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1.
Dig Dis Sci ; 69(4): 1253-1262, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38361148

RESUMO

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse pregnancy outcomes; however, the underlying mechanisms are not fully understood. AIMS: This study aimed to determine the role of exosomal miR-6891-5p in placental trophoblast dysfunction in ICP and identify new biomarkers for ICP diagnosis. METHODS: Serum samples were collected from ICP patients and healthy pregnant women, and serum exosomes were extracted and identified. Fluorescent dye labeling of exosomes and cell-verified cell phagocytosis were performed. In vitro experiments were conducted by adding taurocholic acid to simulate the ICP environment. Cell proliferation and apoptosis levels were detected using flow cytometry and the cell counting kit-8 assay. Mimics were constructed to overexpress miR-6891-5p in cells, and the binding site between miR-6891-5p and YWHAE was verified using luciferase reporter genes. RESULTS: miR-6891-5p expression was significantly decreased in serum exosomes of ICP patients. Co-culturing with exosomes derived from ICP patients' serum (ICP-Exos) decreased HTR-8/SVeno cell proliferation and increased apoptosis levels. miR-6891-5p upregulation in HTR-8/SVeno cells significantly increased cell viability and reduced cell apoptosis levels, as determined by the cell counting kit-8 assay and flow cytometry. A double luciferase assay confirmed that miR-6891-5p affected the expression of the downstream YWHAE protein. CONCLUSIONS: This study indicates that serum exosomes from ICP patients can impact the apoptosis of placental trophoblast HTR-8/SVeno cells through the miR-6891-5P/YWHAE pathway and can serve as specific molecular markers for ICP diagnosis.


Assuntos
Colestase Intra-Hepática , Exossomos , MicroRNAs , Complicações na Gravidez , Feminino , Humanos , Gravidez , Proteínas 14-3-3/metabolismo , Apoptose , Proliferação de Células , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/metabolismo , Exossomos/genética , Luciferases/metabolismo , MicroRNAs/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Placenta/metabolismo , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo
2.
Front Public Health ; 10: 1016680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339131

RESUMO

Cognitive decline is a gradual neurodegenerative process that is affected by genetic and environmental factors. The doctor-patient relationship in the healthcare for cognitive decline is in a "shallow" medical world. With the development of data science, virtual reality, artificial intelligence, and digital twin, the introduction of the concept of the metaverse in medicine has brought alternative and complementary strategies in the intervention of cognitive decline. This article technically analyzes the application scenarios and paradigms of the metaverse in medicine in the field of mental health, such as hospital management, diagnosis, prediction, prevention, rehabilitation, progression delay, assisting life, companionship, and supervision. The metaverse in medicine has made primary progress in education, immersive consultation, dental disease, and Parkinson's disease, bringing revolutionary prospects for non-pharmacological complementary treatment of cognitive decline and other mental problems. In particular, with the demand for non-face-to-face communication generated by the global COVID-19 epidemic, the needs for uncontactable healthcare service for the elderly have increased. The paradigm of self-monitoring, self-healing, and healthcare experienced by the elderly through the metaverse in medicine, especially from meta-platform, meta-community, and meta-hospital, will be generated, which will reconstruct the service modes for the elderly people. The future map of the metaverse in medicine is huge, which depends on the co-construction of community partners.


Assuntos
COVID-19 , Disfunção Cognitiva , Humanos , Idoso , Relações Médico-Paciente , Inteligência Artificial , Disfunção Cognitiva/terapia , Saúde Mental
3.
Life Sci Space Res (Amst) ; 31: 34-42, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34689948

RESUMO

During space flight, astronauts are exposed to various influences of extreme environments and susceptible to develop depression-like behavior. Thus, this study aims to explore the molecular biological mechanism of the cause of depression-like behavior and reveal the effect of Baoyuan Jieyu Formula (BYJYF) on ameliorating depression-like behavior. Here, rats exposed to simulated long-term spaceflight composite stress (LSCS) reduced the sucrose preference rate (P <0.01), and the time of forced swimming immobility and the number of climbing times were also reduced (P < 0.01, P < 0.001). Moreover, the number of neurons in the CA3 region of the hippocampus decreased ( P< 0.01, P < 0.05, P < 0.001), the staining became weak, and the Nissl body decreased. Antibody chip detected a total of 854 protein molecules in the hippocampus, of which 51 and 37 proteins were significantly different in the LSCS group and LSCS+BYJYF group, respectively, focusing on signaling pathways such as MAPK and neurotrophin. Western blot was used to verify the related proteins of these two pathways. Conclusively, simulated LSCS can induce depression-like behavior and neuronal damage. BYJYF can reduce neuronal apoptosis, and promote neuron survival by regulating the MAPK and the neurotrophin signaling pathway to protect neurons and combat LSCS.


Assuntos
Depressão , Voo Espacial , Animais , Fator Neurotrófico Derivado do Encéfalo , Depressão/tratamento farmacológico , Depressão/etiologia , Hipocampo , Ratos , Estresse Psicológico/tratamento farmacológico
4.
J Hazard Mater ; 411: 125150, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-33858106

RESUMO

Frequent cyanobacteria bloom has caused serious environmental consequences and economic loss, especially in aquaculture. Direct algaecide addition, the most commonly used method, suffered from the poor control and overdose of algaecide. In this manuscript, we designed a smart nitrite-responsive hydrogel (DHPG) loading algaecide (BZK@DHPG) based on selective crosslinker: a kind of dihydropyridine derivatives termed DHPL. The network of the polymer could be decomposed by the nitrite-induced cleavage of DHPL. Compared to the traditional method, BZK@DHPG can adjust releasing speed according to the concentration of NO2-, the marker of cyanobacteria bloom level, and elongate the releasing time. Furthermore, BZK@DHPG could shift the effective dose of algaecide much ahead of the safety threshold, thus reducing deterioration of water quality caused by the overdose of algaecide.


Assuntos
Cianobactérias , Herbicidas , Eutrofização , Proliferação Nociva de Algas , Hidrogéis , Nitritos , Qualidade da Água
5.
Biol Pharm Bull ; 44(2): 162-168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33518670

RESUMO

Folic acid (FA) affect human physiology and drug metabolism. Up to now, the effect of microgravity on the pharmacokinetics of FA remains unclear. The pharmacokinetics of FA in Sprague-Dawley (SD) rats are laying a foundation for safe medicine administration of astronauts. Proteins expression of such FA metabolic enzymes as Methyltetrahydrofolate reductase (MTHFR), Cystathionine beta synthase (CBS) and Methionine synthase (MS) in a variety of organs was analyzed with Western-Blot, and mRNA expression was detected by RT-PCR. The plasma concentration-time profile of FA in normal or tail-suspended SD rats was acquired by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after oral administration of FA. Area under curve (AUC) and Cmax of FA in SD rats decreased significantly with extending period of tail-suspension. In terms of expressed level of metabolic enzymes over four suspension terms, as well as the level of the corresponding mRNAs, the following regularities were found: an obvious sharp decline of MTHFR tissue in kidney, a time-dependent increase of CBS in liver tissue and duodenum tissues, the resemblance of MS fluctuation to that of CBS in tested tissues. A four-week simulated microgravity of SD rats exhibits an unequivocal diminish of bioavailability of FA, and simulated microgravity shows a varying effect on the expression of FA-metabolizing enzyme in a variety of tissues.


Assuntos
Ácido Fólico/farmacocinética , Fenômenos Fisiológicos da Nutrição , Voo Espacial , Vitaminas/farmacocinética , Simulação de Ausência de Peso , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , Animais , Cistationina beta-Sintase/metabolismo , Ácido Fólico/administração & dosagem , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Modelos Animais , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Vitaminas/administração & dosagem
6.
Nat Protoc ; 16(2): 937-964, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33318693

RESUMO

Microtissues with specific structures and integrated vessels play a key role in maintaining organ functions. To recapitulate the in vivo environment for tissue engineering and organ-on-a-chip purposes, it is essential to develop perfusable biomimetic microscaffolds. We developed facile all-aqueous microfluidic approaches for producing perfusable hydrogel microtubes with diverse biomimetic sizes and shapes. Here, we provide a detailed protocol describing the construction of the microtube spinning platforms, the assembly of microfluidic devices, and the fabrication and characterization of various perfusable hydrogel microtubes. The hydrogel microtubes can be continuously generated from microfluidic devices due to the crosslinking of alginate by calcium in the coaxial flows and collecting bath. Owing to the mild all-aqueous spinning process, cells can be loaded into the alginate prepolymer for microtube spinning, which enables the direct production of cell-laden hydrogel microtubes. By manipulating the fluid dynamics at the microscale, the composable microfluidic devices and platforms can be used for the facile generation of six types of biomimetic perfusable microtubes. The microfluidic platforms and devices can be set up within 3 h from commonly available and inexpensive materials. After 10-20 min required to adjust the platform and fluids, perfusable hydrogel microtubes can be generated continuously. We describe how to characterize the microtubes using scanning electron or confocal microscopy. As an example application, we describe how the microtubes can be used for the preparation of a vascular lumen and how to perform barrier permeability tests of the vascular lumen.


Assuntos
Materiais Biomiméticos/química , Hidrogéis/síntese química , Técnicas Analíticas Microfluídicas/métodos , Alginatos/química , Biomimética/métodos , Humanos , Hidrogéis/química , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/instrumentação , Microfluídica/instrumentação , Microfluídica/métodos , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos
7.
ACS Appl Mater Interfaces ; 12(46): 51185-51197, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33146508

RESUMO

Nitric oxide (NO) is known as one of the most important biomarkers of many diseases. However, the development of NO-triggered drug releasing platforms is challenging due to the low concentration and short lifetime of NO in vivo. In this work, a novel nitrite (NO2-)-responsive hydrogel (DHPL-GEL), which can be used for smart drug release depending on the severity of the NO-related disease, is demonstrated. A dihydropyridine cross-linking agent is designed to construct DHPL-GEL to enable the responsive degradation of the hydrogel triggered by NO2-. On-demand release of the drug loaded in DHPL-GEL was observed under the stimulation of various concentrations of NO2- at the physiological level both in vitro and in vivo. In the inflammatory arthritis rat model, the DHPL-GEL drug delivery system showed a better therapeutic effect and less side effects than the traditional therapy and nonresponsive hydrogel drug delivery system, demonstrating the promising application of the NO2--responsive hydrogel for the treatment of NO-related diseases.


Assuntos
Materiais Biocompatíveis/química , Portadores de Fármacos/química , Hidrogéis/química , Óxido Nítrico/metabolismo , Nitritos/química , Resinas Acrílicas/química , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Liberação Controlada de Fármacos , Módulo de Elasticidade , Fluoresceína-5-Isotiocianato/química , Fluoresceína-5-Isotiocianato/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metotrexato/química , Metotrexato/metabolismo , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Camundongos , Células RAW 264.7 , Ratos
8.
Molecules ; 25(19)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987831

RESUMO

The present study aimed to investigate the change of intestinal mucosa proteins, especially the alteration of intestinal drug metabolizing enzymes (IDMEs) following 14-day simulated microgravity. Morey-Holton tail-suspension analog was used to simulate microgravity. Intestinal mucosa proteins of rats were determined by label-free quantitative proteomic strategy. A total of 335 differentially expressed proteins (DEPs) were identified, 190 DEPs were upregulated, and 145 DEPs were downregulated. According to bioinformatic analysis, most of DEPs exhibited hydrolase, oxidoreductase, transferase, ligase, or lyase catalytic activity. DEPs were mainly enriched in metabolic pathways, including metabolism of amino acid, glucose, and carbon. Moreover, 11 of DEPs were involved in exogenous drug and xenobiotics metabolism. Owing to the importance of IDMEs for the efficacy and safety of oral drugs, the expression of cytochrome P450 1A2 (CYP1A2), CYP2D1, CYP3A2, CYP2E1, alcohol dehydrogenase 1 (ADH1), and glutathione S-transferase mu 5 (GSTM5) in rat intestine mucosa was determined by Western-blot. The activity of ADH, aldehyde dehydrogenase (ALDH) and GST was evaluated. Compared with control rats, the expression of CYP1A2, CYP2D1, CYP3A2, and ADH1 in the simulated microgravity (SMG) group of rats were dramatically decreased by 33.16%, 21.93%, 48.49%, and 22.83%, respectively. GSTM5 was significantly upregulated by 53.14% and CYP2E1 expression did not show a dramatical change in SMG group rats. Moreover, 14-day SMG reduced ADH activity, while ALDH and GST activities was not altered remarkably. It could be concluded that SMG dramatically affected the expression and activity of some IDMEs, which might alter the efficacy or safety of their substrate drugs under microgravity. The present study provided some preliminary information on IDMEs under microgravity. It revealed the potential effect of SMG on intestinal metabolism, which may be helpful to understand the intestinal health of astronauts and medication use.


Assuntos
Álcool Desidrogenase/biossíntese , Sistema Enzimático do Citocromo P-450/biossíntese , Glutationa Transferase/biossíntese , Mucosa Intestinal/enzimologia , Proteômica , Simulação de Ausência de Peso , Animais , Regulação Enzimológica da Expressão Gênica , Masculino , Ratos , Ratos Sprague-Dawley
9.
Stem Cells Dev ; 29(16): 1084-1095, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32560594

RESUMO

Chronic persistent inflammation is thought to impede axon regeneration and cause demyelinating disease also with neuropathic pain, leading to more severe dysfunction after peripheral nerve injury. Increasing evidence indicates that neural stem cells (NSCs) have immunomodulatory effects, and previous studies have shown that many of the beneficial effects attributed to stem cell therapy may exert their therapeutic effects through paracrine mechanisms. In this research, the repairing effect of NSC-conditioned medium (NSC-CM) on sciatic nerve injury and its mechanism of repair were further explored. The present research showed that NSC-CM promoted histopathological and functional recovery after crush injury in rats, and what counts is that NSC-CM inhibited the inflammation of sciatic nerve in the late stage of injury. NSC-CM significantly downregulated the infiltration of proinflammatory factors [tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-1ß] as well as decreased the CD68 inflammatory macrophages infiltrating in the sciatic nerve. In addition, to study the effect of NSC-CM on the inflammatory state of macrophages in vitro, lipopolysaccharide (LPS) was used to induce the proinflammation of macrophages. The results showed that NSC-CM decreased the expression of macrophage proinflammatory-related proteins (IL-6, IL-1ß, TNF-α, inducible nitric oxide synthase) induced by LPS. The activation of Sirt-1 signaling in macrophages effectively countered the proinflammation induced by LPS in the presence of NSC-CM. Using Sirt-1-specific inhibitor EX527 partially weakened the anti-inflammatory effect of NSC-CM. Altogether, this study demonstrated for the first time that NSC-CM promotes functional recovery after sciatic nerve crush injury in vivo and also inhibits the inflammation in activated macrophages by activating Sirt-1 signaling pathway in vitro.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Inflamação/patologia , Macrófagos/patologia , Células-Tronco Neurais/metabolismo , Recuperação de Função Fisiológica , Nervo Isquiático/lesões , Transdução de Sinais , Sirtuína 1/metabolismo , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , NF-kappa B/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Remielinização/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Transdução de Sinais/efeitos dos fármacos
10.
Cell Tissue Bank ; 21(2): 233-248, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32052220

RESUMO

Injured nerves cannot regenerate on their own, and a lack of engraftable human nerves has been a major obstacle in cell-based therapies for regenerating damaged nerves. A monolayer culture approach to obtain adherent neural stem cells from human embryonic stem cells (hESC-NSCs) was established, and the greatest number of stemness characteristics were achieved by the eighth generation of hESC-NSCs (P8 hESC-NSCs). To overcome deficits in cell therapy, we used microvesicles secreted from P8 hESC-NSCs (hESC-NSC-MVs) instead of entire hESC-NSCs. To investigate the therapeutic efficacy of hESC-NSC-MVs in vitro, hESC-NSC-MVs were cocultured with dorsal root ganglia to determine the length of axons. In vivo, we transected the sciatic nerve in SD rats and created a 5-mm gap. A sciatic nerve defect was bridged using a silicone tube filled with hESC-NSC-MVs (45 µg) in the MVs group, P8 hESC-NSCs (1 × 106 single cells) in the cell group and PBS in the control group. The hESC-NSC-MVs group showed better morphological recovery and a significantly greater number of regenerated axons than the hESC-NSCs group 12 weeks after nerve injury. These results indicated that the hESC-NSC-MVs group had the greatest ability to repair and reconstruct nerve structure and function. As a result, hESC-NSC-MVs may have potential for applications in the field of nerve regenerative repair.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Regeneração Nervosa/fisiologia , Células-Tronco Neurais/metabolismo , Nervo Isquiático/fisiologia , Animais , Animais Recém-Nascidos , Axônios/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular , Linhagem Celular , Gânglios Espinais/metabolismo , Humanos , Músculos/fisiologia , Nanopartículas/química , Células-Tronco Neurais/citologia , Ratos Sprague-Dawley
11.
BMC Genomics ; 21(1): 57, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952470

RESUMO

BACKGROUND: Candida albicans is an opportunistic pathogenic yeast, which could become pathogenic in various stressful environmental factors including the spaceflight environment. In this study, we aim to explore the phenotypic changes and possible mechanisms of C. albicans after exposure to spaceflight conditions. RESULTS: The effect of C. albicans after carried on the "SJ-10" satellite for 12 days was evaluated by proliferation, morphology, environmental resistance and virulence experiment. The result showed that the proliferation rate, biofilm formation, antioxidant capacity, cytotoxicity and filamentous morphology of C. albicans were increased in the spaceflight group compared to the control group. Proteomics and metabolomics technologies were used to analyze the profiles of proteins and metabolites in C. albicans under spaceflight conditions. Proteomic analysis identified 548 up-regulated proteins involved in the ribosome, DNA replication, base excision repair and sulfur metabolism in the spaceflight group. Moreover, 332 down-regulated proteins related to metabolic processes were observed. The metabolomic analysis found five differentially expressed metabolites. The combined analysis of proteomic and metabolomic revealed the accumulation of cysteine and methionine in C. albicans after spaceflight. CONCLUSIONS: Mechanisms that could explain the results in the phenotypic experiment of C. albicans were found through proteomic and metabolomic analysis. And our data provide an important basis for the assessment of the risk that C. albicans could cause under spaceflight environment.


Assuntos
Candida albicans/metabolismo , Metaboloma , Proteoma , Voo Espacial , Candida albicans/citologia , Candida albicans/patogenicidade , Candida albicans/fisiologia , Metabolômica , Proteômica , Virulência
12.
Chin J Integr Med ; 26(6): 428-433, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31456137

RESUMO

OBJECTIVE: To summarize and elucidate the characteristics and evolvement of Chinese medicine (CM) patterns reflecting the physical and mental conditions of participants in the Mars 500 long-term closed environment. METHODS: The DS01-T Digital TCM Four-Diagnostic Instrument and CM Inquiring Diagnostic Questionnaire were used to collect information from 6 participants in the Mars 500 International Joint Research Project, through diagnostic methods of observation, palpation and inquiry according to CM theory. During the 520 days of the experiment, data collection was performed 37 times; a total of over 400 digital images of tongues and facial complexion and over 20,000 data were collected. These data were then analyzed by a team of experts in CM, statistics, and data mining. RESULTS: The CM pattern evolvement of participants in the long-term closed environment followed some common trends. Qi deficiency was the main CM pattern observed, with individual features depending on constitutional differences [manifested in varying degrees of accompanying patterns of Gan (Liver) qi stagnation, Pi (Spleen) deficiency, dampness encumbering, or yin deficiency]. CONCLUSION: The research has verified the effectiveness of CM syndrome differentiation based on the four diagnostic methods, which should serve as a solid foundation for observation, monitoring, and intervention in regard to the health conditions of astronauts in long-term space flights in the future.


Assuntos
Ambiente Controlado , Medicina Tradicional Chinesa/métodos , Deficiência da Energia Yang/diagnóstico , Deficiência da Energia Yin/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Marte , Exame Físico , Voo Espacial , Inquéritos e Questionários , Síndrome
13.
Stem Cells Int ; 2019: 6452684, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772588

RESUMO

Myocardial reperfusion injury (MRI) induced by cardiomyocyte apoptosis plays an important role in the pathogenesis of a variety of cardiovascular diseases. New MRI treatments involving stem cells are currently being developed because these cells may exert their therapeutic effects primarily through paracrine mechanisms. Microvesicles (MVs) are small extracellular vesicles that have become the key mediators of intercellular communication. MVs derived from stem cells have been reported to play an important role in MRI. In this article, we attempted to explore the mechanisms by which MVs derived from human embryonic neural stem cells (hESC-NSC-derived MVs) rescue MRI. hESCs were differentiated into NSCs, and MVs were isolated from their supernatants by ultracentrifugation. H2O2 was used to induce apoptosis in HL-1 cardiomyocytes. Cell viability was detected by using the CCK-8 assay, apoptosis was detected by Annexin V-FITC/PI staining, and apoptosis-related proteins and signalling pathway-related proteins were detected by western blot analysis. Autophagic flux was measured using the tandem fluorescent mRFG-GFP-LC3 assay. Transmission electron microscopy and western blot analysis were adopted to evaluate autophagy levels. hESC-NSC-derived MVs increased the autophagy and inhibited the apoptosis of HL-1 cells exposed to H2O2 for 3 h in a dose-dependent manner. Additionally, hESC-NSC-derived MVs contained high levels of heat shock protein 70 (HSP-70), which can increase the level of HSP-70 in cells. Moreover, the same effect could be achieved by heat shock preconditioning of HL-1 cells overexpressing HSP-70. The benefits of NSC-MVs may be due to the involvement of AKT and mTOR signalling pathways. Importantly, hESC-NSC-derived MVs stimulated the activation of the AKTand mTOR signalling pathway in those cells by transporting HSP-70. Our results suggest that hESC-NSC-derived MVs inhibit the apoptosis of HL-1 cardiomyocytes by promoting autophagy and regulating AKT and mTOR via transporting HSP-70. However, this hypothesis requires in vivo confirmation.

14.
J Mater Sci Mater Med ; 30(7): 82, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273463

RESUMO

Axon regeneration and functional recovery after peripheral nerve injury remains a clinical challenge. Injury leads to axonal disintegration after which Schwann cells (SCs) and macrophages re-engage in the process of regeneration. At present, biomaterials are regarded as the most promising way to repair peripheral nerve damage. As a natural material, keratin has a wide range of sources and has good biocompatibility and biodegradability. Here, a keratin was extracted from human hair by reducing method and a keratin sponge with porous structure was obtained by further processing. The results suggested that keratin can promote cell adhesion, proliferation, migration as well as the secretion of neurotrophic factors by SCs and the regulation of the expression of macrophage inflammatory cytokines in vitro. We report for the first time that human hair keratin can promote the extension of axon in DRG neurons. The motor deficits caused by a sciatic nerve crush injury were alleviated by keratin sponge dressing in vivo. Thus, keratin has been identified as a valuable biomaterial that can enhance peripheral nerve regeneration.


Assuntos
Cabelo/química , Queratinas Específicas do Cabelo/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Nervo Isquiático/lesões , Animais , Axônios/efeitos dos fármacos , Materiais Biocompatíveis , Adesão Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Citocinas/metabolismo , Humanos , Inflamação , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Neurônios/metabolismo , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Células de Schwann/efeitos dos fármacos , Cicatrização
15.
Oncol Rep ; 38(2): 1013-1020, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28627682

RESUMO

Human embryonic stem cell derived-mesenchymal stem cells (hESC­MSCs) are able to inhibit proliferation of leukemia cells. Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells (hESC­MSC­MVs) might play an important part in antitumor activity. Microvesicles were isolated by ultracentrifugation and identified under a scanning electron microscopy and transmission electron microscope separately. After 48-h cocultured with hESC­MSCs and hESC­MSC­MVs, the number of K562 and HL60 was counted and tumor cell viability was measured by CCK8 assay. The expression of proteins Bcl-2 and Bax were estimated by western blotting. Transmission electron microscope and western blot analysis were adopted to evaluate the autophagy level. Results showed that both hESC­MSCs and hESC­MSC­MVs inhibited proliferation of leukemia cells in a concentration-dependent manner. hESC­MSC­MVs reduced the ratio of Bcl/Bax, enhanced the protein level of Beclin-1 and LC3-II conversion, thus upregulating autophagy and apoptosis. In conclusion, microvesicles released from human embryonic stem cell derived-mesenchymal stem cells inhibited tumor growth and stimulated autophagy and excessive autophagy might induce apoptosis.


Assuntos
Apoptose , Proliferação de Células , Micropartículas Derivadas de Células/patologia , Células-Tronco Embrionárias Humanas/citologia , Leucemia/patologia , Células-Tronco Mesenquimais/citologia , Autofagia , Micropartículas Derivadas de Células/metabolismo , Células Cultivadas , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Leucemia/metabolismo , Células-Tronco Mesenquimais/metabolismo
16.
Front Pharmacol ; 8: 315, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28611667

RESUMO

Increasing evidence indicates the occurrence of cognitive impairment in astronauts under spaceflight compound conditions, but the underlying mechanisms and countermeasures need to be explored. In this study, we found that learning and memory abilities were significantly reduced in rats under a simulated long-duration spaceflight environment (SLSE), which includes microgravity, isolation confinement, noises, and altered circadian rhythms. Dammarane sapogenins (DS), alkaline hydrolyzed products of ginsenosides, can enhance cognition function by regulating brain neurotransmitter levels and inhibiting SLSE-induced neuronal injury. Bioinformatics combined with experimental verification identified that the PI3K-Akt-mTOR pathway was inhibited and the MAPK pathway was activated during SLSE-induced cognition dysfunction, whereas DS substantially ameliorated the changes in brain. These findings defined the characteristics of SLSE-induced cognitive decline and the mechanisms by which DS improves it. The results provide an effective candidate for improving cognitive function in spaceflight missions.

17.
Chin J Integr Med ; 23(8): 574-580, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28028716

RESUMO

OBJECTIVE: To comprehensively evaluate the health status of 6 volunteers from the Mars 500 Project through analyzing their pulse graphs and determining the changes in cardiovascular function, degree of fatigue and autonomic nervous function. METHODS: Six volunteers were recruited; all were male aged 26-38 years (average 31.83±4.96 years). Characteristic parameters reflflecting the status of cardiovascular functions were extracted, which included left ventricular contraction, vascular elasticity and peripheral resistance. The degree of fatigue was determined depending on the difference between the calendar age and biological age, which was calculated through the analysis of blood pressure value and characteristic parameters. Based on the values of pulse height variation and pulse time variation on a 30-s pulse graph, autonomic nervous function was evaluated. All parameters examined were marked on an equilateral polygon to form an irregular polygon of the actual fifigure, then health status was evaluated based on the coverage area of the actual fifigure. RESULTS: The results demonstrated: (1) volunteers developed weakened pulse power, increased vascular tension and peripheral resistance, and slight decreased ventricular systolic function; (2) the degree of fatigue was basically mild or moderate; and (3) autonomic nervous function was excited but generally balanced. CONCLUSIONS: These volunteers were in the state of sub-health. According to Chinese medicine theories, such symptoms are mainly caused by the weakening of healthy qi, Gan (Liver) failing in free coursing, and disharmony between Gan and Wei (Stomach), which manifests as a weak and string-like pulse.


Assuntos
Nível de Saúde , Pulso Arterial/métodos , Voluntários , Sistema Nervoso Autônomo/fisiologia , Fadiga/fisiopatologia , Testes de Função Cardíaca , Humanos , Contração Miocárdica , Fatores de Tempo , Resistência Vascular/fisiologia , Função Ventricular/fisiologia
18.
ScientificWorldJournal ; 2015: 125736, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26495414

RESUMO

Mars500 study was a psychological and physiological isolation experiment conducted by Russia, the European Space Agency, and China, in preparation for an unspecified future manned spaceflight to the planet Mars. Its intention was to yield valuable psychological and medical data on the effects of the planned long-term deep space mission. In this paper, we present data mining methods to mine medical data collected from the crew consisting of six spaceman volunteers. The synthesis of the four diagnostic methods of TCM, inspection, listening, inquiry, and palpation, is used in our syndrome differentiation. We adopt statistics method to describe the syndrome factor regular pattern of spaceman volunteers. Hybrid optimization based multilabel (HOML) is used as feature selection method and multilabel k-nearest neighbors (ML-KNN) is applied. According to the syndrome factor statistical result, we find that qi deficiency is a base syndrome pattern throughout the entire experiment process and, at the same time, there are different associated syndromes such as liver depression, spleen deficiency, dampness stagnancy, and yin deficiency, due to differences of individual situation. With feature selection, we screen out ten key factors which are essential to syndrome differentiation in TCM. The average precision of multilabel classification model reaches 80%.


Assuntos
Medicina Tradicional Chinesa , Astronave , Algoritmos , Humanos , Modelos Biológicos , Síndrome
19.
PLoS One ; 10(3): e0120920, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25799561

RESUMO

PURPOSE: The objective was to investigate autonomic control in groups of European and Chinese astronauts and to identify similarities and differences. METHODS: Beat-to-beat heart rate and finger blood pressure, brachial blood pressure, and respiratory frequency were measured from 10 astronauts (five European taking part in three different space missions and five Chinese astronauts taking part in two different space missions). Data recording was performed in the supine and standing positions at least 10 days before launch, and 1, 3, and 10 days after return. Cross-correlation analysis of heart rate and systolic pressure was used to assess cardiac baroreflex modulation. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic blood pressure variability. RESULTS: Although baseline cardiovascular parameters before spaceflight were similar in all astronauts in the supine position, a significant increase in sympathetic activity and a decrease in vagal modulation occurred in the European astronauts when standing; spaceflight resulted in a remarkable vagal decrease in European astronauts only. Similar baseline supine and standing values for heart rate, mean arterial pressure, and respiratory frequency were shown in both groups. Standing autonomic control was based on a balance of higher vagal and sympathetic modulation in European astronauts. CONCLUSION: Post-spaceflight orthostatic tachycardia was observed in all European astronauts, whereas post-spaceflight orthostatic tachycardia was significantly reduced in Chinese astronauts. The basis for orthostatic intolerance is not apparent; however, many possibilities can be considered and need to be further investigated, such as genetic diversities between races, astronaut selection, training, and nutrition, etc.


Assuntos
Povo Asiático , Astronautas , Sistema Nervoso Autônomo/fisiologia , População Branca , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Intolerância Ortostática/etiologia , Intolerância Ortostática/fisiopatologia , Voo Espacial , Taquicardia/etiologia , Taquicardia/fisiopatologia
20.
Chin J Integr Med ; 20(9): 654-60, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24810476

RESUMO

OBJECTIVE: To study the changes in cardiopulmonary function induced by mid/long-term simulated microgravity with 6° head down bed rest (HDBR), and the effects of Taikong Yangxin Prescription (, TYP) as a countermeasure. METHODS: Fourteen healthy male volunteers were randomly divided into a control group and a Chinese medicine (CM) group (7 in each group) by a random digital table based on their body weight. Both groups underwent 6° HDBR for 60 days. Subjects in the CM group received daily TYP pills and subjects in the control group received daily placebo pills. Cardiac systolic and pumping functions were measured by echocardiography before HDBR; on days 20, 42, and 57 of HDBR; and on day 3 of recovery after HDBR (R+3). Cardiopulmonary functional reserve and exercise capacity were evaluated before HDBR, on day 29, and on day R+3 by exercise testing. RESULTS: The heart rate (HR) increased gradually during HDBR. The HR was significantly higher on day 57 than before HDBR in the control group (P<0.05), but did not increase significantly in the CM group. The stroke volume/stroke volume index, ejection fraction, and left ventricular fractional shortening tended to decrease over time in the control group, but not in the CM group. These parameters were significantly higher in the CM group than in the control group on day 42 (P<0.05 or <0.01). Exercise testing showed that maximum O2 consumption (VO2max), metabolic equivalents, relative O2 consumption (VO2), O2 pulse, and exercise duration were significantly lower on day 29 than before HDBR in the control group, but not in the CM group. CONCLUSIONS: Sixty days of 6° HDBR induced a reduction in cardiac systolic and pumping functions, and reduced cardiopulmonary functional reserve and exercise capacity. Administration of TYP significantly improved cardiac systolic and pumping functions, and maintained cardiopulmonary functional reserve and exercise capacity.


Assuntos
Repouso em Cama , Medicamentos de Ervas Chinesas , Coração/fisiologia , Pulmão/fisiologia , Adulto , Teste de Esforço , Humanos , Masculino
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