Altered Neuromagnetic Activity in the Default Mode Network in Migraine and Its Subgroups (Episodic Migraine and Chronic Migraine).

BACKGROUND: The differences in the resting state spectral power and functional connectivity of the default mode network between people with migraine without aura (MwoA) and its subgroups differentiated by frequency (episodic migraine (EM) and chronic migraine (CM)) and healthy controls (HC) were investigated using magnetoencephalography. METHODS: In the resting state, the topological spatial structure of the brain in 33 MwoA patients and 22 HC was first studied using magnetoencephalography, followed by probing the neuroelectrical activity of 17 CM and 16 EM patients, to identify damage to their default mode network (DMN). The techniques used to investigate both spectral power and functional connectivity were minimum-paradigm estimation combined with Welch's technique and corrected amplitude envelope correlation. RESULTS: The differences between MwoA and its subgroups (CM and EM) and HC based on spectral power were mainly in the delta, theta, and alpha bands, while the differences in functional connectivity were primarily in the delta, alpha, and beta bands. In the delta and theta bands, the spectral power of MwoA and its subgroups (CM and EM) was higher than in the HC group. The spectral power of MwoA and its subgroups (CM and EM) was lower in the alpha band. In terms of functional connectivity, the corrected amplitude envelope correlation of MwoA and its subgroups (CM and EM) was lower than the HC group in the bands with spectral differences. People with EM and CM differed in the spectral power in the left medial prefrontal cortex and the right lateral temporal cortex in the alpha band, where correlation analysis and logistic regression analysis showed that the intensity of the spectral power of the left medial prefrontal cortex was negatively correlated with headache frequency. CONCLUSIONS: The spectral power of the left medial prefrontal cortex in the alpha band may serve as a biomarker that is associated with the number of monthly headache attacks and may be a potential neuromodulatory target for controlling migraine chronicity.

Differences in generation and maintenance between ictal and interictal generalized spike-and-wave discharges in childhood absence epilepsy: A magnetoencephalography study.

PURPOSE: Childhood absence epilepsy (CAE) is characterized by impaired consciousness and distinct electroencephalogram (EEG) patterns. However, interictal epileptiform discharges (IEDs) do not lead to noticeable symptoms. This study examines the disparity between ictal and interictal generalized spike-and-wave discharges (GSWDs) to determine the mechanisms behind CAE and consciousness. METHODS: We enrolled 24 patients with ictal and interictal GSWDs in the study. The magnetoencephalography (MEG) data were recorded before and during GSWDs at a sampling rate of 6000 Hz and analyzed across six frequency bands. The absolute and relative spectral power were estimated with the Minimum Norm Estimate (MNE) combined with the Welch technique. All the statistical analyses were performed using paired-sample tests. RESULTS: During GSWDs, the right lateral occipital cortex indicated a significant difference in the theta band (5-7 Hz) with stronger power (P = 0.027). The interictal group possessed stronger spectral power in the delta band (P < 0.01) and weaker power in the alpha band (P < 0.01) as early as 10 s before GSWDs in absolute and relative spectral power. Additionally, the ictal group revealed enhanced spectral power inside the occipital cortex in the alpha band and stronger spectral power in the right frontal regions within beta (15-29 Hz), gamma 1 (30-59 Hz), and gamma 2 (60-90 Hz) bands. CONCLUSIONS: GSWDs seem to change gradually, with local neural activity changing even 10 s before discharge. During GSWDs, visual afferent stimulus insensitivity could be related to the impaired response state in CAE. The inhibitory signal in the low-frequency band can shorten GSWD duration, thereby achieving seizure control through inhibitory effect strengthening.

EphB4 Regulates Self-Renewal, Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro.

BACKGROUND/AIMS: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs). This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs) in vitro. METHODS: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs. RESULTS: Our results show that shRNA-mediated EphB4 reduction profoundly impaired hNSCs self-renewal and proliferation. Furthermore, detection of differentiation revealed that knockdown of EphB4 inhibited hNSCs differentiation towards a neuronal lineage and promoted hNSCs differentiation to glial cells. In contrast, EphB4 overexpression promoted hNSCs self-renewal and proliferation, further induced hNSCs differentiation towards a neuronal lineage and inhibited hNSCs differentiation to glial cells. Moreover, we found that EphB4 regulates cell proliferation mediated by the Abl-CyclinD1 pathway. CONCLUSION: These studies provide strong evidence that fine tuning of EphB4 expression is crucial for the proliferation and neuronal differentiation of hNSCs, suggesting that EphB4 might be an interesting target for overcoming some of the therapeutic limitations of neuronal loss in brain diseases.

Tetrahydroxystilbene glucoside inhibits α-synuclein aggregation and apoptosis in A53T α-synuclein-transfected cells exposed to MPP.

Increasing evidence has solidified the involvement of α-synuclein (α-Syn) and neurotoxins in the pathogenesis of Parkinson's disease (PD), suggesting a combination of genetic and environmental influences. 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) is one of the main active components extracted from Polygonum multiflorum. The purpose of the present study was to investigate the effects of TSG on α-Syn aggregation, mitochondrial dysfunction, oxidative stress, and apoptosis in vitro. A53T mutant α-synuclein-transfected cells (A53T AS cells) plus MPP+ exposure were used as a complex cell model of PD. The expression of proteins was determined by Western blot assay. Flow cytometry was utilized to measure mitochondrial membrane potential and apoptosis. The results showed that MPP+ exposure for 24 h induced more severe damage in A53T AS cells than in vector control cells. Pretreatment of TSG for 24 h significantly increased the cell viability; decreased lactate dehydrogenase leakage; inhibited α-Syn over-expression and aggregation; elevated mitochondrial membrane potential; decreased reactive oxygen species, Bax/Bcl-2 ratio, and caspase-3 activity; and inhibited apoptosis in A53T AS cells exposed to MPP+. These results suggest that TSG may be an attractive candidate for PD therapy.

Impact of carotid atherosclerosis combined with hypercholesterolemia on cerebral microvessels and brain parenchyma in a new complex rat model.

Most previous investigations about stroke caused by carotid atherosclerosis have focused on thromboembolism. There is a lack of knowledge about pathophysiology of the brain before ischemic insults. The objective of this study was to develop a new model of hypercholesterolemia plus carotid injury and to investigate the impact of carotid atherosclerosis combined with hypercholesterolemia in the rat brain. The complex rat model was developed by carotid injury induced by an air-drying endothelial denudation method after high cholesterol diet for 2 weeks. Plasma cholesterol, carotid pathomorphology, oxidative stress and inflammation in cerebral microvessels and brain parenchyma were measured at 7, 14 and 28 days after carotid surgery. The results showed that plasma concentrations of total cholesterol and low density lipoprotein-cholesterol were significantly increased, and severe carotid atherosclerosis and stenosis was observed in the complex rat model at 14 and 28 days after carotid surgery. The activity of superoxide dismutase was decreased, while the content of malondialdehyde was increased in cerebral microvessels and brain parenchyma. The levels of tumor necrosis factor-α and interleukin-1ß were elevated in brain tissues of this model. Almost all above changes were more severe than those in either hypercholesterolemia alone group or carotid injury alone group. These results suggest that this complex rat model may more resemble human disease than the classic acute ischemic insult model for assessing the impact of carotid atherosclerosis as a preexisting disease on cerebral microcirculation and brain tissue.

Interictal magnetic signals in new-onset Rolandic epilepsy may help with timing of treatment selection.

OBJECTIVE: With research progress on Rolandic epilepsy (RE), its "benign" nature has been phased out. Clinicians are exhibiting an increasing tendency toward a more assertive treatment approach for RE. Nonetheless, in clinical practice, delayed treatment remains common because of the "self-limiting" nature of RE. Therefore, this study aimed to identify an imaging marker to aid treatment decisions and select a more appropriate time for initiating therapy for RE. METHODS: We followed up with children newly diagnosed with RE, classified them into medicated and non-medicated groups according to the follow-up results, and compared them with matched healthy controls. Before beginning follow-up visits, interictal magnetic data were collected using magnetoencephalography in treatment-naïve recently diagnosed patients. The spectral power of the whole brain during initial diagnosis was determined using minimum normative estimation combined with the Welch technique. RESULTS: A difference was observed in the magnetic source intensity within the left caudal anterior cingulate and precentral and postcentral gyri in the delta band between the medicated and non-medicated groups. The results revealed good discriminatory ability within the receiver operator characteristic curve. In the medicated group, there was a specific change in the frontotemporal magnetic source intensity, which shifted from high to low frequencies, compared with the healthy control group. SIGNIFICANCE: The intensity of the precentral gyrus magnetic source within the delta band showed good specificity. Considering the rigor of initial treatment, the intensity of the precentral gyrus magnetic source can provide some help as an imaging marker for initial RE treatment, particularly for the timing of treatment initiation.

Inflammation accelerating intestinal fibrosis: from mechanism to clinic.

Intestinal fibrosis is a prevalent complication of IBD that that can frequently be triggered by prolonged inflammation. Fibrosis in the gut can cause a number of issues, which continue as an ongoing challenge to healthcare systems worldwide. The primary causes of intestinal fibrosis are soluble molecules, G protein-coupled receptors, epithelial-to-mesenchymal or endothelial-to-mesenchymal transition, and the gut microbiota. Fresh perspectives coming from in vivo and in vitro experimental models demonstrate that fibrogenic pathways might be different, at least to some extent, independent of the ones that influence inflammation. Understanding the distinctive procedures of intestinal fibrogenesis should provide a realistic foundation for targeting and blocking specific fibrogenic pathways, estimating the risk of fibrotic consequences, detecting early fibrotic alterations, and eventually allowing therapy development. Here, we first summarize the inflammatory and non-inflammatory components of fibrosis, and then we elaborate on the underlying mechanism associated with multiple cytokines in fibrosis, providing the framework for future clinical practice. Following that, we discuss the relationship between modernization and disease, as well as the shortcomings of current studies. We outline fibrosis diagnosis and therapy, as well as our recommendations for the future treatment of intestinal fibrosis. We anticipate that the global review will provides a wealth of fresh knowledge and suggestions for future fibrosis clinical practice.

Impact of subthalamic nucleus deep brain stimulation at different frequencies on neurogenesis in a rat model of Parkinson's disease.

Neurogenesis, play a vital role in neuronal plasticity of adult mammalian brains, and its dysregulation is present in the pathophysiology of Parkinson's disease (PD). While subthalamic nucleus deep brain stimulation (STN-DBS) at various frequencies has been proven effective in alleviating PD symptoms, its influence on neurogenesis remains unclear. This study aimed to investigate the effects of 1-week electrical stimulation at frequencies of 60Hz, 130Hz, and 180Hz on neurogenesis in the subventricular zone (SVZ) of PD rats. A hemiparkinsonian rat model was established using 6-hydroxydopamine and categorized into six groups: control, PD, sham stimulation, 60Hz stimulation, 130Hz stimulation, and 180Hz stimulation. Motor function was assessed using the open field test and rotarod test after one week of STN-DBS at different frequencies. Tyrosine hydroxylase (TH) expression in brain tissue was analyzed via Western blot and immunohistochemistry. Immunofluorescence analysis was conducted to evaluate the expression of BrdU/Sox2, BrdU/GFAP, Ki67/GFAP, and BrdU/DCX in bilateral SVZ and the rostral migratory stream (RMS). Our findings revealed that high-frequency STN-DBS improved motor function. Specifically, stimulation at 130Hz increased dopaminergic neuron survival in the PD rat model, while significantly enhancing the proliferation of neural stem cells (NSCs) and neuroblasts in bilateral SVZ. Moreover, this stimulation effectively facilitated the generation of new NSCs in the ipsilateral RMS and triggered the emergence of fresh neuroblasts in bilateral RMS, with notable presence within the lesioned striatum. Conversely, electrical stimulation at 60Hz and 180Hz did not exhibit comparable effects. The observed promotion of neurogenesis in PD rats following STN-DBS provides valuable insights into the mechanistic basis of this therapeutic approach for PD.

Variation in functional networks between clinical and subclinical discharges in childhood absence epilepsy: A multi-frequency MEG study.

OBJECTIVE: Two types of spike-and-wave discharges (SWDs) exist in childhood absence epilepsy (CAE): clinical discharges are prolonged and manifest primarily as impaired consciousness, whereas subclinical discharges are brief with few objectively visible symptoms. This study aimed to compare neural functional network and default mode network (DMN) activity between clinical and subclinical discharges to better understand the underlying mechanism of CAE. METHODS: Using magnetoencephalography (MEG) data from 21 patients, we obtained 25 segments each of clinical discharges and subclinical discharges. Amplitude envelope correlation analysis was used to construct functional networks and graph theory was used to calculate network topological data. We then compared differences in functional connectivity within the DMN between clinical and subclinical discharges. All statistical comparisons were performed using paired-sample tests. RESULTS: Compared to subclinical discharges, the functional network of clinical discharges exhibited higher synchronization - particularly in the parahippocampal gyrus - as early as 10 s before the seizure. Additionally, the functional network of clinical SWDs presented an anterior shift of key nodes in the alpha frequency band. Regarding clinical discharge progression, there were gradual increases in the parameter node strengths (S), clustering coefficients (C), and global efficiency (E) of the functional networks, while the path lengths (L) decreased. These changes were most prominent at the onset of discharges and followed by some recovery in the high-frequency bands, but no significant change in the low-frequency bands. Furthermore, connections within the DMN during the discharge period were significantly stronger for clinical discharge compared to subclinical discharges. CONCLUSIONS: These findings suggest that a more regular network before abnormal discharges in clinical discharges contributes to SWD explosion and that the parahippocampal gyrus plays an important role in maintaining oscillations. An absence seizure is a gradual process and the emergence of SWDs may be accompanied by initiation of inhibitory mechanisms. Enhanced functional connectivity among DMN brain regions may indicate that patients have entered a state of introspection, and functional abnormalities in the parahippocampal gyrus may be associated with patients' transient memory loss.

Altered neuromagnetic activity in default mode network in childhood absence epilepsy.

Purpose: The electrophysiological characterization of resting state oscillatory functional connectivity within the default mode network (DMN) during interictal periods in childhood absence epilepsy (CAE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in CAE. Methods: Using a cross-sectional design, we analyzed MEG data from 33 children newly diagnosed with CAE and 26 controls matched for age and sex. The spectral power and functional connectivity of the DMN were estimated using minimum norm estimation combined with the Welch technique and corrected amplitude envelope correlation. Results: Default mode network showed stronger activation in the delta band during the ictal period, however, the relative spectral power in other bands was significantly lower than that in the interictal period (p corrected < 0.05 for DMN regions, except bilateral medial frontal cortex, left medial temporal lobe, left posterior cingulate cortex in the theta band, and the bilateral precuneus in the alpha band). It should be noted that the significant power peak in the alpha band was lost compared with the interictal data. Compared with controls, the interictal relative spectral power of DMN regions (except bilateral precuneus) in CAE patients was significantly increased in the delta band (p corrected < 0.01), whereas the values of all DMN regions in the beta-gamma 2 band were significantly decreased (p corrected < 0.01). In the higher frequency band (alpha-gamma1), especially in the beta and gamma1 band, the ictal node strength of DMN regions except the left precuneus was significantly higher than that in the interictal periods (p corrected < 0.01), and the node strength of the right inferior parietal lobe increased most significantly in the beta band (Ictal: 3.8712 vs. Interictal: 0.7503, p corrected < 0.01). Compared with the controls, the interictal node strength of DMN increased in all frequency bands, especially the right medial frontal cortex in the beta band (Controls: 0.1510 vs. Interictal: 3.527, p corrected < 0.01). Comparing relative node strength between groups, the right precuneus in CAE children decreased significantly (ß: Controls: 0.1009 vs. Interictal: 0.0475; γ 1: Controls:0.1149 vs. Interictal:0.0587, p corrected < 0.01) such that it was no longer the central hub. Conclusion: These findings indicated DMN abnormalities in CAE patients, even in interictal periods without interictal epileptic discharges. Abnormal functional connectivity in CAE may reflect abnormal anatomo-functional architectural integration in DMN, as a result of cognitive mental impairment and unconsciousness during absence seizure. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction, and prognosis in CAE patients.

Alternations of neuromagnetic activity across neurocognitive core networks among benign childhood epilepsy with centrotemporal spikes: A multi-frequency MEG study.

Objective: We aimed to investigate the alternations of neuromagnetic activity across neurocognitive core networks among early untreated children having benign childhood epilepsy with centrotemporal spikes (BECTS). Methods: We recorded the Magnetoencephalography (MEG) resting-state data from 48 untreated children having BECTS and 24 healthy children. The fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV) was utilized to divide the children with BECTS into two groups: the cognitive impairment (CI) group with a full-scale intelligence quotient (FSIQ) of < 90 and the cognitive non-impairment (CNI) group with an FSIQ of > 90. We selected 26 bilateral cognitive-related regions of interest based on the triple network model. The neurocognitive core network spectral power was estimated using a minimum norm estimate (MNE). Results: In the CNI group, the spectral power inside the bilateral anterior cingulate cortex (ACC) and the bilateral caudal middle frontal cortex (CMF) enhanced within the delta band and reduced within the alpha band. Both the CI and the CNI group demonstrated enhanced spectral power inside the bilateral posterior cingulate cortex (PCC), bilateral precuneus (PCu) region, bilateral superior and middle temporal cortex, bilateral inferior parietal lobe (IPL), and bilateral supramarginal cortex (SM) region in the delta band. Moreover, there was decreased spectral power in the alpha band. In addition, there were consistent changes in the high-frequency spectrum (> 90 Hz). The spectral power density within the insula cortex (IC), superior temporal cortex (ST), middle temporal cortex (MT), and parahippocampal cortex (PaH) also decreased. Therefore, studying high-frequency activity could lead to a new understanding of the pathogenesis of BECTS. Conclusion: The alternations of spectral power among neurocognitive core networks could account for CI among early untreated children having BECTS. The dynamic properties of spectral power in different frequency bands could behave as biomarkers for diagnosing new BECTS.

Current perspective on biological properties of plasmacytoid dendritic cells and dysfunction in gut.

Plasmacytoid dendritic cells (pDCs), a subtype of DC, possess unique developmental, morphological, and functional traits that have sparked much debate over the years whether they should be categorized as DCs. The digestive system has the greatest mucosal tissue overall, and the pDC therein is responsible for shaping the adaptive and innate immunity of the gastrointestinal tract, resisting pathogen invasion through generating type I interferons, presenting antigens, and participating in immunological responses. Therefore, its alleged importance in the gut has received a lot of attention in recent years, and a fresh functional overview is still required. Here, we summarize the current understanding of mouse and human pDCs, ranging from their formation and different qualities compared with related cell types to their functional characteristics in intestinal disorders, including colon cancer, infections, autoimmune diseases, and intestinal graft-versus-host disease. The purpose of this review is to convey our insights, demonstrate the limits of existing research, and lay a theoretical foundation for the rational development and use of pDCs in future clinical practice.

Morroniside induces cardiomyocyte cell cycle activity and promotes cardiac repair after myocardial infarction in adult rats.

Introduction: Acute myocardial infarction (AMI) is characterized by the loss of cardiomyocytes, which impairs cardiac function and eventually leads to heart failure. The induction of cardiomyocyte cell cycle activity provides a new treatment strategy for the repair of heart damage. Our previous study demonstrated that morroniside exerts cardioprotective effects. This study investigated the effects and underlying mechanisms of action of morroniside on cardiomyocyte cell cycle activity and cardiac repair following AMI. Methods: Neonatal rat cardiomyocytes (NRCMs) were isolated and exposed to oxygen-glucose deprivation (OGD) in vitro. A rat model of AMI was established by ligation of the left anterior descending coronary artery (LAD) in vivo. Immunofluorescence staining was performed to detect newly generated cardiomyocytes. Western blotting was performed to assess the expression of cell cycle-related proteins. Electrocardiography (ECG) was used to examine pathological Q waves. Masson's trichrome and wheat germ agglutinin (WGA) staining assessed myocardial fibrosis and hypertrophy. Results: The results showed that morroniside induced cardiomyocyte cell cycle activity and increased the levels of cell cycle proteins, including cyclin D1, CDK4, cyclin A2, and cyclin B1, both in vitro and in vivo. Moreover, morroniside reduced myocardial fibrosis and remodeling. Discussion: In conclusion, our study demonstrated that morroniside stimulates cardiomyocyte cell cycle activity and cardiac repair in adult rats, and that these effects may be related to the upregulation of cell cycle proteins.

An emerging view on vascular fibrosis molecular mediators and relevant disorders: from bench to bed.

Vascular fibrosis is a widespread pathologic condition that arises during vascular remodeling in cardiovascular dysfunctions. According to previous studies, vascular fibrosis is characterized by endothelial matrix deposition and vascular wall thickening. The RAAS and TGF-ß/Smad signaling pathways have been frequently highlighted. It is, however, far from explicit in terms of understanding the cause and progression of vascular fibrosis. In this review, we collected and categorized a large number of molecules which influence the fibrosing process, in order to acquire a better understanding of vascular fibrosis, particularly of pathologic dysfunction. Furthermore, several mediators that prevent vascular fibrosis are discussed in depth in this review, with the aim that this will contribute to the future prevention and treatment of related conditions.

Composite Indices of the Color-Picture Version of Boston Naming Test Have Better Discriminatory Power: Reliability and Validity in a Chinese Sample with Diverse Neurodegenerative Diseases.

BACKGROUND: The Boston Naming Test (BNT) is the most widely used measure to assess anomia. However, it has been criticized for failing to differentiate the underlying cognitive process of anomia. OBJECTIVE: We validated the color-picture version of BNT (CP-BNT) in a sample with diverse neurodegenerative dementia diseases (NDDs). We also verified the differential ability of the composite indices of CP-BNT across NDDs groups. METHODS: The present study included Alzheimer's disease (n = 132), semantic variant primary progressive aphasia (svPPA, n = 53), non-svPPA (n = 33), posterior cortical atrophy (PCA, n = 35), and normal controls (n = 110). We evaluated psychometric properties of CP-BNT for the spontaneous naming (SN), the percentage of correct responses on semantic cuing and word recognition cuing (% SC, % WR). Receiver operating characteristic analysis was used to examine the discriminatory power of SN alone and the composite indices (SN, % SC, and % WR). RESULTS: The CP-BNT had sufficient internal consistency, good convergent, divergent validity, and criterion validity. Different indices of CP-BNT demonstrated distinct cognitive underpinnings. Category fluency was the strongest predictor of SN (ß= 0.46, p < 0.001). Auditory comprehension tests highly associated with % WR (Sentence comprehension: ß= 0.22, p = 0.001; Word comprehension: ß= 0.20, p = 0.001), whereas a lower visuospatial score predicted % SC (ß= -0.2, p = 0.001). Composite indices had better predictability than the SN alone when differentiating between NDDs, especially for PCA versus non-svPPA (area under the curve increased from 63.9% to 81.2%). CONCLUSION: The CP-BNT is a highly linguistically relevant test with sufficient reliability and validity. Composite indices could provide more differential information beyond SN and should be used in clinical practice.

Top-Emitting Microcavity Light-Emitting Diodes Based on All-Thermally Evaporated Lead-Free Copper Halide Self-Trapped-Exciton Emitters.

Lead-free metal halide light-emitting diodes (LEDs) based on cesium copper halide (CsCu2I3) self-trapped-exciton (STE) emissions show great potential in lighting and color display applications, especially because of their nontoxicity and earth abundance. However, so far, the efficiency and color purity of CsCu2I3-based LEDs remain low. Here we demonstrate the emission of a CsCu2I3 emitter can be enhanced and narrowed in a top-emitting microcavity device. Consequently, the CsCu2I3-based LED device with the assistance of a top-emitting microcavity has significantly narrowed and enhanced the emission spectrum with a full width at half-maximum of 59 nm and a maximum forward brightness of 14767 cd m-2. To the best of our knowledge, this work achieves the narrowest CsCu2I3 LED spectra and demonstrates the potential of employing the microcavity effect to increase the efficiency and color purity of STE-based light-emitting devices.

Morroniside Regulates Endothelial Cell Function via the EphrinB Signaling Pathway after Oxygen-Glucose Deprivation In Vitro.

Proangiogenic treatment is a potential treatment for acute myocardial infarction (AMI). Morroniside was previously discovered to increase post-AMI angiogenesis in rats as well as the proliferation of rat coronary artery endothelial cells (RCAECs). However, the effects of morroniside on other endothelial cell (EC) functions and underlying mechanisms are unknown. To further clarify the vascular biological activity of morroniside, this work focused on investigating how morroniside influenced endothelial cell functions, such as cell viability, tube formation capacity, migration, and adhesion, and to explore the signaling pathway. Oxygen-glucose deprivation causes ischemic damage in RCAECs (OGD). In vitro investigations were carried out to explore the involvement of morroniside in EC function and pathways mediated by ephrinB. The results revealed that the number of BrdU+ cells and cell viability in the high-dose group were considerably greater than in the OGD group (P < 0.05). The ability of tube formation evaluated by total tube length, tube-like structural junction, and tube area was significantly higher in the morroniside group than in the OGD group (P < 0.001). Morroniside considerably improved migration and adhesion abilities compared to OGD group (P < 0.05, P < 0.01, P < 0.001). The protein expression levels of the ephrinB reverse signaling pathway were substantially greater in the morroniside group than in the OGD group (P < 0.05, P < 0.01). In conclusion, the current study demonstrated that morroniside modulates endothelial cell function via ephrinB reverse signaling pathways and provided a novel insight and therapeutic strategy into vascular biology.

Lanthanide-doping enables kinetically controlled growth of deep-blue two-monolayer halide perovskite nanoplatelets.

Impurity doping has been widely applied in nanomaterial synthesis for modulating the crystallographic phase, morphology, and size of nanocrystalline materials, but mostly by altering thermodynamic equilibria of final products. Here, we report the use of lanthanide dopants to manipulate the growing kinetics of halide perovskite nanocrystals to enable the preparation of highly anisotropic two-dimensional (2D) CsPbBr3-based nanoplatelets with precisely controlled thickness. We demonstrate that the incorporation of trivalent lanthanides increases the energy barrier in growing three-monolayer (3 ML) CsPbBr3 from a 2 ML intermediate. It enables the growth of thermodynamically unfavorable 2 ML CsPbBr3 products through kinetic control. This finding provides a novel approach for dimensional control of perovskite nanocrystals with strong quantum confinement. It offers opportunities to generate deep-blue emitting (at 430 nm) CsPbBr3:Lu3+ nanoplatelets with good structural- and photo-stabilities potentially useful for many applications including light-emitting, lasers, and photocatalysis.

Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia.

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.

Morroniside enhances angiogenesis and improves cardiac function following acute myocardial infarction in rats.

Angiogenesis is critical for re-establishing blood supply to the ischemic myocardium after acute myocardial infarction (AMI). This study aimed to investigate the effects of morroniside on angiogenesis after AMI and explored associated proangiogenic mechanisms. A rat model of AMI was established by ligation of the left anterior descending coronary artery followed by administration of three doses of morroniside. Immunofluorescence staining was performed to identify newly generated endothelial cells and arterioles. The protein expression levels associated with angiogenesis were examined by western blots. Echocardiography was used to examine cardiac function. Our data revealed that morroniside promoted angiogenesis and improved cardiac function in rats with AMI. The proangiogenic effect of morroniside might be mediated by the VEGFA/VEGF receptor 2 signaling pathway.