd on CCl4-induced ALI and its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a CCl4-induced ALI model. In the Rd treatment group, Rd (10, 20[Formula: see text]mg/kg) doses were injected intraperitoneally 1[Formula: see text]h before and 23[Formula: see text]h after CCl4 administration. Ferroptosis inducer imidazole ketone erastin (IKE) was injected intraperitoneally 4[Formula: see text]h before CCl4 administration to explore the mechanism. The blood and liver were collected 24[Formula: see text]h after CCl4 administration to investigate the effect and mechanism of ginsenoside Rd on CCl4-induced ALI. Our results showed that ginsenoside Rd inhibited CCl4-induced ALI in mice. Ginsenoside Rd also downregulated CCl4-induced serum and liver iron, 4-hydroxynonenal, and 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione and glutathione peroxidase 4 levels. In addition, ginsenoside Rd downregulated the expression of cGAS and STING. Subsequently, the ferroptosis inducer imidazole ketone erastin significantly reversed the hepatoprotective effect and influence of ginsenoside Rd with regard to the indicators mentioned above. Our study confirmed that ginsenoside Rd ameliorated CCl4-induced ALI in mice, which was related to the reduction of ferroptosis. Simultaneously, the ginsenoside Rd-mediated inhibition of the cGAS/STING pathway contributed to its antiferroptosis effect. In conclusion, our results suggested that ginsenoside Rd inhibited ferroptosis via the cGAS/STING pathway, thereby protecting mice from CCl4-induced ALI. These results suggested ginsenoside Rd may be used as a potential intervention treatment against CCl4-induced ALI.

Neutrophil "plucking" on megakaryocytes drives platelet production and boosts cardiovascular disease.

Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils "plucked" intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events.

Exploration of abnormal dynamic spontaneous brain activity in patients with high myopia via dynamic regional homogeneity analysis.

Aim: Patients with high myopia (HM) reportedly exhibit changes in functional brain activity, but the mechanism underlying such changes is unclear. This study was conducted to observe differences in dynamic spontaneous brain activity between patients with HM and healthy controls (HCs) via dynamic regional homogeneity (dReHo) analysis. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 82 patients with HM and 59 HCs who were closely matched for age, sex, and weight. The dReHo approach was used to assess local dynamic activity in the human brain. The association between mean dReHo signal values and clinical symptoms in distinct brain areas in patients with HM was determined via correlation analysis. Results: In the left fusiform gyrus (L-FG), right inferior temporal gyrus (R-ITG), right Rolandic operculum (R-ROL), right postcentral gyrus (R-PoCG), and right precentral gyrus (R-PreCG), dReHo values were significantly greater in patients with HM than in HCs. Conclusion: Patients with HM have distinct functional changes in various brain regions that mainly include the L-FG, R-ITG, R-ROL, R-PoCG, and R-PreCG. These findings constitute important evidence for the roles of brain networks in the pathophysiological mechanisms of HM and may aid in the diagnosis of HM.

Drying kinetics and physicochemical properties of kumquat under hot air and air-impingement jet dryings.

Kumquat is famous for its unique flavor and nutritional value. In this study, the drying kinetics, moisture effective diffusivity, phytochemical properties, and antioxidant capacities of kumquat dried by hot air drying (HAD) and air-impingement jet drying (AIJD) were comparatively investigated. The results showed that drying rate, moisture effective diffusivity, and nutrient retention under AIJD were better than those under HAD. Fourteen polyphenols were identified by UPLC-QqQ-MS/MS in kumquat slices. The content of limonoid was significantly increased after AIJD. It was also found that high temperature contributed to a higher drying rate. However, most of the polyphenol components decreased at high drying temperatures. Accordingly, AIJD 60 °C was regarded as the optimum condition for kumquat drying. This work contributed to a better understanding of the drying character of kumquat under AIJD and showed the bioactive compounds and antioxidant activities are affected by drying methods.

Comparison of Peripheral Blood Regulatory T Cells and Functional Subsets Between Ocular and Generalized Myasthenia Gravis.

Purpose: This study aims to discuss the function mechanism of regulatory T cells and its subsets in the pathogenic process of myasthenia gravis by contracting the activation levels of those cells in peripheral blood among healthy people, patients with ocular myasthenia gravis (oMG) and patients with generalized myasthenia gravis (gMG). Method: Healthy people, newly diagnosed oMG patients, and gMG patients were enrolled in this study. The percentage of the CD3+CD4+CD25+ Treg cells, CD3+CD4+CD25+Foxp3+ Treg cells, CD3+CD4+CD25+Foxp3hi CD45RA-aTreg cells, CD3+CD4+CD25+Foxp3loCD45RA-n-sTreg cells, and CD3+CD4+CD25+ Foxp3loCD45RA+rTreg cells in the peripheral blood were examined by flow cytometry. And then analyzed the differences of Treg cells and its subsets among the study members. Results: The percentage of the CD4+CD25+Treg cells in the peripheral blood of oMG patients and gMG patients were both lower than that of healthy people (p < 0.05), the percentage of patients with oMG had no distinct difference with that of patients with gMG (p = 0.475), however. Also, the percentage of CD3+CD4+CD25+Foxp3+Treg cells in the oMG and gMG patients' group were both lower than that of healthy group. And the percentage of CD25+Foxp3+Treg cells in the peripheral blood of patients with oMG and healthy people were both higher than that of patients with gMG (p < 0.05). The percentage of rTreg in the CD3+CD4+CD25+Treg of the peripheral blood for both gMG and oMG patients' group were lower than healthy group (p < 0.05), but there was no statistical significance between the oMG and gMG patients' group (p = 0.232). The percentage of the aTreg cells in the CD3+CD4+CD25+Treg cells of the peripheral blood for the oMG patients was higher than that of gMG patients (p < 0.05), but both of them were lower than healthy group (p < 0.05). The percentage of n-sTreg cells in the peripheral blood descended among the gMG patients' group, oMG patients' group, and healthy group (p < 0.05). Conclusion: The changes in the number and function of Treg cells and its subsets can cause the impairment of negative immune regulation, which may mediate the triggering of oMG and its progression to gMG.

Ginsenoside Rc attenuates myocardial ischaemic injury through antioxidative and anti-inflammatory effects.

CONTEXT: Panax ginseng C. A. Meyer (Araliaceae) is a famous Asian medicine. Ginsenoside Rc is a component isolated from Panax ginseng. OBJECTIVE: This study evaluates the effect of ginsenoside Rc on myocardial ischaemic injury. MATERIALS AND METHODS: Male Swiss mice were subcutaneously injected with 50 mg/kg isoproterenol once a day for three days. Ginsenoside Rc (10, 20, or 40 mg/kg) was intragastrically administered 1 h after isoproterenol injection. The mice in the control group were subcutaneously injected with normal saline and intragastrically given 0.5% CMC-Na. CK-MB and troponin T were assayed. Histopathological examination of myocardium was conducted. The expression of Nrf2, GCLC, GCLM and HO-1 in heart tissues was evaluated by Western blot. RESULTS: In myocardial ischaemic mice, ginsenoside Rc reduced the levels of CK-MB (197.1 ± 15.7, 189.9 ± 19.0, 184.0 ± 14.4 vs. 221.6 ± 27.9) and troponin T (10.3 ± 1.7, 9.5 ± 1.3, 8.7 ± 1.7 vs. 13.4 ± 2.4). Ginsenoside Rc attenuated the necrosis and inflammatory cells infiltration in myocardium. Furthermore, ginsenoside Rc not only decreased the contents of MDA, TNF-α but also increased GSH level in the heart tissues. The expression of Nrf2, GCLC, GCLM and HO-1 was significantly increased in the animals treated with ginsenoside Rc. ML385, an Nrf2 inhibitor, blocked partially the ginsenoside Rc-mediated cardioprotective effect. Ginsenoside Rc attenuated myocardial ischaemic injury in mice, which may be, in part, through its antioxidative and anti-inflammatory effects. CONCLUSIONS: This study indicated that ginsenoside Rc might be a novel candidate for treatment of myocardial ischaemia.

Abnormal Large-Scale Neuronal Network in High Myopia.

Aim: Resting state functional magnetic resonance imaging (rs-fMRI) was used to analyze changes in functional connectivity (FC) within various brain networks and functional network connectivity (FNC) among various brain regions in patients with high myopia (HM). Methods: rs-fMRI was used to scan 82 patients with HM (HM group) and 59 healthy control volunteers (HC group) matched for age, sex, and education level. Fourteen resting state networks (RSNs) were extracted, of which 11 were positive. Then, the FCs and FNCs of RSNs in HM patients were examined by independent component analysis (ICA). Results: Compared with the HC group, FC in visual network 1 (VN1), dorsal attention network (DAN), auditory network 2 (AN2), visual network 3 (VN3), and sensorimotor network (SMN) significantly increased in the HM group. FC in default mode network 1 (DMN1) significantly decreased. Furthermore, some brain regions in default mode network 2 (DMN2), default mode network 3 (DMN3), auditory network 1 (AN1), executive control network (ECN), and significance network (SN) increased while others decreased. FNC analysis also showed that the network connection between the default mode network (DMN) and cerebellar network (CER) was enhanced in the HM group. Conclusion: Compared with HCs, HM patients showed neural activity dysfunction within and between specific brain networks, particularly in the DMN and CER. Thus, HM patients may have deficits in visual, cognitive, and motor balance functions.

Bone marrow NLRP3 inflammasome-IL-1ß signal regulates post-myocardial infarction megakaryocyte development and platelet production.

Platelet plays an important role in the progression of atherosclerosis. Recently it has been reported that myocardial infarction (MI) triggers megakaryopoiesis and thrombopoiesis in the bone marrow and leads to increased circulating platelets, which might contribute to the aggravation of atherosclerosis. However, the underlying mechanisms remain unclear. Here, we analyzed post-MI bone marrow tissue and found that MI induced an upregulation of bone marrow NOD-like Receptor Protein 3 (NLRP3) and subsequent secretion of IL-1ß, an essential stimulator of megakaryopoiesis. Targeting NLRP3 using a specific inhibitor MCC950 reduced bone marrow IL-1ß expression. Using bone marrow whole-mount immunofluorescence staining combined with flow cytometry, we demonstrated that MCC950 reduced megakaryocyte cellularity and maturity, and effectively attenuated the excessive platelet production after MI. Importantly, mice subjected to MI treated with MCC950 showed a higher survival rate compared with the only MI group. Taken together, this study shows that bone marrow NLRP3-IL-1ß signal regulates megakaryocyte development and platelet production after myocardial infarction. It provides a new hint that pharmacological inhibition of NLRP3 might become a potential therapeutic approach for controlling excessive thrombopoiesis after MI.

Prevalence of vitiligo and associated comorbidities in adults in Shanghai, China: a community-based, cross-sectional survey.

BACKGROUND: The prevalence of vitiligo has been reported to range from 0.1% to 8% worldwide, and vitiligo has been linked to some autoimmune and non-autoimmune diseases. This study aimed to estimate the prevalence of vitiligo and associated comorbidities in adults in Shanghai. METHODS: A community-based cross-sectional survey was conducted among 9,114 adults (4,288 males) in a community of Shanghai between October 2009 and January 2010. Face-to-face interviews were conducted at the home of each participant, and all respondents had their skin examined by dermatologists. The risks of comorbidities associated with vitiligo were evaluated by multiple logistic regression analysis. RESULTS: The estimated prevalence of vitiligo was 0.91%, and the standardized (age-adjusted) prevalence was 0.67%. Prevalence increased with age from 0.20% in 18-30 years to 1.59% in the 71-80 years age group. The presence of vitiligo was associated with increased risks of atopic dermatitis [adjusted odds ratio (aOR) =2.49; 95% confidence interval (95% CI): 1.46-4.23], urticaria (aOR =1.83; 95% CI: 1.11-3.04). and coronary heart disease (aOR =1.88; 95% CI: 1.03-3.41), although the association with coronary heart disease was only identified in subjects who were aged ≥60 years or overweight. CONCLUSIONS: The prevalence of vitiligo in Shanghai was comparable to that seen in previous studies and increased with age. Vitiligo was associated with increased risks of atopic dermatitis, urticaria, and coronary heart disease in adults.

Ginsenoside Rg2 Ameliorates Brain Injury After Intracerebral Hemorrhage in a Rat Model of Preeclampsia.

The incidence of maternal hemorrhagic stroke is elevated in women with preeclampsia during pregnancy. Panax ginseng is a traditional medicinal herb with numerous applications, and ginsenosides are the key bioactive compounds in Panax ginseng. This study aims to evaluate the effects of ginsenoside Rg2 on pregnancy outcomes and brain injury after intracerebral hemorrhage (ICH) in a rat model of preeclampsia. Preeclampsia was induced in rats by N(ω)-nitro-L-arginine methyl ester. Then, an ICH model was prepared by intrastriatal injection of bacterial collagenase. Ginsenoside Rg2 markedly elevated the survival ratio of fetuses. The placental and body weights were increased in the ginsenoside Rg2 group. Compared with the preeclampsia group, the Garcia test score of ginsenoside Rg2-treated rats was significantly increased. Ginsenoside Rg2 treatment ameliorated the ICH-induced augmentation of Evans blue extravasation, inhibited the ICH-induced elevation of brain water content, and reduced the interleukin-1ß and tumor necrosis factor-α levels in the hemorrhagic hemisphere after ICH in preeclampsia model rats. Furthermore, ginsenoside Rg2 treatment not only inhibited augmentation of TLR-4, MyD88, p-IκBα, and p-NF-κB expression but also abated the reduction of occludin and claudin-5 expression in the hemorrhagic hemisphere. The findings indicated that ginsenoside Rg2 improved pregnancy outcomes in a rat model of preeclampsia without decreasing the blood pressure and urine protein level. The findings also demonstrated that ginsenoside Rg2 ameliorated ICH-induced neurological disorder and blood-brain barrier dysfunction in an animal model of preeclampsia by regulating the TLR4/NF-κB signaling pathway.