Exosomal miR-486 derived from bone marrow mesenchymal stem cells promotes angiogenesis following cerebral ischemic injury by regulating the PTEN/Akt pathway.

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been shown to promote angiogenesis after ischemic stroke, in which microRNAs (miRs) are believed to play an important role in exosome-mediated therapeutic effects, though the mechanism is still not clear. In this study, a series of molecular biological and cellular assays, both in vitro and in vivo, were performed to elucidate the role of exosomal miR-486 in angiogenesis following cerebral ischemic and its molecular mechanisms. Our results revealed that BMSC-Exos significantly improved neurological function and increased microvessel density in ischemic stroke rats.

Therapeutic Strategies for Ischemic Stroke: Modulating the Adult Neural Stem Cell Niche through the Wnt/β-catenin Pathway.

Stroke is a prominent contributor to mortality and impairment on a global scale. Ischemic stroke accounts for approximately 80% of stroke cases and is caused by occlusion of cerebral blood vessels. Enhancing neurogenesis through the modulation of the neural stem cell niche in the adult brain is a promising therapeutic strategy for individuals afflicted with ischemic stroke.

Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy.

Background: Brain tumors are one of the leading causes of epilepsy, and brain tumor-related epilepsy (BTRE) is recognized as the major cause of intractable epilepsy, resulting in huge treatment cost and burden to patients, their families, and society. Although optimal treatment regimens are available, the majority of patients with BTRE show poor resolution of symptoms. BTRE has a very complex and multifactorial etiology, which includes several influencing factors such as genetic and molecular biomarkers.

Quercetin improves cerebral ischemia/reperfusion injury by promoting microglia/macrophages M2 polarization via regulating PI3K/Akt/NF-κB signaling pathway.

The modulation of microglial polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype shows promise as a therapeutic strategy for ischemic stroke. Quercetin, a natural flavonoid abundant in various plants, possesses anti-inflammatory, anti-apoptotic, and antioxidant properties. Nevertheless, its effect and underlying mechanism on microglia/macrophages M1/M2 polarization in the treatment of cerebral ischemia/reperfusion injury (CI/RI) remain poorly explored.

Exploring the mechanism of luteolin by regulating microglia polarization based on network pharmacology and in vitro experiments.

Neuroinflammation manifests following injury to the central nervous system (CNS) and M1/M2 polarization of microglia is closely associated with the development of this neuroinflammation. In this study, multiple databases were used to collect targets regarding luteolin and microglia polarization. After obtaining a common target, a protein-protein interaction (PPI) network was created and further analysis was performed to obtain the core network.

MiR-199a-5p enhances neuronal differentiation of neural stem cells and promotes neurogenesis by targeting Cav-1 after cerebral ischemia.

Aims: MicroRNAs (miRs) are involved in endogenous neurogenesis, enhancing of which has been regarded as a potential therapeutic strategy for ischemic stroke treatment; however, whether miR-199a-5p mediates postischemic neurogenesis remains unclear. This study aims to investigate the proneurogenesis effects of miR-199a-5p and its possible mechanism after ischemic stroke.

Methods: Neural stem cells (NSCs) were transfected using Lipofectamine 3000 reagent, and the differentiation of NSCs was evaluated by immunofluorescence and Western blotting.

Buyang Huanwu decoction promotes angiogenesis of rat brain microvascular endothelial cells after oxygen-glucose deprivation reperfusion injury via activation of PI3K-AKT signaling pathway.

Objective: To investigate the effect and mechanism of Buyang Huanwu decoction (BYHWD) on angiogenesis of rat brain microvascular endothelial cells (RBMECs) after oxygen-glucose deprivation reperfusion (OGD/R) injury.

Methods: RBMECs were pretreated with BYHWD containing serum 24 h before OGD/R injury was induced. Cells were randomly divided into blank control group, model control group, BYHWD group (provided BYHWD containing serum) and LY294002 group [treated with phosphoinositide 3-kinase (PI3K) inhibitor LY294002 for 1 h before provided BYHWD containing serum].

Identification of six hub genes and two key pathways in two rat renal fibrosis models based on bioinformatics and RNA-seq transcriptome analyses.

Renal fibrosis (RF) is the common pathological manifestation and central treatment target of multiple chronic kidney diseases with high morbidity and mortality. Currently, the molecular mechanisms underlying RF remain poorly understood, and exploration of RF-related hub targets and pathways is urgently needed. In this study, two classical RF rat models (adenine and UUO) were established and evaluated by HE, Masson and immunohistochemical staining.

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Promote Angiogenesis in Ischemic Stroke Mice via Upregulation of MiR-21-5p.

Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) are one of the main factors responsible for the therapeutic effects of BMSCs. The study aimed to investigate whether BMSC-Exos could promote angiogenesis in ischemic stroke mice via miR-21-5p. In ischemic stroke mice, the therapeutic effects of BMSC-Exos were evaluated by neurological functions and infarct volume.

The mechanism of action of the combination of Astragalus membranaceus and Ligusticum chuanxiong in the treatment of ischemic stroke based on network pharmacology and molecular docking.

Since 1990, the incidence of stroke has been rising to become the second leading cause of death in the world, posing a huge burden and challenge to society and families. Astragalus membranaceus and Ligusticum chuanxiong (A&L) have been used as traditional Chinese medicine (TCM) prescriptions to treat and prevent the occurrence of ischemic stroke (IS), but their mechanism of action on the disease has not been fully elucidated. The main objective of this study was to reveal the pharmacological mechanism of A&L in the treatment of IS and to perform preliminary validation.

Merger and Acquisitions Integration, Implementation as Innovative Approach Toward Sustainable Competitive Advantage: A Case Analysis From Chinese Sports Brands.

Brand M&A has long been an extremely common strategy for expanding the scale of an organization and entering new business areas, but various signs show that many brand mergers and acquisitions (M&As) do not add value. They often lose money and fail. This research explores the value, scarcity, and non-replicability of resources in corporate M&A, as well as organizational resource management, innovation resource management, and implementation of the combination of resource utilization and brand strategy that incorporate M&As.

[Chinese medicine Buyang Huanwu decoction promotes neurogenesis and angiogenesis in ischemic stroke rats by upregulating miR-199a-5p expression].

Objective: To investigate the mechanism of Chinese medicine Buyang Huanwu decoction (BYHWD) promoting neurogenesis and angiogenesis in ischemic stroke rats.

Methods: Male SD rats were randomly divided into sham operation group, model group, BYHWD group, antagonist group and antagonist control group with 14 rats in each. Focal cerebral ischemia was induced by occlusion of the right middle cerebral artery for 90 min with intraluminal filament and reperfusion for 14 d in all groups except sham operation group.

[Astragaloside Ⅳ inhibits inflammation after cerebral ischemia in rats through promoting microglia/macrophage M2 polarization].

Objective: To investigate the effects of astragaloside Ⅳ (AS-Ⅳ) on microglia/macrophage M1/M2 polarization and inflammatory response after cerebral ischemia in rats.

Methods: Forty eight male SD rats were randomly divided into sham operation control group, model control group and AS-Ⅳ group with 16 rats in each. Focal cerebral ischemia model was induced by occlusion of the right middle cerebral artery (MCAO) using the intraluminal filament.

Astragaloside IV promotes microglia/macrophages M2 polarization and enhances neurogenesis and angiogenesis through PPARγ pathway after cerebral ischemia/reperfusion injury in rats.

Microglia/macrophages play a dual role in brain injury and repair following cerebral ischemia/reperfusion. Promoting microglia/macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype has been considered as a potential treatment for ischemic stroke. Astragaloside IV (AS-IV) is a primary active ingredient of Chinese herb Radix Astragali, which protects against acute cerebral ischemic/reperfusion injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Enhanced Migration of Bone Marrow-Derived Mesenchymal Stem Cells with Tetramethylpyrazine and Its Synergistic Effect on Angiogenesis and Neurogenesis After Cerebral Ischemia in Rats.

Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for treating ischemic stroke owing to their capacity to secrete various trophic factors with potent angiogenic and neurogenic potentials. However, the relatively poor migratory capacity of BMSCs toward infarcted regions limits effective therapies for the treatment of stroke. The combination of BMSCs and pharmacological agent can promote the migration of BMSCs toward infarcted regions and improve the therapeutic effects after stroke.

Long non-coding RNA HIF1A-AS1 is upregulated in intracranial aneurysms and participates in the regulation of proliferation of vascular smooth muscle cells by upregulating TGF-β1.

Long non-coding (lnc)RNA hypoxia inducible factor 1α-antisense RNA 1 (HIF1A-AS1) not only participates in different types of malignancies, but also serves pivotal roles in thoracic aortic aneurysms, which suggests its possible involvement in intracranial aneurysms. Therefore, the present study aimed to investigate its involvement in intracranial aneurysms. Expression levels of HIF1A-AS1 and transforming growth factor (TGF)-β1 in the blood of patients with intracranial aneurysms and healthy controls were detected using reverse transcription-quantitative polymerase chain reaction.

Tetramethylpyrazine Protects Bone Marrow-Derived Mesenchymal Stem Cells against Hydrogen Peroxide-Induced Apoptosis through PI3K/Akt and ERK1/2 Pathways.

Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation is one of the new therapeutic strategies for treating ischemic stroke. However, the poor survival rate of transplanted BMSCs in ischemic tissue limits the therapeutic efficacy of this approach. Oxidative stress is a major mechanism underlying the pathogenesis of brain ischemia and has a negative impact on the survival of transplanted BMSCs.

Preconditioning of bone marrow-derived mesenchymal stromal cells by tetramethylpyrazine enhances cell migration and improves functional recovery after focal cerebral ischemia in rats.

Background: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is one of the new therapeutic strategies for treating ischemic stroke. However, the relatively poor migratory capacity of BMSCs toward infarcted regions limited the therapeutic potential of this approach. Pharmacological preconditioning can increase the expression of CXC chemokine receptor 4 (CXCR4) in BMSCs and enhance cell migration toward the injury site.

[Ligustrazine Promoted the Migration of Bone Marrow Mesenchymal Stem Cells by Up-regulating MMP-2 and MMP-9 Expressions].

Objective: To explore the effect of ligustrazine on the migration of bone marrow mesenchymal stem cells (BMSCs) and protein expressions of matrix metalloproteinase-2 and-9 (MMP-2 and MMP-9) in vitro.

Methods: BMSCs were in vitro isolated and cultured using whole bone marrow adherent method, and phenotypes [surface positive antigens (CD29 and CD90) and negative antigens (CD34 and CD45)] identified using flow cytometry. BMSCs were divided into the blank control group, 25, 50, 100 µmol/L ligustrazine group, and the GM6001 group (100 µmol/L ligustrazine +MMPs inhibitor GM6001 ).

[Buyang Huanwu decoction promotes neuroblast migration from subventricular zone via inducing angiogenesis after ischemia].

Objective: To study the effect of Buyang Huanwu decoction (BYHWD) inducing angiogenesis on the neuroblast migration from the subventricular zone and its mechanisms after focal cerebral ischemia.

Method: The middle cerebral artery occlusion (MCAO) was performed to mice for 30 minutes to establish the model. The rats were divided into sham group, model group, BYHWD group and endostatin group.

[Effect of Buyang Huanwu Decoction and its disassembled recipes on rats' neurogenesis after focal cerebral ischemia].

Objective: To explore the effect of Buyang Huanwu Decoction (BYHWD) and its disassembled recipes on rats' neurogenesis after focal cerebral ischemia and to investigate its underlying molecular mechanisms.

Methods: Focal cerebral ischemia model was induced by occlusion of the right middle cerebral artery for 90 min using the intraluminal filament model. Rats were divided into the sham-operation group, the model group, the BYHWD group, the qi supplementing group, and the blood activating group.

[Nordihydroguaiaretic acid partially inhibits inflammatory responses after focal cerebral ischemia in rats].

The aim of the present study is to investigate the role of nordihydroguaiaretic acid (NDGA) on inflammatory cells accumulation after focal cerebral ischemia and the underlying mechanism. Focal cerebral ischemia was induced by 30 min of middle cerebral artery occlusion (MCAO) followed by 72 h of reperfusion. NDGA (5 and 10 mg/kg) was administered intraperitoneally 30 min, 2, 24, 48 h after reperfusion, respectively.

Minocycline inhibits 5-lipoxygenase expression and accelerates functional recovery in chronic phase of focal cerebral ischemia in rats.

Aims: We previously reported that minocycline attenuates acute brain injury and inflammation after focal cerebral ischemia, and this is partly mediated by inhibition of 5-lipoxygenase (5-LOX) expression. Here, we determined the protective effect of minocycline on chronic ischemic brain injury and its relation with the inhibition of 5-LOX expression after focal cerebral ischemia.

Main Methods: Focal cerebral ischemia was induced by 90 min of middle cerebral artery occlusion followed by reperfusion for 36 days.

[Protective effects of Huanglian-Jiedu-Tang on chronic brain injury after focal cerebral ischemia in mice].

Objective: To investigate the neuroprotective effects of Chinese herb medicine Huanglian-Jiedu-Tang (HJDT) on chronic brain injury after focal cerebral ischemia in mice.

Methods: Focal cerebral ischemia was induced by occlusion of right middle cerebral artery (MCA) for 15 min. HJDT (at dosage of 2 g/kg or 4 g/kg, qd, orally) was administered for 21 d from d 7 before ischemia until d 14 after ischemia.

Minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal cerebral ischemia in rats.

Aim: To determine whether the anti-inflammatory effect of minocycline on postischemic brain injury is mediated by the inhibition of 5-lipoxygenase (5-LOX) expression and enzymatic activation in rats.

Methods: Focal cerebral ischemia was induced for 30 min with middle cerebral artery occlusion, followed by reperfusion. The ischemic injuries, endogenous IgG exudation, the accumulation of neutrophils and macrophage/microglia, and 5-LOX mRNA expression were determined 72 h after reperfusion.