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1.
Nat Commun ; 15(1): 5702, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977693

RESUMO

Anion exchange membrane (AEM) water electrolysis employing non-precious metal electrocatalysts is a promising strategy for achieving sustainable hydrogen production. However, it still suffers from many challenges, including sluggish alkaline hydrogen evolution reaction (HER) kinetics, insufficient activity and limited lifetime of non-precious metal electrocatalysts for ampere-level-current-density alkaline HER. Here, we report an efficient alkaline HER strategy at industrial-level current density wherein a flexible WS2 superstructure is designed to serve as the cathode catalyst for AEM water electrolysis. The superstructure features bond-free van der Waals interaction among the low Young's modulus nanosheets to ensure excellent mechanical flexibility, as well as a stepped edge defect structure of nanosheets to realize high catalytic activity and a favorable reaction interface micro-environment. The unique flexible WS2 superstructure can effectively withstand the impact of high-density gas-liquid exchanges and facilitate mass transfer, endowing excellent long-term durability under industrial-scale current density. An AEM electrolyser containing this catalyst at the cathode exhibits a cell voltage of 1.70 V to deliver a constant catalytic current density of 1 A cm-2 over 1000 h with a negligible decay rate of 9.67 µV h-1.

2.
Phytomedicine ; 130: 155725, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38772181

RESUMO

BACKGROUND: Bidirectional communication between the gut microbiota and the brain may play an essential role in the cognitive dysfunction associated with chronic sleep deprivation(CSD). Salvia miltiorrhiza Bunge (Danshen, DS), a famous Chinese medicine and functional tea, is extensively used to protect learning and memory capacities, although the mechanism of action remains unknown. PURPOSE: The purpose of this research was to explore the efficacy and the underlying mechanism of DS in cognitive dysfunction caused by CSD. METHODS: DS chemical composition was analyzed by UPLC-QTOF-MS/MS. Forty rats were randomly assigned to five groups (n = 8): control (CON), model (MOD), low- (1.35 g/kg, DSL), high-dose (2.70 g/kg, DSH) DS group, and Melatonin(100 mg/kg, MT) group. A CSD rat model was established over 21 days. DS's effects and the underlying mechanism were explored using the open-field test(OFT), Morris water-maze(MWM), tissue staining(Hematoxylin and Eosin Staining, Nissl staining, Alcian blue-periodic acid SCHIFF staining, and Immunofluorescence), enzyme-linked immunosorbent assay, Western blot, quantitative real-time polymerase chain reaction(qPCR), and 16S rRNA sequencing. RESULTS: We demonstrated that CSD caused gut dysbiosis and cognitive dysfunction. Furthermore, 16S rRNA sequencing demonstrated that Firmicutes and Proteobacteria were more in fecal samples from model group rats, whereas Bacteroidota and Spirochaetota were less. DS therapy, on the contrary hand, greatly restored the gut microbial community, consequently alleviating cognitive impairment in rats. Further research revealed that DS administration reduced systemic inflammation via lowering intestinal inflammation and barrier disruption. Following that, DS therapy reduced Blood Brain Barrier(BBB) and neuronal damage, further decreasing neuroinflammation in the hippocampus(HP). Mechanistic studies revealed that DS therapy lowered lipopolysaccharide (LPS) levels in the HP, serum, and colon, consequently blocking the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products(IL-1ß, IL-6, TNF-α, iNOS, and COX2) in the HP and colon. CONCLUSION: DS treatment dramatically improved spatial learning and memory impairments in rats with CSD by regulating the composition of the intestinal flora, preserving gut and brain barrier function, and reducing inflammation mediated by the LPS-TLR4 signaling pathway. Our findings provide novel insight into the mechanisms by which DS treats cognitive dysfunction caused by CSD.


Assuntos
Disfunção Cognitiva , Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Salvia miltiorrhiza , Privação do Sono , Animais , Salvia miltiorrhiza/química , Privação do Sono/complicações , Privação do Sono/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Microbioma Gastrointestinal/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , NF-kappa B/metabolismo , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos
3.
Small ; : e2401019, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38757438

RESUMO

As a sustainable energy technology, electrocatalytic energy conversion requires electrocatalysts, which greatly motivates the exploitation of high-performance electrocatalysts based on nonprecious metals. Molybdenum-based nanomaterials have demonstrated promise as electrocatalysts because of their unique physiochemical and electronic properties. Among them, atomic Mo catalysts, also called Mo-based single-atom catalysts (Mo-SACs), have the most accessible active sites and tunable microenvironments and are thrivingly explored in various electrochemical conversion reactions. A timely review of such rapidly developing topics is necessary to provide guidance for further exploration of optimized Mo-SACs toward electrochemical energy technologies. In this review, recent advances in the synthetic strategies for Mo-SACs are highlighted, focusing on the microenvironment engineering of Mo atoms. Then, the representative achievements of their applications in various electrocatalytic reactions involving the N2, H2O, and CO2 cycles are summarized by combining experimental and computational results. Finally, prospects for the future development of Mo-SACs in electrocatalysis are provided and the key challenges that require further investigation and optimization are highlighted.

4.
J Nanobiotechnology ; 22(1): 178, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38614985

RESUMO

BACKGROUND: Clearance of apoptotic cells by efferocytosis is crucial for prevention of atherosclerosis progress, and impaired efferocytosis contributes to the aggravated atherosclerosis. RESULTS: In this study, we found that diabetic ApoE-/- mice showed aggravated atherosclerosis as hyperglycemia damaged the efferocytosis capacity at least partially due to decreased expression of Mer tyrosine kinase (MerTK) on macrophages. To locally restore MerTK in the macrophages in the plaque, hybrid membrane nanovesicles (HMNVs) were thus developed. Briefly, cell membrane from MerTK overexpressing RAW264.7 cell and transferrin receptor (TfR) overexpressing HEK293T cell were mixed with DOPE polymers to produce nanovesicles designated as HMNVs. HMNVs could fuse with the recipient cell membrane and thus increased MerTK in diabetic macrophages, which in turn restored the efferocytosis capacity. Upon intravenous administration into diabetic ApoE-/- mice, superparamagnetic iron oxide nanoparticles (SMN) decorated HMNVs accumulated at the aorta site significantly under magnetic navigation, where the recipient macrophages cleared the apoptotic cells efficiently and thus decreased the inflammation. CONCLUSIONS:  Our study indicates that MerTK decrease in macrophages contributes to the aggravated atherosclerosis in diabetic ApoE-/- mice and regional restoration of MerTK in macrophages of the plaque via HMNVs could be a promising therapeutic approach.


Assuntos
Aterosclerose , Diabetes Mellitus , Humanos , Animais , Camundongos , Eferocitose , Células HEK293 , Membrana Celular , Proteínas Tirosina Quinases , Apolipoproteínas E/genética , Nanopartículas Magnéticas de Óxido de Ferro
5.
ACS Appl Mater Interfaces ; 16(14): 17120-17128, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38554083

RESUMO

Cell-based therapies offer tremendous potential for skin flap regeneration. However, the hostile microenvironment of the injured tissue adversely affects the longevity and paracrine effects of the implanted cells, severely reducing their therapeutic effectiveness. Here, an injectable hydrogel (nGk) with reactive oxygen species (ROS) scavenging capability, which can amplify the cell viability and functions of encapsulated mesenchymal stem cells (MSCs), is employed to promote skin flap repair. nGk is formulated by dispersing manganese dioxide nanoparticles (MnO2 NPs) in a gelatin/κ-carrageenan hydrogel, which exhibits satisfactory injectable properties and undergoes a sol-gel phase transition at around 40 °C, leading to the formation of a solid gel at physiological temperature. MnO2 NPs enhance the mechanical properties of the hydrogel and give it the ability to scavenge ROS, thus providing a cell-protective system for MSCs. Cell culture studies show that nGk can mitigate the oxidative stress, improve cell viability, and boost stem cell paracrine function to promote angiogenesis. Furthermore, MSC-loaded nGk (nGk@MSCs) can improve the survival of skin flaps by promoting angiogenesis, reducing inflammatory reactions, and attenuating necrosis, providing an effective approach for tissue regeneration. Collectively, injectable nGk has substantial potential to enhance the therapeutic benefits of MSCs, making it a valuable delivery system for cell-based therapies.


Assuntos
Hidrogéis , Células-Tronco Mesenquimais , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Compostos de Manganês/farmacologia , Óxidos/farmacologia
6.
ACS Biomater Sci Eng ; 10(2): 1031-1039, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38215215

RESUMO

Surgical bleeding and cumulative oxidative stress are significant factors in the development of postoperative adhesions, which are always associated with adverse patient outcomes. However, effective strategies for adhesion prevention are currently lacking in clinical practice. In this study, we propose a solution using polydopamine-decorated manganese dioxide nanoparticles (MnO2@PDA) with rapid hemostasis and remarkable antioxidant properties to prevent postsurgical adhesion. The PDA modification provides MnO2@PDA with enhanced tissue adhesiveness and hemocompatibility with negligible hemolysis. Furthermore, MnO2@PDA exhibits impressive antioxidant and free radical scavenging properties, protecting cells from the negative effects of oxidative stress. The hemostatic activity of MnO2@PDA is evaluated in a mouse truncated tail model and a liver injury model, with results demonstrating reduced bleeding time and volume. The in vivo test on a mouse cecal abrasion model shows that MnO2@PDA exhibits excellent antiadhesion properties coupled with alleviated inflammation around the damaged tissue. Therefore, MnO2@PDA, which exhibits high biosafety, rapid hemostasis, and beneficial antioxidant capacity, displays exceptional antiadhesion performance, holding great potential for clinical applications to prevent postoperative adhesion.


Assuntos
Antioxidantes , Indóis , Nanopartículas , Polímeros , Humanos , Camundongos , Animais , Antioxidantes/farmacologia , Compostos de Manganês/farmacologia , Contenção de Riscos Biológicos , Óxidos/farmacologia , Hemostasia
7.
Small ; 20(27): e2306598, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38295133

RESUMO

Postoperative adhesion is a noteworthy clinical complication in abdominal surgery due to the existing physical barriers are unsatisfactory and inefficient in preventing its occurrence. In this work, an elaborate nanoparticle-in-microgel system (nMGel) is presented for postoperative adhesion prevention. nMGel is facilely formed by crosslinking manganese dioxide (MnO2) nanoparticles-loaded gelatin microspheres with polydopamine using a modified emulsification-chemical crosslinking method, generating a nano-micron spherical hydrogel. After drying, powdery nMGel with sprayability can perfectly cover irregular wounds and maintains robust tissue adhesiveness even in a wet environment. Additionally, nMGel possesses prominent antioxidant and free radical scavenging activity, which protects cell viability and preserves cell biological functions in an oxidative microenvironment. Furthermore, nMGel displays superior hemostatic property as demonstrated in mouse tail amputation models and liver trauma models. Importantly, nMGel can be conveniently administrated in a mouse cecal defect model to prevent adhesion between the injured cecum and the peritoneum by reducing inflammation, oxidative stress, collagen synthesis, and angiogenesis. Thus, the bioactive nMGel offers a practical and efficient approach for ameliorating postsurgical adhesion.


Assuntos
Nanopartículas , Espécies Reativas de Oxigênio , Animais , Nanopartículas/química , Aderências Teciduais/prevenção & controle , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Óxidos/química , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Adesivos/química , Adesivos/farmacologia , Humanos , Complicações Pós-Operatórias/prevenção & controle , Polímeros/química
8.
Small ; 20(24): e2309841, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38217292

RESUMO

The demand for the exploration of highly active and durable electro/photocatalysts for renewable energy conversion has experienced a significant surge in recent years. Metal-organic frameworks (MOFs), by virtue of their high porosity, large surface area, and modifiable metal centers and ligands, have gained tremendous attention and demonstrated promising prospects in electro/photocatalytic energy conversion. However, the small pore sizes and limited active sites of 3D bulk MOFs hinder their wide applications. Developing 2D MOFs with tailored thickness and large aspect ratio has emerged as an effective approach to meet these challenges, offering a high density of exposed active sites, better mechanical stability, better assembly flexibility, and shorter charge and photoexcited state transfer distances compared to 3D bulk MOFs. In this review, synthesis methods for the most up-to-date 2D MOFs are first overviewed, highlighting their respective advantages and disadvantages. Subsequently, a systematic analysis is conducted on the identification and electronic structure modulation of catalytic active sites in 2D MOFs and their applications in renewable energy conversion, including electrocatalysis and photocatalysis (electro/photocatalysis). Lastly, the current challenges and future development of 2D MOFs toward highly efficient and practical electro/photocatalysis are proposed.

9.
Biomed J ; : 100651, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37562773

RESUMO

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is an important component of tumorigenesis. Aberrant expression of lncRNA taurine upregulated gene 1 (lncTUG1) has been reported in various tumors; however, its precise role and key targets critically involved in osteosarcoma (OS) progression remains unclear. METHODS: The expression profiles of lncRNAs and its regulated miRNAs related to OS progression were assessed by bioinformatics analysis and confirmed by qRT-PCR of OS cells. The miRNA targets were identified by transcriptome sequencing and verified by luciferase reporter and RNA pull-down assays. Several in vivo and in vitro approaches, including CCK8 assay, western blot, qRT-PCR, lentiviral transduction and OS cell xenograft mouse model were established to validate the effects of lncTUG1 regulation of miRNA and the downstream target genes on OS cell growth, apoptosis and progression. RESULTS: We found that lncTUG1 and miR-26a-5p were inversely up or down-regulated in OS cells, and siRNA-mediated lncTUG1 knockdown reversed the miR-26a-5p down-regulation and suppressed proliferation and enhanced apoptosis of OS cells. Further, we identified that an oncoprotein ZBTB7C was also upregulated in OS cells that were subjected to lncTUG1/miR-26a-5p regulation. More importantly, ZBTB7C knockdown reduced the ZBTB7C upregulation and ZBTB7C overexpression diminished the anti-OS effects of lncTUG1 knockdown in the OS xenograft model. CONCLUSIONS: Our data suggest that lncTUG1 acts as a miR-26a-5p sponge and promotes OS progression via up-regulating ZBTB7C, and targeting lncTUG1 might be an effective strategy to treat OS.

10.
Cell Tissue Res ; 393(2): 265-279, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37247031

RESUMO

Osteoblast differentiation is regulated by various transcription factors, signaling molecules, and posttranslational modifiers. The histone acetyltransferase Mof (Kat8) is involved in distinct physiological processes. However, the exact role of Mof in osteoblast differentiation and growth remains unknown. Herein, we demonstrated that Mof expression with histone H4K16 acetylation increased during osteoblast differentiation. Inhibition of Mof by siRNA knockdown or small molecule inhibitor, MG149 which is a potent histone acetyltransferase inhibitor, reduced the expression level and transactivation potential of osteogenic key markers, Runx2 and Osterix, thus inhibiting osteoblast differentiation. Besides, Mof overexpression also enhanced the protein levels of Runx2 and Osterix. Mof could directly bind the promoter region of Runx2/Osterix to potentiate their mRNA levels, possibly through Mof-mediated H4K16ac to facilitate the activation of transcriptional programs. Importantly, Mof physically interacts with Runx2/Osterix for the stimulation of osteoblast differentiation. Yet, Mof knockdown showed indistinguishable effect on cell proliferation or apoptosis in MSCs and preosteoblast cells. Taken together, our results uncover Mof functioning as a novel regulator of osteoblast differentiation via the promotional effects on Runx2/Osterix and rationalize Mof as a potential therapeutic target, like possible application of inhibitor MG149 for the treatment of osteosarcoma or developing specific Mof activator to ameliorate osteoporosis.


Assuntos
Osteogênese , Fatores de Transcrição , Diferenciação Celular , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Histona Acetiltransferases/metabolismo , Osteoblastos , Fator de Transcrição Sp7/genética , Fator de Transcrição Sp7/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Animais , Camundongos
11.
Front Psychiatry ; 14: 1157587, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091700

RESUMO

Background: Major depressive disorder (MDD) is a disabling and severe psychiatric disorder with a high rate of prevalence, and adolescence is one of the most probable periods for the first onset. The neurobiological mechanism underlying the adolescent MDD remains unexplored. Methods: In this study, we examined the cortical and subcortical alterations of neuroanatomical structures and spontaneous functional activation in 50 unmedicated adolescents with MDD vs. 39 healthy controls through the combined structural and resting-state functional magnetic resonance imaging. Results: Significantly altered regional gray matter volume was found at broader frontal-temporal-parietal and subcortical brain areas involved with various forms of information processing in adolescent MDD. Specifically, the increased GM volume at the left paracentral lobule and right supplementary motor cortex was significantly correlated with depression severity in adolescent MDD. Furthermore, lower cortical thickness at brain areas responsible for visual and auditory processing as well as motor movements was found in adolescent MDD. The lower cortical thickness at the superior premotor subdivision was positively correlated with the course of the disease. Moreover, higher spontaneous neuronal activity was found at the anterior cingulum and medial prefrontal cortex, and this hyperactivity was also negatively correlated with the course of the disease. It potentially reflected the rumination, impaired concentration, and physiological arousal in adolescent MDD. Conclusion: The abnormal structural and functional findings at cortico-subcortical areas implied the dysfunctional cognitive control and emotional regulations in adolescent depression. The findings might help elaborate the underlying neural mechanisms of MDD in adolescents.

12.
Transl Res ; 259: 62-71, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37121538

RESUMO

Aberrant N6-methyladenosine (m6A) modification of mRNAs contributes significantly to the epigenetic tumorigenesis, however, its precise role and the key targets in osteosarcoma (OS) are not defined. Here we reported that selective METTL3 (methyltransferase like 3) elevation and the consequential increase of m6A modification causally affect OS progression. The fast-growing OS cells displayed preferential upregulation of METTL3 and increased m6A modification. Conversely, m6A inhibition by 3-deazaadenosine, siRNA-mediated METTL3 knockdown or a METTL3-selective inhibitor STM2457 effectively inhibits OS cell growth and induced OS cell apoptosis. Further investigation revealed that an oncogenic protein ZBTB7C was likely a critical m6A target that mediated the oncogenic effects. ZBTB7C mRNA contains a typical m6A motif of high confidence and its mRNA and protein were enriched with increased m6A modification in OS samples/cells. In an OS xenograft model, STM2457 or siRNA-mediated METTL3 knockdown effectively lowed ZBTB7C abundance. More importantly, the anti-OS effects of STM2457 were significantly reduced when ZBTB7C was overexpressed by lentivirus. Together, our results demonstrate that the METTL3 aberration and the resultant ZBTB7C m6A modification form an important epigenetic regulatory loop that promotes OS progression, and targeting the METTL3/ZBTB7C axis may provide novel insights into the potential strategies for OS therapy.


Assuntos
Metiltransferases , Osteossarcoma , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Metiltransferases/genética , Metiltransferases/metabolismo , Osteossarcoma/genética , RNA Mensageiro/genética , RNA Interferente Pequeno
13.
Nano Lett ; 23(4): 1435-1444, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36752657

RESUMO

A light-activated chemically reactive fibrous patch (ChemPatch) with tissue adhesion and wound healing activity was developed for preventing postoperative peritoneal adhesion. ChemPatch was constructed by an integrative electrospinning fabrication strategy, generating multifunctional PCL-NHS fibers encapsulating antioxidant curcumin and MnO2 nanoparticles. ChemPatch exhibited excellent photothermal conversion, which not only reformed the physical state to match the tissue but also improved conjugation between ChemPatch and tissues, allowing for strong attachment. Importantly, ChemPatch possessed good antioxidant and radical scavenging activity, which protected cells in an oxidative microenvironment and improved tissue regeneration. Particularly, ChemPatch acted as a multifunctional barrier and could not only promote reepithelialization and revascularization in wound defect model but simultaneously ameliorate inflammation and prevent postoperative peritoneal adhesion in a mouse cecal defect model. Thus, ChemPatch represents a dual-active bioadhesive barrier for reducing the incidence and severity of peritoneal adhesions.


Assuntos
Cirurgia Geral , Complicações Pós-Operatórias , Telas Cirúrgicas , Aderências Teciduais , Cicatrização , Cavidade Peritoneal/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Luz , Telas Cirúrgicas/normas , Cirurgia Geral/instrumentação , Cirurgia Geral/métodos , Curcumina/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Óxido de Magnésio/uso terapêutico , Resultado do Tratamento , Camundongos Endogâmicos ICR , Animais , Camundongos , Linhagem Celular
14.
J Appl Toxicol ; 43(5): 694-705, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36451259

RESUMO

Bisphenol A (BPA), a commonly used plasticizer in the production of polycarbonate plastics and epoxy resins, has been shown to induce male reproductive toxicity. However, the effects of BPA exposure on early testicular development have not been thoroughly studied, and the underlying mechanism is yet to be elucidated. In the current study, neonatal male mice were exposed to BPA at 0, 0.1, and 5 mg/kg, respectively, by daily subcutaneous injection during postnatal day (PND) 1-35 to explore its effects on testicular development at PND 36 (the end of the first round of spermatogenesis). Morphological analyses showed that BPA exposure significantly induced apoptosis of testicular cells (p < 0.01 and p < 0.001) and reduced the thickness of seminiferous epithelium (p < 0.01). In addition, BPA exposure significantly decreased the total antioxidant capacity of testes and levels of transcription factor Nrf2 as well as its downstream antioxidant molecules of NQO1 and GPx-1 (p < 0.05 and p < 0.01). Furthermore, global m6A modifications of mRNAs were upregulated accompanied by declined m6A demethylase (FTO) in the testes of BPA groups (p < 0.05 and p < 0.01). MeRIP-quantitative real-time polymerase chain reaction (qPCR) demonstrated that BPA exposure markedly increased the m6A modification of Nrf2 mRNA (p < 0.05 and p < 0.01). These findings suggest that upregulation of m6A induced by inhibited FTO may be involved in BPA-induced testicular oxidative stress and developmental injury during postnatal development, which provides a new idea to reveal the mechanism underlying BPA interfering with testicular development.


Assuntos
Fator 2 Relacionado a NF-E2 , Testículo , Camundongos , Animais , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/metabolismo , Compostos Benzidrílicos/toxicidade , Estresse Oxidativo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo
16.
Int J Biol Macromol ; 221: 723-735, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36099995

RESUMO

Although cellular therapy holds enormous promise in treating intractable diseases, its application potential has been significantly hampered due to the scarcity of reliable and consistent cell sources. Therefore, a high-efficiency strategy that improves cell production and storage is desperately needed. Herein, we develop a versatile 3D bioinspired scaffold (Cryosilk) for improving scalable cell manufacture and cryopreservation. A bottom-up fabrication technique integrating electrospinning, in situ surface functionalization and freeze-shaping was explored to construct Cryosilk with biomimetic features and functions of silkworm cocoons. Cryosilk is composed of a core-shell heterostructure with silk fibroin/poly alanine fiber core and silk sericin shell, generating a 3D cocoon-mimicking fibrous structure. Importantly, Cryosilk possesses improved thermal conductivity and ice crystal resistance capability, thus enabling to cryopreserve biological samples with minimal cryodamage. Furthermore, Cryosilk not only promotes cell adhesion and growth, but achieves rapid and uniform rewarming process, which provides high cryopreservation efficacy for immune cells and stem cells. Particularly, Cryosilk can maintain cell viability and biofunctions of stem cell-scaffold constructs after freeze-thawing, which can be directly implanted to promote wound healing. Thus, Cryosilk offers unprecedented efficacy in cell manufacture and cryopreservation, which provides sufficient and high-quality precious cells and tissue engineered scaffolds for cellular therapy.


Assuntos
Bombyx , Fibroínas , Animais , Bombyx/química , Alicerces Teciduais/química , Criopreservação , Adesão Celular , Engenharia Tecidual/métodos
17.
Drug Deliv ; 29(1): 2610-2620, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35938574

RESUMO

Compelling data have indicated menopause-associated increase in cardiovascular disease in women, while the underlying mechanisms remain largely unknown. It is established that changes of intestinal microbiota affect cardiovascular function in the context of metabolic syndrome. We here aimed to explore the possible link between host intestinal function, microbiota, and cardiac function in the ovariectomy (OVX) mouse model. Mice were ovariectomized to induce estrogen-related metabolic syndrome and cardiovascular defect. Microbiota was analyzed by 16s rRNA sequencing. miRNA and mRNA candidates expression were tested by qPCR. Cardiac function was examined by echocardiography. Colon specific delivery of miRNA candidates was achieved by oral gavage of Eudragit S100 functionalized microspheres. In comparison with the sham-operated group, OVX mice showed compromised cardiac function, together with activated inflammation in the visceral adipose tissue and heart. Lactobacillus abundance was significantly decreased in the gut of OVX mice. Meanwhile, miR-155 was mostly upregulated in the intestinal epithelium and thus the feces over other candidates, which in turn decreased Lactobacillus abundance in the intestine when endocytosed. Oral delivery of miR-155 antagonist restored the protective microbiota and thus protected the cardiac function in the OVX mice. This study has established a possible regulatory axis of intestinal miRNAs-microbiota-estrogen deficiency related phenotype in the OVX model. Colon specific delivery of therapeutic miRNAs would possibly restore the microbiota toward protective phenotype in the context of metabolic syndrome.


Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , MicroRNAs , Animais , Colo/metabolismo , Estrogênios , Feminino , Humanos , Camundongos , MicroRNAs/genética , Fenótipo , RNA Ribossômico 16S
18.
Neuropsychiatr Dis Treat ; 18: 1469-1477, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35899094

RESUMO

Purpose: Uric acid (UA) is thought to exert neuroprotective roles. The purpose of this study was to examine the association of serum UA with suicide attempts (SA) in adolescents and young adults with major depressive disorder (MDD). Patients and Methods: We retrospectively recruited 533 participants with MDD aged 13 to 25 years, of which 168 had a history of SA in the past three months and 365 did not have a history of SA. Serum UA levels were measured using the uricase-peroxidase coupling method. In addition to overall serum UA level comparison in MDD individuals with and without SA, a stratified analysis by biological sex was carried out. Results: Compared to MDD individuals without a history of SA, serum UA levels were significantly lower in MDD individuals with SA (P < 0.001). Female MDD, but not male MDD individuals, with SA exhibited lower levels of UA than those without SA (P < 0.01). Importantly, serum UA remained significantly associated with SA in MDD individuals (OR = 0.996, 95% CI: 0.993~0.999, P < 0.01) when controlling for possible confounding variables. Conclusion: This research identifies a relationship between serum UA levels and SA in adolescents and young adults with MDD. UA may represent a biological risk marker for SA, in particular for female MDD individuals.

19.
Nano Lett ; 22(14): 5723-5734, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35787105

RESUMO

Despite the great promise, cell therapy still faces practical challenges because of the scarcity of a reliable cell source. Herein, a bioinspired 3D dynamic culture system (CellMatrix) with rational structure, composite and function, was developed for improving cell supply. CellMatrix was composed of unique core-shell fibers with a core of black phosphorus-incorporated fibroin and a shell of sericin, which together formed a 3D silkworm cocoon-mimicking structure via a bottom-up fabrication technique. CellMatrix not only provided optimal engineered biomimetic niche to facilitate cell growth but exhibited good photothermal conversion to dynamically regulate cell fates. Importantly, cell-CellMatrix construct could be directly implanted into defected tissues and improved tissue remodeling. Meanwhile, CellMatrix displayed good ice resistance and thermal conductivity, which maximally maintained cell viability and proliferation after the freeze-thawing process, allowing for storing precious cells and cell-CellMatrix construct. Thus, CellMatrix represents an all-in-one biomimetic platform for the culture-production-storage of therapeutically qualified cells.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Diferenciação Celular , Proliferação de Células , Terapia Baseada em Transplante de Células e Tecidos , Hidrogéis/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química
20.
Clin Exp Nephrol ; 26(10): 1030-1038, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35662387

RESUMO

BACKGROUND: Peritonitis is a serious complication of peritoneal dialysis (PD). Gut microbiota alterations occur in end-stage renal disease (ESRD) patients. The relationship between the gut microbiota and PD-related peritonitis (PRP) is still poorly understood. It is unclear whether the intestinal flora is involved in the pathogenesis of PRP. METHODS: We collected fecal samples from PRP patients and normal group (NG) PD patients. 16S rRNA sequencing was used to analyze the gut microbiota of PRP and NG patients while also comparing the gram-positive peritonitis (GPP), Escherichia coli peritonitis (EP) and culture-negative peritonitis (CNP) groups in the subgroup analysis. The demographic data and clinical indicators of all patients were collected. RESULTS: Seventeen PRP patients and 28 NG patients were recruited for this study. The analysis of fecal community diversity with 16S rDNA sequencing showed an obvious change in the microbial structure of PRP patients, where Bacteroidetes and Synergistetes were upregulated at different levels, while Bacilli and Lactobacillus were downregulated at different levels compared to levels in the NG group. In the subgroup analysis, Saccharimonadaceae was significantly increased in the GPP group compared to the EP and CNP group. In addition, decreased gene function associated with metabolic pathways was observed in PRP patients. CONCLUSIONS: Bacteroidetes and Synergistetes were the dominant orders in PRP patients. The altered composition of the gut microbiota in PRP patients provided deeper insights into the pathogenesis of PRP, and these biomarkers might be established as potential therapeutic targets that deserve further exploration.


Assuntos
Microbioma Gastrointestinal , Diálise Peritoneal , Peritonite , Bactérias/genética , Biomarcadores , DNA Ribossômico , Humanos , Diálise Peritoneal/efeitos adversos , Peritonite/etiologia , RNA Ribossômico 16S/genética
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