Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59.893
Filtrar
1.
Adv Exp Med Biol ; 1232: 33-38, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893391

RESUMO

Monitoring of cerebral tissue oxygen saturation (StO2) by near-infrared spectroscopy (NIRS oximetry) has great potential to reduce the incidence of hypoxic and hyperoxic events and thus prevent long-term disabilities in preterm neonates. Since the light has to penetrate superficial layers (bone, skin and cerebrospinal fluid) before it reaches the brain, the question arises whether these layers influence cerebral StO2 measurement. We assessed this influence on the accuracy of cerebral StO2 values. For that purpose, we simulated light propagation with 'N-layered medium' software. It was found that with a superficial layer thickness of ≤6 mm, typical for term and preterm neonates, StO2 accurately reflects cerebral tissue oxygenation.


Assuntos
Oximetria , Oxigênio , Crânio , Encéfalo/metabolismo , Humanos , Hipóxia/diagnóstico , Recém-Nascido , Oximetria/normas , Crânio/anatomia & histologia , Espectroscopia de Luz Próxima ao Infravermelho
2.
Adv Exp Med Biol ; 1232: 131-143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893404

RESUMO

Hypoxia, one of the hallmarks of cancer, is caused by an insufficient oxygen supply, mostly due to a chaotic, deficient tumor microcirculation. Apart from a hypoxia-mediated resistance to standard therapies, modulated gene and protein expression, genetic instability and malignant progression, hypoxia also plays a pivotal role in anti-cancer immune responses by (a) reducing survival, cytolytic and migratory activity of effector cells such as CD4+ cells, CD8+ cytotoxic T cells, natural killer-like T cells and natural killer cells, (b) reducing the production and release of effector cytokines, (c) supporting immunosuppressive cells such as regulatory T cells, myeloid-derived suppressor cells and M2 macrophages, (d) increasing the production and release of immunosuppressive cytokines, and (e) inducing the expression of immune checkpoint inhibitors. In this minireview, immunosuppressive effects of hypoxia- and HIF-1a-driven traits in cancers are described.


Assuntos
Hipóxia , Células Supressoras Mieloides , Neoplasias , Humanos , Hipóxia/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias/imunologia , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/imunologia
5.
Zhonghua Yan Ke Za Zhi ; 55(12): 933-941, 2019 Dec 11.
Artigo em Chinês | MEDLINE | ID: mdl-31874508

RESUMO

Objective: To study the effects of human umbilical mesenchymal stem cells (HUMSCs) exosomes on the proliferation and apoptotic as well as migration of human retinal pigment epithelial cells (HRPE) in hypoxia, and explore its mechanism. Method: Direct adherent culture was adopted to cultivate umbilical cord mesenchymal stem cells and amplified to the fourth generation. Markers on the cell surface were identified by flow cytometry. Culture medium was collect without serum from the 4th generation umbilical cord mesenchymal stem cells. Exosomes were separated and extracted, then the ultrastructure was observed under electron microscope and examined expression of CD63 and CD9 protein by Western blot method with isolated and extracted exosomes. HRPE was cultivated in vitro culture, proliferation was detected at the time point of 0, 1, 2, 3, 4, 5 d with MTT assay under hypoxic condition. Meanwhile, the cell migration was quantified by Wound-Healing Assay under hypoxic condition at 0, 24, 48 and 72 h respectively combined with apoptosis test. The HRPE cells in the growth period were divided into 5 groups: the control group, the hypoxia group and the pretreated exosomes group (100, 200, 300 µg/ml). In all groups, apoptosis was observed by Annexin V/PI dual-dye flow cytometry after 48 h's incubation. Proliferation was observed by MTT assay and the migration was observed with Wound-Healing Assay. Results: Flow cytometry detection of the surface marker of HUMSCs in the 4th generation showed strong positive expression of CD105, CD73, CD90. It was suggested that HUMSCs with isolated culture had MSC specific phenotype with duction of lipids and osteoblasts in vitro. The separated exosomes were observed with spherical membranous structures in different sizes by scanning electron microscopy, and Western blot detected positive expression of CD63 and CD9. In vitro culture of HRPE detected by MTT assay for cell proliferation at the time of hypoxic 0, 1, 2, 3, 4, 5 d, the results showed that, comparing with time point 0 d, other groups had statistically significant OD values. In the first 2 days, the proliferation ability of RPE cells gradually increased as the time of hypoxia prolonged(1.862±0.135, 2.278±0.244). After 3 d, the proliferation ability of RPE cells gradually decreased(1.419±0.124, 1.599±0.156). Wound-Healing Assay results showed that the migration distance gradually increased as[(29.883±4.504), (36.200±1.928) µm] the time of hypoxia increased from 0 to 72 h. The cells were fully covering at the point of 72 h [(1.223±0.194), (0.430±0.299) µm]. Apoptosis test results showed that the number of apoptotic cells was different(3.628%±1.348%, 20.123%±1.183%) with the extension of hypoxia Oxygen before 2 d from 0 to 72 h. At the time of d3, there were more apoptotic cells(42.290%±3.217%). There is a significant difference from pre-2d.RPE cells were divided into 5 groups: the control group, the hypoxia group and the pretreated exosomes group (100, 200, 300 µg/ml).After 48 h hypoxia incubation, MTT assay results showed that, compared with the control group (1.870±0.499), the number of cell proliferation was significantly increased (t=-3.116, P<0.05), while compared with the hypoxia group(2.616±0.307), the proliferation number of exosomes was significantly reduced [(2.041±0.115), (1.931±0.205), (1.929±0.025); t=-4.920, -4.540, -5.286, P<0.01], and there was no significant difference between groups with different doses of the exosomes (F=1.181,P>0.05). Annexin V/PI dual-dye flow cytometry was used to observe the apoptosis results. Compared with the control group 1.180%±0.689%, the number of apoptosis in hypoxia group was significantly increased (19.273%±1.194%, t=-32.141, P<0.01), while compared with the hypoxia group, the number of apoptosis in the exosomes was significantly decreased (12.318%±1.087%, 11.878%±1.348%, 11.090%±1.716%; t=-10.547, -10.057, 9.589, P<0.01). There was no significant difference between the groups with different doses of exosomes (F=1.173, P>0.05). Wound-Healing Assay results showed that, compared with the control group(68.047±2.851) µm, the migration distance of the hypoxia group was significantly increased [(13.470±2.255)µm, t=36.778, P<0.01] while compared with the hypoxia group, the migration distance of the exosomes was reduced (33.110±1.774, 24.650±1.175, 26.440±1.674; t=11.766, 10.770, 11.311, P<0.01), and there was no significant difference between the groups of the exosomes (F=1.179, P>0.05). Conclusion: Human umbilical cord mesenchymal stem cells can effectively inhibit the apoptosis and migration of HRPE cells in hypoxia. It provides a theoretical basis for the research and treatment of RPE related diseases. (Chin J Ophthalmol, 2019, 55: 933-941).


Assuntos
Apoptose , Proliferação de Células , Exossomos , Hipóxia , Células-Tronco Mesenquimais , Retina , Células Cultivadas , Células Epiteliais , Humanos , Retina/citologia , Retina/metabolismo , Pigmentos da Retina , Cordão Umbilical
6.
Biomed Khim ; 65(6): 485-497, 2019 Oct.
Artigo em Russo | MEDLINE | ID: mdl-31876519

RESUMO

In socially isolated male outbred albino mice, the changes of monoaminergic systems under acute hypoxia with hypercapnia were studied. In cerebral cortex, hippocampus and striatum of the right and left sides of the brain, the concentrations of norepinephrine, dopamine, serotonin and their metabolites - dihydroxyphenylacetic, homovanillic and 5-hydroxyindoleacetic acids were investigated using the HPLC method. In isolated mice, which were not subjected to hypoxia with hypercapnia, higher levels of dopamine and serotonin in the left cortex were found. There was no asymmetry in monoamines and their metabolites in other studied brain structures. 10 min after the onset of exposure, acute hypoxia with hypercapnia resulted in a right-sided increase in norepinephrine levels and a decrease in dopamine levels in the striatum and serotonin levels in the hippocampus. In the cerebral cortex, 10 min after of hypoxic exposure beginning, there was a left-sided decrease in the dopamine content, while the original asymmetry found in the cortex of intact animals disappeared. In isolated mice perished of hypoxia with hypercapnia, almost all parameters returned to the control level. The exception was the ratio of serotonin metabolite level to the neurotransmitter, which in the right cortex became lower than in control animals. In white outbred mice, the brain monoaminergic systems are suggested to be relatively resistant to the negative consequences of hypoxia and hypercapnia, and corresponding shifts resulting in the reflex brain response to changes in the gas composition of the respiratory air.


Assuntos
Química Encefálica , Dopamina/química , Hipercapnia/metabolismo , Hipóxia/metabolismo , Norepinefrina/química , Serotonina/química , Animais , Encéfalo , Ácido Homovanílico , Masculino , Camundongos
7.
Stomatologiia (Mosk) ; 98(5): 60-65, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31701931

RESUMO

OBJECTIVE: To study interrelation of maintenance of α-defensins 1-3 and a hypoxia-inducible factor 1-alpha (HIF-1α) in gingival liquid of patients with caries. MATERIAL AND METHODS: 75 patients with the diagnosis dentine caries were enrolled in the study and divided into two groups: in group 1 (n=30) caries was diagnosed in earlier untreated tooth, the 2nd group (n=45) included patients with the recurrence of carious process (in earlier treated tooth). Controls involved 25 caries-free individuals. The level of α-defensins 1-3 was studied in gingival fluid by ELISA method. RESULTS: The level of α-defensins 1-3 and antimicrobic peptide in gingival liquid in group 2 was 28 and 36% higher than in the 1st group, correspondingly (p<0.001). Concentration of HIF-1α in gingival liquid in the 2nd group was almost twice higher (p<0.001) than in group 1 and 82% higher than in controls (p<0.001), while in group 1 it decreased by 11% when compared to controls (p<0.001). All controls showed a close correlation between the level of α-defensins 1-3 and HIF-1α in gingival fluid (R=0.78, p<0.001), not observed in group 1 (R=0.32, p>0.05) but statistically significant in group 2 (R=0.78, p<0.001). Thus, the recurrence of carious process in caries-associated tooth is associated with the hypoxia-dependent activation of a congenital antimicrobial immunity by means of accumulation of HIF-1α and pronounced increase of α-defensins 1-3 in gingival fluid.


Assuntos
Anti-Infecciosos , Cárie Dentária , Dentina , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia
8.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(5): 463-468, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31721490

RESUMO

OBJECTIVE: To investigate the mechanism of the participation of osteocytes in the formation of osteoclasts under hypoxia. METHODS: The hypoxia culture system of osteocyte-like cell line MLO-Y4 was established by deferoxamine mesylate (DFO) in vitro. The proliferation of MLO-Y4 cells was examined by CCK-8 cell proliferation/toxicity assay. RAW264.7 cells were induced to osteoclasts by the conditioned medium containing the cultured MLO-Y4. Tartrate-resistant acid phosphatase (TRAP) staining was performed on day 7. Quantitative real-time fluorescence polymerase chain reaction, immunofluorescence, and Western blot were used to detect the expression levels of hypoxia-inducible factor (HIF)-1α and receptor activator of nuclear factor-κB ligand (RANKL) in MLO-Y4 under hypoxia. The effects of siHIF-1α on the expression levels of HIF-1α and RANKL in MLO-Y4 under the same conditions were detected. RESULTS: DFO (100 µmol·L⁻¹) promoted the proliferation of MLO-Y4 at 24 h, which decreased with time (P<0.01). After the addition of soluble sRANKL, the formation of osteoclasts was significantly increased in the DFO group (P<0.001). The expression of RANKL mRNA in MLO-Y4 under 100 µmol·L⁻¹ DFO increased first and then decreased with the duration of hypoxia. This expression reached a peak at 24 h (P<0.01). Hypoxia up-regulated the expression of HIF-1α and RANKL protein (P<0.01). Under hypoxia, siHIF-1α downregulated the expression of HIF-1α and RANKL (P<0.01). siHIF-1α also decreased the number of osteoclasts (P<0.01). CONCLUSIONS: Under hypoxia, MLO-Y4 could facilitate the formation of RANKL through upre-gulating the expression of HIF-1α protein, thereby accelerate the differentiation of RAW264.7 cells into osteoclasts.


Assuntos
Osteoclastos , Osteócitos , Diferenciação Celular , Linhagem Celular , Humanos , Hipóxia
9.
AANA J ; 87(2): 16, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31587732
11.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(10): 748-753, 2019 Oct 07.
Artigo em Chinês | MEDLINE | ID: mdl-31606987

RESUMO

Objective: To study the correlation between the standardized palatal sensory threshold and airway obstruction and hypoxia during sleep, and to infer its role in the pathogenesis of OSAHS. Methods: From August 2016 to May 2017, 92 OSAHS patients as experimental group and 48 non-OSAHS volunteers as control group were recruited in Department of Otorhinolaryngology Head and Neck Surgery, Changhai Hospital Affiliated to the Naval Medical University. The tactile sense was measured by Smmes-Weinstein Monofilaments in the middle of uvula and both side of hard palate,then the threshold of the uvula minus, the average threshold of the hard palate as the standardized palatal sensory threshold(SPST). The control point of both groups was located in the central underlip. Mann-Whitney U test for comparing two independent samplesand partial correlation analysis. Results: There was no difference in tactile threshold of underlip between the experimental group and the control group(0.020[0.008,0.020] g/mm(2) vs. [0.020(0.008,0.020] g/mm(2), Z=293.0, P=0.221); the tactile sense of the experimental group was larger than that of the control group in thehardpalate(0.040[0.140,0.055] g/mm(2) vs. 0.138[0.064,0.400] g/mm(2), Z=4.5, P=0.000), soft palate(0.400[0.280,0.400] g/mm(2) vs. 1.400[1.000,4.000] g/mm(2), Z=0, P=0.000) and SPST(0.355[0.125,0.373] g/mm(2) vs. 1.285[0.896,3.025] g/mm(2), Z=0, P=0.000). The SPST was positive correlation with apnea hypopneaindex(AHI)(r=0.835, P=0.000) and negative correlation with the nadir oxyhemoglobin saturation (r=-0.636, P=0.000). Conclusion: The greater the standardized palatal sensory threshold, the worse the condition of OSAHS, the lower, the lowest blood oxygen at night, and the impaired upper airway sensory function plays an important role in the pathogenesis of OSAHS.


Assuntos
Obstrução das Vias Respiratórias/fisiopatologia , Hipóxia/fisiopatologia , Palato Duro/fisiopatologia , Limiar Sensorial , Apneia Obstrutiva do Sono/fisiopatologia , Úvula/fisiopatologia , Obstrução das Vias Respiratórias/complicações , Humanos , Apneia Obstrutiva do Sono/etiologia , Tato , Percepção do Tato
13.
Life Sci ; 237: 116952, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622608

RESUMO

Cancer stem cells (CSC) constitute a small area of the tumor mass and are characterized by self-renewal, differentiation and the ability to promote the development of secondary chemo-resistant tumors. Self-renewal of CSCs is regulated through various signaling pathways including Hedgehog, Notch, and Wnt/ß-catenin pathways. A few surface markers have been identified, which provide a means of targeting CSCs according to tumor type. Depending on the proximity of CSCs to the tumor hypoxic niche, hypoxia-inducible factors (HIFs) can play a critical role in modulating several CSC-related characteristics. For instance, the upregulation of HIF-1 and HIF-2 at tumor sites, which correlates with the expansion of CSCs and poor cancer prognosis, has been demonstrated. In this review, we will discuss the mechanisms by which hypoxia enhances the development of CSCs in the tumor microenvironment. Targeting HIFs in combination with other common therapeutics is pre-requisite for effective eradication of CSCs.


Assuntos
Antineoplásicos/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Hipóxia/fisiopatologia , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Animais , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
14.
Analyst ; 144(22): 6609-6616, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31616873

RESUMO

Maintaining the redox balance of biological systems is a key point to maintain a healthy physiological environment. Excessive iron ions (Fe3+) can cause apoptosis, tissue damage and death. Fortunately, ascorbic acid (AA) as a reducing agent has been evaluated for the reduction of Fe3+. Moreover, AA plays an important role in relieving hypoxia-induced oxidative stress. Therefore, the real-time imaging of the Fe3+ and AA fluctuations is important for understanding their biofunctions in cells and in vivo. In this work, we developed a fluorescent nanoprobe carbon dot-desferrioxamine B (CD-DB) by the conjugate connection of CDs and desferrioxamine B (a complexing agent for Fe3+) for the associated detection of Fe3+ and AA. CD-DB exhibited excellent sensitivity and selectivity for the detection of Fe3+ and AA. The nanoprobe CDs-DB@Fe obtained by the reaction of CD-DB and Fe3+ was suitable for tracing the dynamic changes of AA in cells and in vivo. Therefore, CDs-DB@Fe was used for monitoring the fluctuation of AA in hypoxic cell models, hypoxic zebrafish models and liver ischemia mice models. These results exhibited the decrease in AA under hypoxic conditions because AA was consumed to neutralize free radicals and relieve hypoxia-induced oxidative stress damage. The ideal biocompatibility and low toxicity make our nanoprobe a potential candidate for the research of the physiological effects of AA in vivo.


Assuntos
Ácido Ascórbico/análise , Corantes Fluorescentes/química , Hipóxia/metabolismo , Ferro/análise , Pontos Quânticos/química , Animais , Carbono/química , Hipóxia Celular , Desferroxamina/química , Corantes Fluorescentes/síntese química , Células Hep G2 , Humanos , Isquemia/metabolismo , Limite de Detecção , Fígado/irrigação sanguínea , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Estresse Oxidativo , Peixe-Zebra
15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(8): 721-726, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31638570

RESUMO

Objective To study the effects of compound porcine cerebroside and ganglioside injection (CPCGI) on brain injury and expression of cerebellin 4 (CBLN4) in neonatal mice after intrauterine hypoxia. Methods A total of 15 healthy adult pregnant mice were randomly divided into 3 groups: control group with 3 mice, model group and CPCGI treatment group with 6 mice in each group. From the 14th day of pregnancy, the pregnant mice in the CPCGI treatment group and model group were put into the animal hypoxia box to produce the intrauterine hypoxia fetal mouse models. After the delivery of mother, the neonatal mice in the CPCGI treatment group and model group were given CPCGI (1 mL/kg) and PBS via abdominal cavity, respectively, while the control group received no treatment. At 40 days postpartum, the memory ability of mice was trained with a platform jumper test. After the platform test, the brain tissue of the mice was taken out. The expression of neurogenolase (NSE), interleukin-1 beta (IL-1ß), CBLN4 and synaptophsin (SYN) were detected by immunofluorescence staining. The relative expression of CBLN4 protein in the hippocampus of mice was detected by Western blot analysis. Results Compared with the control group, hypoxia caused a significant decrease in learning and memory ability of newborn mice, and CPCGI could significantly improve the memory of mice. After hypoxia, the expression of NSE, CBLN4 and SYN in the neonatal cerebellum significantly decreased, and the expression of IL-1ß significantly increased. The expression of NSE, CBLN4 and SYN in CPCGI treatment group was significantly higher than those in the model group, and the expression of IL-1ß was significantly lower than that in the model group. Conclusion CPCGI can reduce neuronal damage in neonatal mice after hypoxia, which may be related to the reduction of IL-1ß expression and the promotion of synaptic reconstruction.


Assuntos
Lesões Encefálicas , Cerebrosídeos , Gangliosídeos , Regulação da Expressão Gênica , Hipóxia , Animais , Animais Recém-Nascidos , Lesões Encefálicas/tratamento farmacológico , Cerebrosídeos/farmacologia , Cerebrosídeos/uso terapêutico , Feminino , Gangliosídeos/farmacologia , Gangliosídeos/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Hipóxia/genética , Camundongos , Gravidez , Suínos
16.
BMC Bioinformatics ; 20(1): 507, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638911

RESUMO

BACKGROUND: Human tumor is a complex tissue with multiple heterogeneous hypoxic regions and significant cell-to-cell variability. Due to the complexity of the disease, the explanation of why anticancer therapies fail cannot be attributed to intrinsic or acquired drug resistance alone. Furthermore, there are inconsistent reports of hypoxia-induced kinase activities in different cancer cell-lines, where increase, decreases, or no change has been observed. Thus, we asked, why are there widely contrasting results in kinase activity under hypoxia in different cancer cell-lines and how does hypoxia play a role in anti-cancer drug sensitivity? RESULTS: We took a modeling approach to address these questions by analyzing the model simulation to explain why hypoxia driven signals can have dissimilar impact on tumor growth and alter the efficacy of anti-cancer drugs. Repeated simulations with varying concentrations of biomolecules followed by decision tree analysis reveal that the highly differential effects among heterogeneous subpopulation of tumor cells could be governed by varying concentrations of just a few key biomolecules. These biomolecules include activated serine/threonine-specific protein kinases (pRAF), mitogen-activated protein kinase kinase (pMEK), protein kinase B (pAkt), or phosphoinositide-4,5-bisphosphate 3-kinase (pPI3K). Additionally, the ratio of activated extracellular signal-regulated kinases (pERK) or pAkt to its respective total was a key factor in determining the sensitivity of pERK or pAkt to hypoxia. CONCLUSION: This work offers a mechanistic insight into how hypoxia can affect the efficacy of anti-cancer drug that targets tumor signaling and provides a framework to identify the types of tumor cells that are either sensitive or resistant to anti-cancer therapy.


Assuntos
Hipóxia/patologia , Neoplasias/patologia , Transdução de Sinais , Linhagem Celular Tumoral , Humanos , Sistema de Sinalização das MAP Quinases , Modelos Teóricos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinases raf/metabolismo
17.
Cell Physiol Biochem ; 53: 794-804, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31661199

RESUMO

BACKGROUND/AIMS: Red blood cell (RBC) death could contribute to anemia in chronic kidney disease (CKD) patients. Recent observational research has suggested a relationship between RBC death (eryptosis) and hypoxemia in hemodialysis patients. Thus, we studied the isolated and joint effects of a uremic toxin (indoxyl sulfate; IS) and hypoxia on RBC biology. METHODS: We incubated RBC from healthy donors with IS at concentrations of 0.01mM, 0.09mM and 0.17mM under both normoxic (21% O2) and hypoxic (5% O2) conditions for 24 hours. Eryptosis was evaluated by RBC phosphatidylserine (PS) exposure, cell volume, and cytosolic calcium which were quantified by Annexin-V+, forward scatter, and Fluo-3AM+ binding, respectively. RBC redox balance was reported by reactive oxygen species (ROS) production and intracellular reduced glutathione (GSH). Analyses were performed by flow cytometry. RESULTS: Hypoxia induced a 2-fold ROS production compared to normoxia. PS exposure and cytosolic calcium increased, while cell volume decreased by hypoxia and likewise by IS. IS increased ROS production in a dose-dependent manner under conditions of both normoxia and hypoxia. The same conditions promoted a GSH decrease with IS intensifying the hypoxia-induced effects. CONCLUSION: In summary, our results indicate that the concurrent presence of hypoxia and uremia augments RBC death and may therefore, contribute to the genesis of anemia in CKD.


Assuntos
Eriptose/efeitos dos fármacos , Eritrócitos/química , Indicã/toxicidade , Adulto , Cálcio/metabolismo , Citosol/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Glutationa , Humanos , Hipóxia , Masculino , Oxirredução , Fosfatidilserinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Uremia/patologia , Adulto Jovem
19.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(10): 755-759, 2019 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-31594109

RESUMO

Objective: To analyze the clinical characteristics of pulmonary embolism patients from different altitudes in plateau areas. Methods: A retrospective cross-sectional study was used to analyze the patients with acute pulmonary embolism diagnosed definitely by pulmonary angiography or pulmonary artery CT angiography admitted to Tibet Autonomous Region People's Hospital from August 2014 to December 2018. The subjects were divided into 3 groups according to the altitude of long-term residence before onset, i.e. low-altitude group (group 1, 2 700 m ≤ altitude ≤3 700 m, n=44), medium-altitude group (group 2, 3 700 m

Assuntos
Altitude , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Dor no Peito/epidemiologia , China/epidemiologia , Angiografia por Tomografia Computadorizada , Estudos Transversais , Dispneia/epidemiologia , Humanos , Hipóxia , Incidência , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos
20.
Nature ; 574(7779): 575-580, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31645732

RESUMO

The Warburg effect, which originally described increased production of lactate in cancer, is associated with diverse cellular processes such as angiogenesis, hypoxia, polarization of macrophages and activation of T cells. This phenomenon is intimately linked to several diseases including neoplasia, sepsis and autoimmune diseases1,2. Lactate, which is converted from pyruvate in tumour cells, is widely known as an energy source and metabolic by-product. However, its non-metabolic functions in physiology and disease remain unknown. Here we show that lactate-derived lactylation of histone lysine residues serves as an epigenetic modification that directly stimulates gene transcription from chromatin. We identify 28 lactylation sites on core histones in human and mouse cells. Hypoxia and bacterial challenges induce the production of lactate by glycolysis, and this acts as a precursor that stimulates histone lactylation. Using M1 macrophages that have been exposed to bacteria as a model system, we show that histone lactylation has different temporal dynamics from acetylation. In the late phase of M1 macrophage polarization, increased histone lactylation induces homeostatic genes that are involved in wound healing, including Arg1. Collectively, our results suggest that an endogenous 'lactate clock' in bacterially challenged M1 macrophages turns on gene expression to promote homeostasis. Histone lactylation thus represents an opportunity to improve our understanding of the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer.


Assuntos
Epigênese Genética , Glicólise/genética , Histonas/química , Histonas/metabolismo , Ácido Láctico/metabolismo , Acetilação , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , Homeostase , Humanos , Hipóxia/metabolismo , Lisina/química , Lisina/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Transcrição Genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA