Reperfusion Injury Research Articles

Cardioprotective microRNAs (protectomiRs) in a pig model of acute myocardial infarction and cardioprotection by ischaemic conditioning: MiR-450a.

Cardioprotective miRNAs (protectomiRs) are promising therapeutic tools. Here, we aimed to identify protectomiRs in a translational porcine model of acute myocardial infarction (AMI) and to validate their cardiocytoprotective effect. ProtectomiR candidates were selected after systematic analysis of miRNA expression changes in cardiac tissue samples from a closed-chest AMI model in pigs subjected to sham operation, AMI and ischaemic preconditioning, postconditioning or remote preconditioning, respectively. Cross-species orthologue protectomiR candidates were validated in simulated ischaemia-reperfusion injury (sI/R) model of isolated rat ocardiomyocytes and in human AC16 cells as well. For miR-450a, we performed target prediction and analysed the potential mechanisms of action by GO enrichment and KEGG pathway analysis. Out of the 220 detected miRNAs, four were up-regulated and 10 were down-regulated due to all three conditionings versus AMI. MiR-450a and miR-451 mimics at 25 nM were protective in rat cardiomyocytes, and miR-450a showed protection in human cardiomyocytes as well. MiR-450a has 3987 predicted mRNA targets in pigs, 4279 in rats and 8328 in humans. Of these, 607 genes are expressed in all three species. A total of 421 common enriched GO terms were identified in all three species, whereas KEGG pathway analysis revealed 13 common pathways. This is the first demonstration that miR-450a is associated with cardioprotection by ischaemic conditioning in a clinically relevant porcine model and shows cardiocytoprotective effect in human cardiomyocytes, making it a promising drug candidate. The mechanism of action of miR-450a involves multiple cardioprotective pathways.

Mitophagy Regulates Kidney Diseases

Background: Mitophagy is a crucial process involved in maintaining cellular homeostasis by selectively eliminating damaged or surplus mitochondria. As the kidney is an organ with a high dynamic metabolic rate and abundant mitochondria, it is particularly crucial to control mitochondrial quality through mitophagy. Dysregulation of mitophagy has been associated with various renal diseases, including acute and chronic kidney diseases, and therefore a better understanding of the links between mitophagy and these diseases may present new opportunities for therapeutic interventions. Summary: Mitophagy plays a pivotal role in the development of kidney diseases. Upregulation and downregulation of mitophagy have been observed in various kidney diseases, such as renal ischemia-reperfusion injury, contrast-induced acute kidney injury, diabetic nephropathy, kidney fibrosis, and several inherited renal diseases. A growing body of research has suggested that PINK1 and Parkin, the main mitophagy regulatory proteins, represent promising potential therapeutic targets for kidney diseases. In this review, we summarize the latest insights into how the progression of renal diseases can be mitigated through the regulation of mitophagy, while highlighting their performance in clinical trials. Key Message: This review comprehensively outlines the mechanisms of mitophagy and its role in numerous kidney diseases. While early research holds promise, most mitophagy-centered therapeutic approaches have yet to reach the clinical application stage.

Malate dehydrogenase-2 inhibition shields renal tubular epithelial cells from anoxia-reoxygenation injury by reducing reactive oxygen species.

Ischemia-reperfusion (I-R) injury is the most common cause of acute kidney injury. In experiments involving primary human renal proximal tubular epithelial cells (RPTECs) exposed to anoxia-reoxygenation, we explored the hypothesis that mitochondrial malate dehydrogenase-2 (MDH-2) inhibition redirects malate metabolism from the mitochondria to the cytoplasm, towards the malate-pyruvate cycle and reversed malate-aspartate shuttle. Colorimetry, fluorometry, and western blotting showed that MDH2 inhibition accelerates the malate-pyruvate cycle enhancing cytoplasmic NADPH, thereby regenerating the potent antioxidant reduced glutathione. It also reversed the malate-aspartate shuttle and potentially diminished mitochondrial reactive oxygen species (ROS) production by transferring electrons, in the form of NADH, from the mitochondria to the cytoplasm. The excessive ROS production induced by anoxia-reoxygenation led to DNA damage and protein modification, triggering DNA damage and unfolded protein response, ultimately resulting in apoptosis and senescence. Additionally, ROS induced lipid peroxidation, which may contribute to the process of ferroptosis. Inhibiting MDH-2 proved effective in mitigating ROS overproduction during anoxia-reoxygenation, thereby rescuing RPTECs from death or senescence. Thus, targeting MDH-2 holds promise as a pharmaceutical strategy against I-R injury.

Cerebral Ischemia-Reperfusion Induced Neuronal Damage, Inflammation, miR-374a-5p, MAPK6, NLRP3, and Smad6 Alterations: Rescue Effect of N-acetylcysteine

Background: Ischemic stroke (IS) is still a major cause of neurological disability. This study aimed to ascertain potential markers closely related to IS diagnosis and treatment and then we examined the neuroprotective effect of N-acetylcysteine (NAC) in a transient cerebral ischemia. Methods: Male Wistar rats were randomly divided into three groups (n=6), including sham, IR (ischemia-reperfusion), IR+NAC (150 mg/kg, ip; intraperitoneally, 1 hour prior to ischemia and 5 min before reperfusion). The infarct volume was evaluated by 2,3,5-triphenyl tetrazolium chloride staining. H&E and Nissle staining were performed to evaluate cerebral ischemia-reperfusion injury. miR-374a-5p gene expression, MAPK6, NLRP3, smad6, TNF-α, and IL-1β protein levels were determined by Real-time PCR, Western blot, and Elisa in the cerebral cortex exposed to IR. Results: Herein, we found that IR increased infarct volume and pathological damage to the cerebral cortex after global cerebral artery occlusion/reperfusion. In addition, miR-374a-5p gene expression decreased, while MAPK6, NLRP3, and smad6 protein expressions increased in the IR group. TNF-α and IL-1β protein levels increased in the ischemic cortex. Treatment with NAC significantly attenuated infarct size, inflammation and reversed aforementioned molecule levels. Conclusion: Taken together, these results suggested that ischemic insult can increase infarct size, neuronal damage, and inflammation may in part by modulating miR-374a-5p, MAPK6, NLRP3, and smad6 pathway in the brain cortex after cerebral IR insult and providing new clues to molecular mechanisms and treatment targets in IS. It can be alleviated by NAC as a potential therapy for someone afflicted with ischemia.

Use of N-acetyl-cysteine in the Perioperative Period of Liver Transplantation: A Scoping Review

Objective: To !nd evidence on the use of N-acetyl-cysteine (NAC) in the perioperative period of liver transplantation, since NAC, as it is the acetylated precursor of L-cysteine and reduced glutathione, contributes to the hepatic supply of glutathione, helping the liver to recover from ischemia and reperfusion injury. Methodology: "is is a scoping review of the PubMed, VHL and Web of Science databases. "e descriptors “Liver transplantation”, “N-acetyl-cysteine” and “Reperfusion Ischemia” were used, with the Boolean operator “AND”, and articles relevant to the topic were selected. Initially, 60 articles were selected, all published in the last 24 years, in Portuguese and/or English. After analysis, eight articles corresponded to the proposed objective. Results:"e groups that received NAC during TxF showed post-reperfusion hypotension, lower intraoperative pH values, higher plasma concentrations of IL-4 and a signi!cant increase in IL-10 levels !ve minutes before reperfusion. Inhibition of α-glutathione S-transferase (α-GST) was also observed after reperfusion, unlike the control group, which showed a signi!cant increase in this enzyme. Furthermore, sVCAM-1 and sICAM-1 levels were signi!cantly lower in the NAC group 24 hours after reperfusion compared with the placebo group. "e maximum AST value during the !rst 72 postoperative hours was similar in both groups, although the peak ALT was lower in the NAC group than in the placebo group. In grafts that received NAC in the perfusion solution, survival rates at 3 and 12 months were 93% and 90%, respectively, and in the control group were 82% and 70%, respectively. "e incidence of postoperative complications was 23% in the NAC group and 51% in the control group. "e incidence of EPD was lower for the NAC group, which was 15% versus 32% in the control group. Regarding the administration of NAC during the intraoperative TxF, the one-year patient survival rate was 78.4% in the NAC group compared to 80.9% in the placebo group. Conclusion: Intraoperative administration of NAC during the anhepatic phase was associated with a protective effect against reperfusion injury, however in other studies limitations were observed in protection against liver injury, in biomarkers of oxidative stress, in in$ammation and in the functioning of liver enzymes.

APP-CD74 axis mediates endothelial cell-macrophage communication to promote kidney injury and fibrosis.

Kidney injuries often carry a grim prognosis, marked by fibrosis development, renal function loss, and macrophage involvement. Despite extensive research on macrophage polarization and its effects on other cells, like fibroblasts, limited attention has been paid to the influence of non-immune cells on macrophages. This study aims to address this gap by shedding light on the intricate dynamics and diversity of macrophages during renal injury and repair. During the initial research phase, the complexity of intercellular communication in the context of kidney injury was revealed using a publicly available single-cell RNA sequencing library of the unilateral ureteral obstruction (UUO) model. Subsequently, we confirmed our findings using an independent dataset from a renal ischemia-reperfusion injury (IRI) model. We treated two different types of endothelial cells with TGF-β and co-cultured their supernatants with macrophages, establishing an endothelial cell and macrophage co-culture system. We also established a UUO and an IRI mouse model. Western blot analysis, flow cytometry, immunohistochemistry and immunofluorescence staining were used to validate our results at multiple levels. Our analysis revealed significant changes in the heterogeneity of macrophage subsets during both injury processes. Amyloid β precursor protein (APP)-CD74 axis mediated endothelial-macrophage intercellular communication plays a dominant role. In the in vitro co-culture system, TGF-β triggers endothelial APP expression, which subsequently enhances CD74 expression in macrophages. Flow cytometry corroborated these findings. Additionally, APP and CD74 expression were significantly increased in the UUO and IRI mouse models. Immunofluorescence techniques demonstrated the co-localization of F4/80 and CD74 in vivo. Our study unravels a compelling molecular mechanism, elucidating how endothelium-mediated regulation shapes macrophage function during renal repair. The identified APP-CD74 signaling axis emerges as a promising target for optimizing renal recovery post-injury and preventing the progression of chronic kidney disease.

Impact of propofol versus desflurane anesthesia on postoperative hepatic and renal functions in infants with living-related liver transplantation: a randomized controlled trial

BackgroundThe effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia–reperfusion injury (HIRI).MethodsSeventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI.ResultsThere were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58–366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L, P < 0.001 (95% CI: 3.0–8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) μmol/L, P = 0.02 (95% CI: 0.0–5.0) respectively). Moreover, the incidence of severe acute kidney injury was significantly lower in group P compared to that in group D (15.8% vs. 39.5%, P = 0.038).ConclusionsPropofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations.

Phillygenin attenuates cell apoptosis and microglia activation in cerebral ischaemia-reperfusion rats through activation of peroxisome proliferator-activated receptor γ.

Ischaemic stroke is a common condition that can lead to cerebral ischaemia-reperfusion injury. Phillygenin (PHI), a natural bioactive compound derived from Forsythia suspensa, has been shown to play a crucial role in regulating inflammation across various diseases. However, its specific regulatory effects in ischaemic stroke progression remain unclear. In this study, we established a middle cerebral artery occlusion (MCAO) rat model. Treatment with PHI (50 or 100 mg/kg) significantly reduced cerebral infarction in MCAO rats. PHI treatment also mitigated the increased inflammatory response observed in these rats. Additionally, PHI suppressed microglial activation by reducing iNOS expression, a marker of M1-type polarization of microglia, and attenuated increased brain tissue apoptosis in MCAO rats. Furthermore, PHI's anti-inflammatory effects in MCAO rats were abrogated upon co-administration with GW9662, a peroxisome proliferator-activated receptor γ (PPARγ) inhibitor. In summary, PHI attenuated microglial activation and apoptosis in cerebral ischaemia-reperfusion injury through PPARγ activation, suggesting its potential as a therapeutic agent for mitigating cerebral ischaemia-reperfusion injury.

Carbon Monoxide: A Pleiotropic Redox Regulator of Life and Death.

Despite recent technological progress, carbon monoxide poisoning is still one of the leading causes of domestic and industrial morbidity and mortality. The brain is particularly vulnerable to CO toxicity, and thus the majority of survivors develop delayed movement and cognitive complications. CO binds to haemoglobin in erythrocytes, preventing oxygen delivery to tissues, and additionally inhibits mitochondrial respiration. This renders the effect of CO to be closely related to hypoxia reperfusion injury. Oxygen deprivation, as well as CO poisoning and re-oxygenation, are shown to be able to activate the production of reactive oxygen species and to induce oxidative stress. Here, we review the role of reactive oxygen species production and oxidative stress in the mechanism of neuronal cell death induced by carbon monoxide and re-oxygenation. We discuss possible protective mechanisms used by brain cells with a specific focus on the inhibition of CO-induced ROS production and oxidative stress.

Novel Models for Assessing and Pathophysiology of Hepatic Ischemia-Reperfusion Injury Mechanisms.

Hepatic ischemia-reperfusion injury (IRI) is a major cause of postoperative hepatic dysfunction and liver failure involving cellular damage to previously ischemic tissues to which blood flow is restored. The reestablishment of blood flow is essential for salvaging ischemic tissues. The reperfusion itself, however, can paradoxically lead to further cellular damage, which involves a multi-factorial process resulting in extensive tissue damage, which can threaten the function and viability of the liver and other organ systems. The following review outlines multiple models for in-lab analysis of the various hepatic IRI mechanisms, including murine, porcine, cell lines, and machine perfusion models.

CircRNA_0003307 promoted brain microvascular endothelial cell angiogenesis, invasion, and migration in cerebral ischemia-reperfusion injury: Potential involvement of miRNA-191-5p/CDK6 pathway

BackgroundsThe role of miR-191-5p in cerebral ischemia–reperfusion (I/R) injury has been established, with its expression in endothelial cells demonstrating anti-angiogenic effects. A potential circular RNA, circRNA_0003307, has been identified through bioinformatics analysis as a candidate for interaction with miR-191-5p, yet its functional significance in brain I/R injury remains unexplored. We aimed to investigate whether circRNA_0003307 regulates brain microvascular endothelial cell (BMEC) vascular tube formation, invasion, and migration by regulating the miR-191-5p cascade. MethodsMouse BMECs (bEnd.3) were culturedand exposed to oxygen-glucose deprivation (OGD). The effects of circRNA_0003307 on vessel-like tube formation and cellular migration were examined. In addition, we investigated the protective effects of circRNA_0003307 on I/R injury in mice. ResultsThe results showed the level of circRNA_0003307 was concentration-dependently increased in OGD-induced bEnd.3 cells. ODG-induction enhanced angiogenesis, migration, and invasion of bEnd.3 cells, which were further promoted by the transfection of pcDNA-0003307. Silencing circRNA_0003307 expression showed the opposite results. The dual luciferase assay demonstrated miRNA-191-5p interacted with circRNA_00033073′ UTR, and miRNA-191-5p could bind with CDK6. Meanwhile, circRNA_0003307 promoted the expression of CDK6 by sponging miRNA-191-5p. The overexpression of circRNA_0003307 activated the angiogenesis, migration, and invasion of OGD-induced bEnd.3 cells, which were hindered by miRNA-191-5p mimic or siRNA-CDK6. Thus, circRNA_0003307 promoted ODG-induced angiogenesis, migration, and invasion of bEnd.3 cells by targeting miR-191-5p/CDK6 axis. In vivo, circRNA_0003307 had protective effects on brain I/R injury, including neuroprotection, anti-apoptosis and angiogenesis. ConclusionCircRNA_0003307 may be a promisingtherapeutictarget forthe treatment of cerebral I/R injury.

Activating PKA signaling increases exosome production and attenuates cerebral ischemia-reperfusion injury by regulating Cx43 expression

BackgroundConnexin 43 (Cx43) plays a crucial role in mediating intracellular communication and facitating the interaction between exosomes and recipient cells. This study investigates whether the activation of cAMP/protein kinase A (PKA) can regulate exosomal Cx43 expression and contribute to the functional recovery following ischemia-reperfusion (I/R) injury. MethodsAn intraluminal vascular occlusion was performed on Lewis rats to simulate I/R injury. Concurrently, a PKA activator (8-Bromo-cAMP, 5 mg kg-1) or PKA inhibitor (H 89 2HCl, 20 mg kg-1) was administered intravenously via the tail vein (n = 10). Exosomes were isolated from cerebrospinal fluid, and the expression of exosomal markers (CD63 and CD81) and Cx43 was analyzed using Western blot. The expression of CD63 and CD81 in astrocytes was measured to assess exosome uptake. Spatial learning and memory capability were evaluated using the Morris water maze test. Results8-Bromo-cAMP significantly increased exosome release in cerebrospinal fluid, accompanied by elevated Cx43 expression. Additionally, 8-Bromo-cAMP enhanced exosome uptake by astrocytes, alleviated blood-brain barrier damage and edema, and improved cognitive function. ConclsionsPKA activation enhances exosome production, promotes cognitive function recovery, and attenuates cerebral I/R injury by up-regulating exosomal Cx43 expression.

Inner Mitochondrial Membrane Peptidase 2-Like Deletion Aggravates Mitochondrial Apoptosis and Inhibits Autophagy After Hyperglycemia Stroke.

This study investigated the effects of inner mitochondrial membrane peptidase 2-like (Immp2l) deletion on mitochondrial apoptosis and mitochondrial autophagy under hyperglycemic conditions. The middle cerebral artery occlusion (MCAO) model was established in wild-type (WT) mice and Immp2l+/- mice; animals were then exposed to hyperglycemic (induced using 1% streptozotocin) and normoglycemic conditions. Tissues were collected at various time points post-reperfusion. The production of reactive oxygen species (ROS) was assessed by fluorescent measurements, and mitochondrial membrane potential was evaluated using a JC-1 assay kit. Autophagy was analyzed by measuring LC3II/LC3I protein expression and Beclin 1 expression. Mitochondrial ultrastructure was examined through transmission electron microscopy (TEM); neuronal autophagosomes were also assessed. Immp2l mutation in a hyperglycemic environment exacerbated brain injury by increasing ROS production, compromising mitochondrial membrane potential, inducing apoptotic cascades, and impairing mitochondrial autophagy. These findings highlight the critical role of Immp2l in modulating the response to hyperglycemic cerebral ischemia-reperfusion (I/R) injury. Furthermore, the deficiency of Immp2l appears to contribute to increased oxidative stress, mitochondrial dysfunction, and cell death, thereby exacerbating brain injury. These data may provide new insights into therapeutic strategies for reducing the impact of diabetes on stroke outcomes.

Protective effects of tetramethylpyrazine on myocardial ischemia/reperfusion injury involve NLRP3 inflammasome suppression by autophagy activation

Tetramethylpyrazine (TMP) belongs to the active ingredients of the traditional Chinese medicine Chuanxiong, which has a certain protective effect in myocardial ischemia–reperfusion (I/R) injury. It can improve postoperative cardiac function and alleviate ventricular remodeling in acute myocardial infarction patients. However, its specific protective mechanism is still unclear. In this study, a certain concentration of TMP was introduced into I/R mice or H9C2 cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment to observe the effects of TMP on cardiomyocyte activity, cytotoxicity, apoptosis, autophagy, pyroptosis, and NLRP3 inflammasome activation. The results displayed that TMP intervention could reduce OGD/R and I/R-induced cardiomyocyte apoptosis, accelerate cellular activity and autophagy levels, and ameliorate myocardial tissue necrosis in I/R mice in a dose-dependent manner. Further, TMP prevented the formation of NLRP3 inflammasomes to suppress pyroptosis by increasing the level of cardiomyocyte autophagy after I/R and OGD/R modelling, the introduction of chloroquine to suppress autophagic activity in vivo and in vitro was further analyzed to confirm whether TMP inhibits NLRP3 inflammasome activation and pyroptosis by increasing autophagy, and we found the inhibitory effect of TMP on NLRP3 inflammasomes and its protective effect against myocardial injury were blocked when autophagy was inhibited with chloroquine. In conclusion, this experiment demonstrated that TMP unusually attenuated I/R injury in mice, and this protective effect was achieved by inhibiting the activation of NLRP3 inflammasomes through enhancing autophagic activity.

Review of Gene Therapy on Myocardial Ischemia-Reperfusion Injury Treatment

This article aims to summarize decade research which utilizing gene therapy method on myocardial ischemia-reperfusion injury. Relative articles are collected from CNKI retrieval. By analyzing and comparing the relative research articles published decade, the recent research conclusions are summarized. Methods and conclusions are compared on each upside and downside. The recent research is center on the gene transduction or stem cell transplantation. The adenovirus and adeno-associated virus are introduced into the gene transfer. The pretreatment of stem cell transplantation is also researched in recent research. All research conclusions claim that positive results are observed after treatment, including injury reduced or reversed, myocardial protect effects. Due to the complexity of mechanism in myocardial ischemia-reperfusion injury, the works may show conflicting results at the conclusion part. However, the results are roughly positive at the practical application in treatment. Still, the conclusions are limited at laboratory research on pigs and mice, and the safety evaluates are absence in some research, which confined the clinical research and further utilizing.

The impact of PIRCHE-II and ischemia reperfusion injury on dynamics of CD4+ T memory cells in liver transplant recipients

The impact of PIRCHE-II and ischemia reperfusion injury on dynamics of CD4+ T memory cells in liver transplant recipients

The effect of vitamin C on the recovery of activity and survival of autografted ovaries through inhibition of oxidation and inflammation

Ovarian tissue autografting is a valuable clinical option to help restore fertility in women with cancer. However, many follicles are lost due to ischemia-reperfusion (IR) injury, which depletes follicles after grafting. We aimed to investigate the effect of vitamin C, an antioxidant with anti-apoptotic and anti-inflammatory properties, on improving the structure and function of autografted ovaries in mice. Thirty-six female NMRI mice (4–5 weeks old) were divided into three groups of 12: control (no grafting), autograft + vitamin C (50 mg/kg/day intraperitoneally), and autograft + saline (100 µl/day/animal, intraperitoneally). After the ovarian autografting and before the start of the experiment, each group was further divided into 7-day and 28-day subgroups. Seven days after ovary autografting, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and inflammatory factors were measured. On day 28, ovarian histology, DNA fragmentation, and estradiol and progesterone levels were assessed. Results were analyzed using one-way ANOVA and Tukey’s test, with significance set at p<0.05. In the autograft + vitamin C group, there were significant increases in the mean total volume of the ovary, cortex (p<0.05), medulla, number of follicles, and levels of IL-10, progesterone, estradiol, and TAC (p<0.001), compared to the autograft group. Conversely, the rate of apoptosis and serum levels of MDA, IL-6, and TNF-α were notably reduced in the autograft + vitamin C group (p<0.001). These results suggest that vitamin C can significantly enhance the recovery of autografted ovaries through its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Therapeutic Correlation of TLR-4 Mediated NF-κB Inflammatory Pathways in Ischemic Injuries.

Ischemia-reperfusion (I/R) injury refers to the tissue damage that happens when blood flow returns to tissue after a period of ischemia. I/R injuries are implicated in a large array of pathological conditions, such as cerebral, myocardial, renal, intestinal, retinal and hepatic ischemia. The hallmark of these pathologies is excessive inflammation. Toll-like receptors (TLRs) are recognized as significant contributors to inflammation caused by pathogens and, more recently, inflammation caused by injury. TLR-4 activation initiates a series of events that results in activation of nuclear factor kappa-B (NF-κB), which stimulates the production of pro-inflammatory cytokines and chemokines, exacerbating tissue injury. Therefore, through a comprehensive review of current research and experimentation, this investigation elucidates the TLRs signalling pathway and the role of TLR-4/NF-κB in the pathophysiology of I/R injuries. Furthermore, this review highlights the various pharmacological agents (TLR-4/NF-κB inhibitors) with special emphasis on the various ischemic injuries (cerebral, myocardial, renal, intestinal, retinal and hepatic). Future research should prioritise investigating the specific molecular pathways that cause TLR-4/NF-κBmediated inflammation in ischemic injuries. Additionally, efforts should be made to enhance treatment approaches in order to enhance patient outcomes.

Ischemia reperfusion injury drives post-operative monocyte differentiation and alloreactivity in orthotopic liver transplant patients

Ischemia reperfusion injury drives post-operative monocyte differentiation and alloreactivity in orthotopic liver transplant patients

Hypothermia for Cardioprotection in Acute Coronary Syndrome Patients: From Bench to Bedside.

Early revascularization for patients with acute myocardial infarction (AMI) is of outmost importance in limiting infarct size and associated complications, as well as for improving long-term survival and outcomes. However, reperfusion itself may further damage the myocardium and increase the infarct size, a condition commonly recognized as myocardial reperfusion injury. Several strategies have been developed for limiting the associated with reperfusion myocardial damage, including hypothermia. Hypothermia has been shown to limit the degree of infarct size increase, when started before reperfusion, in several animal models. Systemic hypothermia, however, failed to show any benefit, due to adverse events and potentially insufficient myocardial cooling. Recently, the novel technique of intracoronary selective hypothermia is being tested, with preclinical and clinical results being of particular interest. Therefore, in this review, we will describe the pathophysiology of myocardial reperfusion injury and the cardioprotective mechanics of hypothermia, report the animal and clinical evidence in both systemic and selective hypothermia and discuss the potential future directions and clinical perspectives in the context of cardioprotection for myocardial reperfusion injury.