Acute kidney injury (AKI) is characterized by a sudden and rapid decline of renal function and associated with high morbidity and mortality. AKI can be caused by various factors, and ischemia-reperfusion injury (IRI) is one of the most common causes of AKI. An increasing number of studies found out that exosomes of mesenchymal stem cells (MSCs) could alleviate IRI-AKI by the adjustment of the immune response, the suppression of oxidative stress, the reduction of cell apoptosis, and the promotion of tissue regeneration. This article summarizes the effect and mechanism of MSC-derived exosomes in the treatment of renal ischemia-reperfusion injury, in order to provide useful information for the researches on this field.
Objective To investigate the protective effect of the exosome on the organ damage induced by ische-mia-reperfusion (I/R) so as to provide a new way for the treatment of I/R damage. Methods The literature related to the treatment of I/R damage was reviewed and analyzed. Results The exosome volume is small and it is present in blood, cerebrospinal fluid, and urine, which has the function to cross the blood-brain barrier, and protect the heart, brain and other organs after I/R damage. Conclusion Exosome is a new material for the treatment of I/R organ injury, and it is important to understand the protective effect and possible mechanism.
ObjectiveTo investigate the protective effect of Shenfu injection on liver injury in rats with hind limb ischemia-reperfusion and its mechanism. MethodsSixty-four male rats were randomly divided into sham operation group, ischemia-reperfusion group, Shenfu group〔Shenfu injection 7.5 mL/kg injection of peritoneal(ip), given 10 min before ischemia-reperfusion〕, Shenfu+Znpp group(Shenfu injection 7.5 mL/kg+Znpp 5 mg/kg ip, given 10 min before ischemia-reperfusion), 16 rats in each group. The rat model of hind limb ischemia-reperfusion injury was reproduced by occluding the hind limb artery of the rats for 3 h and subsequent reperfusing for 4 h. The liver tissues were gathered for malondialdehyde(MDA)and superoxide dismutase(SOD)determination. The expression of hemeoxygenase 1(HO-1)protein in the liver tissues was detected by immunohistochemistry. The pathological changes of liver were observed under the light microscope. The changes of serum glutamate-pyruvate transaminase(GPT)and glutamine oxaloacetic transaminase(GOT)were observed respectively. Results①Compared with the sham operation group, the contents of MDA, GPT, GOT, and the expression of HO-1 protein were markedly increased in the ischemia-reperfusion group, Shenfu group, and Shenfu+Znpp group(P < 0.05), the activities of SOD were markedly decreased in the ischemia-reperfusion group and Shenfu+Znpp group(P < 0.05).②Compared with the ischemia-reperfusion group, the contents of MDA, serum GPT, GOT, and the expression of HO-1 protein were markedly decreased, the activity of SOD was markedly increased in the Shenfu group(P < 0.05).③Compared with the Shenfu group, the contents of MDA, GPT, GOT were markedly increased, the activity of SOD was markedly decreased in the Shenfu+Znpp group(P < 0.05). Unde ther light microscope, the pathological changes induced by ischemia-reperfusion were significantly attenuated by the Shenfu injection in the Shenfu group and were reversed by the Znpp in the Shenfu+Znpp group. ConclusionShenfu injection inhibits liver tissue injury during hind limb ischemia-reperfusion, this protective effect might be partly through induction of HO-1.
CD4+ T cells play a dual role in both the protection and injury of retinal ganglion cells (RGC), participating in the critical immunopathological processes associated with retinal ischemia reperfusion injury (RIRI). T helper (Th) 1 and Th17 cells drive retinal inflammation by secreting pro-inflammatory cytokines, leading to RGC damage. In contrast, Th2 and regulatory T (Treg) cells secrete anti-inflammatory factors that modulate immune responses and reduce inflammation, thereby playing a crucial role in protecting RGC. However, under certain disease conditions, their roles may be reversed. Additionally, an imbalance between Th1 and Th2 cells, specifically the imbalance in the cytokines they secrete can influence disease progression. Therefore, a deeper understanding of the complex functions of CD4+ T cells and their subsets in both protecting and damaging retinal health is essential for immune-targeted therapies for RIRI.
ObjectiveTo observe the effects of overexpression of S100A4 protein on retinal capillary cells and retinal ganglion cells (RGC) after retinal ischemia-reperfusion injury (RIRI). MethodsOne hundred healthy adult male C57BL/6 mice were randomly divided into normal control group (group C), RIRI group, adeno-associated virus (AAV2)-S100A4 green fluorescent protein (GFP) intravitreal injection group (group S), RIRI+AAV2-GFP intravitreal injection group (group GIR), and RIRI+AAV2-S100A4-GFP intravitreal injection group (group SIR), with 20 mice in each group. The RIRI model was established using the high intraocular pressure anterior chamber method in the RIRI, GIR and SIR groups of mice. Eyes were enucleated 3 days after modelling by over anaesthesia. The number of retinal capillary endothelial cells and pericytes in the retinal capillaries of mice in each group was observed by retinal trypsinised sections and hematoxylin-eosin and periodic acid-Schiff staining; immunofluorescence staining was used to observe endothelial cell, pericyte coverage and RGC survival; The relative expression of Toll-like receptor 4 (TLR4), p38 MAPK and nuclear factor erythroid 2-related factor 2 (NRF2) in retinal tissues was measured by Western blot. One-way analysis of variance was used to compare data between groups. ResultsThree days after modeling, the endothelial cell to pericyte ratio in group C was compared with group S and SIR, and the difference was not statistically significant (F=106.30, P＞0.05); the SIR group was compared with group RIRI and GIR, and the difference was statistically significant (F=106.30, P＜0.000 1). Comparison of endothelial cell coverage in each group, the difference was not statistically significant (F=3.44, P＞0.05); compared with the pericyte coverage in group C, the RIRI group and the GIR group were significantly lower, and the difference was statistically significant (F=62.69, P＜0.001). Compared with the RGC survival rate in group C, it was significantly lower in RIRI and GIR groups, and the difference was statistically significant (F=171.60, P＜0.000 1); compared with RIRI and GIR groups, the RGC survival rate in SIR group was significantly higher, and the difference was statistically significant (F=171.60, P＜0.000 1). The relative expression levels of TLR4, p38 and NRF2 proteins were statistically significant among all groups (F=42.65, 20.78, 11.55; P＜0.05). ConclusionsPericytes are more sensitive to ischemia than endothelial cells after retinal RIRI in mice, and early vascular cell loss is dominated by pericytes rather than endothelial cells. The overexpression of S100A4 protein protects against loss of pericytes and RGC after RIRI by inhibiting the TLR4/p38/NRF2 signaling pathway.
Objective To investigate the effect of N-acetylserotonin (NAS) on the retinal microglia polarization in retinal ischemia-reperfusion injury (RIRI) rats and explore its mechanism via nucleotide-bound oligomeric domain 1 (NOD1)/receptor interacting protein 2 (Rip2) pathway. MethodsHealthy male Sprague Dawley rats were randomly divided into Sham (n=21), RIRI (n=21) and NAS (injected intraperitoneally 30 min before and after modeling with NAS, 10 mg/kg, n=18) groups, using random number table. And the right eye was used experimental eye. The RIRI model of rats in RIRI group and NAS group was established by anterior chamber high intraocular pressure method. Rats in NAS group were intraperitoneally injected with 10 mg/kg NAS before and 30 min after modeling, respectively. The retinal morphology and the number of retinal ganglion cell (RGC) in each group were detected by hematoxylin-eosin staining and immunohistochemical staining. The effect of NAS on polarization of retinal microglia was detected by immunofluorescence staining. Transcriptome sequencing technology was used to screen out the differentially expressed genes between Sham and RIRI groups. Western blot and real-time quantitative polymerase chain reaction (RT-PCR) were used to examine the differentially expressed genes. Immunohistochemical staining, Western blot and RT-PCR were used to investigate the effect of NAS on the expression of NOD1 and Rip2 protein and mRNA in retinal tissue and microglia of rats. General linear regression analysis was performed to determine the correlation between the number difference of NOD1+ cells and the number difference of M1 and M2 microglia in retinal tissues of rats in NAS group and RIRI group. ResultsA large number of RGC were observed in the retina of rats in Sham group. 24 h after modeling, compared with Sham group, the inner retinal thickness of rats in RIRI group was significantly increased and the number of RGC was significantly decreased. The thickness of inner retina in NAS group was significantly thinner and the number of RGC was significantly increased. Compared with Sham group, the number of retinal microglia of M1 and M2 in RIRI group was significantly increased. Compared with RIRI group, the number of M1 microglia decreased significantly and the number of M2 microglia increased significantly in NAS group. There was statistical significance in the number of M1 and M2 microglia in the retina of the three groups (P＜0.05). Transcriptome sequencing results showed that retinal NOD1 and Rip2 were important differential genes 24 h after modeling. The mRNA and protein relative expressions of NOD1 and Rip2 in retina of RIRI group were significantly higher than those of Sham group, with statistical significance (P＜0.05). The number of NOD1+ and Rip2+ cells and the relative expression of mRNA and protein in retinal microglia in RIRI group were significantly higher than those in Sham group, and NAS group was also significantly higher than that in Sham group, but lower than that in RIRI group, with statistical significance (P＜0.05). The number of Iba-1+/NOD1+ and Iba-1+/Rip2+ cells in retinal microglia in RIRI group was significantly increased compared with that in Sham group, and the number of Iba-1+/Rip2+ cells in NAS group was significantly decreased compared with that in RIRI group, but still significantly higher than that in Sham group, with statistical significance (P＜0.05). Correlation analysis results showed that the difference of retinal NOD1+ and Rip2+ cells in NAS group and RIRI group was positively correlated with that of M1 microglia (r=0.851, 0.895), and negatively correlated with that of M2 microglia (r=−0.797, −0.819). The differences were statistically significant (P＜0.05). ConclusionNAS can regulate the microglial polarization from M1 to M2 phenotype, the mechanism is correlated with the NOD1/Rip2 pathway.
Cardiac arrest (CA) represents a significant global public health challenge, severely endangering both individual lives and public safety. Over the past years, cardiopulmonary resuscitation (CPR) techniques have advanced significantly. In 2013, the American Heart Association proposed high-quality CPR (HQ-CPR) as a key component for enhancing survival and neurological prognosis in patients with CA. HQ-CPR extends beyond the fundamental skills of compression and ventilation by prioritizing key metrics such as compression rate and depth, full chest recoil, minimal interruptions, and early defibrillation, representing a pivotal shift of CPR toward evidence-based, standardized, and precision-oriented practices. Despite the widespread recognition and adoption of HQ-CPR in Western nations, China continues to encounter multiple barriers in CPR dissemination and quality assurance, including low public training rates, variable instructional quality, delayed emergency responses, and disparities in healthcare resource allocation. Accordingly, this article provides a comprehensive review of the essential components of HQ-CPR. By analyzing the key challenges in China’s current clinical implementation, this paper focuses on exploring the latest research on enhancing resuscitation efficacy in recent years, especially focusing on new strategies to minimizing myocardial ischemia and improving reperfusion efficiency, in order to provide information for clinical optimization and improving patient outcomes following CA.
ObjectiveTo understand the current research progress on the role of hydrogen sulfide (H2S) in liver diseases. MethodThe relevant literature on the role of H2S in the liver diseases published in recent years was retrieved and reviewed. ResultsCurrent research focused primarily on exploring the mechanisms of H2S in various liver diseases. Studies had shown that H₂S played an important role in the occurrence and development of liver diseases through mechanisms such as antioxidative stress, anti-inflammatory effects, regulation of autophagy, endoplasmic reticulum stress, angiogenesis, and cell death. ConclusionsBy supplementing exogenous H2S, adjusting the gut microbiota, or inhibiting key enzymes involved in H₂S synthesis, the concentration of H2S in the body can be modulated, providing new strategies for treating liver diseases. However, the related mechanisms are still controversial. Future research should further investigate the specific role of H2S in different liver diseases and how to precisely control its level in the body to achieve targeted drug delivery.
Objective To investigate the mechanism of bone morphogenetic protein-4 (BMP4) in promoting the recovery of small intestinal mucosal barrier function during the recovery period of small intestine ischemia-reperfusion (I/R) injury. Methods Twenty-eight C57BL/6J male mice aged 6–8 weeks were randomly selected and assigned to small intestine I/R group (n=24) and sham operation (SO) group (n=4) by random number table method. Small intestine I/R injury models of 24 mice were established, then 4 mice were randomly selected at 6, 12, 24 and 48 h after I/R established modeling and killed to observe the morphological changes of small intestinal mucosa and detect the expression of BMP4 mRNA in the jejunal epithelial cells, the other 8 mice were allocated for the experimental observation at the recovery period of small intestine I/R injury (24 h after I/R was selected as the observation time point of recovery period of small intestine I/R injury according to the pre-experimental results). Twelve mice were randomly divided into I/R-24 h-BMP4 group (recombinant human BMP4 protein was injected intraperitoneally), I/R-24 h-NS (normal saline) group (NS was injected intraperitoneally), and I/R-24 h-blank group (did nothing), 4 mice in each group. Then the small intestinal transmembrane electrical impedance (TER) was measured by Ussing chamber. The expressions of BMP4 protein and tight junction proteins (occludin and ZO-1), Notch signaling pathway proteins (Notch1 and Jagged1), and Smad6 protein were detected by Western blot. Results At 24 h after I/R injury, the injuries of villous epithelium, edema, and a small part of villi were alleviated. The BMP4 mRNA expressions at 6, 12, 24 and 48 h after I/R injury in the small intestinal epithelial cells were increased as compared with the SO group. Compared with the I/R-24 h-NS group and the I/R-24 h-blank group, the TER was increased, and the expression levels of occludin, ZO-1, p-Smad6, Notch1, Jagged1 were increased in the I/R-24 h-BMP4 group. Conclusion From the preliminary results of this study, during recovery period of small intestine I/R injury, the expression of BMP4 in small intestinal epithelial cells is increased, permeability of jejunal mucosal barrier is increased, which might promote the recovery of small intestinal mucosal barrier function by activating the Notch signaling pathway (Notch1 and Jagged1), Smad classic signaling pathway, and promoting the increase of tight junction protein expression (occludin and ZO-1).
ObjectiveTo investigate relationship between liver non-parenchymal cells and hepatic ischemia-reperfusion injury (HIRI).MethodThe relevant literatures on researches of the relationship between HIRI and liver non-parenchymal cells were analyzed and reviewed.ResultsDuring HIRI, hepatocytes could be severely damaged by aseptic inflammatory reaction and apoptosis. The liver non-parenchymal cells included Kupffer cells, sinusoidal endothelial cells, hepatic stellate cells, and dendritic cells, which could release a variety of cytokines and inflammatory mediators to promote the damage, and some liver non-parenchymal cells also had effect on reducing HIRI, for example: Kupffer cells could express heme oxygenase-1 to reduce HIRI, and hepatic stellate cells may participate in the repair process after HIRI. The role of liver non-parenchymal cells in HIRI was complex, but it also had potential therapeutic value.ConclusionLiver non-parenchymal cells can affect HIRI through a variety of mechanisms, which provide new goals and strategies for clinical reduction of HIRI.