We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts ...Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a lifetime.The cost of disability associated with preterm brain injury continues to rise.Prevention of this injury,and disability,would significantly reduce this socioeconomic burden.展开更多
As a reducing salt,sodium sulfite could deprive oxygen in solution,which could mimic hypoxic stress in Caenorhabditis elegans.In this study,the wildtype Escherichia coli strain MG1655 was used to examine the inhibitio...As a reducing salt,sodium sulfite could deprive oxygen in solution,which could mimic hypoxic stress in Caenorhabditis elegans.In this study,the wildtype Escherichia coli strain MG1655 was used to examine the inhibition of sodium sulfite-induced hypoxia by observing the bacterial growth curves.展开更多
Hypoxic hepatitis, also known as ischemic hepatitis, is characterized by acute hepatocellular injury due to inadequate oxygen delivery to the liver. Celiac trunk stenosis can lead to hepatic ischemia and subsequent li...Hypoxic hepatitis, also known as ischemic hepatitis, is characterized by acute hepatocellular injury due to inadequate oxygen delivery to the liver. Celiac trunk stenosis can lead to hepatic ischemia and subsequent liver damage. We present the case of an 81-year-old patient with a history of hypertension, ischemic heart disease, hypothyroidism, and biliary lithiasis, who developed hypoxic hepatitis secondary to Dunbar syndrome and a stenosis of the superior mesenteric artery. The patient improved symptoms and liver function tests with conservative management, including intravenous fluids and supportive care. Long-term management involved continued antiplatelet therapy and statins, with consideration of further interventions for celiac trunk stenosis. This case underscores the importance of recognizing Dunbar syndrome as well as superior mesentery trunk stenosis as a potential cause of hypoxic hepatitis. It highlights the need for multidisciplinary management in such cases.展开更多
Background:Low levels of antioxidant paraoxonase 1(PON 1)enzyme activity,PON1-Q192R polymorphism(a glutamine(Q)to arginine(R)substitution at position 192),PON1-L55M polymorphism(a leucine(L)to methionine(M)substitutio...Background:Low levels of antioxidant paraoxonase 1(PON 1)enzyme activity,PON1-Q192R polymorphism(a glutamine(Q)to arginine(R)substitution at position 192),PON1-L55M polymorphism(a leucine(L)to methionine(M)substitution at position 55),and oxidized low-density lipoprotein(oxLDL)are risk factors for coronary heart disease.Aerobic exercise improves PON1 activity,but the effects of hypoxic exercise are yet unclear.The aim of this study was to determine the effects of hypoxic underwater rugby training on PON1 activity and oxLDL levels and the role of the mentioned polymorphisms.Methods:Serum PON1 and arylesterase activities(ARE),PON1,PON3,and oxLDL protein levels(by using the enzyme-linked immunosorbent assays)were determined in an athletic group(42 trained male underwater rugby players;age=21.7±4.2 years,mean±SD)and a control group(43 sedentary men;age=23.9±3.2 years).The polymorphisms were determined from genomic DNA samples.Results:PON1 activity(25.1%,p=0.052),PON3(p<0.001),and oxLDL(p<0.001)of the athletic group,including most genotype groups,were higher than those of the control group.In comparison to the controls,PON1 activity levels(p=0.005)of the PON1-Q192R homozygote QQ genotype group and PON1 activity levels(30%,p=0.116)of the PON1-L55M homozygote LL genotype group were higher,whereas ARE activity values of athletic R allele carrier(Rc=QR+RR)(p=0.005)and LL group(p=0.002)were lower than the control genotype groups related to their polymorphisms.Conclusion:Hypoxic training can cause(1)significant oxidative stress,including oxLDL,and an antioxidant response(increase in PON1 activity and PON3),(2)differences in the activity of PON1 and ARE,which are modified by PON1-Q192R and PON1-L55M polymorphisms,respectively,and(3)improvements in PON1 activity of QQ and LL groups.However,hypoxic training can cause a disadvantage of LL and Rc groups for ARE.展开更多
The spatial distribution and seasonal variations of the hypoxic zone in the eastern equatorial Indian Ocean were investigated using survey data collected from four cruises from 2013 to 2018.Results showed that hypoxic...The spatial distribution and seasonal variations of the hypoxic zone in the eastern equatorial Indian Ocean were investigated using survey data collected from four cruises from 2013 to 2018.Results showed that hypoxic zone occurred all year round in the eastern equatorial Indian Ocean,and it spread southward in the shape of a double tongue at two depths with one at subsurface centered at a depth of 150 m and the other in intermediate water centered at a depth of 800 m.The southward expansion and maximum thickness of the hypoxic zone were greatest in the spring inter-monsoon and least in the summer monsoon.The hypoxic zone originated from the southward expansion of the hypoxic water in the Bay of Bengal and its spatial distribution was driven by southward output flux of mid-deep(100–1000 m)hypoxic water from the Bay of Bengal.The hypoxia southward expansion was blocked near the equator in the subsurface layer,because of mixing with multiple zonal circulations(e.g.,Wyrtki Jets and the equatorial undercurrent),which meant that the hypoxic zone extended over a smaller area than in the intermediate water.These new findings will contribute to an improved understanding of the hypoxic zone and will contribute to circulation research,particularly about intermediate circulation in the eastern equatorial Indian Ocean.展开更多
Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerati...Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs.This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned(2%oxygen for 72 hours)autologous ADSPCs(n=9).This treatment mode was compared with three others:fibrin conduit seeded with ADSPCs cultivated under normoxic conditions(n=9);non-cell-carrying conduit(n=9);and nerve autograft only(n=9).A 16-week follow-up included functional testing(sciatic functional index and static sciatic index)as well as postmortem muscle mass analyses and morphometric nerve evaluations(histology,g-ratio,axon density,and diameter).At 8 weeks,the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups,indicating faster functional regeneration.Furthermore,histologic evaluation showed significantly increased axon outgrowth/branching,axon density,remyelination,and a reduced relative connective tissue area.Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts.Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.展开更多
Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical problem.It is not fully elucidated where in the circulation the regulation of resistance takes place.It is often referred to as if it i...Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical problem.It is not fully elucidated where in the circulation the regulation of resistance takes place.It is often referred to as if it is in the arteries,but we hypothesized that it is in the venous side of the pulmonary circulation.Methods:In an open thorax model,pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels.At the same time the lungs were ventilated with extreme variations of inspired air from 5%to 100%oxygen,making it possible to make combinations of high and low oxygen content through the pulmonary circulation.A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests.Under different combinations of oxygenation,pulmonary vascular resistance(PVR)was calculated.Results:With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein,PVR was doubled.With more extreme hypoxia PVR suddenly decreased.Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins.Discussion:The impact of hypoxia occurs from the alveolar level and forward with the blood flow.The experiments indicated that the regulation of PVR is mediated from the venous side.展开更多
Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve rep...Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.展开更多
Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to impr...Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.展开更多
BACKGROUND: It has been previously shown that hyperbaric oxygen may promote proliferation of neural stem cells and reduce death of endogenous neural stem cells (NSCs). OBJECTIVE: To explore the effects of hyperbar...BACKGROUND: It has been previously shown that hyperbaric oxygen may promote proliferation of neural stem cells and reduce death of endogenous neural stem cells (NSCs). OBJECTIVE: To explore the effects of hyperbaric oxygen on the differentiation of hypoxic/ischemic brain-derived NSCs into neuron-like cells and compare with high-concentration oxygen and high pressure. DESIGN, TIME AND SETTING: An in vitro contrast study, performed at Laboratory of Neurology, Central South University between January and May 2006. MATERIALS: A hyperbaric oxygen chamber (YLC 0.5/1A) was provided by Wuhan Shipping Design Research Institute; mouse anti-rat microtubule-associated protein 2 monoclonal antibody by Jingmei Company, Beijing; mouse anti-rat glial fibrillary acidic protein monoclonal antibody by Neo Markers, USA; mouse anti-rat galactocerebroside monoclonal antibody by Santa Cruz Biotechnology Inc., USA; and goat anti-mouse fluorescein isothiocyanate-labeled secondary antibody by Wuhan Boster Bioengineering Co., Ltd., China. METHODS: Brain-derived NSCs isolated from brain tissues of neonatal Sprague Dawley rats were cloned and passaged, and assigned into five groups: normal control, model, high-concentration oxygen, high pressure, and hyperbaric oxygen groups. Cells in the four groups, excluding the normal control group, were incubated in serum-containing DMEM/F12 culture medium. Hypoxic/ischemic models of NSCs were established in an incubator comprising 93% N2, 5% 002, and 2% 02. Thereafter, cells were continuously cultured as follows: compressed air (0.2 MPa, 1 hour, once a day) in the high pressure group, compressed air + a minimum of 80% 02 in the hyperbaric oxygen group, and a minimum of 80% Q2 in the high-concentration oxygen group. Cells in the normal control and model groups were cultured as normal. MAIN OUTCOME MEASURES: At day 7 after culture, glial fibrillary acidic protein, microtubule-associated protein 2, and galactocerebroside immunofluorescence staining were examined to observe differentiation and calculate the percentage of NSCs differentiating into neuron-like cells or neuroglia-like cells. RESULTS: Neuron-like cells or neuroglia-like cells were visualized in all five groups. There were no significant differences in the percentage of differentiating cells between the hyperbaric oxygen group and the normal control group (P 〉 0.05). The percentage of NSCs differentiating into neuron-like cells in the hyperbaric oxygen group was significantly greater than model, high-concentration oxygen, and high pressure groups; however, the percentage differentiating into neuroglia-like cells was significantly lower (P 〈 0.01 ). CONCLUSION: Hyperbaric oxygen promotes the differentiation of brain-derived neural stem cells into neuron-like cells but inhibits differentiation into neuroglia-like cells. Furthermore, the efficacy of hyperbaric oxygen is superior to high-concentration oxygen and high pressure.展开更多
BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is consider...BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS: A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria. RESULTS: The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P < 0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P < 0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P < 0.05). CONCLUSIONS: Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.展开更多
In order to investigate the protective effect of hypoxic preconditioning on the cerebral ischemia-reperfusion injury, the expression of Bcl-2 and Bax was detected by using immunohistochemical staining after 3 h cerebr...In order to investigate the protective effect of hypoxic preconditioning on the cerebral ischemia-reperfusion injury, the expression of Bcl-2 and Bax was detected by using immunohistochemical staining after 3 h cerebral ischemia followed by 1, 6, 12, 24 and 48 h reperfusion respectively in rats treated with or without hypoxic preconditioning before cerebral ischemia. In addition, the apoptosis of neural cells and the behavioral scores for neurological functions recovery were evaluated by TUNEL staining and "crawling method", respectively. Compared with control group (cerebral ischemia-reperfusion without hypoxic preconditioning), the expression of Bcl-2 was significantly increased, but that of Bax decreased in the hypoxic preconditioning group (cerebral ischemiareperfusion with hypoxie preconditioning), both P〈0.05. The pre-treatment with hypoxic preconditioning could reduce the apoptosis of neural cells and promote the neurological function recovery as compared to control group. It was suggested that hypoxic preconditioning may have protective effects on the cerebral ischemia-reperfusion injury by inhibiting the apoptosis of neural cells, increase the expression of Bcl-2 and decrease the expression of Bax.展开更多
Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms ...Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we in- duced a photochemical model of cerebral infarction in an inbred line of mice (BALB/c). Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved neu- rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.展开更多
Background: Vascular endothelial growth factor A (VEGFA) can induce endothelial cell proliferation, promote cell migration, and inhibit apoptosis. These processes play key roles in physiological blood vessel format...Background: Vascular endothelial growth factor A (VEGFA) can induce endothelial cell proliferation, promote cell migration, and inhibit apoptosis. These processes play key roles in physiological blood vessel formation and pathological angiogenesis. Methods: In this study, we examined VEGFA gene expression in the heart, liver, and kidney of Tibetan pigs (-I-P), Yorkshire pigs that migrated to high altitudes (YH), and Yorkshire pigs that lived at low altitudes (YL). We used PCR and Sanger sequencing to screen for single nucleotide polymorphisms (SNPs) in 5'-flanking DNA and exons of the VEGFA gene. Quantitative real-time PCR and western blots were used to measure expression levels and PCR products were sequenced. Results: Results showed that the VEGFA mRNA and protein expression in heart, liver and kidney of TP was higher than that in YH and YL. In addition, the mRNA sequence of the pig VEGFA gene was conserved among pig breeds, and only five SNPs were found in the 5'-flanking region of the VEGFA gene, the allele frequency distributions of the 5 SNPs were not significantly different between the TP, Yorkshire (YL), and Diannan small-ear (DN) pig populations. Conclusion: In conclusion, the Tibetan pig showed high tissues, which suggests that the VEGFA gene may play a levels of VEGFA gene expression in several hypoxic major functional role in hypoxic adaptation.展开更多
AIM To evaluate the incidence, etiology, and predictors of mortality of severe hypoxic hepatitis. METHODS We used computerized patient records to identify consecutive cases of severe hypoxic hepatitis admitted to a te...AIM To evaluate the incidence, etiology, and predictors of mortality of severe hypoxic hepatitis. METHODS We used computerized patient records to identify consecutive cases of severe hypoxic hepatitis admitted to a tertiary hospital in Singapore over a one-year period. We defined severe hypoxic hepatitis as elevation of serum transaminases more than 100 times upper limit of normal in the clinical setting of cardiac, circulatory or respiratory failure after exclusion of other causes of hepatitis. We used multivariable regression analysis to determine predictors for mortality. RESULTS We identified 75 cases of severe hypoxic hepatitis out of 71380 hospital admissions over one year, providing an incidence of 1.05 cases per 1000 admissions. Median age was 65 years(range 19-88); 57.3% males. The most common etiologies of severe hypoxic hepatitis were acute myocardial infarction and sepsis. Fifty-three patients(71%) died during the hospitalization. The sole independent predictive factor for mortality was serum albumin measured at the onset of severe hypoxic hepatitis. Patients with low serum albumin of less than 28 g/L have more than five-fold increase risk of death(OR = 5.39, 95%CI: 1.85-15.71).CONCLUSION Severe hypoxic hepatitis is uncommon but has a high mortality rate. Patients with low serum albumin are at highest risk of death.展开更多
BACKGROUND: Hypoxic preconditioning can protect hepatocytes against hypoxic injury, but its mechanism has not been elucidated. The aim of this study was to profile gene expression patterns involved in hypoxic precondi...BACKGROUND: Hypoxic preconditioning can protect hepatocytes against hypoxic injury, but its mechanism has not been elucidated. The aim of this study was to profile gene expression patterns involved in hypoxic preconditioning and probable mechanism at the level of gene expression. METHODS: Hepatocytes were divided into 2 groups: control group and hypoxic preconditioning group. Biotinlabeled cRNA from the control group and the hypoxic preconditioning group was hybridized by oligonucleotide microarray. Genes that were significantly associated with hypoxic preconditioning were filtered, and validated at the level of transcript expression. RESULTS: Forty-three genes with significantly altered expression patterns were discovered and most of them had not been previously reported. Among these genes,genes encoding superoxide dismutase 2 (SOD2)and interleukin 10 (IL-10) in the hypoxic preconditioning group were confirmed to be up-regulated with real-time quantitative PCR. CONCLUSIONS: Many cytokines are involved in hypoxic preconditioning and protect hepatocytes from hypoxiareoxygenation injury, and the increase of oxygen freeradical scavengers and anti-inflammatory factors may play a key role in this phenomenon. Diverse signal pathways are probably involved.展开更多
Background:Tibetan chickens,a unique native breed in the Qinghai-Tibet Plateau of China,possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment.Increasing evidence sugge...Background:Tibetan chickens,a unique native breed in the Qinghai-Tibet Plateau of China,possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment.Increasing evidence suggests that long non-coding RNAs(lncRNAs)and microRNAs(miRNAs)play roles in the hypoxic adaptation of high-altitude animals,although their exact involvement remains unclear.Results:This study aimed to elucidate the global landscape of mRNAs,lncRNAs,and miRNAs using transcriptome sequencing to construct a regulatory network of competing endogenous RNAs(ceRNAs)and thus provide insights into the hypoxic adaptation of Tibetan chicken embryos.In total,354 differentially expressed genes(DE genes),389 differentially expressed lncRNAs(DE lncRNAs),and 73 differentially expressed miRNAs(DE miRNAs)were identified between Tibetan chickens(TC)and control Chahua chickens(CH).GO and KEGG enrichment analysis revealed that several important DE miRNAs and their target DE lncRNAs and DE genes are involved in angiogenesis(including blood vessel development and blood circulation)and energy metabolism(including glucose,carbohydrate,and lipid metabolism).The ceRNA network was then constructed with the predicted DE gene-DE miRNA-DE lncRNA interactions,which further revealed the regulatory roles of these differentially expressed RNAs during hypoxic adaptation of Tibetan chickens.Conclusions:Analysis of transcriptomic data revealed several key candidate ceRNAs that may play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and energy metabolism.These results provide insights into the molecular mechanisms of hypoxic adaptation regulatory networks from the perspective of coding and non-coding RNAs.展开更多
Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases rema...Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 termborn infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital(approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1800016409) and the protocol version is 1.0.展开更多
Hypoxic-ischemic brain injury models were generated by bilateral carotid artery ligation in Sprague-Dawley rats. Successful models were treated with a combination of Xuefuzhuyu decoction and 10g of astragalus. The exp...Hypoxic-ischemic brain injury models were generated by bilateral carotid artery ligation in Sprague-Dawley rats. Successful models were treated with a combination of Xuefuzhuyu decoction and 10g of astragalus. The experimental results showed that neuronal morphology and structure recovered, nerve growth factor mRNA expression increased in brain tissues, and neurological function signifi-cantly improved. There was no significant difference in these measures compared with rats treated with Xuefuzhuyu decoction alone or a combined treatment of Xuefuzhuyu decoction with 40 g as-tragalus. These experimental findings revealed that, Xuefuzhuyu decoction combined with astra-galus may up-regulate the expression of nerve growth factor mRNA and accordingly exert a neu-roprotective effect; however, this protection is not dependent on astragalus dosage.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
基金This work was supported by Health Research Council of New Zealand(grants 17/601 and 22/559)the Auckland Medical Research Foundation,the Lottery Health Grants Board of New Zealand,the C.J.Martin Postdoctoral Fellowship and project grant from the National Health and Medical Research Council of Australia(APP1090890 and APP1164954)the Victorian Government’s Operational Infrastructure Support Program(to RG).
文摘Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a lifetime.The cost of disability associated with preterm brain injury continues to rise.Prevention of this injury,and disability,would significantly reduce this socioeconomic burden.
基金supported by the Air Force Characteristic Medical Center Youth Talent Program 22YXQN020。
文摘As a reducing salt,sodium sulfite could deprive oxygen in solution,which could mimic hypoxic stress in Caenorhabditis elegans.In this study,the wildtype Escherichia coli strain MG1655 was used to examine the inhibition of sodium sulfite-induced hypoxia by observing the bacterial growth curves.
文摘Hypoxic hepatitis, also known as ischemic hepatitis, is characterized by acute hepatocellular injury due to inadequate oxygen delivery to the liver. Celiac trunk stenosis can lead to hepatic ischemia and subsequent liver damage. We present the case of an 81-year-old patient with a history of hypertension, ischemic heart disease, hypothyroidism, and biliary lithiasis, who developed hypoxic hepatitis secondary to Dunbar syndrome and a stenosis of the superior mesenteric artery. The patient improved symptoms and liver function tests with conservative management, including intravenous fluids and supportive care. Long-term management involved continued antiplatelet therapy and statins, with consideration of further interventions for celiac trunk stenosis. This case underscores the importance of recognizing Dunbar syndrome as well as superior mesentery trunk stenosis as a potential cause of hypoxic hepatitis. It highlights the need for multidisciplinary management in such cases.
基金Science and Technology Centre unit of Ege University for its financial support(No.33.102.2014.0001)。
文摘Background:Low levels of antioxidant paraoxonase 1(PON 1)enzyme activity,PON1-Q192R polymorphism(a glutamine(Q)to arginine(R)substitution at position 192),PON1-L55M polymorphism(a leucine(L)to methionine(M)substitution at position 55),and oxidized low-density lipoprotein(oxLDL)are risk factors for coronary heart disease.Aerobic exercise improves PON1 activity,but the effects of hypoxic exercise are yet unclear.The aim of this study was to determine the effects of hypoxic underwater rugby training on PON1 activity and oxLDL levels and the role of the mentioned polymorphisms.Methods:Serum PON1 and arylesterase activities(ARE),PON1,PON3,and oxLDL protein levels(by using the enzyme-linked immunosorbent assays)were determined in an athletic group(42 trained male underwater rugby players;age=21.7±4.2 years,mean±SD)and a control group(43 sedentary men;age=23.9±3.2 years).The polymorphisms were determined from genomic DNA samples.Results:PON1 activity(25.1%,p=0.052),PON3(p<0.001),and oxLDL(p<0.001)of the athletic group,including most genotype groups,were higher than those of the control group.In comparison to the controls,PON1 activity levels(p=0.005)of the PON1-Q192R homozygote QQ genotype group and PON1 activity levels(30%,p=0.116)of the PON1-L55M homozygote LL genotype group were higher,whereas ARE activity values of athletic R allele carrier(Rc=QR+RR)(p=0.005)and LL group(p=0.002)were lower than the control genotype groups related to their polymorphisms.Conclusion:Hypoxic training can cause(1)significant oxidative stress,including oxLDL,and an antioxidant response(increase in PON1 activity and PON3),(2)differences in the activity of PON1 and ARE,which are modified by PON1-Q192R and PON1-L55M polymorphisms,respectively,and(3)improvements in PON1 activity of QQ and LL groups.However,hypoxic training can cause a disadvantage of LL and Rc groups for ARE.
基金supported by the National Natural Science Foundation of China(No.41806099)the Global Change and Air-Sea Interaction Project of China(No.GASI-04-HYST-06).
文摘The spatial distribution and seasonal variations of the hypoxic zone in the eastern equatorial Indian Ocean were investigated using survey data collected from four cruises from 2013 to 2018.Results showed that hypoxic zone occurred all year round in the eastern equatorial Indian Ocean,and it spread southward in the shape of a double tongue at two depths with one at subsurface centered at a depth of 150 m and the other in intermediate water centered at a depth of 800 m.The southward expansion and maximum thickness of the hypoxic zone were greatest in the spring inter-monsoon and least in the summer monsoon.The hypoxic zone originated from the southward expansion of the hypoxic water in the Bay of Bengal and its spatial distribution was driven by southward output flux of mid-deep(100–1000 m)hypoxic water from the Bay of Bengal.The hypoxia southward expansion was blocked near the equator in the subsurface layer,because of mixing with multiple zonal circulations(e.g.,Wyrtki Jets and the equatorial undercurrent),which meant that the hypoxic zone extended over a smaller area than in the intermediate water.These new findings will contribute to an improved understanding of the hypoxic zone and will contribute to circulation research,particularly about intermediate circulation in the eastern equatorial Indian Ocean.
基金support by the Faculty of Medicine,Ludwig-Maximilians-University(FöFoLe,Project 843 and 955,to TH and MMS).
文摘Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs.This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned(2%oxygen for 72 hours)autologous ADSPCs(n=9).This treatment mode was compared with three others:fibrin conduit seeded with ADSPCs cultivated under normoxic conditions(n=9);non-cell-carrying conduit(n=9);and nerve autograft only(n=9).A 16-week follow-up included functional testing(sciatic functional index and static sciatic index)as well as postmortem muscle mass analyses and morphometric nerve evaluations(histology,g-ratio,axon density,and diameter).At 8 weeks,the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups,indicating faster functional regeneration.Furthermore,histologic evaluation showed significantly increased axon outgrowth/branching,axon density,remyelination,and a reduced relative connective tissue area.Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts.Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.
文摘Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical problem.It is not fully elucidated where in the circulation the regulation of resistance takes place.It is often referred to as if it is in the arteries,but we hypothesized that it is in the venous side of the pulmonary circulation.Methods:In an open thorax model,pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels.At the same time the lungs were ventilated with extreme variations of inspired air from 5%to 100%oxygen,making it possible to make combinations of high and low oxygen content through the pulmonary circulation.A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests.Under different combinations of oxygenation,pulmonary vascular resistance(PVR)was calculated.Results:With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein,PVR was doubled.With more extreme hypoxia PVR suddenly decreased.Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins.Discussion:The impact of hypoxia occurs from the alveolar level and forward with the blood flow.The experiments indicated that the regulation of PVR is mediated from the venous side.
基金supported by the National Natural Science Foundation of China,No.31870977(to HYS)the National Key Technologies Research and Development Program of China,No.2017YFA0104700(to FD)+2 种基金2022 Jiangsu Funding Program for Excellent Postdoctoral Talent(to MC)Priority Academic Program Development of Jiangsu Higher Education Institutions[PAPD]the Major Project of Basic Science(Natural Science)Research in Higher Education Institutions of Jiangsu Province,No.22KJA180001(to QRH)。
文摘Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.
基金supported by the Natural Science Fund of Fujian Province,No.2020J011058(to JK)the Project of Fujian Provincial Hospital for High-level Hospital Construction,No.2020HSJJ12(to JK)+1 种基金the Fujian Provincial Finance Department Special Fund,No.(2021)848(to FC)the Fujian Provincial Major Scientific and Technological Special Projects on Health,No.2022ZD01008(to FC).
文摘Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.
文摘BACKGROUND: It has been previously shown that hyperbaric oxygen may promote proliferation of neural stem cells and reduce death of endogenous neural stem cells (NSCs). OBJECTIVE: To explore the effects of hyperbaric oxygen on the differentiation of hypoxic/ischemic brain-derived NSCs into neuron-like cells and compare with high-concentration oxygen and high pressure. DESIGN, TIME AND SETTING: An in vitro contrast study, performed at Laboratory of Neurology, Central South University between January and May 2006. MATERIALS: A hyperbaric oxygen chamber (YLC 0.5/1A) was provided by Wuhan Shipping Design Research Institute; mouse anti-rat microtubule-associated protein 2 monoclonal antibody by Jingmei Company, Beijing; mouse anti-rat glial fibrillary acidic protein monoclonal antibody by Neo Markers, USA; mouse anti-rat galactocerebroside monoclonal antibody by Santa Cruz Biotechnology Inc., USA; and goat anti-mouse fluorescein isothiocyanate-labeled secondary antibody by Wuhan Boster Bioengineering Co., Ltd., China. METHODS: Brain-derived NSCs isolated from brain tissues of neonatal Sprague Dawley rats were cloned and passaged, and assigned into five groups: normal control, model, high-concentration oxygen, high pressure, and hyperbaric oxygen groups. Cells in the four groups, excluding the normal control group, were incubated in serum-containing DMEM/F12 culture medium. Hypoxic/ischemic models of NSCs were established in an incubator comprising 93% N2, 5% 002, and 2% 02. Thereafter, cells were continuously cultured as follows: compressed air (0.2 MPa, 1 hour, once a day) in the high pressure group, compressed air + a minimum of 80% 02 in the hyperbaric oxygen group, and a minimum of 80% Q2 in the high-concentration oxygen group. Cells in the normal control and model groups were cultured as normal. MAIN OUTCOME MEASURES: At day 7 after culture, glial fibrillary acidic protein, microtubule-associated protein 2, and galactocerebroside immunofluorescence staining were examined to observe differentiation and calculate the percentage of NSCs differentiating into neuron-like cells or neuroglia-like cells. RESULTS: Neuron-like cells or neuroglia-like cells were visualized in all five groups. There were no significant differences in the percentage of differentiating cells between the hyperbaric oxygen group and the normal control group (P 〉 0.05). The percentage of NSCs differentiating into neuron-like cells in the hyperbaric oxygen group was significantly greater than model, high-concentration oxygen, and high pressure groups; however, the percentage differentiating into neuroglia-like cells was significantly lower (P 〈 0.01 ). CONCLUSION: Hyperbaric oxygen promotes the differentiation of brain-derived neural stem cells into neuron-like cells but inhibits differentiation into neuroglia-like cells. Furthermore, the efficacy of hyperbaric oxygen is superior to high-concentration oxygen and high pressure.
基金supported by grants from the Health Bureau(H200770)Technology Bureau(BS2005038)of Jiangsu Province,China
文摘BACKGROUND: Hepatocyte apoptosis is a severe form of cell death after hepatic ischemia-reperfusion injury (HIRI), and its relief is an important issue in liver transplantation. Hypoxic preconditioning (HP) is considered to have protective effects on HIRI. This study was designed to explore the impact of HP on apoptosis and its possible mechanism during orthotopic liver autotransplantation. METHODS: A modified orthotopic liver autotransplantation model was used to simulate HIRI. Sprague-Dawley rats were randomly divided into normal control, autotransplantation (AT) and HP groups. The HP group was subjected to an 8% oxygen atmosphere for 90 minutes before surgery. At 1, 6 and 24 hours after surgery, the rats were killed and their liver tissue was sampled to assess the expression of Bcl-2 protein. The samples were subjected to blood chemistry study, morphological study under a light or transmission electron microscope, and quantitative study of mitochondria. RESULTS: The serum levels of ALT and AST in the HP group were lower than those in the AT group at 1, 6 and 24 hours after orthotopic liver autotransplantation (P < 0.05). Bcl-2 protein expression was increased in the HP group at each measurement point (P < 0.05). Light microscopy showed that hepatic injury in the AT group was much more severe than in the HP group. Hepatocytes in the AT group showed typical apoptosis signs under a transmission electron microscope. The ultrastructural appearance of hepatocytes in the HP group was much better than in the AT group, and the area, perimeter and diameter of the mitochondria were smaller in the HP group than in the AT group (P < 0.05). CONCLUSIONS: Hepatocytes sense and respond to decreased tissue oxygenation. Stimulation by HP relieves apoptosis by upregulating expression of Bcl-2 protein and its protection of mitochondria after orthotopic liver autotransplantation.
文摘In order to investigate the protective effect of hypoxic preconditioning on the cerebral ischemia-reperfusion injury, the expression of Bcl-2 and Bax was detected by using immunohistochemical staining after 3 h cerebral ischemia followed by 1, 6, 12, 24 and 48 h reperfusion respectively in rats treated with or without hypoxic preconditioning before cerebral ischemia. In addition, the apoptosis of neural cells and the behavioral scores for neurological functions recovery were evaluated by TUNEL staining and "crawling method", respectively. Compared with control group (cerebral ischemia-reperfusion without hypoxic preconditioning), the expression of Bcl-2 was significantly increased, but that of Bax decreased in the hypoxic preconditioning group (cerebral ischemiareperfusion with hypoxie preconditioning), both P〈0.05. The pre-treatment with hypoxic preconditioning could reduce the apoptosis of neural cells and promote the neurological function recovery as compared to control group. It was suggested that hypoxic preconditioning may have protective effects on the cerebral ischemia-reperfusion injury by inhibiting the apoptosis of neural cells, increase the expression of Bcl-2 and decrease the expression of Bax.
基金supported by the National Natural Science Foundation of China,No.30870854the Natural Science Foundation of Beijing,No.7111003the Natural Science Foundation of Shandong Province,No.ZR2010HM029
文摘Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we in- duced a photochemical model of cerebral infarction in an inbred line of mice (BALB/c). Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved neu- rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.
基金supported by the National Major Special Project on New Varieties Cultivation for Transgenic Organisms (2016ZX08009-003-006)the National Key Technology R&D Program (2012BAD03B03)the Program for Changjiang Scholar and Innovation Research Team in University (IRT1191)
文摘Background: Vascular endothelial growth factor A (VEGFA) can induce endothelial cell proliferation, promote cell migration, and inhibit apoptosis. These processes play key roles in physiological blood vessel formation and pathological angiogenesis. Methods: In this study, we examined VEGFA gene expression in the heart, liver, and kidney of Tibetan pigs (-I-P), Yorkshire pigs that migrated to high altitudes (YH), and Yorkshire pigs that lived at low altitudes (YL). We used PCR and Sanger sequencing to screen for single nucleotide polymorphisms (SNPs) in 5'-flanking DNA and exons of the VEGFA gene. Quantitative real-time PCR and western blots were used to measure expression levels and PCR products were sequenced. Results: Results showed that the VEGFA mRNA and protein expression in heart, liver and kidney of TP was higher than that in YH and YL. In addition, the mRNA sequence of the pig VEGFA gene was conserved among pig breeds, and only five SNPs were found in the 5'-flanking region of the VEGFA gene, the allele frequency distributions of the 5 SNPs were not significantly different between the TP, Yorkshire (YL), and Diannan small-ear (DN) pig populations. Conclusion: In conclusion, the Tibetan pig showed high tissues, which suggests that the VEGFA gene may play a levels of VEGFA gene expression in several hypoxic major functional role in hypoxic adaptation.
文摘AIM To evaluate the incidence, etiology, and predictors of mortality of severe hypoxic hepatitis. METHODS We used computerized patient records to identify consecutive cases of severe hypoxic hepatitis admitted to a tertiary hospital in Singapore over a one-year period. We defined severe hypoxic hepatitis as elevation of serum transaminases more than 100 times upper limit of normal in the clinical setting of cardiac, circulatory or respiratory failure after exclusion of other causes of hepatitis. We used multivariable regression analysis to determine predictors for mortality. RESULTS We identified 75 cases of severe hypoxic hepatitis out of 71380 hospital admissions over one year, providing an incidence of 1.05 cases per 1000 admissions. Median age was 65 years(range 19-88); 57.3% males. The most common etiologies of severe hypoxic hepatitis were acute myocardial infarction and sepsis. Fifty-three patients(71%) died during the hospitalization. The sole independent predictive factor for mortality was serum albumin measured at the onset of severe hypoxic hepatitis. Patients with low serum albumin of less than 28 g/L have more than five-fold increase risk of death(OR = 5.39, 95%CI: 1.85-15.71).CONCLUSION Severe hypoxic hepatitis is uncommon but has a high mortality rate. Patients with low serum albumin are at highest risk of death.
基金This study was supported by a grant from Shanghai Technology and Science Commission Foundation (No. 024107010).
文摘BACKGROUND: Hypoxic preconditioning can protect hepatocytes against hypoxic injury, but its mechanism has not been elucidated. The aim of this study was to profile gene expression patterns involved in hypoxic preconditioning and probable mechanism at the level of gene expression. METHODS: Hepatocytes were divided into 2 groups: control group and hypoxic preconditioning group. Biotinlabeled cRNA from the control group and the hypoxic preconditioning group was hybridized by oligonucleotide microarray. Genes that were significantly associated with hypoxic preconditioning were filtered, and validated at the level of transcript expression. RESULTS: Forty-three genes with significantly altered expression patterns were discovered and most of them had not been previously reported. Among these genes,genes encoding superoxide dismutase 2 (SOD2)and interleukin 10 (IL-10) in the hypoxic preconditioning group were confirmed to be up-regulated with real-time quantitative PCR. CONCLUSIONS: Many cytokines are involved in hypoxic preconditioning and protect hepatocytes from hypoxiareoxygenation injury, and the increase of oxygen freeradical scavengers and anti-inflammatory factors may play a key role in this phenomenon. Diverse signal pathways are probably involved.
基金supported by the National Natural Science Foundation of China(31972532)the China Agricultural Research System(CARS-40-K05)the Innovation Base Cu。
文摘Background:Tibetan chickens,a unique native breed in the Qinghai-Tibet Plateau of China,possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment.Increasing evidence suggests that long non-coding RNAs(lncRNAs)and microRNAs(miRNAs)play roles in the hypoxic adaptation of high-altitude animals,although their exact involvement remains unclear.Results:This study aimed to elucidate the global landscape of mRNAs,lncRNAs,and miRNAs using transcriptome sequencing to construct a regulatory network of competing endogenous RNAs(ceRNAs)and thus provide insights into the hypoxic adaptation of Tibetan chicken embryos.In total,354 differentially expressed genes(DE genes),389 differentially expressed lncRNAs(DE lncRNAs),and 73 differentially expressed miRNAs(DE miRNAs)were identified between Tibetan chickens(TC)and control Chahua chickens(CH).GO and KEGG enrichment analysis revealed that several important DE miRNAs and their target DE lncRNAs and DE genes are involved in angiogenesis(including blood vessel development and blood circulation)and energy metabolism(including glucose,carbohydrate,and lipid metabolism).The ceRNA network was then constructed with the predicted DE gene-DE miRNA-DE lncRNA interactions,which further revealed the regulatory roles of these differentially expressed RNAs during hypoxic adaptation of Tibetan chickens.Conclusions:Analysis of transcriptomic data revealed several key candidate ceRNAs that may play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and energy metabolism.These results provide insights into the molecular mechanisms of hypoxic adaptation regulatory networks from the perspective of coding and non-coding RNAs.
基金supported by the Jiangsu Maternal and Child Health Research Project of China,No.F201612(to HXL)Changzhou Science and Technology Support Plan of China,No.CE20165027(to HXL)+1 种基金Changzhou City Planning Commission Major Science and Technology Projects of China,No.ZD201515(to HXL)Changzhou High Level Training Fund for Health Professionals of China,No.2016CZBJ028(to HXL)
文摘Resting-state functional magnetic resonance imaging has revealed disrupted brain network connectivity in adults and teenagers with cerebral palsy. However, the specific brain networks implicated in neonatal cases remain poorly understood. In this study, we recruited 14 termborn infants with mild hypoxic ischemic encephalopathy and 14 term-born infants with severe hypoxic ischemic encephalopathy from Changzhou Children's Hospital, China. Resting-state functional magnetic resonance imaging data showed efficient small-world organization in whole-brain networks in both the mild and severe hypoxic ischemic encephalopathy groups. However, compared with the mild hypoxic ischemic encephalopathy group, the severe hypoxic ischemic encephalopathy group exhibited decreased local efficiency and a low clustering coefficient. The distribution of hub regions in the functional networks had fewer nodes in the severe hypoxic ischemic encephalopathy group compared with the mild hypoxic ischemic encephalopathy group. Moreover, nodal efficiency was reduced in the left rolandic operculum, left supramarginal gyrus, bilateral superior temporal gyrus, and right middle temporal gyrus. These results suggest that the topological structure of the resting state functional network in children with severe hypoxic ischemic encephalopathy is clearly distinct from that in children with mild hypoxic ischemic encephalopathy, and may be associated with impaired language, motion, and cognition. These data indicate that it may be possible to make early predictions regarding brain development in children with severe hypoxic ischemic encephalopathy, enabling early interventions targeting brain function. This study was approved by the Regional Ethics Review Boards of the Changzhou Children's Hospital(approval No. 2013-001) on January 31, 2013. Informed consent was obtained from the family members of the children. The trial was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1800016409) and the protocol version is 1.0.
基金a grant by Bureau of Traditional Chinese Medicine of Zhejiang Province, No.491040-W50434
文摘Hypoxic-ischemic brain injury models were generated by bilateral carotid artery ligation in Sprague-Dawley rats. Successful models were treated with a combination of Xuefuzhuyu decoction and 10g of astragalus. The experimental results showed that neuronal morphology and structure recovered, nerve growth factor mRNA expression increased in brain tissues, and neurological function signifi-cantly improved. There was no significant difference in these measures compared with rats treated with Xuefuzhuyu decoction alone or a combined treatment of Xuefuzhuyu decoction with 40 g as-tragalus. These experimental findings revealed that, Xuefuzhuyu decoction combined with astra-galus may up-regulate the expression of nerve growth factor mRNA and accordingly exert a neu-roprotective effect; however, this protection is not dependent on astragalus dosage.