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
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
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
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
Hypoxic preconditioning is able to increase the body’s resistance to hypoxic/ischemic stress. Understanding how to apply the hypoxic response to initiate the protective mechanism of ischemic preconditioning is a high...Hypoxic preconditioning is able to increase the body’s resistance to hypoxic/ischemic stress. Understanding how to apply the hypoxic response to initiate the protective mechanism of ischemic preconditioning is a high priority. However, the relationship between innate resistance to hypoxic stress and preconditioning efficiency of moderate hypoxia has been poorly studied. In our work, the efficiency of single moderate hypobaric hypoxia (HBH) for resistance to severe hypobaric hypoxia (SHBH) was studied on intact rats and those pre-tested under SHBH with low, intermediate and high resistance to hypoxia. HBH has a significant preconditioning action on the resistance to hypoxia over a wide range from 270 to 1464 s (4.5 to 24.5 min) and at the same time eliminates the differences in the endurance under SHBH between all rat groups. It is concluded that 1) HBH preconditioning efficiency does not depend on an innate resistance to SHBH and prior hypoxic experience of rats;and 2) the pretesting to severe hypoxia has no value for predicting the hypoxic preconditioning efficiency and study of adaptive mechanisms.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 considered t...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
Hypoxic preconditioning can protect against cerebral ischemia/reperfusion injury. However, the underlying mechanisms that mediate this effect are not completely clear. In this study, mice were pretreated with continuo...Hypoxic preconditioning can protect against cerebral ischemia/reperfusion injury. However, the underlying mechanisms that mediate this effect are not completely clear. In this study, mice were pretreated with continuous, intermittent hypoxic preconditioning;1 hour later, cerebral ischemia/reperfusion models were generated by middle cerebral artery occlusion and reperfusion. Compared with control mice, mice with cerebral ischemia/reperfusion injury showed increased Bederson neurological function scores, significantly increased cerebral infarction volume, obvious pathological damage to the hippocampus, significantly increased apoptosis;upregulated interleukin-1β, interleukin-6, and interleukin-8 levels in brain tissue;and increased expression levels of NOD-like receptor family pyrin domain containing 3(NLRP3), NLRP inflammasome-related protein caspase-1, and gasdermin D. However, hypoxic preconditioning significantly inhibited the above phenomena. Taken together, these data suggest that hypoxic preconditioning mitigates cerebral ischemia/reperfusion injury in mice by reducing NLRP3 inflammasome expression. This study was approved by the Medical Ethics Committee of the Fourth Hospital of Baotou, China(approval No. DWLL2019001) in November 2019.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
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
A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neona...A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive.Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model.SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing.Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism.We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2.Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis,wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels.Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses,long-term depression and oxytocin signaling.Moreover,intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1,DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy.Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons.Our results indicate that CSRNP1,DUSP5 and LRRC25,containing SNPs,may be involved in the pathogenesis of hypoxic ischemic encephalopathy.These findings indicate a novel direction for further hypoxic ischemic encephalopathy research.This animal study was approved on February 5,2017 by the Animal Care and Use Committee of Kunming Medical University,Yunnan Province,China(approval No.kmmu2019038).Cerebral tissue collection from a human fetus was approved on September 30,2015 by the Ethics Committee of Kunming Medical University,China(approval No.2015-9).展开更多
Background: Hypoxia is a primary cause of mountain sickness and a common pathological condition in patients with heart failure, shock, stroke, and chronic obstructive pulmonary disease(COPD). Thus far, little advancem...Background: Hypoxia is a primary cause of mountain sickness and a common pathological condition in patients with heart failure, shock, stroke, and chronic obstructive pulmonary disease(COPD). Thus far, little advancement in countering hypoxic damage has been achieved, and one of the main reasons is the absence of an ideal algorithm or calculation method to normalize hypoxia tolerance scores when evaluating an animal model. In this study, we improved a traditional calculation formula for assessment of hypoxia tolerance.Methods: We used a sealed bottle model in which the oxygen is gradually consumed by a mouse inside. To evaluate the hypoxia tolerance of mice, the survival time(ST) of the mouse is recorded and was used to calculate standard hypoxia tolerance time(STT) and adjusted standard hypoxia tolerance time(ASTT). Mice administered with methazolamide and saline were used as positive and negative controls, respectively.Results: Since mice were grouped according to either body weight(BW) or bottle volume, we found a strongly negative correlation between STT and BW instead of between STT and bottle volume, suggesting that different BWs could cause false positive or negative errors in the STT results. Furthermore, both false positive and negative errors could be rectified when ASTT was used as the evaluation index. Screening for anti-hypoxic medicines by using mice as the experimental subjects would provide more credible results with the improved ASTT method than with the STT method.Conclusions: ASTT could be a better index than STT for the evaluation of hypoxia tolerance abilities as it could eliminate the impact of animal BW.展开更多
AIM: To evaluate donation after circulatory death(DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy(HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor trans...AIM: To evaluate donation after circulatory death(DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy(HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS Donor Net included preoperative systolic and diastolic blood pressure, heart rate, p H, SpO_2, PaO_2, FiO_2, and hemoglobin. Mean arterial bloodpressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O_2 content was computed as [hemoglobin(gm/d L) × 1.37(m L O_2/gm) × SpO_2%) +(0.003 × PaO_2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mm Hg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was(ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin.RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age(33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion(9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin(10.7 ± 2.2 gm/d L vs 12.3 ± 2.1 gm/d L, P = 0.017), lower preoperative arterial oxygen content(14.8 ± 2.8 m L O_2/100 m L blood vs 16.8 ± 3.3 m L O_2/100 m L blood, P = 0.049), greater hypoxia score >2.0(69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure(92.7 ± 16.2 mm Hg vs 83.8 ± 18.5 mm Hg, P = 0.10). HC was independently associated with age, multi-pressor/redcell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure(r^2 = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2(7.1/year)], compared to our early experience [era 1(2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1(P = 0.03). Era 2 donors had longer times for extubation-to-asystole(14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia(13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia(16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate(73.1% vs 28.6%, P = 0.006).CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.展开更多
[Objective] The paper was to investigate the effect of hypoxic environment on life rhythm of Apodemus peninsulae. [Method] A. peninsulae were captured and fed in indoor hypoxic environment from May 2015 to October 201...[Objective] The paper was to investigate the effect of hypoxic environment on life rhythm of Apodemus peninsulae. [Method] A. peninsulae were captured and fed in indoor hypoxic environment from May 2015 to October 2016. The respiratory frequency, activity level, food intake and water intake of A. peninsulae were analyzed under different oxygen concentrations. [Result] With the decrease of oxygen concentration, the respiratory frequency of A. peninsulae decreased, and the respiratory depth deepened, while the activity level, food intake and water intake de-creased. [Conclusion] The hypoxic environment had an impact on the respiratory frequency, activity level, food intake and water intake of A. peninsulae.展开更多
The Changjiang River Estuary(CRE)in the East China Sea suffers from seasonal hypoxia in summer.The vertical distributions and seasonal changes of microbial communities in the CRE were well documented.However,little is...The Changjiang River Estuary(CRE)in the East China Sea suffers from seasonal hypoxia in summer.The vertical distributions and seasonal changes of microbial communities in the CRE were well documented.However,little is known about the diurnal changes of bacterial communities in the hypoxic zone of the CRE.Here,16 S rRNA gene analysis was used to explore the changes of bacterial communities in the oxic surface and hypoxic middle seawater layers during 24 h in the CRE.Significant differences between the hypoxic and oxic layers were observed:the phyla Cyanobacteria,Bacteroidetes and Acidimicrobiia were enriched in the oxic layer,whereas the phylum SAR406 and the class Deltaproteobacteria were more abundant in the hypoxic layer.In addition,some subtle diurnal variations of the bacterial relative abundance were found in both two layers.The relative abundance of Synechococcus increased at night,and this change was more obvious in the hypoxic layer.The similar trend was also found in some phototrophic and several heterotrophic bacteria,such as Rhodobacteraceae,OM60 and Flavobacteriaceae.Their relative abundances peaked at 16:00 in the oxic layer,while the relative abundances peaked at around 7:00 and decreased until 13:00 in the hypoxic layer.Together,the results of the present study suggest that some photosynthetic bacteria and several heterotrophic bacteria have similar diurnal variations implying the light and physicochemical heterogeneity in the course of a day are important for bacterial diurnal changes in the CRE.展开更多
Through investigating the effect of mild hypothermia on activity of nitric oxide snythase (NOS) in cortical neurons and glycemia levels of neonatal rats with hypoxic ischemic brain damage (HIBD). We studied the mechan...Through investigating the effect of mild hypothermia on activity of nitric oxide snythase (NOS) in cortical neurons and glycemia levels of neonatal rats with hypoxic ischemic brain damage (HIBD). We studied the mechanism of protecting hypoxic ischemic neurons of mild hypothermia. We established neonatal rat HIBD models, used NOS immunohistochemistry and glycemia determination by micromethod. The number of cortical NOS positive neurons after hypoxic ischemia was significantly decreased as compared with controls. The glycemia levels was significantly increased than that controls. No significant difference was found in number of cortical NOS positive neurons and glycemia levels between 31℃ and 34℃ mild hypothemia. The results imply that hypothermia can decrease overproduction of NO through inhibiting the increase of the activity of NOS, and increase the glycemia levels, thus protect the hypoxic ischemic neurons.展开更多
Objective:Based on the BDNF/TrkB/CREB pathway,to explore the mechanism of neuronal apoptosis and brain developmental injury in the hippocampus of hypoxic-ischemic neonatal rats.Methods:Wistar young rats were ligated o...Objective:Based on the BDNF/TrkB/CREB pathway,to explore the mechanism of neuronal apoptosis and brain developmental injury in the hippocampus of hypoxic-ischemic neonatal rats.Methods:Wistar young rats were ligated on one side of the common carotid artery and placed in an 8%oxygen and 92%nitrogen hypoxia box for 2 h to prepare hypoxic-ischemic brain injury models.Healthy rats were used as the control group.Control group and model group were selected,with 10 rats in each group,and the learning and memory ability was tested by Y-maze;2,3,5-triphenyltetrazolium chloride(TTC)staining was used to detect brain tissue damage;Western blot was performed to determine the expression of brain-derived neurotrophic factor(BDNF),tyrosine protein kinase B(TrKB)and cAMP-response element binding protein(CREB)in hippocampal tissue.Another 15 mice in the control group and 60 mice in the model group were divided into negative control group(NC),BDNF overexpression group(LV-BDNF),TrkB overexpression group(LV-TrkB),and CREB overexpression group(LV-CREB),blank vector,BDNF,TrkB,CREB adenovirus overexpression vector was injected into the tail vein.Y-maze test for learning and memory ability;TTC staining method to detect brain tissue damage;neuronal apoptosis in the hippocampus were detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling;Western blot to detect the level of neuronal apoptosis in the hippocampus.Apoptosis-related protein B-cell lymphoma-2(Bcl-2),BCL2associated X protein(Bcl-2 Assaciated X,Bax)and nuclear factor kappaB(NFκB)expression.Results:The learning and memory ability of the young mice in the model group was significantly reduced,the brain infarct volume was significantly increased,the expressions of BDNF and TrkB proteins in the hippocampus were significantly increased,and the expression of CREB proteins was significantly decreased;After overexpression of BDNF and TrkB CREB,in the LVBDNF,LVTrkB,and LVCREB group,the learning and memory ability of young mice were significantly improved,the brain infarct volume were significantly reduced,the hippocampal neuronal apoptosis were significantly reduced,The protein expression of Bax and NFκB were significantly decreased and the protein expression of Bcl2 were significantly enhanced.Conclusion:The expression of BDNF/TrkB/CREB is abnormal in HIBI model young mice.Overexpression of BDNF/TrkB/CREB can improve the learning and memory ability of young mice,repair brain tissue damage,and inhibit neuronal apoptosis.Therefore,the mechanism of HIBI may be related to BDNF/TrkB/CREB pathways.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.
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Hypoxic preconditioning is able to increase the body’s resistance to hypoxic/ischemic stress. Understanding how to apply the hypoxic response to initiate the protective mechanism of ischemic preconditioning is a high priority. However, the relationship between innate resistance to hypoxic stress and preconditioning efficiency of moderate hypoxia has been poorly studied. In our work, the efficiency of single moderate hypobaric hypoxia (HBH) for resistance to severe hypobaric hypoxia (SHBH) was studied on intact rats and those pre-tested under SHBH with low, intermediate and high resistance to hypoxia. HBH has a significant preconditioning action on the resistance to hypoxia over a wide range from 270 to 1464 s (4.5 to 24.5 min) and at the same time eliminates the differences in the endurance under SHBH between all rat groups. It is concluded that 1) HBH preconditioning efficiency does not depend on an innate resistance to SHBH and prior hypoxic experience of rats;and 2) the pretesting to severe hypoxia has no value for predicting the hypoxic preconditioning efficiency and study of adaptive mechanisms.
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.
基金supported by National Natural Science Foundation of China,No.81771270(to QP)Inner Mongolia Science Foundation of China,No.2020MS08063(to YQP)+3 种基金Health and Family Planning Scientific Research Plan Project of Inner Mongolia Autonomous Region of China,No.201702138(to YQP)Baotou Science and Technology Plan Project of China,No.2018C2007-4-10(to YQP)Baotou Medical and Health Science and Technology Project of China,No.wsjj2019036(to JY)Baotou Medical College Foundation of China,No.BSJJ201904(to JY)。
文摘Hypoxic preconditioning can protect against cerebral ischemia/reperfusion injury. However, the underlying mechanisms that mediate this effect are not completely clear. In this study, mice were pretreated with continuous, intermittent hypoxic preconditioning;1 hour later, cerebral ischemia/reperfusion models were generated by middle cerebral artery occlusion and reperfusion. Compared with control mice, mice with cerebral ischemia/reperfusion injury showed increased Bederson neurological function scores, significantly increased cerebral infarction volume, obvious pathological damage to the hippocampus, significantly increased apoptosis;upregulated interleukin-1β, interleukin-6, and interleukin-8 levels in brain tissue;and increased expression levels of NOD-like receptor family pyrin domain containing 3(NLRP3), NLRP inflammasome-related protein caspase-1, and gasdermin D. However, hypoxic preconditioning significantly inhibited the above phenomena. Taken together, these data suggest that hypoxic preconditioning mitigates cerebral ischemia/reperfusion injury in mice by reducing NLRP3 inflammasome expression. This study was approved by the Medical Ethics Committee of the Fourth Hospital of Baotou, China(approval No. DWLL2019001) in November 2019.
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.
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 program Innovative Research Team in Science and Technology in Yunnan Province of China(to THW)the National Natural Science Foundation of China,No.81601074Sichuan Provincial Scientific Foundation Grant of China,No.2017SZ0145
文摘A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive.Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model.SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing.Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism.We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2.Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis,wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels.Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses,long-term depression and oxytocin signaling.Moreover,intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1,DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy.Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons.Our results indicate that CSRNP1,DUSP5 and LRRC25,containing SNPs,may be involved in the pathogenesis of hypoxic ischemic encephalopathy.These findings indicate a novel direction for further hypoxic ischemic encephalopathy research.This animal study was approved on February 5,2017 by the Animal Care and Use Committee of Kunming Medical University,Yunnan Province,China(approval No.kmmu2019038).Cerebral tissue collection from a human fetus was approved on September 30,2015 by the Ethics Committee of Kunming Medical University,China(approval No.2015-9).
基金supported by the grants from the Natural Science Foundation of China(No.81071610 and No.81471814)Consultative Project of Transformation Medicine in Southwest Hospital of the Third Military Medical University(SWH2014ZH05)
文摘Background: Hypoxia is a primary cause of mountain sickness and a common pathological condition in patients with heart failure, shock, stroke, and chronic obstructive pulmonary disease(COPD). Thus far, little advancement in countering hypoxic damage has been achieved, and one of the main reasons is the absence of an ideal algorithm or calculation method to normalize hypoxia tolerance scores when evaluating an animal model. In this study, we improved a traditional calculation formula for assessment of hypoxia tolerance.Methods: We used a sealed bottle model in which the oxygen is gradually consumed by a mouse inside. To evaluate the hypoxia tolerance of mice, the survival time(ST) of the mouse is recorded and was used to calculate standard hypoxia tolerance time(STT) and adjusted standard hypoxia tolerance time(ASTT). Mice administered with methazolamide and saline were used as positive and negative controls, respectively.Results: Since mice were grouped according to either body weight(BW) or bottle volume, we found a strongly negative correlation between STT and BW instead of between STT and bottle volume, suggesting that different BWs could cause false positive or negative errors in the STT results. Furthermore, both false positive and negative errors could be rectified when ASTT was used as the evaluation index. Screening for anti-hypoxic medicines by using mice as the experimental subjects would provide more credible results with the improved ASTT method than with the STT method.Conclusions: ASTT could be a better index than STT for the evaluation of hypoxia tolerance abilities as it could eliminate the impact of animal BW.
文摘AIM: To evaluate donation after circulatory death(DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy(HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS Donor Net included preoperative systolic and diastolic blood pressure, heart rate, p H, SpO_2, PaO_2, FiO_2, and hemoglobin. Mean arterial bloodpressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O_2 content was computed as [hemoglobin(gm/d L) × 1.37(m L O_2/gm) × SpO_2%) +(0.003 × PaO_2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mm Hg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was(ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin.RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age(33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion(9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin(10.7 ± 2.2 gm/d L vs 12.3 ± 2.1 gm/d L, P = 0.017), lower preoperative arterial oxygen content(14.8 ± 2.8 m L O_2/100 m L blood vs 16.8 ± 3.3 m L O_2/100 m L blood, P = 0.049), greater hypoxia score >2.0(69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure(92.7 ± 16.2 mm Hg vs 83.8 ± 18.5 mm Hg, P = 0.10). HC was independently associated with age, multi-pressor/redcell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure(r^2 = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2(7.1/year)], compared to our early experience [era 1(2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1(P = 0.03). Era 2 donors had longer times for extubation-to-asystole(14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia(13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia(16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate(73.1% vs 28.6%, P = 0.006).CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.
基金Supported by Project of Mudanjiang Science and Technology Bureau:Rodent Pest Investigation in Agriculture and Forestry in Eastern Heilongjiang(2017H45)Ecological and Hazard Control of Forest Rodents(8033006)+1 种基金Investigation on Forest Rodent Resources in Eastern Heilongjiang and Development of Rodenticides(1353PT012)Research Team Project of Zoology
文摘[Objective] The paper was to investigate the effect of hypoxic environment on life rhythm of Apodemus peninsulae. [Method] A. peninsulae were captured and fed in indoor hypoxic environment from May 2015 to October 2016. The respiratory frequency, activity level, food intake and water intake of A. peninsulae were analyzed under different oxygen concentrations. [Result] With the decrease of oxygen concentration, the respiratory frequency of A. peninsulae decreased, and the respiratory depth deepened, while the activity level, food intake and water intake de-creased. [Conclusion] The hypoxic environment had an impact on the respiratory frequency, activity level, food intake and water intake of A. peninsulae.
基金The National Key R&D Program of China under contract No.2019YFD0901305the Science and Technology Program of Zhoushan under contract No.2019C21011+4 种基金the National Natural Science Foundation of China under contract Nos31270160 and J1310037the Natural Science Foundation of Zhejiang ProvinceChina under contract No.LY12C03003the Zhejiang Public Welfare Technology Application Research Project under contract No.2016C33084the Research Project of Ecological Environment Protection and Restoration of Yangtze River in Zhoushan under contract No.SZGXZS2020068。
文摘The Changjiang River Estuary(CRE)in the East China Sea suffers from seasonal hypoxia in summer.The vertical distributions and seasonal changes of microbial communities in the CRE were well documented.However,little is known about the diurnal changes of bacterial communities in the hypoxic zone of the CRE.Here,16 S rRNA gene analysis was used to explore the changes of bacterial communities in the oxic surface and hypoxic middle seawater layers during 24 h in the CRE.Significant differences between the hypoxic and oxic layers were observed:the phyla Cyanobacteria,Bacteroidetes and Acidimicrobiia were enriched in the oxic layer,whereas the phylum SAR406 and the class Deltaproteobacteria were more abundant in the hypoxic layer.In addition,some subtle diurnal variations of the bacterial relative abundance were found in both two layers.The relative abundance of Synechococcus increased at night,and this change was more obvious in the hypoxic layer.The similar trend was also found in some phototrophic and several heterotrophic bacteria,such as Rhodobacteraceae,OM60 and Flavobacteriaceae.Their relative abundances peaked at 16:00 in the oxic layer,while the relative abundances peaked at around 7:00 and decreased until 13:00 in the hypoxic layer.Together,the results of the present study suggest that some photosynthetic bacteria and several heterotrophic bacteria have similar diurnal variations implying the light and physicochemical heterogeneity in the course of a day are important for bacterial diurnal changes in the CRE.
文摘Through investigating the effect of mild hypothermia on activity of nitric oxide snythase (NOS) in cortical neurons and glycemia levels of neonatal rats with hypoxic ischemic brain damage (HIBD). We studied the mechanism of protecting hypoxic ischemic neurons of mild hypothermia. We established neonatal rat HIBD models, used NOS immunohistochemistry and glycemia determination by micromethod. The number of cortical NOS positive neurons after hypoxic ischemia was significantly decreased as compared with controls. The glycemia levels was significantly increased than that controls. No significant difference was found in number of cortical NOS positive neurons and glycemia levels between 31℃ and 34℃ mild hypothemia. The results imply that hypothermia can decrease overproduction of NO through inhibiting the increase of the activity of NOS, and increase the glycemia levels, thus protect the hypoxic ischemic neurons.
基金Hainan Provincial Natural Science Foundation of China(NO.819QN388)。
文摘Objective:Based on the BDNF/TrkB/CREB pathway,to explore the mechanism of neuronal apoptosis and brain developmental injury in the hippocampus of hypoxic-ischemic neonatal rats.Methods:Wistar young rats were ligated on one side of the common carotid artery and placed in an 8%oxygen and 92%nitrogen hypoxia box for 2 h to prepare hypoxic-ischemic brain injury models.Healthy rats were used as the control group.Control group and model group were selected,with 10 rats in each group,and the learning and memory ability was tested by Y-maze;2,3,5-triphenyltetrazolium chloride(TTC)staining was used to detect brain tissue damage;Western blot was performed to determine the expression of brain-derived neurotrophic factor(BDNF),tyrosine protein kinase B(TrKB)and cAMP-response element binding protein(CREB)in hippocampal tissue.Another 15 mice in the control group and 60 mice in the model group were divided into negative control group(NC),BDNF overexpression group(LV-BDNF),TrkB overexpression group(LV-TrkB),and CREB overexpression group(LV-CREB),blank vector,BDNF,TrkB,CREB adenovirus overexpression vector was injected into the tail vein.Y-maze test for learning and memory ability;TTC staining method to detect brain tissue damage;neuronal apoptosis in the hippocampus were detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling;Western blot to detect the level of neuronal apoptosis in the hippocampus.Apoptosis-related protein B-cell lymphoma-2(Bcl-2),BCL2associated X protein(Bcl-2 Assaciated X,Bax)and nuclear factor kappaB(NFκB)expression.Results:The learning and memory ability of the young mice in the model group was significantly reduced,the brain infarct volume was significantly increased,the expressions of BDNF and TrkB proteins in the hippocampus were significantly increased,and the expression of CREB proteins was significantly decreased;After overexpression of BDNF and TrkB CREB,in the LVBDNF,LVTrkB,and LVCREB group,the learning and memory ability of young mice were significantly improved,the brain infarct volume were significantly reduced,the hippocampal neuronal apoptosis were significantly reduced,The protein expression of Bax and NFκB were significantly decreased and the protein expression of Bcl2 were significantly enhanced.Conclusion:The expression of BDNF/TrkB/CREB is abnormal in HIBI model young mice.Overexpression of BDNF/TrkB/CREB can improve the learning and memory ability of young mice,repair brain tissue damage,and inhibit neuronal apoptosis.Therefore,the mechanism of HIBI may be related to BDNF/TrkB/CREB pathways.
