Fe3+-induced coordination cross-linking gallic acid-carboxymethyl cellulose self-healing hydrogel.

Self-healing hydrogel is a promising soft material for applications in wound dressings, drug delivery, tissue engineering, biomimetic electronic skin, and wearable electronic devices. However, it is a challenge to fabricate the self-healing hydrogels without external stimuli. Inspired by mussel, the metal-catechol complexes were introduced into the hydrogel systems to prepare the mussel-inspired hydrogels by regulating the gelation kinetics of Fe3+ crosslinkers with gallic acid (GA) in this research. The amine-functionalized carboxymethyl cellulose (CMC) was grafted with GA and then chelated with Fe3+ to form a multi-response system. The crosslinking of carboxymethyl cellulose-ethylenediamine-gallic acid (CEG) hydrogel was controlled by adjusting the pH to affect the iron coordination chemistry, which could enhance the self-healing properties and mechanical strength of hydrogels. In addition, the CEG hydrogel exhibited great antibacterial and antioxidant properties. And the CEG hydrogel could strongly adhere to the skin tissue. The adhesion strength of CEG hydrogel on pigskin was 11.44 kPa, which is higher than that of commercial wound dressings (∼5 kPa). Moreover, the thixotropy of the CEG hydrogel was confirmed with rheological test. In summary, it has great potential in the application field of wound dressing.

Fabrication of carboxymethyl cellulose-based thermo-sensitive hydrogels and inhibition of corneal neovascularization.

Corneal neovascularization (CNV) is a common multifactorial sequela of anterior corneal segment inflammation, which could lead to visual impairment and even blindness. The main treatments available are surgical sutures and invasive drug injections, which could cause serious ocular complications. To solve this problem, a thermo-sensitive drug-loaded hydrogel with high transparency was prepared in this study, which could achieve the sustained-release of drugs without affecting normal vision. In briefly, the thermo-sensitive hydrogel (PFNOCMC) was prepared from oxidized carboxymethyl cellulose (OCMC) and aminated poloxamer 407 (PF127-NH2). The results proved the PFNOCMC hydrogels possess high transparency, suitable gel temperature and time. In the CNV model, the PFNOCMC hydrogel loading bone morphogenetic protein 4 (BMP4) showed significant inhibition of CNV, this is due to the hydrogel allowed the drug to stay longer in the target area. The animal experiments on the ocular surface were carried out, which proved the hydrogel had excellent biocompatibility, and could realize the sustained-release of loaded drugs, and had a significant inhibitory effect on the neovascularization after ocular surface surgery. In conclusion, PFNOCMC hydrogels have great potential as sustained-release drug carriers in the biomedical field and provide a new minimally invasive option for the treatment of neovascular ocular diseases.

A novel prognostic model of breast cancer based on cuproptosis-related lncRNAs.

OBJECTIVE: Breast cancer (BC) is a deadly form of malignancy responsible for the death of a large number of women every year. Cuproptosis is a newly discovered form of cell death that may have implications for the prognosis of BC. Long non-coding RNAs (lncRNAs) have been shown to be involved in the progression and development of BC. Here within, a novel model capable of predicting the prognosis of patients with BC was established based on cuproptosis-related lncRNAs. METHODS: Data of breast cancer patients was downloaded, including clinical information from The Cancer Genome Atlas (TCGA) database and lncRNAs related to cuproptosis were isolated. In total, nine lncRNAs related to copper death were obtained by Cox regression model based on Least Absolute Shrinkage and Selector Operation (LASSO) algorithm for model construction. The model was verified by overall survival (OS), progression-free survival (PFS) and receiver operating characteristic (ROC) curve. The differences in immune function, tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) between patients with different risk scores were analyzed. RESULTS: Based on cuproptosis-related lncRNAs, a prognostic model for predicting BC was constructed. Each patient was assigned a risk score based on our model formula. We found that patients with higher risk scores had significantly lower OS and PFS, increased TMB, and higher sensitivity to immunotherapy. CONCLUSIONS: The model established in this study based on cuproptosis-related lncRNAs may be capable of improving the OS of patients with BC.

Bone morphogenetic protein 4 thermosensitive hydrogel inhibits corneal neovascularization by repairing corneal epithelial apical junctional complexes.

Corneal neovascularization (CNV) is a heavy attribute of blinding disease changes. Existing medications need numerous infusions and have a limited absorption. Investigating novel drugs with safety, efficacy, and convenience is crucial. In this study, we developed a bone morphogenetic protein 4 (BMP4)-loaded poloxamer-oxidized sodium alginate (F127-OSA) thermosensitive hydrogel. The 14 % F127-OSA hydrogel transformed from sol to gel at 31-32 °C, which might extend the application period on the ocular surface. The hydrogel's porous structure and uniform dispersion made it possible for drugs to release gradually. We used a suture-induced rat CNV model to investigate the mechanism of CNV inhibition by hydrogel. We discovered that F127-OSA hydrogel loaded with BMP4 could significantly reduce the length and area of CNV, relieve corneal edema, and stop aberrant epithelial cell proliferation. The hydrogel's efficacy was superior to that of the common solvent group. Additionally, BMP4 thermosensitive hydrogel repaired ultrastructure, including microvilli, intercellular junctions, and damaged apical junctional complexes (AJCs), suggesting a potential mechanism by which the hydrogel prevented CNV formation. In conclusion, our investigation demonstrates that F127-OSA thermosensitive hydrogel loaded with BMP4 can repair corneal epithelial AJCs and is a promising novel medication for the treatment of CNV.

Chitosan-based mussel-inspired hydrogel for rapid self-healing and high adhesion of tissue adhesion and wound dressings.

The hydrogel wound dressing with self-healing and adhesive property can provide better protection to the wound and prolong the service life of the material. Inspired by mussels, a high-adhesion, injectable, self-healing and antibacterial hydrogel was designed in this study. The lysine (Lys) and the catechol compound 3,4-dihydroxyphenylacetic acid (DOPAC) were grafted onto chitosan (CS). The presence of catechol group endows the hydrogel strong adhesion and antioxidation. In the experiment of wound healing in vitro, the hydrogel can adhere to the wound surface and promote wound heal. In addition, it has been proved the hydrogel has good antibacterial properties against S. aureus and E. coli. The treatment of CLD hydrogel, the degree of wound inflammation was significantly alleviated. The levels of TNF-α, IL-1ß, IL-6 and TGF-ß1 were reduced from 39.8379 %, 31.6768 %, 32.1015 % and 38.4911 % to 18.5931 %, 12.2275 %, 13.0524 % and 16.9959 %, respectively. And the levels of PDGFD and CD31 were increased from 35.6054 %, 21.7394 % to 51.8555 %, 43.9326 %, respectively. These results indicated that the CLD hydrogel has a good ability to promote angiogenesis, thickening of skin and epithelial structures.

Injectable chitosan-based self-healing supramolecular hydrogels with temperature and pH dual-responsivenesses.

In this study, a supramolecular hydrogel was fabricated with orotic acid (OA) modified chitosan (OACS) and 2,6-diaminopurine (DAP). The obtained OACS-DAP supramolecular hydrogels have dual responsiveness to temperature and pH. Phase transition experiments indicate this is a temperature-dependent thermoreversible supramolecular hydrogel. Rheological experiments proved the formation of the supramolecular hydrogel and its thixotropic properties. FTIR spectra confirmed that hydrogen bonds and π-π interactions are the main driving forces for OACS and DAP to form hydrogels through intermolecular self-assembly. XRD pattern confirmed the amorphous morphology of OACS-DAP hydrogels. The hydrogel has excellent electrical conductivity with a conductivity of 9.48 µ S·cm-1. And can achieve the precise release of gastrointestinal drugs. OACS-DAP hydrogel is expected to have better applications in the field of gastrointestinal drug release.

Ketamine Induces Delirium-Like Behavior and Interferes With Endosomal Tau Trafficking.

BACKGROUND: Ketamine is an intravenous anesthetic. However, whether ketamine can induce neurotoxicity and neurobehavioral deficits remains largely unknown. Delirium is a syndrome of acute brain dysfunction associated with anesthesia and surgery in patients, and tau protein may contribute to postoperative delirium. Finally, ketamine may affect the function of the endosome, the key organelle for tau release from neurons. Therefore, we set out to determine the effects of ketamine on delirium-like behavior in mice and on tau trafficking in cultured cells. METHODS: We used the buried-food test, open-field test, and Y-maze test in adult mice to assess the presence of delirium-like behavior in mice. We quantified tau amounts in the serum of mice. We used cell fraction methods to determine the effects of ketamine on tau intracellular trafficking, extracellular release, and endosome trafficking in cultured cells. RESULTS: Ketamine induced delirium-like behavior in mice and increased tau amounts in serum of mice. The ketamine treatments also led to increased accumulation of endosomes, as evidenced by increased endosomal markers Rab5 and Rab7. Moreover, ketamine inhibited endosome maturation, demonstrated by decreased membrane-bound but increased cytoplasm amounts of Rab5 and Rab7. Consequently, ketamine increased tau in the endosomes of cultured cells and the cell culture medium. CONCLUSIONS: These data suggest that ketamine may interfere with intracellular tau trafficking and induce delirium-like behavior, promoting future research regarding the potential neurotoxicity of anesthetics.

Tandem mass tag-based quantitative proteomic analysis of effects of multiple sevoflurane exposures on the cerebral cortex of neonatal and adult mice.

Introduction: Sevoflurane is the most commonly used general anesthetic in pediatric surgery, but it has the potential to be neurotoxic. Previous research found that long-term or multiple sevoflurane exposures could cause cognitive deficits in newborn mice but not adult mice, whereas short-term or single inhalations had little effect on cognitive function at both ages. The mechanisms behind these effects, however, are unclear. Methods: In the current study, 6- and 60-day-old C57bl mice in the sevoflurane groups were given 3% sevoflurane plus 60% oxygen for three consecutive days, each lasting 2 hours, while those in the control group only got 60% oxygen. The cortex tissues were harvested on the 8th or 62nd day. The tandem mass tags (TMT)pro-based quantitative proteomics combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, Golgi staining, and western blotting analysis were applied to analyze the influences of multiple sevoflurane anesthesia on the cerebral cortex in mice with various ages. The Morris water maze (MWM) test was performed from postnatal day (P)30 to P36 or P84 to P90 after control or multiple sevoflurane treatment. Sevoflurane anesthesia affected spatial learning and memory and diminished dendritic spines primarily in newborn mice, whereas mature animals exhibited no significant alterations. Results: A total of 6247 proteins were measured using the combined quantitative proteomics methods of TMTpro-labeled and LC-MS/MS, 443 of which were associated to the age-dependent neurotoxic mechanism of repeated sevoflurane anesthesia. Furthermore, western blotting research revealed that sevoflurane-induced brain damage in newborn mice may be mediated by increasing the levels of protein expression of CHGB, PTEN, MAP2c, or decreasing the level of SOD2 protein expression. Conclusion: Our findings would help to further the mechanistic study of age-dependent anesthetic neurotoxicity and contribute to seek for effective protection in the developing brain under general anesthesia.

Schiff Base Aggregation-Induced Emission Luminogens for Sensing Applications: A Review.

Fluorescence sensing can not only identify a target substrate qualitatively but also achieve the purpose of quantitative detection through the change of the fluorescence signal. It has the advantages of immense sensitivity, rapid response, and excellent selectivity. The proposed aggregation-induced emission (AIE) concept solves the problem of the fluorescence of traditional fluorescent molecules becoming weak or quenched in high concentration or aggregated state conditions. Schiff base fluorescent probes have the advantages of simple synthesis, low toxicity, and easy design. They are often used for the detection of various substances. In this review we cover late developments in Schiff base compounds with AIE characteristics working as fluorescence sensors.

Effect of Different Vitamin D Levels on Cognitive Function in Aged Mice After Sevoflurane Anesthesia.

Although the biological relationship between vitamin D (VD) deficiency and cognitive function has been recognized by many scholars, the theoretical mechanisms involved are still not well-understood. In this study, we demonstrated the role of VD in alleviating the cognitive dysfunction in aged mice caused by sevoflurane anesthesia. Forty female C57BL/6 mice aged 12 months were selected for the experiment. VD (-) and VD (+) mouse models and sevoflurane anesthesia models were established. Mice were randomly divided into normal elderly group (NC group), normal aged mice + sevoflurane anesthesia treatment group (NS group), aged VD (-) mice + sevoflurane anesthesia treatment group [VD (-) group], and aged VD (+) + sevoflurane anesthesia treatment group [VD (+) group]. To compare the emergence time after sevoflurane anesthesia in aged mice with different levels of VD and to test the cognitive function of four groups through the water maze. Inflammatory factor expression and cholinergic activity in hippocampus tissue of all mice were measured at the end of behavioral tests. These data show that, low levels of VD aggravated the delayed emergence and cognitive dysfunction in aged mice caused by sevoflurane anesthesia, while higher levels of VD mitigated this impairment by enhancing cholinergic activity and reducing inflammatory factor expression in the hippocampus.

Correlation Analysis of Serum Vitamin D Levels and Postoperative Cognitive Disorder in Elderly Patients With Gastrointestinal Tumor.

Purpose: Vitamin D prevents hypocalcaemia, osteoporosis, and infections, among other problems, and is involved in the prevention and treatment of cardiovascular and neurological diseases. Recently, vitamin D was shown to improve cognitive dysfunction caused by Alzheimer's disease and vascular dementia. This study aims to explore the correlation between preoperative serum vitamin D and postoperative cognitive disorder (POCD) occurrence in elderly patients with gastrointestinal tumors to guide perioperative medication use and promote early patient recovery. Methods: This study recruited 238 elderly patients (65 ≤ age ≤ 85) who underwent gastrointestinal tumor surgery; 117 cases were enrolled, and 55 controls of the same age and education level as the cases were included. Blood samples were taken preoperatively and at 7, 15, 30, and 90 days postoperatively, and plasma vitamin D (25OH-D3) and glutathione (GSH) was measured. Different from the previous diagnosis of POCD was obtained by telephone interview through Cognitive Status Modified Telephone Interview (TICS-m), mainly for memory impairment, a series of neuropsychological tests was used to evaluate cognitive function, Picture Recollect Test, Stroop Color-word Test, and Digit Symbol Substitution Test were used to comprehensively evaluate the three domains of cognitive function of patients, namely memory, attention and information processing ability. All neuropsychiatric assessments were performed at the bedside and completed face-to-face by the assessment staff and the patient. Results: A total of 65.8% (77/117) of elderly patients undergoing gastrointestinal tumor surgery had preoperative vitamin D deficiency (serum 25OH-D concentration < 12 ng/ml), of whom 46.7% (36/77, 7 days after surgery), 31.2% (24/77, 15 days after surgery), 15.6% (12/77, 30 days after surgery), and 9% (7/77, 90 days after surgery) of patients developed POCD; 7.5% (3/40) of patients without vitamin D deficiency developed PNDs, which was detected only on the 7th day after surgery. Conclusions: Vitamin D deficiency can increase neurocognitive disorder risk in elderly patients during the perioperative period, possibly because low vitamin D levels cannot effectively inhibit the postoperative oxidative stress increase. Trial Registration: This experiment was approved and registered by the China Clinical Trial Registration Center, registration number ChiCTR2100046900 (30/05/2021).

Corrigendum to "Photoluminescence of Tilapia skin collagen: Aggregation-induced emission with clustering triggered emission mechanism and its multiple applications" [Int. J. Biol. Macromol. 182 (2021) 1437-1444].

There is an urgent need for natural sources of aggregation-induced emission (AIE) materials which have good water solubility, biocompatibility, and can be produced in large quantities. Here, Tilapia skin collagen (Tsc) is a very abundant protein in nature, with solid-phase and solution-state fluorescence emission effect and its multiple applications was explored.Due to Tsc was in high concentration or aggregation state which shown AIE property. This obvious emission can be account for clustering-triggered emission (CTE) mechanism. The photoluminescence property of Tsc not only provide a deeper understanding of the emission characteristics of proteins, but also has important guiding significance for further elucidating the basis of fluorescence properties.

Recent advances in polysaccharide-based self-healing hydrogels for biomedical applications.

Hydrogels are a class of polymer materials with three-dimensional networks structure, which can absorb a large number of water and biological fluids. Natural polysaccharides are ideal materials for the preparation of biomimetic hydrogels because of their good biocompatibility and biodegradability. The self-healing hydrogel can achieve healing without external force and prolong the service life of the hydrogel. Therefore, self-healing hydrogels are of great interest in tissue engineering, wound dressings, drug delivery, and tissue engineering. This review aims to introduce the preparation methods, self-healing properties of polysaccharide-based self-healing hydrogels and its potential applications in biomedicine and other fields.

Testosterone attenuates sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice.

BACKGROUND: Sevoflurane anaesthesia induces phosphorylation of the microtubule-associated protein tau and cognitive impairment in neonatal, but not adult, mice. The underlying mechanisms remain largely to be determined. Sex hormones can be neuroprotective, but little is known about the influence of testosterone on age-dependent anaesthesia effects. METHODS: Six- and 60-day-old male mice received anaesthesia with sevoflurane 3% for 2 h daily for 3 days. Morris water maze, immunoassay, immunoblotting, co-immunoprecipitation, nanobeam technology, and electrophysiology were used to assess cognition; testosterone concentrations; tau phosphorylation; glycogen synthase kinase-3ß (GSK3ß) activation; binding or interaction between tau and GSK3ß; and neuronal activation in mice, cells, and neurones. RESULTS: Compared with 60-day-old male mice, 6-day-old male mice had lower testosterone concentrations (3.03 [0.29] vs 0.44 [0.12] ng ml-1; P<0.01), higher sevoflurane-induced tau phosphorylation in brain (133 [20]% vs 100 [6]% in 6-day-old mice, P<0.01; 103 [8]% vs 100 [13]% in 60-day-old mice, P=0.77), and sevoflurane-induced cognitive impairment. Testosterone treatment increased brain testosterone concentrations (1.76 [0.10] vs 0.39 [0.05] ng ml-1; P<0.01) and attenuated the sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal male mice. Testosterone inhibited the interaction between tau and GSK3ß, and attenuated sevoflurane-induced inhibition of excitatory postsynaptic currents in hippocampal neurones. CONCLUSIONS: Lower brain testosterone concentrations in neonatal compared with adult male mice contributed to age-dependent tau phosphorylation and cognitive impairment after sevoflurane anaesthesia. Testosterone might attenuate the sevoflurane-induced tau phosphorylation and cognitive impairment by inhibiting the interaction between tau and GSK3ß.

Temperature-sensitive poly(N-isopropylacrylamide)-chitosan hydrogel for fluorescence sensors in living cells and its antibacterial application.

It is meaningful and challenging to design and develop a fluorescent probe for living cell temperature sensors since it should have good cell compatibility and high-resolution features. In this work, the temperature-sensitive polymer of PA-loaded cysteine (Cys) modified chitosan (Cs) grafted PNIPAM (Cs-Cys-PN/PA) with aggregation-induced emission enhancement (AIEE) properties that reversible hydrogel in an aqueous solution is synthesized. Here, we interpret the temperature stimulus as a monochromatic signal through the AIEE active reversible hydrogel of Cs-Cys-PN. In addition, the cytotoxicity test shown that Cs-Cys-PN has good biocompatibility. Cs-Cys-PN can be used to build antibacterial drugs carrier, thereby providing a new platform of self-released drugs for the treatment of bacterial infections.

Photoluminescence of Tilapia skin collagen: Aggregation-induced emission with clustering triggered emission mechanism and its multiple applications.

There is an urgent need for natural sources of aggregation-induced emission (AIE) materials which have good water solubility, biocompatibility, and can be produced in large quantities. Here, Tilapia skin collagen (Tsc) is a very abundant protein in nature, with solid-phase and solution-state fluorescence emission effect and its multiple applications was explored. Due to Tsc was in high concentration or aggregation state which shown AIE property. This obvious emission can be account for clustering-triggered emission (CTE) mechanism. The photoluminescence property of Tsc not only provide a deeper understanding of the emission characteristics of proteins, but also has important guiding significance for further elucidating the basis of fluorescence properties.

Tau Contributes to Sevoflurane-induced Neurocognitive Impairment in Neonatal Mice.

BACKGROUND: Sevoflurane anesthesia induces Tau phosphorylation and cognitive impairment in neonatal but not in adult mice. This study tested the hypothesis that differences in brain Tau amounts and in the activity of mitochondria-adenosine triphosphate (ATP)-Nuak1-Tau cascade between the neonatal and adult mice contribute to the age-dependent effects of sevoflurane on cognitive function. METHODS: 6- and 60-day-old mice of both sexes received anesthesia with 3% sevoflurane for 2 h daily for 3 days. Biochemical methods were used to measure amounts of Tau, phosphorylated Tau, Nuak1, ATP concentrations, and mitochondrial metabolism in the cerebral cortex and hippocampus. The Morris water maze test was used to evaluate cognitive function in the neonatal and adult mice. RESULTS: Under baseline conditions and compared with 60-day-old mice, 6-day-old mice had higher amounts of Tau (2.6 ± 0.4 [arbitrary units, mean ± SD] vs. 1.3 ± 0.2; P < 0.001), Tau oligomer (0.3 ± 0.1 vs. 0.1 ± 0.1; P = 0.008), and Nuak1 (0.9 ± 0.3 vs. 0.3 ± 0.1; P = 0.025) but lesser amounts of ATP (0.8 ± 0.1 vs. 1.5 ± 0.1; P < 0.001) and mitochondrial metabolism (74.8 ± 14.1 [pmol/min] vs. 169.6 ± 15.3; P < 0.001) in the cerebral cortex. Compared with baseline conditions, sevoflurane anesthesia induced Tau phosphorylation at its serine 202/threonine 205 residues (1.1 ± 0.4 vs. 0.2 ± 0.1; P < 0.001) in the 6-day-old mice but not in the 60-day-old mice (0.05 ± 0.04 vs. 0.03 ± 0.01; P = 0.186). The sevoflurane-induced Tau phosphorylation and cognitive impairment in the neonatal mice were both attenuated by the inhibition of Nuak1 and the treatment of vitamin K2. CONCLUSIONS: Higher brain Tau concentrations and lower brain mitochondrial metabolism in neonatal compared with adult mice contribute to developmental stage-dependent cognitive dysfunction after sevoflurane anesthesia.

Hemopexin alleviates cognitive dysfunction after focal cerebral ischemia-reperfusion injury in rats.

BACKGROUND: Ischemia-reperfusion (I/R) is a critical pathophysiological basis of cognitive dysfunction caused by ischemia stroke. Heme-oxygenase-1 (HO-1) is the rate-limiting enzyme for the elimination of excessive free heme by combining with hemopexin (HPX), a plasma protein that contributes to eliminating excessive free heme during ischemia stroke. This study aimed to elucidate whether HPX could alleviate cognitive dysfunction in rats subjected to cerebral I/R. METHODS: Rats were randomly divided into five groups: sham, MCAO, Vehicle, HPX and HPX + protoporphyrin IX (ZnPPIX). Cerebral I/R was induced by MCAO. Saline, vehicle, HPX and HPX + ZnPPIX were injected intracerebroventricularly at the moment after reperfusion. Morris water maze (MWM) test was used to detect the learning and cognitive function. Western blot was used to detect the expression of HO-1 in ischemic penumbra. CD31/vWF double labeling immunofluorescence was used to detect the neovascularization in the penumbra hippocampus. The structure and function of blood-brain barrier (BBB) was detected by the permeability of Evans Blue (EB), water content of the brain tissue, the Ang1/Ang2 and VE-cadherin expression. RESULTS: Our study verified that HPX improved the learning and memory capacity. Hemopexin up-regulated HO-1 protein expression, the average vessel density in the penumbra hippocampus and the VE- cadherin expression but decreased the permeability of EB, the water content of brain tissue and the ratio of Ang1/Ang2. The effects were reversed by ZnPPIX, an inhibitor of HO-1. CONCLUSION: HPX can maintain the integrity of the blood-brain barrier and alleviate cognitive dysfunction after cerebral I/R through the HO-1 pathway.

Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2/HO-1-dependent pathway.

BACKGROUND: Lung injury is a vital contributor of mortality in septic patients. Our previous studies have found that molecular hydrogen (H2), which has anti-oxidant, anti-inflammatory, and anti-apoptosis effects, had a therapeutic effect on a septic animal model through increasing expression of nuclear factor-erythroid 2-related factor 2 (Nrf2). The aim of this research was to investigate the effects of 2% H2 gas inhalation on sepsis-induced lung injury and its underlying mechanisms. METHODS: Male wild-type (WT) and Nrf2-knockout (Nrf2-KO) ICR mice underwent sham or cecal ligation and puncture (CLP) operation. Two percent of H2 gas was inhaled for 60 min beginning at both 1 h and 6 h after sham or CLP surgery. To assess the severity of septic lung injury, the 7-day survival rate, wet/dry (W/D) weight ratio of lung tissue, lung histopathologic score, pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), high-mobility group box 1 (HMGB1)), anti-inflammatory cytokine (interleukin 10 (IL-10)), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and heme oxygenase 1 (HO-1)), and an oxidative product (malondialdehyde (MDA)) were detected after sham or CLP operation. The histopathologic changes were observed in lung tissues by hematoxylin and eosin (HE) staining, and pro-inflammatory cytokines (TNF-α and IL-6), anti-inflammatory cytokine (IL-10), antioxidant enzymes (SOD and CAT), and MDA were detected in lung tissues by an enzyme-linked immunosorbent assay (ELISA). RESULTS: The results indicated that 2% H2 gas treatment increased the survival rates, decreased the W/D weight ratio and the lung injury score, alleviated the injuries caused by oxidative stress and inflammation, and induced HO-1 level but reduced HMGB1 level in WT but not Krf2-KO mice. These data reveal that H2 gas could suppress lung injury in septic mice through regulation of HO-1 and HMGB1 expression and that Nrf2 plays a main role in the protective effects of H2 gas on lung damage caused by sepsis.

Hemopexin reduces blood-brain barrier injury and protects synaptic plasticity in cerebral ischemic rats by promoting EPCs through the HO-1 pathway.

Ischemic stroke causes endothelial dysfunction and blood-brain barrier dysfunction, thus damages synaptic plasticity such as learning and memory. In this study we aim to investigate the effect of hemopexin (HPX) in protecting synaptic plasticity and blood brain barrier integrity from toxic heme, and determine whether this effect is via the activation of endothelial progenitor cells (EPCs) through the heme oxygenase-1 (HO-1) pathway. Our data indicates HPX showed a significant effect in inducing the expression of HO-1, promoting the migration and differentiation of EPCs, facilitating new blood vessel formation thus protecting blood-brain barrier integrity. Also the magnitude of synaptic plasticity of rats recovered with HPX treatment. And in the presence of HO-1 blocker Zinc protoporphyrin-9 (ZnppIX), HPX lost its protective effect. This suggests that HPX protects endothelial and blood brain barrier integrity from toxic heme, thus protects neurologic function in cerebral ischemic rats in HO-1 pathway.