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1.
PLoS Biol ; 21(12): e3002429, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38079456

RESUMEN

Motile bacteria navigate toward favorable conditions and away from unfavorable environments using chemotaxis. Mechanisms of sensing attractants are well understood; however, molecular aspects of how bacteria sense repellents have not been established. Here, we identified malate as a repellent recognized by the MCP2201 chemoreceptor in a bacterium Comamonas testosteroni and showed that it binds to the same site as an attractant citrate. Binding determinants for a repellent and an attractant had only minor differences, and a single amino acid substitution in the binding site inverted the response to malate from a repellent to an attractant. We found that malate and citrate affect the oligomerization state of the ligand-binding domain in opposing way. We also observed opposing effects of repellent and attractant binding on the orientation of an alpha helix connecting the sensory domain to the transmembrane helix. We propose a model to illustrate how positive and negative signals might be generated.


Asunto(s)
Proteínas Bacterianas , Malatos , Proteínas Quimiotácticas Aceptoras de Metilo/química , Proteínas Bacterianas/metabolismo , Ligandos , Escherichia coli/metabolismo , Quimiotaxis/fisiología , Bacterias/metabolismo , Citratos
2.
Immun Ageing ; 20(1): 44, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37649035

RESUMEN

BACKGROUND: Fasting is known to influence the immune functions of leukocytes primarily by regulating their mobilization and redistribution between the bone marrow and the peripheral tissues or circulation, in particular via relocalization of leukocytes back in the bone marrow. However, how the immune system responds to the increased risk of invasion by infectious pathogens with fewer leukocytes in the peripheral blood during fasting intervention remains an open question. RESULTS: We used proteomic, biochemical and flow cytometric tools to evaluate the impact of short-term intensive fasting (STIF), known as beego, on red blood cells by profiling the cells from the STIF subjects before and after 6 days of fasting and 6 days of gradual refeeding. We found that STIF, by triggering the activation of the complement system via the complement receptor on the membrane of red blood cells, boosts fairly sustainable function of red blood cells in immune responses in close relation to various pathogens, including viruses, bacteria and parasites, particularly with the pronounced capacity to defend against SARS-CoV-2, without compromising their oxygen delivery capacity and viability. CONCLUSION: STIF fosters the immune function of red blood cells and therefore, it may be considered as a nonmedical intervention option for the stronger capacity of red blood cells to combat infectious diseases.

3.
Geriatr Nurs ; 49: 199-206, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36577289

RESUMEN

OBJECTIVES: This study aimed to develop transcutaneous electrical acupoint stimulation combined with an integrated perioperative nursing program and evaluate its effects on preventing subsyndromal delirium (SSD) and postoperative delirium (POD) in older patients after joint replacement surgery. METHODS: Participants were randomly divided into two groups, the experimental group (n = 48) was given transcutaneous electrical acupoint stimulation combined with an integrated perioperative nursing program based on the routine care of the control group (n = 49). The incidence of SSD and POD in a week after surgery was recorded. Assessments of delirium severity, cognition, anxiety, and depression were also conducted at baseline and on postoperative day 7. RESULTS: The findings indicate that the intervention program had significant advances in alleviating the severity of delirium, cognitive impairment, anxiety, and depression but failed to reduce the incidence of SSD and POD. CONCLUSIONS: Our study indicated that TEAS combined with an integrated perioperative nursing program has a beneficial effect on alleviating symptoms of delirium, cognitive dysfunction, anxiety, and depression in older adults after joint replacement surgery.


Asunto(s)
Artroplastia de Reemplazo , Delirio , Humanos , Anciano , Puntos de Acupuntura , Enfermería Perioperatoria , Delirio/prevención & control
4.
Biochem Biophys Res Commun ; 589: 229-233, 2022 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-34929446

RESUMEN

The SMC (structural maintenance of chromosomes) proteins are known to be involved in chromosome pairing or aggregation and play an important role in cell cycle and division. Different from SMC-ScpAB complex maintaining chromosome structure in most bacteria, the MukB-MukE-MukF complex is responsible for chromosome condensation in E. coli and some γ-proteobacter. Though different models were proposed to illustrate the mechanism of how the MukBEF complex worked, the assembly of the MukBEF complex is a key. The MukE dimer interacted with the middle region of one MukF molecule, and was clamped by the N- and C-terminal domain of the latter, and then was involved in the interaction with the head domain of MukB. To reveal the structural basis of MukE involved in the dynamic equilibrium of potential different MukBEF assemblies, we determined the MukE structure at 2.44 Å resolution. We found that the binding cavity for the α10, ß4 and ß5 of MukF (residues 296-327) in the MukE dimer has been occupied by the α9 and ß7 strand of MukE. We proposed that the highly dynamic C-terminal region (173-225) was important for the MukE-F assembly and then involved in the MukBEF complex formation.


Asunto(s)
Cromosomas Bacterianos/metabolismo , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Proteínas Represoras/química , Secuencia de Aminoácidos , Cristalografía por Rayos X , Proteínas de Escherichia coli/metabolismo , Modelos Moleculares , Multimerización de Proteína , Estructura Secundaria de Proteína , Homología Estructural de Proteína
5.
Small ; 14(11): e1703001, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29280289

RESUMEN

Next-generation rechargeable batteries that offer high energy density, efficiency, and reversibility rely on cell configurations that enable synergistic operations of individual components. They must also address multiple emerging challenges,which include electrochemical stability, transport efficiency, safety, and active material loss. The perspective of this Review is that rational design of the polymeric separator, which is used widely in rechargeable batteries, provides a rich set of opportunities for new innovations that should enable batteries to meet many of these needs. This perspective is different from the conventional view of the polymer separator as an inert/passive unit in a battery, which has the sole function to prevent direct contact between electrically conductivecomponents that form the battery anode and cathode. Polymer separators, which serve as the core component in a battery, bridge the electrodes and the electrolyte with a large surface contact that can be utilized to apply desirable functions. This Review focuses specifically on recent advances in polymer separator systems, with a detailed analysis of several embedded functional agents that are incorporated to improve mechanical robustness, regulate ion and mass transport, and retard flammability. The discussion is also extended to new composite separator concepts that are designated traditionally as polymer/gel electrolytes.

6.
Plants (Basel) ; 13(6)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38592865

RESUMEN

The rapid growth of industrialization and urbanization in China has led to an increase in soil heavy metal pollution, which poses a serious threat to ecosystem safety and human health. The advancement of spectral technology offers a way to rapidly and non-destructively monitor soil heavy metal content. In order to explore the potential of rice leaf spectra to indirectly estimate soil heavy metal content. We collected farmland soil samples and measured rice leaf spectra in Xushe Town, Yixing City, Jiangsu Province, China. In the laboratory, the heavy metals Cd and As were determined. In order to establish an estimation model between the pre-processed spectra and the soil heavy metals Cd and As content, a genetic algorithm (GA) was used to optimise the partial least squares regression (PLSR). The model's accuracy was evaluated and the best estimation model was obtained. The results showed that spectral pre-processing techniques can extract hidden information from the spectra. The first-order derivative of absorbance was more effective in extracting spectral sensitive information from rice leaf spectra. The GA-PLSR model selects only about 10% of the bands and has better accuracy in spectral modeling than the PLSR model. The spectral reflectance of rice leaves has the capacity to estimate Cd content in the soil (relative percent difference [RPD] = 2.09) and a good capacity to estimate As content in the soil (RPD = 2.97). Therefore, the content of the heavy metals Cd and As in the soil can be estimated indirectly from the spectral data of rice leaves. This study provides a reference for future remote sensing monitoring of soil heavy metal pollution in farmland that is quantitative, dynamic, and non-destructive over a large area.

7.
ACS Appl Mater Interfaces ; 16(6): 7950-7960, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38306456

RESUMEN

Polysaccharide-based adhesives, especially chitosan (CS)-derived adhesives, serve as promising sustainable alternatives to traditional adhesives. However, most demonstrate a poor adhesive strength. Inspired by the inherent layered structure of marine arthropods (lobsters), a core-shell structure (SiO2-NH2@OPG) with amine-functionalized silica (SiO2-NH2) as the core and oxidized pyrogallol (OPG) as the shell is prepared in this study. The compound is blended with CS to produce a structural biomimetic wood adhesive (SiO2-NH2@OPG/CS) with excellent performance. In addition to thermocompressive curing, this adhesive exhibits a water-evaporation-induced curing behavior at room temperature. With reference to the design mechanism of the lobster cuticle, this microphase-separated structure consists of clustered nanofibers with varying amounts of SiO2-NH2@OPG particles between the fibers. This intriguing microphase structure and its mechanical effects could offer a powerful solution for improving the functional modification of wood composites.


Asunto(s)
Quitosano , Quitosano/química , Adhesivos/química , Biomimética , Dióxido de Silicio
8.
Clin Nutr ; 43(2): 453-467, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38181523

RESUMEN

BACKGROUND & AIMS: Short-term intensive fasting (STIF), known as beego in Chinese phonetic articulation, has been practiced for more than two thousand years. However, the potential risk of STIF and the body's response to the risk have not been adequately evaluated. This study aims to address this issue, focusing on the STIF-triggered metabolic response of the liver and kidney. METHODS: The STIF procedure in the clinical trial includes a 7-day water-only intensive fasting phase and a 7-day gradual refeeding phase followed by a regular diet. The intensive fasting in humans was assisted with psychological induction. To gain insights not available in the clinical trial, we designed a STIF program for mice that resulted in similar phenotypes seen in humans. Plasma metabolic profiling and examination of gene expression as well as liver and kidney function were performed by omics, molecular, biochemical and flow cytometric analyses. A human cell line model was also used for mechanistic study. RESULTS: Clinically significant metabolites of fat and protein were found to accumulate during the fasting phase, but they were relieved after gradual refeeding. Metabolomics profiling revealed a universal pattern in the consumption of metabolic intermediates, in which pyruvate and succinate are the two key metabolites during STIF. In the STIF mouse model, the accumulation of metabolites was mostly counteracted by the upregulation of catabolic enzymes in the liver, which was validated in a human cell model. Kidney filtration function was partially affected by STIF but could be recovered by refeeding. STIF also reduced oxidative and inflammatory levels in the liver and kidney. Moreover, STIF improved lipid metabolism in mice with fatty liver without causing accumulation of metabolites after STIF. CONCLUSIONS: The accumulation of metabolites induced by STIF can be relieved by spontaneous upregulation of catabolic enzymes, suggesting an adaptive and protective metabolic response to STIF stress in the mammalian body.


Asunto(s)
Dieta , Ayuno , Ratones , Humanos , Animales , Hígado/metabolismo , Metabolismo de los Lípidos , Mamíferos
9.
Clin Interv Aging ; 18: 1675-1685, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37810954

RESUMEN

Background: Delirium is common in older patients during the postoperative period, increasing the number of adverse events, and grip strength is associated with delirium. Subsyndromal delirium (SSD) is a prostate of clinical delirium; nevertheless, the relationship between grip strength and SSD has not been elucidated. This study aimed to examine the association between grip strength and SSD in the elderly after arthroplasty. Methods: A total of 181 patients were recruited from two Chinese hospitals. SSD and delirium were evaluated before the surgery and the first week after surgery using the confusion assessment method. The Mini-mental State Examination was used to assess patients' cognitive function, and their grip strength was evaluated with an electronic hand dynamometer before surgery. Logistic regression and ROC curve analysis were conducted to determine the odds ratio and predictive value of grip strength for SSD. Results: The incidence of SSD and postoperative delirium (POD) was 41.44% and 14.36% for the elderly following arthroplasty respectively, and approximately 1/3 of SSD progressed into POD. Older age, declined cognitive function, fall history, and lower grip strength were risk factors for SSD (P<0.05). The area under the ROC curve of grip strength was 0.863 and 0.900 for males and females respectively, and the cut-off point of it was determined to be 22.050 kg for men and 18.050 kg for women. Conclusion: SSD and POD are common among older people. Decreased grip strength, advanced age, lower cognitive function, and fall history were independent risk factors for SSD, and grip strength was a significant predictor for SSD in aged patients after the arthroplasty.


Asunto(s)
Artroplastia de Reemplazo , Delirio , Delirio del Despertar , Fuerza de la Mano , Anciano , Femenino , Humanos , Masculino , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de Riesgo
10.
ACS Nano ; 17(19): 19087-19097, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37726178

RESUMEN

Uneven zinc (Zn) deposition typically leads to uncontrollable dendrite growth, which renders an unsatisfactory cycling stability and Coulombic efficiency (CE) of aqueous zinc ion batteries (ZIBs), restricting their practical application. In this work, a lightweight and flexible three-dimensional (3D) carbon nanofiber architecture with uniform Zn seeds (CNF-Zn) is prepared from bacterial cellulose (BC), a kind of biomass with low cost, environmental friendliness, and abundance, as a host for highly reversible Zn plating/stripping and construction of high-performance aqueous ZIBs. The as-prepared 3D CNF-Zn with a porous interconnected network significantly decreases the local current density, and the functional Zn seeds provide uniform nuclei to guide the uniform Zn deposition. Benefiting from the synergistic effect of Zn seeds and the 3D porous framework in the flexible CNF-Zn host, the electrochemical performance of the as-constructed ZIBs is significantly improved. This flexible 3D CNF-Zn host delivers a high and stable CE of 99.5% over 450 cycles, ensuring outstanding rate performance and a long cycle life of over 500 cycles at 4 A g-1 in the CNF-Zn@Zn//NaV3O8·1.5H2O full battery. More importantly, owing to the flexibility of the 3D CNF-Zn host, the as-assembled pouch cell shows outstanding mechanical flexibility and excellent energy storage performance. This strategy of producing readily accessible carbon from biomass can be employed to develop advanced functional nanomaterials for next-generation flexible energy storage devices.

11.
Aging Cell ; 22(8): e13889, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37226323

RESUMEN

The bone marrow niche maintains hematopoietic stem cell (HSC) homeostasis and declines in function in the physiologically aging population and in patients with hematological malignancies. A fundamental question is now whether and how HSCs are able to renew or repair their niche. Here, we show that disabling HSCs based on disrupting autophagy accelerated niche aging in mice, whereas transplantation of young, but not aged or impaired, donor HSCs normalized niche cell populations and restored niche factors in host mice carrying an artificially harassed niche and in physiologically aged host mice, as well as in leukemia patients. Mechanistically, HSCs, identified using a donor lineage fluorescence-tracing system, transdifferentiate in an autophagy-dependent manner into functional niche cells in the host that include mesenchymal stromal cells and endothelial cells, previously regarded as "nonhematopoietic" sources. Our findings thus identify young donor HSCs as a primary parental source of the niche, thereby suggesting a clinical solution to revitalizing aged or damaged bone marrow hematopoietic niche.


Asunto(s)
Médula Ósea , Células Madre Mesenquimatosas , Ratones , Animales , Células Endoteliales , Nicho de Células Madre/fisiología , Células Madre Hematopoyéticas , Células de la Médula Ósea , Hematopoyesis/fisiología
12.
World Neurosurg ; 166: 212-219, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35398326

RESUMEN

BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) is a syndrome of excessive sympathetic activity, mainly occurring in severe traumatic brain injury. However, few studies have reported the frequency of PSH and its related risk factors in adult patients with brain injury. METHODS: We performed this systematic review and meta-analysis to estimate the combined incidence of PSH and the associated risk factors in adult patients with brain injury. This study was registered with the PROSPERO international prospective register of systematic reviews (https://www.crd.york. ac.uk/PROSPERO/Identifier: CRD 42021260493), and a systematic search was conducted of the scientific databases Embase, PubMed, Web of Science, Cochrane Library, and Google Scholar. All identified observational studies regarding the incidence and risk factors of PSH in adult patients with brain injury were included. Two authors extracted data independently; data were analyzed by STATA version 16. RESULTS: The search yielded 9 studies involving 1643 adult patients. PSH was detected in 438 patients. The combined incidence of PSH in adult patients with brain injury was 27.4% (95% confidence interval [CI], 0.190-0.358). The risk factors include patients' age (SMD = -0.592; I2 = 77.5%; 95% CI, -1.027 to -0.156; P = 0.008), traffic accident (odds ratio [OR], 1.783; I2 =18.0%; 95% CI, 1.128-2.820; P = 0.013), admission Glasgow Coma Scale score (SMD = -1.097; I2 =28.3%; 95% CI, -1.500 to -0.693; P = 0.000), hydrocephalus (OR, 3.936; I2 =67.9%; 95% CI, 1.144-13.540; P = 0.030), and diffuse axonal injury (OR, 4.747; I2 =71.1%; 95% CI, 1.221-18.463; P = 0.025) and were significantly associated with the presence of PSH after brain injury. CONCLUSIONS: PSH occurs in nearly a quarter of adult patients with brain injury. Patient's age, traffic accident, admission Glasgow Coma Scale score, hydrocephalus, and diffuse axonal injury were risk factors for PSH in adult patients with brain injury. These findings may contribute to novel strategies for early diagnosis and interventions that aid in the rehabilitation of patients with brain injury.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Lesiones Encefálicas , Lesión Axonal Difusa , Hidrocefalia , Adulto , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades del Sistema Nervioso Autónomo/etiología , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/diagnóstico , Escala de Coma de Glasgow , Humanos , Hidrocefalia/complicaciones
13.
Artículo en Inglés | MEDLINE | ID: mdl-36361176

RESUMEN

Microseismic monitoring systems have been widely installed to monitor potential water hazards in limestone of the coal floor. The temporal and spatial distribution of rock fracture-induced microseismic events can be used as early warning indicators of potential water inrush from the coal floor. We established a microseismic monitoring system in the working face of Wangjialing coal mine. Besides traditional fluid-independent rock fracture-induced microseismic waveforms, fluid-dependent hybrid-frequency microseismic waveforms also play important roles in determining the microseismic precursors of water inrush. Hybrid-frequency microseismic waveforms have a sharp P wave and no obvious S wave phase. We infer that the first high-frequency signal is caused by the brittleness of the rock in the floor under the influence of the water pressure. The second low-frequency signal is caused by the water oscillations in the fractures. These hybrid-frequency waveforms represent the development of fracturing. In addition, the lifting height of the complete aquiclude above the confined water is very limited, and the water inrush from the floor is often closely related to these hidden faults. Therefore, the activation signal of hidden faults in the working face of coal mining can be monitored to effectively warn about the water inrush from the coal seam floor caused by faults. By analyzing different microseismic events, the monitoring and early warning of water disaster in the coal mine floor can be improved. This will help in taking measures in advance within the mine to ensure personnel safety and to reduce property losses.

14.
Aging Cell ; 20(11): e13507, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34705313

RESUMEN

Previous studies have shown that long-term light or moderate fasting such as intermittent fasting can improve health and prolong lifespan. However, in humans short-term intensive fasting, a complete water-only fasting has little been studied. Here, we used multi-omics tools to evaluate the impact of short-term intensive fasting on immune function by comparison of the CD45+ leukocytes from the fasting subjects before and after 72-h fasting. Transcriptomic and proteomic profiling of CD45+ leukocytes revealed extensive expression changes, marked by higher gene upregulation than downregulation after fasting. Functional enrichment of differentially expressed genes and proteins exposed several pathways critical to metabolic and immune cell functions. Specifically, short-term intensive fasting enhanced autophagy levels through upregulation of key members involved in the upstream signals and within the autophagy machinery, whereas apoptosis was reduced by down-turning of apoptotic gene expression, thereby increasing the leukocyte viability. When focusing on specific leukocyte populations, peripheral neutrophils are noticeably increased by short-term intensive fasting. Finally, proteomic analysis of leukocytes showed that short-term intensive fasting not only increased neutrophil degranulation, but also increased cytokine secretion. Our results suggest that short-term intensive fasting boost immune function, in particular innate immune function, at least in part by remodeling leukocytes expression profile.


Asunto(s)
Ayuno/sangre , Inmunidad Innata , Neutrófilos/inmunología , Proteoma/inmunología , Transcriptoma/inmunología , Adolescente , Adulto , Anciano , Apoptosis/genética , Apoptosis/inmunología , Autofagia/genética , Autofagia/inmunología , Citocinas/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Antígenos Comunes de Leucocito/metabolismo , Masculino , Persona de Mediana Edad , Proteómica/métodos , Regulación hacia Arriba/genética , Regulación hacia Arriba/inmunología , Adulto Joven
15.
BMJ Nutr Prev Health ; 4(1): 4-17, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34308107

RESUMEN

Beego is a traditional Chinese complete water-only fasting practice initially developed for spiritual purposes, later extending to physical fitness purposes. Beego notably includes a psychological induction component that includes meditation and abdominal breathing, light body exercise and ends with a specific gradual refeeding program before returning to a normal diet. Beego has regained its popularity in recent decades in China as a strategy for helping people in subhealthy conditions or with metabolic syndrome, but we are unaware of any studies examining the biological effects of this practice. To address this, we here performed a longitudinal study of beego comprising fasting (7 and 14 day cohorts) and a 7-day programmed refeeding phase. In addition to detecting improvements in cardiovascular physiology and selective reduction of blood pressure in hypertensive subjects, we observed that beego decreased blood triacylglycerol (TG) selectively in TG-high subjects and increased cholesterol in all subjects during fasting; however, the cholesterol levels were normalised after completion of the refeeding program. Strikingly, beego reduced platelet formation, activation, aggregation and degranulation, resulting in an alleviated thrombosis risk, yet maintained haemostasis by sustaining levels of coagulation factors and other haemostatic proteins. Mechanistically, we speculate that downregulation of G6B and MYL9 may influence the observed beego-mediated reduction in platelets. Fundamentally, our study supports that supervised beego reduces thrombosis risk without compromising haemostasis capacity. Moreover, our results support that beego under medical supervision can be implemented as non-invasive intervention for reducing thrombosis risk, and suggest several lines of intriguing inquiry for future studies about this fasting practice (http://www.chictr.org.cn/index.aspx, number, ChiCTR1900027451).

16.
Mol Biol Rep ; 37(6): 2621-8, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19757184

RESUMEN

A Bombyx mori (B. mori) cDNA was isolated from silkworm pupae cDNA library encoding a homologue of translationally controlled tumor protein (BmTCTPk). BmTCTPk was expressed in E. coli; SDS-PAGE and Western blot showed the molecular weight of recombinant and native BmTCTPk is approximately 28 and 25 kDa, respectively; they are larger than the theoretical molecular weight. Immunohistochemical studies showed that BmTCTPk is uniformly distributed throughout the cytoplasm of BmN cells. In silkworm pupae, BmTCTPk is expressed in the midgut wall, the midgut cavity, and some fat body tissues lying between the midgut wall and body wall. Western blot and ELISAs performed on total protein extracts isolated from silkworm pupae at different development stages showed that, although BmTCTPk is expressed during all pupae stages, its expression level increases dramatically during late pupae stages, suggesting that BmTCTPk may play an important role during the developmental transition from pupa to imago.


Asunto(s)
Bombyx/enzimología , Bombyx/genética , Proteínas de Insectos/metabolismo , Proteínas de Neoplasias/genética , Biosíntesis de Proteínas/genética , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Secuencia de Bases , Western Blotting , Clonación Molecular , Biología Computacional , ADN Complementario/genética , Femenino , Genoma de los Insectos/genética , Sueros Inmunes , Inmunohistoquímica , Proteínas de Insectos/química , Proteínas de Insectos/genética , Masculino , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Especificidad de Órganos , Células Procariotas/metabolismo , Transporte de Proteínas , Pupa/enzimología , Pupa/genética , Proteínas Recombinantes/metabolismo , Fracciones Subcelulares/metabolismo
17.
Aging Cell ; 19(10): e13232, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32951306

RESUMEN

Autophagy suppresses mitochondrial metabolism to preserve hematopoietic stem cells (HSCs) in mice. However, the mechanism by which autophagy regulates hematopoietic aging, in particular in humans, has largely been unexplored. Here, we demonstrate that reduction of autophagy in both hematopoietic cells and their stem cells is associated with aged hematopoiesis in human population. Mechanistically, autophagy delays hematopoietic aging by activating the downstream expression of Sirt3, a key mitochondrial protein capable of rejuvenating blood. Sirt3 is the most abundant Sirtuin family member in HSC-enriched population, though it declines as the capacity for autophagy deteriorates with aging. Activation of autophagy upregulates Sirt3 in wild-type mice, whereas in autophagy-defective mice, Sirt3 expression is crippled in the entire hematopoietic hierarchy, but forced expression of Sirt3 in HSC-enriched cells reduces oxidative stress and prevents accelerated hematopoietic aging from autophagy defect. Importantly, the upregulation of Sirt3 by manipulation of autophagy is validated in human HSC-enriched cells. Thus, our results identify an autophagy-Sirt3 axis in regulating hematopoietic aging and suggest a possible interventional solution to human blood rejuvenation via activation of the axis.


Asunto(s)
Células Madre Hematopoyéticas/metabolismo , Sirtuina 3/sangre , Envejecimiento/sangre , Animales , Autofagia/fisiología , Células Madre Hematopoyéticas/citología , Humanos , Ratones
18.
Aging (Albany NY) ; 12(24): 25673-25683, 2020 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-33232280

RESUMEN

Atg7, a critical component of autophagy machinery, is essential for counteracting hematopoietic aging. However, the non-autophagic role of Atg7 on hematopoietic cells remains fundamentally unclear. In this study, we found that loss of Atg7, but not Atg5, another autophagy-essential gene, in the hematopoietic system reduces CD11b myeloid cellularity including CD11b+Ly6G+ and CD11b+Ly6G- populations in mouse bone marrow. Surprisingly, Atg7 deletion causes abnormally accumulated histone H3.1 to be overwhelmingly trapped in the cytoplasm in the CD11b+Ly6G-, but not the CD11b+Ly6G+ compartment. RNA profiling revealed extensively chaotic expression of the genes required in nucleosome assembly. Functional assays further indicated upregulated aging markers in the CD11b+Ly6G- population. Therefore, our study suggests that Atg7 is essential for maintaining proper nucleosome assembly and limiting aging in the bone marrow CD11b+Ly6G- population.


Asunto(s)
Antígenos Ly/metabolismo , Proteína 7 Relacionada con la Autofagia/genética , Antígeno CD11b/metabolismo , Células Mieloides/metabolismo , Nucleosomas/metabolismo , Animales , Proteína 7 Relacionada con la Autofagia/metabolismo , Células de la Médula Ósea/metabolismo , Ratones , Ratones Noqueados
19.
Aging Cell ; 19(5): e13114, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32212304

RESUMEN

Hematopoietic disorders are known to increase the risk of complications such as osteoporosis. However, a direct link between hematopoietic cellular disorders and osteoporosis has been elusive. Here, we demonstrate that the deterioration of hematopoietic autophagy is coupled with osteoporosis in humans. With a conditional mouse model in which autophagy in the hematopoietic system is disrupted by deletion of the Atg7 gene, we show that incapacitating hematopoietic autophagy causes bone loss and perturbs osteocyte homeostasis. Induction of osteoporosis, either by ovariectomy, which blocks estrogen secretion, or by injection of ferric ammonium citrate to induce iron overload, causes dysfunction in the hematopoietic stem and progenitor cells (HSPCs) similar to that found in autophagy-defective mice. Transcriptomic analysis of HSPCs suggests promotion of iron activity and inhibition of osteocyte differentiation and calcium metabolism by hematopoietic autophagy defect, while proteomic profiling of bone tissue proteins indicates disturbance of the extracellular matrix pathway that includes collagen family members. Finally, screening for expression of selected genes and an immunohistological assay identifies severe impairments in H vessels in the bone tissue, which results in disconnection of osteocytes from hematopoietic cells in the autophagy-defective mice. We therefore propose that hematopoietic autophagy is required for the integrity of H vessels that bridge blood and bone cells and that its deterioration leads to osteoporosis.


Asunto(s)
Autofagia , Células Madre Hematopoyéticas/metabolismo , Osteoporosis/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Persona de Mediana Edad , Proteómica
20.
Aging (Albany NY) ; 11(14): 4910-4922, 2019 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-31327762

RESUMEN

Autophagy has been well studied in regulating aging; however, the impact of autophagy in one organ on the aging of other organs has not been documented. In this study, we used a mouse model with deletion of an autophagy-essential gene Atg7 in hematopoietic system to evaluate the intrinsic role of hematopoietic autophagy on the aging of non-hematopoietic organs. We found that autophagy defect in hematopoietic system causes growth retardation and shortened lifespan, along with aging-like phenotypes including hypertrophic heart, lung and spleen, but atrophic thymus and reduced bone mineral density at organismal level. Hematopoietic autophagy defect also causes increased oxidative stress and mitochondrial mass or aging gene expression at cellular level in multiple non-hematopoietic organs. The organ aging in the Atg7-deleted mice was reversed by anatomic connection to wild-type mice with intact blood autophagy via parabiosis, but not by injection of blood cell-free plasma. Our finding thus highlights an essential role of hematopoietic autophagy for decelerating aging in non-hematopoietic organs.


Asunto(s)
Envejecimiento/patología , Proteína 7 Relacionada con la Autofagia/deficiencia , Autofagia/genética , Eliminación de Gen , Animales , Modelos Animales de Enfermedad , Sistema Hematopoyético/patología , Ratones , Ratones Noqueados , Mitocondrias , Estrés Oxidativo , Parabiosis
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