Ferroptosis and endoplasmic reticulum stress in ischemic stroke

Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum stress.Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival.Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke.However,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke.This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Early antiplatelet therapy used for acute ischemic stroke and intracranial hemorrhage

In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the patient.However,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this disease.Such a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous system.Further,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention strategies.As treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention strategy.As the most vital component of the limbs,skeletal muscles have become potential points of concern.Despite this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal muscle.The current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke survivors.In addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

Emerging strategies for nerve repair and regeneration in ischemic stroke:neural stem cell therapy

Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.

Next-generation regenerative therapy for ischemic stroke using peripheral blood mononuclear cells

Stroke is the second leading cause of death and the third leading cause of disability worldwide after heart disease.Researchers predict that stroke deaths and permanent disabilities will increase worldwide by the year 2050.Single-target therapies may be insufficient,because ischemic cerebral injury involves several mechanisms.Cell-mediated therapies are ideal,because they target multiple cell types to enhance protection and recovery.

Contribution of Stress Testing to the Management of Ischemic Heart Disease in Mali

Introduction: Exercise stress testing (on a treadmill or ergometer bicycle) is an important test in cardiology for diagnosing myocardial ischemia. This test in Mali is still in its beginning compared to other countries in the sub-region. The lack of data in Mali prompted this study, which aimed to evaluate the indications of this activity and its diagnostic contribution to cardiology in Mali. Materials and Methods: This was a retrospective, descriptive study. The study was conducted at the “TOUCAM” medical clinic in Kati based on the analysis of stress test reports between January 2016 and August 2022. Result: During the study period, we documented 73 patients who underwent exercise testing on a bicycle ergometer for suspected coronary heart disease. The mean age of our patients was 47.5 ± 13.8 years (14 and 79 years). Males accounted for the majority (78.1%). The sex ratio is 3.5. More than half of our patients were overweight or obese (77.1%). Hypertension and diabetes affected 52.1% and 25.8% of patients, respectively. 20.8% of patients had coronary artery disease. renin-angiotensin-aldosterone system blockers (56.8%) and beta-blockers (51.3%). The main indications were chest pain (63.0%) and ischemia detection (15.1%). A modified STEEP protocol was used. The majority of our patients (71.2%) achieved at least 85% of their maximum theoretical heart rate. The main reason for the termination of the study was fatigue (57.3%). The average duration was 11.3 ± 4.2 minutes. 24.7% thought the stress tests were positive and 17.8% thought they were controversial. Conclusion: This study demonstrates the importance of stress testing in the diagnosis and treatment of ischemic heart disease, especially in settings where we have very limited access to coronary angiography.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

The potential mechanism and clinical application value of remote ischemic conditioning in stroke

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

Lacidipine,thiamine pyrophosphate and their combination on the ocular ischemic syndrome induced by bilateral common carotid artery ligation

AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats.METHODS:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same route.After anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the midline.Ischemia was created for 10min by placing clips on the right and left common carotid arteries.Rats in the SG only underwent subcutaneous incision.After 10min,the clips were removed and reperfusion was achieved for six days.Then,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were determined.The retinal tissue of the eye was also examined histopathologically.RESULTS:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats.The impact of these drugs on protection is determined to be LTC>lacidipine>TPP.CONCLUSION:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.

Congestive ischemic colitis successfully treated with antiinflammatory therapy: A case report

BACKGROUND Congestive ischemic colitis is a rare subtype of ischemic colitis with an unknown pathophysiology.Excluding conservative management,such as fasting,no established treatment exists;therefore,surgical intervention should be considered in some cases if symptoms worsen.Current literature suggests that anti-inflam-matory agents may effectively treat congestive ischemic colitis.CASE SUMMARY We present the case of a 68-year-old female patient who underwent laparoscopic left hemicolectomy for transverse colon cancer 3 years ago.Postoperatively,follow-up included an annual colonoscopy and abdominal computed tomography(CT)at a local clinic.However,progressive erythema and edema of the sigmoid colon were observed 1 year postoperatively.Upon admission to our hospital,she complained of abdominal pain and diarrhea.Abdominal CT showed thickening of the sigmoid colon walls,and colonoscopy revealed erythema,edema,and multiple ulcers with exudate in the sigmoid colon.CT angiography showed engorgement of the sigmoid vasa recta without any vascular abnormalities.The diagnosis was congestive ischemic colitis,and we treated the patient with anti-inflammatory agents.After 2 mo of glucocorticoid therapy(20 mg once daily)and 7 mo of 5-aminosalicylate therapy(1 g twice daily),the ulcers completely healed.She has not experienced any recurrence for 2 years.CONCLUSION Anti-inflammatory therapy,specifically glucocorticoids and 5-aminosalicylate,has demonstrated promising efficacy and introduces potential novel treatment options for congestive ischemic colitis.

Application of Time-Tracking Platform in the Reperfusion Treatment of Patients with Acute Ischemic Stroke in Primary Hospitals

Objective To explore the application effect of time tracking platform in improving the reperfusion treatment of patients with acute ischemic stroke in primary hospitals. Methods and Results Patients with acute ischemic stroke who carried out emergency intravenous thrombolysis and arterial thrombectomy in our hospital in 2021, 2022 and 2023 were selected. The time tracking mode was implemented, and the patients were recorded at each time node of the hospital and the whole-process digital management was conducted. Compared the mean DNT (Door to Needle Time) of intravenous thrombolysis in emergency stroke patients in 2021, 2022 and 2023, the total number of hospital cases within 4.5 h of onset, the total number of thrombolysis cases within 4.5 h of onset, the number of intravenous thrombolysis in 60 minutes of acute ischemic stroke, and the number of thrombolysis cases. The results show that from 2021 to 2023 our emergency stroke patients with intravenous thrombolysis average DNT shortened year by year, to the hospital within 4.5 h after the onset of the difference is statistically significant (all P < 0.05) conclusion through the application of stroke time tracking platform, is beneficial to shorten the treatment time of each link, can effectively reduce the hospital time delay, improve the rate of thrombolysis, improve the reperfusion of stroke centers in primary hospitals.

Ischemic colitis induced by a platelet-raising capsule: A case report

BACKGROUND Ischemic colitis(IC)is also known as colon ischemia and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon and is not significant enough to maintain the metabolic function of cells,leading to intestinal wall ischemia.Its main symptoms include abdominal pain,diarrhea,and bloody stool.In severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may occur.IC induced by long-term use of certain special drugs is relatively rare in clinical practice.This article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of IC.CASE SUMMARY The patient was admitted to the hospital with"abdominal pain for half a month and bloody stool with mucous and pus for 3 d"and was diagnosed with"IC".Symptomatic and supportive treatment,such as antibiotics(levofloxacin),acid inhibition and stomach protection,fluid replenishment,and intravenous nutrition,was given.The patient's colonic ulcers were considered to be related to the oral administration of platelet(PLT)-raising capsules;the patient was asked to stop PLT-raising drugs for selective review via colonoscopy,and antibiotics and mesalazine enteric-coated tablets were stopped.Under the guidance of hematology consultation,60 mg of methylprednisolone was given in combination with PLT infusion to increase the PLT.After treatment,the patient's condition stabilized,the patient’s stool turned yellow,the patient’s symptoms improved,and the patient was allowed to leave the hospital.CONCLUSION PLT-raising capsules can lead to IC,so clinicians should have a full understanding of the application of these drugs in the treatment of various causes of thrombocyt-INTRODUCTION Ischemic colitis(IC)is also known as colon ischemia(CI)and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon;this process is not significant enough to maintain the metabolic function of cells,leading to intestinal wall ischemia[1].Its main symptoms include abdominal pain,diarrhea,and bloody stool.In severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may occur[2,3].The pathogenesis of this disease has not been extensively studied,but increased clotting ability has been recognized as an important factor in the pathogenesis of IC[4].People older than 60 years(especially women)who suffer from certain underlying diseases,such as cardiovascular and cerebrovascular diseases,diabetes,and shock,are the most prone to colon IC.The lesions can involve any segment of the colon,among which the left half of the colon,such as the sigmoid colon,descending colon and spleen region,is the most common site of lesions.This is because the region south of the sigmoid colon is the"watershed region"of the colonic blood supply,where vascular dysplasia may easily cause ischemia.In addition,the left half of the colon is supplied by the inferior mesenteric artery,which is at an acute angle to the abdominal aorta and affects blood perfusion.The rectum is supplied by both the inferior mesenteric artery and the rectal artery,and ischemia is rare.Therefore,the IC lesions were mainly in the left colon,and most of them were of the first pass type.The disease is relatively mild and can be cured after conservative medical treatment,so the prognosis is favorable[5-7].Once ischemia improves,the patient’s condition can recover in a relatively short time,and this condition can be distin-guished from other types of enteritis[5-7],such as infectious colitis,inflammatory bowel disease,pseudomembranous enteritis,diverticulitis,colon cancer,and acute mesenteric ischemia.Clinically,ischemic colitis can be divided into gangrene and nongrene.The latter can also be subdivided into transient and chronic types.Treatment for IC usually includes fasting,gastrointestinal decompression,intravenous nutritional support,improved circulation,fluid resuscitation,empirical use of antibiotics and other symptomatic supportive treatments,and attention should be given to the treatment of the primary disease.Most patients will experience improvements in clinical symp-toms within 1 to 2 d,and patients with complications may require surgery.However,IC induced by long-term use of certain special drugs is relatively rare in clinical practice.This article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of ischemic colitis.

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

Ischemic stroke with concomitant clear cell carcinoma of the ovary:A case report and review of literature

BACKGROUND Ischemic stroke is a rare event associated with an elevated risk of blood clot formation owing to an underlying malignancy.Herein,we present a case of ovarian carcinoma that led to cerebral infarction.CASE SUMMARY A 43-year-old woman experienced sudden onset right-sided paralysis and difficulty speaking two days after discovery of a large ovarian tumor measuring approximately 14 cm,which was suspected to be malignant.Further examination revealed left middle cerebral artery infarction.The patient had a history of hypertension and adenomyosis.Following stabilization with heparin treatment and vital signs management,the patient underwent debulking surgery,including total hysterectomy,bilateral salpingo-oophorectomy,omentectomy,and bilateral pelvic and para-aortic lymph node dissection.The final diagnosis was clear cell carcinoma of the right ovary(stage IA).Subsequently,the patient completed six rounds of adjuvant chemotherapy while simultaneously undergoing rehabilitation.Presently,the patient is able to walk independently,although she still experiences aphasia.CONCLUSION Prompt medical intervention and interdisciplinary care are crucial in the setting of incidental findings such as a large ovarian tumor.

Integrated gut microbiota,plasma metabolomics and network pharmacology to reveal the anti-ischemic stroke effect of cooked rhubarb

Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum Maxim.ex Balf.)with millet wine.It is used as a traditional Chinese medicine for treating cerebral stroke,where patients often face severe constipation.This study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in rats.We used integrated analysis of gut microbiota,metabolomics,and network pharmacology.Methods:The compounds in CR were identified using LC-MS/MS.The impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE staining.Changes in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also determined.Gut microbiota composition was analyzed through 16S rRNA gene sequencing.Serum metabolites were examined using untargeted metabolomics and Spearman correlation analysis.The pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut microbiota.Results:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction area.CR also ameliorates brain and intestinal barrier damage caused by stroke.It also decreased inflammation and oxidative stress in IS rats.Furthermore,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier repair.Notably,CR primarily influences the primary bile acid biosynthesis pathway.The pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential targets.CR relies on gut microbiota for its anti-inflammatory effects to improve IS.Conclusion:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid metabolism.It emerges as a potential therapeutic agent for IS.