hypoxia

摘要： Alzheimer’s disease(AD)is a degenerative neurological disease that primarily affects the elderly.Drug therapy is the main strategy for AD treatment,but current treatments suffer from poor efficacy and a number of side effects.Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD.Hypoxia is one of the important factors that contribute to the pathogenesis of AD.Multiple cellular processes synergistically promote hypoxia,including aging,hypertension,diabetes,hypoxia/obstructive sleep apnea,obesity,and traumatic brain injury.Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD,such as amyloid-beta metabolism,tau phosphorylation,autophagy,neuroinflammation,oxidative stress,endoplasmic reticulum stress,and mitochondrial and synaptic dysfunction.Treatments targeting hypoxia may delay or mitigate the progression of AD.Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD.Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism,tau phosphorylation,neuroinflammation,neuronal apoptosis,oxidative stress,neurotrophic factors,mitochondrial function,cerebral blood volume,and protein synthesis.In this review,we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations.We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.

摘要： 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.

摘要： Inhibiting retinal neovascularization is the optimal strategy for the treatment of retina-related diseases, but there is currently no effective treatment for retinal neovascularization. P-element-induced wimpy testis(PIWI)-interacting RNA(piRNA) is a type of small non-coding RNA implicated in a variety of diseases. In this study, we found that the expression of piR-1245 and the interacting protein PIWIL2 were remarkably increased in human retinal endothelial cells cultured in a hypoxic environment, and cell apoptosis, migration, tube formation and proliferation were remarkably enhanced in these cells. Knocking down piR-1245 inhibited the above phenomena. After intervention by a p-JAK2 activator, piR-1245 decreased the expression of hypoxia inducible factor-1α and vascular endothelial growth factor through the JAK2/STAT3 pathway. For in vivo analysis, 7-day-old newborn mice were raised in 75 ± 2% hyperoxia for 5 days and then piR-1245 in the retina was knocked down. In these mice, the number of newly formed vessels in the retina was decreased, the expressions of inflammationrelated proteins were reduced, the number of apoptotic cells in the retina was decreased, the JAK2/STAT3 pathway was inhibited, and the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor were decreased. Injection of the JAK2 inhibitor JAK2/TYK2-IN-1 into the vitreous cavity inhibited retinal neovascularization in mice and reduced expression of hypoxia inducible factor-1α and vascular endothelial growth factor. These findings suggest that piR-1245 activates the JAK2/STAT3 pathway, regulates the expression of hypoxia inducible factor-1α and vascular endothelial growth factor, and promotes retinal neovascularization. Therefore, piR-1245 may be a new therapeutic target for retinal neovascularization.

摘要： Neural progenitor cells(NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox(VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR(0.5 mM valproic acid, 3 μM CHIR99021, and 1 μM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition(5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6(Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs(ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson’s disease.

摘要： Cervical spondylotic myelopathy is the main cause of non-traumatic spinal cord injury,with chronic static and/or dynamic compressive spinal cord injury as the unique pathogenesis.In the progression of this condition,the microvascular network is compressed and destroyed,resulting in ischemia and hypoxia.The main pathological changes are inflammation,damage to the blood spinal cord barriers,and cell apoptosis at the site of compression.Studies have confirmed that vascular regeneration and remodeling contribute to neural repair by promoting blood flow and the reconstruction of effective circulation to meet the nutrient and oxygen requirements for nerve repair.Surgical decompression is the most effective clinical treatment for this condition;however,in some patients,residual neurological dysfunction remains after decompression.Facilitating revascularization during compression and after decompression is therefore complementary to surgical treatment.In this review,we summarize the progress in research on chronic compressive spinal cord injury,covering both physiological and pathological changes after compression and decompression,and the regulatory mechanisms of vascular injury and repair.

摘要： The intrusion of the Kuroshio into the East China Sea(ECS)aff ects the development of hypoxia off the Changjiang(Yangtze)River estuary;however,quantitative analysis of its impacts is lacking.In this study,the Regional Ocean Modeling Systems(ROMS)model coupled with the Carbon,Silicate and Nitrogen Ecosystem(CoSiNE)model was used to investigate the relative importance of dissolved oxygen(DO)and diff erent nutrients(silicate,nitrate,and phosphate)in the Kuroshio on hypoxia in the ECS.Results show that changes in DO concentrations in the Kuroshio modify the distribution and intensity of hypoxia through direct onshore transport by hydrodynamic processes.An increase in Kuroshio DO concentration by 25%or 50%would result in a decrease of the maximum hypoxia extent(MHE)in the ECS by 76%or 86%,respectively,while a 25%decrease in Kuroshio DO would increase the MHE by up to 219%.The contribution of DO in the Taiwan Strait is almost negligible.In contrast to Kuroshio DO,nutrients aff ect hypoxia in the ECS through onshore transport by hydrodynamic and biochemical processes.Changes in phosphate and nitrate concentrations by 25%in the Kuroshio would change the MHE by up to 30%and 18%,respectively,accompanied by apparent changes in surface chlorophyll-a concentrations.The eff ect of silicate on hypoxia is negligible because a 25%change in silicate concentrations in the Kuroshio would result in less than 1%change in the MHE.Our results reveal a hierarchical rank of importance for environmental variables in the Kuroshio(i.e.,DO>phosphate>nitrate>silicate)in modifying the development of hypoxia in the ECS.

摘要： Intermittent hypoxia or hypoxia therapy is exposing an individual to oxygenation conditions that are below atmospheric levels in a planned or acute timeframe. Hypoxia therapy is a potentially novel therapeutic strategy for a variety of pathologies including: mitochondrial disorders, exercise training, and mild cognitive impairments. Mitochondrial dysfunction, hyperkinetic movements, and cognitive impairments are hallmarks of seizures and status epilepticus (SE). A seizure can be considered uncontrolled electrical activity in the brain and SE is a seizure lasting more than 30 minutes, or multiple seizures without regaining consciousness in between. We examined the possibility of using the Pilocarpine model for seizure like activity on brown planaria (Dugesia tigrine). Pilocarpine is a muscarinic acetylcholine receptor agonist capable of creating seizure related brain damage. We utilized 5 mM dosages of pilocarpine and then measured open field behaviour for 3 minutes. Mobility and aversive hyperkinetic movements were observed throughout the measurement phase. After exposure to 5 mM pilocarpine, the planaria displayed behaviours consistent with seizures (e.g. aversive hyperkinetic movements and decreased mobility). Additionally, we measured the effects of an acute hypoxic event on Planaria behaviour. We used 25% carbonated water to create a hypoxic environment for the planaria and then measured mobility and hyperkinetic movements for 3 minutes. We noted that exposure to the hypoxic en-vironment produced no changes in behaviour. However, the aversive hyperkinetic move-ments produced with pilocarpine administration were completely absent when a brief (3 minutes) hypoxic episode followed the pilocarpine exposure (p < 0.05). Aversive behav-iours remained present when the ordering of pilocarpine and hypoxia were counterbal-anced. This ordering effect was consistent across 40 trials. Further evaluation of the pilo-carpine seizure model and intermittent hypoxia on planarian behaviour is warranted.

摘要： Waterlogging is an illustrious abiotic stress and the constrictions it enforces on plant roots have negative effects on growth and development.This study was undertaken to investigate waterlogging stress tolerant potential in chilli(Capsicum annum L.)genotypes through evaluating morphological,physiological,biochemical and anatomical parameters.Thirty-five days old seedlings of 10 chilli genotypes were exposed to waterlogging stress maintaining water height 3–5 cm over the soil surface artificially for three days.This duration(36–38 DAE)was termed as waterlogging period,and subsequent withdrawal of waterlogging condition(39–45 DAE)was regarded as a recovery phase.Based on their survival performance,two tolerant genotypes viz.,SRC-517 and BARI morich-2 and two susceptible genotypes viz.,AHM-206 and RI-1(6)were selected for studying stress tolerance mechanism.Under waterlogging,however,both genotypes(tolerant and susceptible)exhibited reduced root shoot length,dry weight ratio,petiole weight and leaf area,and noticeable reduction regarding these parameters was observed in susceptible genotypes.Moreover,tolerant genotypes displayed a higher recovery than susceptible genotypes after removal of waterlogging stress.Lower reduction of leaf area and photosynthetic pigments as well as higher reduction of relative water content(RWC)were noticed in susceptible genotypes.Higher accumulation of proline and total antioxidant capacity(TAC)during waterlogging condition in tolerant genotypes suggested lower oxidative damage.Although both genotypes lost total soluble sugar(TSS)relative to control at waterlogging stress,better performance was recorded in tolerant genotypes.During the period after the removal of extra water,a similar genotypic response in terms of TSS gain was seen.Undoubtedly,under flooding conditions,the development of aerenchyma cells in tolerant genotypes is a means of tolerance mechanism for long-term survival.Thus,the morpho-physiological and biochemical changes help to understand the tolerance mechanism in chilli under waterlogging stress.

摘要： BACKGROUND The most common causes of compartment syndrome in the lower extremities include lower limb fractures,trauma-induced crushing injuries,severe burns,and non-traumatic factors.However,there have been no reports of compartment syndrome secondary to toxic inhalation.CASE SUMMARY A 59-year-old man,who lost consciousness after applying polyurethane-based paint on a water tank,was brought to the emergency room.The initial blood test showed apparent rhabdomyolysis.One day later,pain and swelling in both legs were observed,and the physical examination confirmed the presence of compartment syndrome.Double-incision fasciotomy was performed on both legs.Frequent dressings and negative pressure wound treatment were done on both legs,and skin grafting was performed after healthy granulation tissue had been identified.No other complications were observed after treatment.However,symptoms of peroneal neuropathy,particularly limited ankle dorsiflexion and reduced sensation on the lower extremities,were observed.CONCLUSION Workers using polyurethane agents should wear gas masks and be evaluated for compartment syndrome and rhabdomyolysis secondary to toxic inhalation.

摘要： The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.

摘要： Hypoxia remains a major characteristic of tumors. Malignant cell growth requires the presence of a local vascular network that supplies oxygen and nutrients. However，a highly proliferating mass of tumor cells develops faster than the vasculature and rapidly meet up with anavascular environment deficient in oxygen. Hypoxia affects a variety of cell properties such as cellgrowth，apopfosis，metastasis and sensitivity to treatment. Nevertheless，the responses of cells tohypoxia are essential questions in understanding tumor progression，which may lead to novelstrategies for diagnosis and treatment. microRNAs (miRNAs) are about 22 nucleotide RNAmolecules that participate in a wide variety of physiological and pathological cellular processes such as cell differentiation，proliferation，death，metabolism and more recently tumori genesis Recent studies have established a link between a distinct miRNAs expression profile with hypoxiaand global miRNAs expression changes have been described and in some cases shown to correlatewith the clinicopathological features of the tumor. However，there is still few mechanism has been proposed to date and relatively little is known about miRNAs regulation in hypoxia.