The migrasome, an organelle for cell-cell communication.

Migrasomes, newly identified extracellular organelles produced by migrating cells, are observed widely across both in vivo and in vitro studies. These organelles, rich in signaling and bioactive molecules, are pivotal in a range of physiological functions. This opinion summarizes current understanding of migrasomes, highlighting their importance as a versatile mechanism for cell-cell communication. Furthermore, it examines their roles in health and disease and potential diagnostic and therapeutic applications, and addresses the emerging challenges and open questions in this developing field.

Imaging and blood flow characteristics of cerebrovascular fenestration malformation and its relationship with the occurrence of ischemic cerebrovascular disease.

OBJECTIVE: To explore the imaging and transcranial Doppler cerebral blood flow characteristics of cerebrovascular fenestration malformation and its relationship with the occurrence of ischemic cerebrovascular disease. METHODS: A retrospective analysis was conducted on the imaging data of 194 patients with cerebrovascular fenestration malformation who visited the Heyuan People's Hospital from July 2021 to July 2023. The location and morphology of the fenestration malformation blood vessels as well as the presence of other cerebrovascular diseases were analyzed. Transcranial Doppler cerebral blood flow detection data of patients with cerebral infarction and those with basilar artery fenestration malformation were also analyzed. RESULTS: A total of 194 patients with cerebral vascular fenestration malformation were found. Among the artery fenestration malformation, basilar artery fenestration was the most common, accounting for 46.08% (94/194). 61 patients (31.44%) had other vascular malformations, 97 patients (50%) had cerebral infarction, of which 30 were cerebral infarction in the fenestrated artery supply area. 28 patients with cerebral infarction in the fenestrated artery supply area received standardized antiplatelet, lipid-lowering and plaque-stabilizing medication treatment. During the follow-up period, these patients did not experience any symptoms of cerebral infarction or transient ischemic attack again. There were no differences in peak systolic flow velocity and end diastolic flow velocity, pulsatility index and resistance index between the ischemic stroke group and the no ischemic stroke group in patients with basal artery fenestration malformation (P > 0.05). CONCLUSION: Cerebrovascular fenestration malformation is most common in the basilar artery. Cerebrovascular fenestration malformation may also be associated with other cerebrovascular malformations. Standardized antiplatelet and statin lipid-lowering and plaque-stabilizing drugs are suitable for patients with cerebral infarction complicated with fenestration malformation. The relationship between cerebral blood flow changes in basilar artery fenestration malformation and the occurrence of ischemic stroke may not be significant.

Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): a randomized, double-blind, placebo-controlled trial.

Background: Glibenclamide alleviates brain edema and improves neurological outcomes in experimental models of stroke. We aimed to assess whether glibenclamide improves functional outcomes in patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Methods: In this randomized, double-blind, placebo-controlled trial, patients with acute ischemic stroke were recruited to eight academic hospitals in China. Patients were eligible if they were aged 18-74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4-25, and had been treated with rtPA within 4.5 h of symptom onset. We used web-based randomization (1:1) to allocate eligible participants to the glibenclamide or placebo group, stratified according to endovascular treatment and baseline stroke severity. Glibenclamide or placebo was taken orally or via tube feeding at a loading dose of 1.25 mg within 10 h after symptom onset, followed by 0.625 mg every 8 h for 5 days. The primary outcome was the proportion of patients with good outcomes (modified Rankin Scale of 0-2) at 90 days, assessed in all randomly assigned patients who had been correctly diagnosed and had begun study medication. The study is registered with ClinicalTrials.gov, NCT03284463, and is closed to new participants. Findings: Between January 1, 2018, and May 28, 2022, 305 patients were randomly assigned, of whom 272 (142 received glibenclamide and 130 received placebo) were included in the primary efficacy analysis. 103 (73%) patients in the glibenclamide group and 94 (72%) in the placebo group had a good outcome (adjusted risk difference 0.002, 95% CI -0.098 to 0.103; p = 0.96). 12 (8%) patients allocated to glibenclamide and seven (5%) patients allocated to placebo died from any cause at 90 days (p = 0.35). The number and type of adverse events were similar between the two groups. There were no drug-related adverse events and no drug-related deaths. Interpretation: The addition of glibenclamide to thrombolytic therapy did not increase the proportion of patients who achieved good outcomes after stroke compared with placebo, but it did not lead to any safety concerns. Funding: Southern Medical University and Nanfang Hospital.

Taurine promotes axonal sprouting via Shh-mediated mitochondrial improvement in stroke.

PURPOSE: Motor function is restored by axonal sprouting in ischemic stroke. Mitochondria play a crucial role in axonal sprouting. Taurine (TAU) is known to protect the brain against experimental stroke, but its role in axonal sprouting and the underlying mechanism are unclear. METHODS: We evaluated the motor function of stroke mice using the rotarod test on days 7, 14, and 28. Immunocytochemistry with biotinylated dextran amine was used to detect axonal sprouting. We observed neurite outgrowth and cell apoptosis in cortical neurons under oxygen and glucose deprivation (OGD), respectively. Furthermore, we evaluated the mitochondrial function, adenosine triphosphate (ATP), mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG-1α), transcription factor A of mitochondria (TFAM), protein patched homolog 1 (PTCH1), and cellular myelocytomatosis oncogene (c-Myc). RESULTS: TAU recovered the motor function and promoted axonal sprouting in ischemic mice. TAU restored the neuritogenesis ability of cortical neurons and reduced OGD-induced cell apoptosis. TAU also reduced reactive oxygen species, stabilized mitochondrial membrane potential, enhanced ATP and mtDNA content, increased the levels of PGC-1α, and TFAM, and restored the impaired levels of PTCH1, and c-Myc. Furthermore, these TAU-related effects could be blocked using an Shh inhibitor (cyclopamine). CONCLUSION: Taurine promoted axonal sprouting via Shh-mediated mitochondrial improvement in ischemic stroke.

Non responsible vascular area hyperperfusion syndrome after mechanical thrombectomy for vertebral artery occlusion: A case report.

Introduction: There are currently no published reports of hyperperfusion syndrome in the non responsible vascular area after mechanical thrombectomy for acute cerebral infarction with large vessel occlusion. Here, we report a case of hyperperfusion syndrome in the blood supply area of the right middle cerebral artery after mechanical thrombectomy for acute cerebral infarction after vertebral artery occlusion. Patient concerns: A 21-year-old woman developed left vertebral artery occlusion, for which she received mechanical thrombectomy and successful recanalization of her occluded cerebral vessel. Subsequently, the patient became extremely agitated, with high blood pressure and headache. Diagnosis: Two hours after the operation, bedside transcranial Doppler ultrasound examination found that the cerebral blood flow velocity of the M1 segment of the right middle cerebral artery was more than twice that of the left middle cerebral artery. Combined with the symptoms, signs and examination results of the patient, hyperperfusion syndrome in the blood supply area of the right middle cerebral artery was considered. Interventions: The patient was administered sedation, and her pressure and ventricular rate were strictly controlled. She was no longer agitated, and her headache was significantly relieved at 36 hours after the operation. Outcomes: On the 5th day after the operation, the blood flow velocity of her right middle cerebral artery decreased to normal level, and the patient recovered well. Conclusion: In this case, after mechanical thrombectomy, such patients with acute posterior circulation cerebral infarction can experience hyperperfusion syndrome in the non responsible vascular area of the anterior circulation. Bedside transcranial Doppler cerebral blood flow examination can identify the hyperperfusion state of cerebral vessels in a timely manner and effectively guide treatment.

Hypokalemic periodic paralysis presenting as asymmetric focal flaccid paralysis: A case report and literature review.

Patients with the most common form of hypokalemic periodic paralysis (HypoKPP) exhibit symmetrical limb weakness. However, few patients present with asymmetric limb weakness. Here, we describe a unique case of HypoKPP presenting as asymmetric focal flaccid paralysis. In addition, a literature review is performed to provide a perspective for clinical management of similar cases. We present a detailed characterization of this rare type of HypoKPP. The initial presentation was right hand weakness, which progressed to bilateral lower limb weakness. Neurological examination showed that the affected muscles were uniquely confined to specific nerve innervation, i.e., right distal median nerve-innervated muscle, right deep peroneal nerve-innervated muscle and left side. The patient's serum level of potassium was lower than normal; the decline of long exercise test (LET) was higher than normal range; neurophysiological assessment revealed low amplitude compound muscle action potential (CMAP) during attack, the CMAP and patient's weakness rapidly returned to normal level after potassium supplementation. Therefore, HypoKPP can be formally diagnosed based on neurological examination, medical history, timely neural electrophysiological examinations and measurement of blood potassium level.

Influencing factors of futile recanalization after endovascular therapy for cerebral infarction with posterior circulation occlusion of large vessels: a retrospective study.

BACKGROUND: The optimal treatment for cerebral infarction caused by posterior circulation occlusion of large vessels has not yet been determined. Intravascular interventional therapy is an important treatment for cerebral infarction with posterior circulation occlusion of large vessels. However, endovascular therapy (EVT) of some posterior circulation cerebrovascular is ineffective and eventually become futile recanalization. Therefore, we performed a retrospective study to explore the factors influencing futile recanalization after EVT in patients with posterior circulation large-vessel occlusion. METHODS: Eighty-six patients with acute cerebral infarction and posterior circulation large vessel occlusion after intravascular intervention were divided into two groups according to their modified Rankin scale (mRS) scores after 3 months: group 1, mRS scores less than or equal to 3 (the effective recanalization group); group 2, mRS scores greater than 3 (the ineffective recanalization group). The basic clinical data, imaging index scores, time from onset to recanalization, and operation time between the two groups were compared and analyzed. Logistic regression was used to analyze the factors influencing indicators of good prognosis, and the ROC curve and Youden index were used to determine the best cutoff value. RESULTS: Between the two groups, there were significant differences in the posterior circulation CT angiography (pc-CTA) scores, GCS scores, pontine midbrain index scores, time from discovery to recanalization, operation time, NIHSS score and incidence of gastrointestinal bleeding. The logistic regression revealed that the NIHSS score and time from discovery to recanalization were associated with good prognoses. CONCLUSION: NIHSS score and recanalization time were independent influencing factors of ineffective recanalization of cerebral infarctions caused by posterior circulation occlusion. EVT is relatively effective for cerebral infarction caused by posterior circulation occlusion when the NIHSS score is less than or equal to 16 and the time from onset to recanalization is less than or equal to 570 min.

Aquaporins in Diabetes Insipidus.

Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understanding the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI). This is followed by a discussion of regulatory mechanisms underlying CDI and NDI, with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R) and the water channel molecule, aquaporin 2 (AQP2). The clinical manifestation, diagnosis, and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.

Identification of ISG15 in golden pompano, Trachinotus ovatus, and its role in virus and bacteria infections.

Interferon (IFN)-stimulated gene product 15 (ISG15) is a ubiquitin-like protein critical for the control of microbial infections. Golden pompano, Trachinotus ovatus is one of the precious marine economic fish in the southern coast of China, always suffering from viruses, bacteria, and parasite infections. To date, the roles of golden pompano genes involved in viral and bacterial infections, especially IFN-related genes remained largely unknown. To identify the interferon system genes of golden pompano and explore their function, in this study, the ISG15 homolog (ToISG15) was cloned from golden pompano, and its role in response to grouper iridovirus (SGIV), nervous necrosis virus (NNV), and Aeromonas hydrophila infection was investigated. The whole ORF of ToISG15 was composed of 465 bp and encoded a polypeptide of 154 amino acids with different identity with the known ISG15 homologs from other fish species. Two conserved ubiquitin-like (UBL) domains and an Ub-conjugation domain (LRGG) were found in ToISG15 sequence. Expression analysis showed that ToISG15 was located mainly in the cytoplasm of golden pompano cells, and dramatically induced following SGIV, Aeromonas hydrophila, or poly I:C treatment, but little change was observed when NNV infection. Overexpression of ToISG15 in vitro significantly inhibited the replication of SGIV and NNV. Interestingly, ToISG15 possessed the ability to restrain the growth of Aeromonas hydrophila. Furthermore, To-ISG15 overexpression enhanced the expression of IFNc, IFNh, IRF3, IRF7, and viperin genes as well as, to a lesser extent, the IL-6 gene. Taken together, our results demonstrated the antiviral and antibacterial effect of To-ISG15, shedding light on the evolutionary conservation of ISG15 in the immune response to microbial infection.

1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/ß-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.

Acute cerebral infarction of posterior circulation in a patient with vertebral artery fenestration deformity: A case report.

Introduction: Cerebrovascular fenestration malformation is a rare congenital vascular variation. Cerebrovascular fenestration malformation rarely directly leads to cerebral infarction, and the mechanism of cerebral infarction is not clear. Cases of young patients with vertebral artery fenestration malformation who suffered from acute cerebral infarction of posterior circulation are rare and have not been reported widely. Patient concerns: A 36-year-old male patient, who had been in good health and without a family history of stroke, was admitted to our hospital with a 6-h history of dizziness and unstable walking. Diagnosis: Brain MR examination showed multiple irregular high signal lesions in the left thalamus, left occipital lobe and left cerebellum. Brain MR enhancement examination confirmed multiple cerebral infarction in left thalamus, left occipital lobe and left cerebellum. CT angiography of head and neck showed fenestration deformity of V2-V3 segment of left vertebral artery. Interventions: Considering that the patient was suffering from acute cerebral infarction of posterior circulation, he was treated with antiplatelet, lipid-lowering and plaque stabilization, etc. Outcomes: After receiving our treatment, the patient's symptoms were relieved. At 3 and 6 months after discharge, there was no dizziness, unstable walking, no acute cerebral infarction, which meant that the patient recovered well. Conclusion: In the absence of traditional risk factors and other evidence of cryptogenic stroke, the cerebral infarction in the blood supply area of fenestration malformation should be considered to be related to fenestration malformation, but its pathogenesis is not clear. Antiplatelet therapy, lipid-lowering and plaque stabilization, etc. are effective in prevention of new infarction for such patients.

Dapagliflozin protects against nonalcoholic steatohepatitis in db/db mice.

Nonalcoholic fatty liver disease (NAFLD), which is the most common liver disease, is associated with type 2 diabetes mellitus and metabolic syndrome. Although there is no consensus on the treatment of NAFLD, growing evidence suggests that tight glycemic control would contribute to the improvement of NAFLD. However, some insulin sensitizers cannot improve NAFLD, especially nonalcoholic steatohepatitis (NASH). Whether insulin-independent hypoglycemic drug dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, may improve NAFLD keeps unclear. Therefore, 12-week-old male C57BL/6 wild-type and db/db mice were treated with 1 mg/kg dapagliflozin or vehicle for 12 weeks. Dapagliflozin alleviated NASH, manifesting as decreased alanine aminotransferase and NAFLD activity score in db/db mice. Also, dapagliflozin reduced de novo lipogenesis by the upregulation of FXR/SHP and downregulation of LXRα/SREBP-1c in the liver of db/db mice. Moreover, dapagliflozin treatment reduced inflammatory response by inhibiting the NF-κB pathway and alleviated fibrosis by restoring the balance between fibrogenesis and fibrolysis in the liver of db/db mice. In summary, dapagliflozin alleviates NASH mostly by reducing lipid accumulation, inflammation, and fibrosis. These findings provide new insights for understanding the protective effect of dapagliflozin in NASH and suggest that dapagliflozin may be used to treat NASH.

Streptococcus suis meningitis complicated with acute cerebral infarction: A case report.

A case of suppurative meningitis complicated with acute cerebral infarction caused by Streptococcus suis was reported to provide reference for the diagnosis and treatment of Streptococcus suis infection. The diagnosis, treatment, follow-up and epidemiological materials in the case of suppurative meningitis complicated with acute cerebral infarction caused by Streptococcus suis in Heyuan People's Hospital were reviewed, and the relevant literature was reviewed. The clinical manifestations of this case were headache and fever, which progressed rapidly. After effective anti-infection treatment, the patient improved and discharged from the hospital, but there was profound hearing impairment.

Long-segment spinal cord infarction complicated with multiple cerebral infarctions: a case report.

BACKGROUND: Spinal cord infarction is a rare disorder, constituting only 1% to 2% of all neurological vascular emergencies (making it less frequent than ischaemic brain injury); however, it is severe. A case of long-segment spinal cord infarction complicated with multiple cerebral infarctions has not been reported to date. CASE PRESENTATION: Here, we describe one such case: a patient with spinal cord infarction from the cervical 7 (C7) to thoracic 6 (T6) vertebrae, along with anterior spinal artery syndrome and complicated by multiple cerebral infarctions. A 65-year-old farmer experienced sudden onset of severe pain in his chest, back and upper limbs while unloading heavy objects. Subsequently, both his lower limbs became weak and hypoaesthetic, and he was unable to walk. Spinal magnetic resonance imaging (MRI) revealed equal T1 and long T2 signals centred on the anterior horn of the spinal cord. The axial slice of these signals was shaped like an owl's eye. After receiving drug treatment and active rehabilitation treatment, the patient's ability to walk was restored. CONCLUSIONS: Long-segment spinal cord infarction is rare and can be complicated with cerebral infarction. The specific aetiology is worth exploring.

Acute pontine infarction in a patient with 8-shaped basilar artery fenestration malformation: A case report.

INTRODUCTION: Cerebrovascular fenestration malformation is a relatively rare vascular dysplasia, and an 8-shaped basilar artery fenestration malformation is even rarer. The characteristics of transcranial Doppler cerebral blood flow in cerebrovascular fenestration malformations have rarely been studied or reported. PATIENT CONCERNS: A 58-year-old woman presented with hypertension, diabetes, with no history of smoking or drinking. The patient had no relevant family history. The patient experienced left limb weakness for 2 days, which gradually worsened. DIAGNOSIS: Head and neck computed tomography angiography revealed an 8-shaped fenestration deformity of the lower segment of the basilar artery with multiple stenoses of the local vessels. Transcranial Doppler cerebral blood flow examination at a depth of 85 cm revealed an eddy current in the lower segment of the basilar artery. INTERVENTIONS: Tirofiban was administered intravenously for 3 days and subsequently changed to oral clopidogrel antiplatelet treatment. OUTCOMES: The modified Rankin Scale score at 3 months after disease onset was 0, indicating that the patient recovered well after treatment. CONCLUSION: A basilar artery 8-shaped fenestration is extremely rare and has seldom been reported. Cerebral vascular fenestration can lead to an acute cerebral infarction and its pathogenesis may include local hemodynamic abnormalities and thrombosis. Eddy currents can be detected by transcranial Doppler cerebral blood flow examination.

Emergency thrombectomy for cerebrovascular occlusion in a patient with mirror-image dextrocardia: a case report.

Cases of patients complicated with dextrocardia who suffer from acute cerebral infarction with large vessel occlusion and receive emergency thrombectomy are particularly rare and have not been widely reported. This article aimed to increase the awareness and knowledge of these cases. We report the case of a patient with mirror-image dextrocardia who suffered from cerebral infarction with large vessel occlusion and received emergency thrombectomy. A male patient in his early 60s with dextrocardia had acute cerebral infarction with posterior circulation large vessel occlusion and underwent emergency thrombectomy. During the operation, the rapid confirmation of dextrocardia and use of flexible interventional instruments helped establish a pathway for blood flow. We used an intracranial thrombectomy stent and intracranial balloon dilation catheter to restore the cerebral blood supply. The Modified Rankin Scale score was 0 at 3 months after thrombectomy, indicating a good prognosis of the patient. Acute cerebral infarction with large vessel occlusion in patients with dextrocardia is extremely rare. Emergency thrombectomy is feasible to recanalize cerebral blood flow and give patients a chance to recover.

Interventional treatment for acute cerebral infarction with large vessel occlusion combined with aortic arch interruption: A case report.

RATIONALE: Aortic arch interruption is a type of congenital vascular malformation that is often observed in childhood. Most children die of congestive heart failure due to rapid deterioration. Children can only survive to adulthood if they have extremely rich collateral circulation. Cases of acute cerebral infarction with large vessel occlusion receiving interventional treatment in adult patients with interrupted aortic arch have not been reported. PATIENT CONCERNS: A 55-year-old man with a history of atrial fibrillation and smoking but without a family history of stroke was admitted to our hospital with a 5-hour history of left limb weakness and speech difficulties. DIAGNOSES: Emergency brain computed tomography showed a large cerebral infarction in the right frontal temporal parietal lobe. He was suspected to have aortic arch interruption in the early stage of endovascular interventional therapy through the femoral artery approach, and was converted to the transradial artery pathway. The aortic arch was disconnected, and the right internal carotid artery was occluded. INTERVENTIONS: Considering the possibility of cardiogenic embolism, a middle catheter was used for thrombus aspiration of the right internal carotid artery. After removal of the dark red thrombus was removed, the right internal carotid artery was successfully recanalized. OUTCOMES: The patient recovered well after the operation. However, the patient and his family refused further treatment for aortic arch interruption. The modified Rankin Scale score was 0 at 3 months and 1 year of follow-up which meant that he recovered quite well. LESSONS: Adult patients with acute cerebral infarction with large vessel occlusion are rarely complicated with aortic arch interruption, and emergency thrombectomy via the radial artery approach is feasible.

Ganoderic Acids Prevent Renal Ischemia Reperfusion Injury by Inhibiting Inflammation and Apoptosis.

Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), which can lead to acute renal failure. The development of RIRI is so complicated that it involves many factors such as inflammatory response, oxidative stress and cell apoptosis. Ganoderic acids (GAs), as one of the main pharmacological components of Ganoderma lucidum, have been reported to possess anti-inflammatory, antioxidant, and other pharmacological effects. The study is aimed to investigate the protective effect of GAs on RIRI and explore related underlying mechanisms. The mechanisms involved were assessed by a mouse RIRI model and a hypoxia/reoxygenation model. Compared with sham-operated group, renal dysfunction and morphological damages were relieved markedly in GAs-pretreatment group. GAs pretreatment could reduce the production of pro-inflammatory factors such as IL-6, COX-2 and iNOS induced by RIRI through inhibiting TLR4/MyD88/NF-kB signaling pathway. Furthermore, GAs reduced cell apoptosis via the decrease of the ratios of cleaved caspase-8 and cleaved caspase-3. The experimental results suggest that GAs prevent RIRI by alleviating tissue inflammation and apoptosis and might be developed as a candidate drug for preventing RIRI-induced AKI.