Investigating the relationship between intracranial atherosclerotic plaque remodelling and diabetes using high-resolution vessel wall imaging

BACKGROUND Intracranial atherosclerosis,a leading cause of stroke,involves arterial plaque formation.This study explores the link between plaque remodelling patterns and diabetes using high-resolution vessel wall imaging(HR-VWI).AIM To investigate the factors of intracranial atherosclerotic remodelling patterns and the relationship between intracranial atherosclerotic remodelling and diabetes mellitus using HR-VWI.METHODS Ninety-four patients diagnosed with middle cerebral artery or basilar artery INTRODUCTION Intracranial atherosclerotic disease is one of the main causes of ischaemic stroke in the world,accounting for approx-imately 10%of transient ischaemic attacks and 30%-50%of ischaemic strokes[1].It is the most common factor among Asian people[2].The adaptive changes in the structure and function of blood vessels that can adapt to changes in the internal and external environment are called vascular remodelling,which is a common and important pathological mechanism in atherosclerotic diseases,and the remodelling mode of atherosclerotic plaques is closely related to the occurrence of stroke.Positive remodelling(PR)is an outwards compensatory remodelling where the arterial wall grows outwards in an attempt to maintain a constant lumen diameter.For a long time,it was believed that the degree of stenosis can accurately reflect the risk of ischaemic stroke[3-5].Previous studies have revealed that lesions without significant luminal stenosis can also lead to acute events[6,7],as summarized in a recent meta-analysis study in which approximately 50%of acute/subacute ischaemic events were due to this type of lesion[6].Research[8,9]has pointed out that the PR of plaques is more dangerous and more likely to cause acute ischaemic stroke.Previous studies[10-13]have found that there are specific vascular remodelling phenomena in the coronary and carotid arteries of diabetic patients.However,due to the deep location and small lumen of intracranial arteries and limitations of imaging techniques,the relationship between intracranial arterial remodelling and diabetes is still unclear.In recent years,with the development of magnetic resonance technology and the emergence of high-resolution(HR)vascular wall imaging,a clear and multidimensional display of the intracranial vascular wall has been achieved.Therefore,in this study,HR wall imaging(HR-VWI)was used to display the remodelling characteristics of bilateral middle cerebral arteries and basilar arteries and to explore the factors of intracranial vascular remodelling and its relationship with diabetes.

Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction

Objective: This study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction. Methods: Forty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson’s trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis. Results: The fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group, ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4 groups. Conclusion: Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.

Neural regeneration after peripheral nerve injury repair is a system remodelling process of interaction between nerves and terminal effector

In China, there are approximately 20 million people suffering from peripheral nerve injury and this number is increasing at a rate of 2 million per year. These patients cannot live or work independently and are a heavy responsibility on both family and society because of extreme disability and dysfunction caused by peripheral nerve injury （PNI）. Thus, repair of PNI has become a major public health issue in China.

From Sméagol to Gollum: Mechanical Stress and Bone Remodelling

This imaginary transformation from Sméagol to Gollum is a dramatization of the illusive repercussions of mechanical stress affecting bone. This paper presents the main ideas of mechanical stress and bone remodelling from a novel’s perspective. The object of this study is to provide evidence for new ways to explore bone’s functional adaptation to mechanical stress made through the copious interpretation and integration of new and existing literature. It tackles the underlying biology of bone cells and how they detect and react to strain stimuli. The different types of mechanical demands in daily activities are sifted through and any misconceptions found fallible in literature are refined. A personal experience of a stress fracture is reviewed to parallel the implications that lead to the incident with the findings on the link between mechanical stress and bone remodelling. Some factors regarding age, gender and ethnicity and the interplay with mechanical stress influencing bone remodelling are considered. Brief overviews of three new medical novelties in bone healing are outlined, hoping that these interventions of proper medical techniques can be a change for the better: one from Gollum to Sméagol rather than vice versa.

Contribution of mi RNAs to ion-channel remodelling in atrial fibrillation

Atrial fibrillation(AF) is the most commonly encountered clinical arrhythmia associated with pronounced mortality and morbidity, which are related to palpitations, fainting, congestive heart failure, and stroke. Prolonged episodes of AF promote AF persistence mainly due to electrical remodelling that alters ion-channel expression and/or function. Micro RNAs(mi RNAs), a new class of noncoding mR NAs of around 22 nucleotides in length, have recently emerged as one of the key players in the geneexpression regulatory networks. The potential roles of miR NAs in controlling AF have recently been investigated. Several recent studies have provided promising results for a better understanding of the molecular mechanisms of AF. In this review, we summarize the mechanism of miR NAs as regulators of ion-channel gene expression and their role in causing AF through electrical remodelling.

Effects of omacor^®on left ventricular remodelling consecutive to post myocardial infarction special issue-myocardial infarction

Ventricular remodelling is the main trigger of the development of heart failure. Therefore, the reduction of structural remodelling is known to prevent the development of heart failure. The aim of the present study was to investigate the effects of OMACOR?, a well known mixture of EPA and DHA in an experimental model of heart failure induced by occlusion of left descending coronary artery and the reperfusion within 2 months. After a long term treatment of 2 months;OMACOR? (100 mg/kg) statistically significantly reduced the expansion of infarcted zone (35% ± 4%, P ± 3% in the vehicle group). The phosphorylation of Cx43 as biomarker of the cardiac remodelling was visualised by immunofluorescence in rat’s heart at the end of the study. In the vehicle-infarcted group, a significant de-phosphorylation of Cx43 was observed (8.2 ± 1.0 u.a, n = 8 compared to 11.8 ± 1.3 u.a in the sham group, n = 9) confirming a remodelling process in the infarcted group. In the group treated with OMACOR?,the de-phosphorylation of Cx43 was no longer observed compared to the sham group (16.4 ± 2.9 u.a, n = 9, NS). The present results demonstrate that a long term treatment with OMA-COR? reduced the infarcted size in experimental models of heart failure and that these anti-remodelling effects are due at least in part by resynchronizing the gap junction activity.

EXPERIMENTAL STUDY OF THE BIOCHEMICAL REMODELLING OF VENTRICULAR COLLAGEN FOLLOWING MYOCARDIAL INFARCTION IN RATS TREATED WITH CAPTOPRIL

The present study is to determine the effects of captoprll treatment on myocyte hypertropay. collagen concentration, the total collagen content, type Ⅰ and type,Ⅲ collaged Protein ratio[Ⅰ / Ⅲ (p)] and their mRNA ratio [Ⅰ / Ⅲ (R)]3 In non-infarcted area(NⅡA), infarcted area(ⅡA) ofleft ventricle (LV) and right ventricle(RV) rollowing myocardial inrarction (MⅡ) in rats. The results showed: ①Captopril treatment can prevent myocyte hypertrophy in CⅡA and RV, but its effectson biochemical remodelling or collaged in CⅡA, RV and ⅡA were different. In NⅡA, the total collagencontent, collagen concentration and the Ⅰ /Ⅲ (P) were returned to their control values respectively.However, captopril treatment only decreased the total collagen content in RV and had no significanteffects on the total collagen content, collagen concentration and Ⅰ /Ⅲ (P) in ⅡA; ② The changes ofⅠ /Ⅲ (R) In CⅡA, ⅡA aam RV showed similar patterns to their Ⅰ /Ⅲ (P) respctily The resultssuggest:① The adulatory mechanism of collageu remodelling may be different in various hypertrophy models. Accompanied'by the regression of myocyte hypertrophy, the changes of collagen matrixmay not occur concurrently; ② The efects of captopril treatment on collagen remodelling may bedue to its decreasing angiotensiu Ⅱ level, and then influencing collagen synthesis of cardiac fibroblast on the level of gene expression.

Evaluation of left atrial remodelling following percutaneous left atrial appendage closure

Atrial fibrillation prevalence is increasing with age, reaching up to 5% of patients older than 65 years, and is associated with 20%-30% of stroke episodes in that population.

Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties

The treatment of chronic and non-healing wounds in diabetic patients remains a major medical problem.Recent reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity,good drug-loading ability and sustained drug release properties.As a typical example,hyaluronic acid dressing(Healoderm)has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ulcers.However,the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound microenvironment.Due to the intricacy of diabetic wounds,antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice,although these medications are easily hindered by the hostile environment.In this case,scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds(such as high glucose and low pH)or combined with external stimuli(such as light or magnetic field)to achieve controllable drug release,gel degradation,and microenvironment improvements in order to overcome these clinical issues.These responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound dressings.Here,we review recent advances on responsive-hydrogel dressings towards diabetic wound healing,with focus on hydrogel structure design,the principle of responsiveness,and the behavior of degradation.Last but not least,the advantages and limitations of these responsive-hydrogels in clinical applications will also be discussed.We hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.

Reconstruction of Postinfarcted Cardiac Functions Through Injection of Tanshinone ⅡA@Reactive Oxygen Species-Sensitive Microspheres Encapsulated in a Thermoreversible Hydrogel

Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death,highlighting the urgent clinical need for effective therapies.Recently,tanshinoneⅡA has been identified as a promising therapeutic agent for myocardial infarction.However,efficient delivery remains a major issue that limits clinical translation.To address this problem,an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid)gel(PLGA-PEG-PLGA)system encapsulating tanshinoneⅡA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinoneⅡA)has been designed and synthesized in this study.The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature.Microspheres initially immobilized by the gel exhibit excellent reactive oxygen species-triggered release properties in a high-reactive oxygen species environment after myocardial infarction onset.As a result,encapsulated tanshinoneⅡA is effectively released into the infarcted myocardium,where it exerts local anti-pyroptotic and anti-inflammatory effects.Importantly,the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinoneⅡA.Therefore,this novel,precision-guided intra-tissue therapeutic system allows for customized local release of tanshinoneⅡA,presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.

Effect of nifekalant on acute electrical remodelling in rapid atrial pacing canine model

Background Nifekalant may prevent atrial fibrillation （AF） and possibly be useful in treatment of atrial tachyarrhythmia in patients with severe heart failure. This study investigated the electophysiologic effect of nifekalant on the acute atrial remodeling in rapid atrial pacing （RAP） model of canine. Methods Twelve mongrel dogs subjected to rapid stimulation （400 beats/min） at left atrial appendage （LAA） for 24 hours, were randomized into the control group （rapid pacing only, n=6） and the nifekalant group （intravenous nifekalant therapy immediately after RAP, n=6）. Atrial electrophysiological parameters were measured in right atrium, coronary sinus, LAA, posterior wall of left atrium （PWLA） and left superior pulmonary vein （LSPV）, before and after the RAP. Results In the control group, the effective refractory periods （ERP） were shortened greatly at all sites, paced dogs had substantially shorter ERPs in the high right atrium, LAA, and LSPV, but fewer changes in the PWLA, the coefficient variation of ERP （COV ERP） was increased significantly. After rapid atrial stimulation, the inducibility of AF increased significantly [induction number： pre-RAP vs post-RAP, 1.00 ± 0.89 vs 8.17 ± 2.79, P〈0.01; duration of AF： pre-RAP vs post-RAP, （450.34± 362.59） ms vs （9975.77±4376.99） ms, P〈0.01]. In the nifekalant group, although the ERPs were prolonged at all sites compared with those in pre-RAP state, only the value at LSPV differed significantly from that in pre-RAP state [pre-RAP vs post-RAP, （102.50±5.24） ms vs （132.51 ±5.20） ms, P〈0.01]; the COV ERP did not change statistically in this group. The inducibility of AF slightly increased but insignificantly after pacing [induction number： pre-RAP vs post-RAP, 0.83 ±0.75 vs 1.67±0.82, P=0.19; duration of AF： pre-RAP vs post-RAP, （378.67±317.88） ms vs （1124.08± 1109.77） ms, P=0.06]. Conduction time values did not alter significantly in either of the two groups after RAP. Condusions In canine RAP model, nifekalant inhibited ERP shortening and ERP heterogeneity increasing, decreased AF induction. Nifekalant can reverse acute electrical remodeling effect in this model.

AMPK and cardiac remodelling

Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with cardiac remodelling.AMP-activated protein kinase(AMPK) is known as an energy sensor and a regulator of cardiac metabolism under normal and ischaemic conditions. Additionally, AMPK has been shown to play roles in cardiac remodelling extending well beyond metabolic regulation. In this review, we discuss the currently defined roles of AMPK in cardiac remodelling and summarize the effects of AMPK on cardiac hypertrophy, inflammatory responses and fibrosis and the molecular mechanisms underlying these effects. In addition, we discuss some pharmacological activators of AMPK that are promising treatments for cardiac remodelling.

Global gene expression profiling of perirenal brown adipose tissue whitening in goat kids reveals novel genes linked to adipose remodeling

Background Brown adipose tissue(BAT)is known to be capable of non-shivering thermogenesis under cold stimulation,which is related to the mortality of animals.In the previous study,we observed that goat BAT is mainly located around the kidney at birth,and changes to white adipose tissue(WAT)in the perirenal adipose tissue of goats within one month after birth.However,the regulatory factors underlying this change is remain unclear.In this study,we systematically studied the perirenal adipose tissue of goat kids in histological,cytological,and accompanying molecular level changes from 0 to 28 d after birth.Results Our study found a higher mortality rate in winter-born goat kids,with goat birthing data statistics.Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d.This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids.Additionally,we found a series of changes of BAT during the first 28 d after birth,such as whitening,larger lipid droplets,decreased mitochondrial numbers,and down-regulation of key thermogenesis-related genes(UCP1,DIO2,UCP2,CIDEA,PPARGC1a,C/EBPb,and C/EBPa).Then,we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats.Furthermore,12 candidate genes were found to potentially regulate goat BAT thermogenesis.The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.While apoptosis may play a limited role,it is largely not critical in this transition process.Conclusions We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids,with notable species differences in the expression of adipose tissue marker genes,and we highlighted some potential marker genes for goat BAT and WAT.Additionally,the change from BAT to WAT does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.

Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions:an intravascular ultrasound study

OBJECTIVES To investigate whether negative remodeling(NR) detected by intravascular ultrasound(IVUS) of the side branch ostium(SBO) would affect in-stent neointimal hyperplasia(NIH) at the one-year follow-up and the clinical outcome of target lesion failure(TLF) at the long-term follow-up for patients with left main bifurcation(LMb) lesions treated with a two-stent strategy.METHODS A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention(PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre-and post-PCI and at the 1-year follow-up were enrolled in phase Ⅰ analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index(RI) for predicting NIH ≥ 50% was analyzed next. The phase Ⅱ analysis focused on the incidence of TLF as the primary endpoint at the 1-to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI.RESULTS In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic(ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893(0.778, 1.000), P = 0.002. In phase Ⅱ: the TLR rate(35.8% vs. 5.3%, P < 0.0001)was significantly higher in the several NR(s NR, defined as RI ≤ 0.85) group than in the non-s NR group.CONCLUSION The NR of LCx O is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy,and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process.METHODS A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay.RESULTS Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fcgroup.CONCLUSIONS In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Proximal Femur Bionic Nail (PFBN): A Panacea for Unstable Intertrochanteric Femur Fracture

With the aging population,intertrochanteric femur fracture in the elderly has become one of the most serious public health issues and a hot topic of research in trauma orthopedics.Due to the limitations of internal fixation techniques and the insufficient mechanical design of nails,the occurrence of complications delays patient recovery after surgical treatment.Design of a proximal femur bionic nail(PFBN)based on Zhang’s N triangle theory provides triangular supporting fixation,which dramatically decreases the occurrence of complications and has been widely used for clinical treatment of unstable intertrochanteric femur fracture worldwide.In this work,we developed an equivalent biomechanical model to analyze improvement in bone remodeling of unstable intertrochanteric femur fracture through PFBN use.The results show that compared with proximal femoral nail antirotation(PFNA)and InterTan,PFBN can dramatically decrease the maximum strain in the proximal femur.Based on Frost’s mechanostat theory,the local mechanical environment in the proximal femur can be regulated into the medium overload region by using a PFBN,which may render the proximal femur in a state of physiological overload,favoring post-operative recovery of intertrochanteric femur fracture in the elderly.This work shows that PFBN may constitute a panacea for unstable intertrochanteric femur fracture and provides insights into improving methods of internal fixation.

The role of axon guidance molecules in the pathogenesis of epilepsy

Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.

Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

Rapid correction of chronic hyperglycemia and bone remodeling,warning against overdoing

It is widely recognized that chronic hyperglycemia decreases bone quality,although little is known about the impact of the rapid correction of chronic hyperglycemia on the quality of bone remodeling.This spotlight article explores this correlation by focusing on the stages of bone remodeling linked to glucose levels.