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1.
Fish Shellfish Immunol ; 149: 109555, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615703

RESUMO

Developing a low-protein feed is important for the sustainable advancement of aquaculture. The aim of this study was to investigate the effects of essential amino acid (EAA) supplementation in a low-protein diet on the growth, intestinal health, and microbiota of the juvenile blotched snakehead, Channa maculata in an 8-week trial conducted in a recirculating aquaculture system. Three isoenergetic diets were formulated to include a control group (48.66 % crude protein (CP), HP), a low protein group (42.54 % CP, LP), and a low protein supplementation EAA group (44.44 % CP, LP-AA). The results showed that significantly lower weight gain (WG), specific growth rate (SGR), protein efficiency ratio (PER), and feed efficiency ratio (FER) were observed in fish that were fed LP than in the HP and LP-AA groups (P < 0.05). The HP and LP-AA groups exhibited a significant increase in intestinal villus length, villus width, and muscular thickness compared to the LP group (P < 0.05). Additionally, the HP and LP-AA groups demonstrated significantly higher levels of intestinal total antioxidant capacity (T-AOC), catalase (CAT), and superoxide dismutase (SOD) and lower levels of malondialdehyde (MDA) compared to the LP group (P < 0.05). The apoptosis rate of intestinal cells in the LP group was significantly higher than those in the LP and HP groups (P < 0.05). The mRNA expression levels of superoxide dismutase (sod), nuclear factor kappa B p65 subunit (nfκb-p65), heat shock protein 70 (hsp70), and inhibitor of NF-κBα (iκba) in the intestine were significantly higher in the LP group than those in the HP and LP-AA groups (P < 0.05). The 16s RNA analysis indicated that EAA supplementation significantly increased the growth of Desulfovibrio and altered the intestinal microflora. The relative abundances of Firmicutes and Cyanobacteria were positively correlated with antioxidant parameters (CAT and T-AOC), whereas Desulfobacterota was negatively correlated with sod and T-AOC. The genera Bacillus, Bacteroides, and Rothia were associated with the favorable maintenance of gut health. In conclusion, dietary supplementation with EAAs to achieve a balanced amino acid profile could potentially reduce the dietary protein levels from 48.66 % to 44.44 % without adversely affecting the growth and intestinal health of juvenile blotched snakeheads.


Assuntos
Aminoácidos Essenciais , Ração Animal , Suplementos Nutricionais , Microbioma Gastrointestinal , Intestinos , Animais , Ração Animal/análise , Suplementos Nutricionais/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Aminoácidos Essenciais/administração & dosagem , Perciformes/crescimento & desenvolvimento , Perciformes/imunologia , Dieta com Restrição de Proteínas/veterinária , Dieta/veterinária , Distribuição Aleatória , Peixes/crescimento & desenvolvimento , Aquicultura , Channa punctatus
2.
Animals (Basel) ; 14(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38338122

RESUMO

The Asian yellow pond turtle (Mauremys mutica) is widely traded in China, and its artificial breeding has now become a major industry. However, the insufficient offspring supply and reproductive decline of farmed turtles make the wild turtles more vulnerable. The present study was mainly designed to quantify the fecundity of M. mutica and attempt to screen for good reproductive performance in females. The genetic variability of the population and its genetic structure were also analysed. The parent-offspring relationships of all offspring in four consecutive years were confirmed using sixteen microsatellite loci. The genetic variability between the parents and offspring was low, and offspring of different years also showed little variability. We summarised the reproductive results of all females and counted the annual number of offspring and the variation in the number of offspring. The females were then divided into three types (stable, undulating and levelling off) according to the continuity. We selected seven females with good reproductive ability, which provided 16.94% of the annual contributions, while there were two females that had no offspring in four years. We also analysed the possible reasons for this difference and the importance of carrying out a family survey. This research can provide the basis and materials for the creation of a good reproductive group and the study of the reproductive biology of turtles in M. mutica aquaculture.

3.
Ageing Res Rev ; 94: 102183, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38218465

RESUMO

Brain diseases present a significant obstacle to both global health and economic progress, owing to their elusive pathogenesis and the limited effectiveness of pharmaceutical interventions. Phototherapy has emerged as a promising non-invasive therapeutic modality for addressing age-related brain disorders, including stroke, Alzheimer's disease (AD), and Parkinson's disease (PD), among others. This review examines the recent progressions in phototherapeutic interventions. Firstly, the article elucidates the various wavelengths of visible light that possess the capability to penetrate the skin and skull, as well as the pathways of light stimulation, encompassing the eyes, skin, veins, and skull. Secondly, it deliberates on the molecular mechanisms of visible light on photosensitive proteins, within the context of brain disorders and other molecular pathways of light modulation. Lastly, the practical application of phototherapy in diverse clinical neurological disorders is indicated. Additionally, this review presents novel approaches that combine phototherapy and pharmacological interventions. Moreover, it outlines the limitations of phototherapeutics and proposes innovative strategies to improve the treatment of cerebral disorders.


Assuntos
Doença de Alzheimer , Doença de Parkinson , Humanos , Fototerapia , Pele , Doença de Parkinson/patologia , Doença de Alzheimer/patologia
4.
Anim Reprod Sci ; 261: 107406, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141547

RESUMO

In ruminants, establishment and maintenance of pregnancy depends upon a well-coordinated interaction between the conceptus and the maternal endometrium. Epidermal growth factor (EGF) is important for embryo implantation and pregnancy establishment. However, the regulatory mechanisms of EGF expression remain unclear. FOXO1, a member of the Forkhead box O (FOXO) subfamily of transcription factors, is currently accepted as a novel endometrial receptivity marker for humans and mice owing to its timely and specific expression at the window of implantation. In this study, we examined the spatiotemporal expression profile of EGF in goat uterus during early pregnancy (Day 0 to Day 50 of pregnancy) and verified that EGF expression was regulated by FOXO1 and interferon tau (IFNT). Our results showed that EGF was highly expressed in the luminal epithelium (LE) and the glandular epithelium (GE) during conceptus adhesion (Day 16 to Day 25 of pregnancy). After implantation, EGF protein signals were continuously detected in the endometrial epithelia and appeared in the conceptus trophectoderm. Furthermore, EGF expression could be up-regulated by IFNT in goat uterus and primary endometrial epithelium cells (EECs). The luciferase assay results showed that FOXO1 could promote EGF transcription by binding to its promoter. And FOXO1 positively regulates EGF expression in goat EECs. These findings contribute to better understanding the role and regulation mechanisms of EGF during ruminant early pregnancy.


Assuntos
Endométrio , Fator de Crescimento Epidérmico , Interferon Tipo I , Proteínas da Gravidez , Gravidez , Humanos , Feminino , Animais , Camundongos , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Endométrio/metabolismo , Implantação do Embrião/fisiologia , Útero/metabolismo , Ruminantes , Cabras , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo
5.
Front Neurol ; 14: 1273822, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37941571

RESUMO

Background: Cerebral extracranial-intracranial (EC-IC) revascularization technique (superficial temporal artery-middle cerebral artery (STA-MCA) bypass grafting) has become the preferred surgical method for the treatment of Moyamoya disease (MMD). We attempted to completely free the two branches of the superficial temporal artery without disconnection. Extracranial and intracranial blood flow reconstruction were then modified by selectively performing a direct bypass technique on one branch and a patch fusion technique on the other of the STA based on the blood flow and the vascular diameter of the intracranial surface blood vessels. Methods: A series of modified STA-MCA bypass surgeries performed consecutively between March 2022 and March 2023 were reviewed and compared to conventional combined bypass surgeries performed during the same period. The following information was collected from all enrolled patients: demographic characteristics, clinical symptoms, and preoperative and postoperative imaging, including Suzuki stage and Matsushima grade. The modified Rankin scale (mRS) was used to assess the changes in neurological status before and after surgery. Results: A total of 41 patients with Moyamoya disease (MMD) who underwent cerebral revascularization were included in this study, of which 30 were conventional revascularization and 11 were modified revascularization. The mean age was 49.91 years, and 18 (43.9%) of the patients were women. The modified group had a lower incidence of cerebral hyperperfusion syndrome (18.2%) than the conventional group (23.3%). After at least 3 months of follow-up, the bypass patency rate remained 100% in the modified group and 93.3% in the conventional group. All patients in the modified group achieved a better Matsushima grade (A + B), with six (54.5%) having an A and five (45.5%) having a B. In contrast, four patients (13.3%) in the conventional group had a Matsushima grade of C. In all, 72.8% of the modified group had postoperative mRS scores of 0 and 1, which was higher than that of the traditional group (63.3%). Conclusion: The improved STA-MCA bypass could provide blood flow to multiple cerebral ischemic areas, reduce excessive blood perfusion, and ensure blood supply to the scalp, with lower complications and better clinical benefits than the traditional combined bypass.

6.
Fish Physiol Biochem ; 49(6): 1215-1227, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37857788

RESUMO

Many fish species exhibit remarkable sexual dimorphism, with males possessing numerous advantageous traits for commercial production by aquaculture such as faster growth rate, more efficient food energy utilization for muscle development, and better breeding performance. Several studies have shown that a decrease in the number of primordial germ cells (PGCs) during early development leads predominantly to male progeny. In this study, we developed a method to obtain all-male zebrafish (Danio rerio) by targeted PGC ablation using the nitroreductase/metronidazole (NTR/Mtz) system. Embryos generated by female heterozygous Tg(nanos3:nfsB-mCherry-nanos3 3'UTR) and male wild-types (WTs) were treated with vehicle or Mtz. Compared to vehicle-treated controls, 5.0 and 10.0 mM Mtz treatment for 24 h significantly reduced the number of PGCs and yielded an exclusively male phenotype in adulthood. The gonads of offspring treated with 5.0 mM Mtz exhibited relatively normal morphology and histological characteristics. Furthermore, these males were able to chase females, spawn, and produce viable offspring, while about 20.0% of males treated with 10.0 mM Mtz were unable to produce viable offspring. The 5.0 mM Mtz treatment protocol may thus be suitable for large-scale production of fertile male offspring. Moreover, about half of these males were WT as evidenced by the absence of nfsB gene expression. It may thus be possible to breed an all-male WT fish population by Mtz-mediated PGC ablation.


Assuntos
Perciformes , Peixe-Zebra , Animais , Masculino , Feminino , Peixe-Zebra/fisiologia , Proteínas de Peixe-Zebra/genética , Células Germinativas , Fertilidade , Perciformes/metabolismo
7.
Biology (Basel) ; 12(10)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37887041

RESUMO

Based on obtaining mstnb gene knockout in Pelteobagrus fulvidraco, a study on the effect of the mstn gene on skeletal morphology and growth was performed by comparing the number and length of the vertebrae of mutant and wild-type fish in a sibling group of P. fulvidraco, combined with the differences in cells at the level of vertebral skeletal tissue. It was found that mstnb gene knockdown resulted in a reduction in the number of vertebrae, the length, and the intervertebral distance in P. fulvidraco, and these changes may be the underlying cause of the shorter body length in mutant P. fulvidraco. Further, histological comparison of the same sites in the mstn mutant and wild groups of P. fulvidraco also revealed that the number and density of osteocytes were greater in mstnb knockout P. fulvidraco than in wild-type P. fulvidraco. Our results demonstrated that when using genome editing technology to breed new lines, the effects of knockout need to be analyzed comprehensively and may have some unexpected effects due to insufficient study of the function of certain genes.

8.
bioRxiv ; 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37905115

RESUMO

Long-term, real-time molecular monitoring in complex biological environments is critical for our ability to understand, prevent, diagnose, and manage human diseases. Aptamer-based electrochemical biosensors possess the promise due to their generalizability and a high degree of selectivity. Nevertheless, the operation of existing aptamer-based biosensors in vivo is limited to a few hours. Here, we report a first-generation long-term in vivo molecular monitoring platform, named aptamer-graphene microtransistors (AGMs). The AGM incorporates a layer of pyrene-(polyethylene glycol)5-alcohol and DNase inhibitor-doped polyacrylamide hydrogel coating to reduce biofouling and aptamer degradation. As a demonstration of function and generalizability, the AGM achieves the detection of biomolecules such as dopamine and serotonin in undiluted whole blood at 37 °C for 11 days. Furthermore, the AGM successfully captures optically evoked dopamine release in vivo in mice for over one week and demonstrates the capability to monitor behaviorally-induced endogenous dopamine release even after eight days of implantation in freely moving mice. The results reported in this work establish the potential for chronic aptamer-based molecular monitoring platforms, and thus serve as a new benchmark for molecular monitoring using aptamer-based technology.

9.
Stem Cell Res Ther ; 14(1): 233, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667370

RESUMO

BACKGROUND: To explore whether local transplantation of mesenchymal stem cells (MSCs) in temporal muscle can promote collateral angiogenesis and to analyze its main mechanisms of promoting angiogenesis. METHODS: Bilateral carotid artery stenosis (BCAS) treated mice were administrated with encephalo-myo-synangiosis (EMS), and bone marrow mesenchymal stem cells (BMSCs) were transplanted into the temporal muscle near the cerebral cortex. On the 30th day after EMS, the Morris water maze, immunofluorescence, laser speckle imaging, and light sheet microscopy were performed to evaluate angiogenesis; In addition, rats with bilateral common carotid artery occlusion were also followed by EMS surgery, and BMSCs from GFP reporter rats were transplanted into the temporal muscle to observe the survival time of BMSCs. Then, the concentrated BMSC-derived conditioned medium (BMSC-CM) was used to stimulate HUVECs and BMECs for ki-67 immunocytochemistry, CCK-8, transwell and chick chorioallantoic membrane assays. Finally, the cortical tissue near the temporal muscle was extracted after EMS, and proteome profiler (angiogenesis array) as well as RT-qPCR of mRNA or miRNA was performed. RESULTS: The results of the Morris water maze 30 days after BMSC transplantation in BCAS mice during the EMS operation, showed that the cognitive impairment in the BCAS + EMS + BMSC group was alleviated (P < 0.05). The results of immunofluorescence, laser speckle imaging, and light sheet microscopy showed that the number of blood vessels, blood flow and astrocytes increased in the BCAS + EMS + BMSC group (P < 0.05). The BMSCs of GFP reporter rats were applied to EMS and showed that the transplanted BMSCs could survive for up to 14 days. Then, the results of ki-67 immunocytochemistry, CCK-8 and transwell assays showed that the concentrated BMSC-CM could promote the proliferation and migration of HUVECs and BMECs (P < 0.05). Finally, the results of proteome profiler (angiogenesis array) in the cerebral cortex showed that the several pro-angiogenesis factors (such as MMP-3, MMP-9, IGFBP-2 or IGFBP-3) were notably highly expressed in MSC transplantation group compared to others. CONCLUSIONS: Local MSCs transplantation together with EMS surgery can promote angiogenesis and cognitive behavior in chronic brain ischemia mice. Our study illustrated that MSC local transplantation can be the potential therapeutical option for improving EMS treatment efficiency which might be translated into clinical application.


Assuntos
Isquemia Encefálica , Células-Tronco Mesenquimais , Camundongos , Ratos , Animais , Antígeno Ki-67 , Proteoma , Sincalida , Neovascularização Patológica , Isquemia Encefálica/terapia
10.
Macromol Rapid Commun ; 44(17): e2300170, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37243910

RESUMO

Herein, a novel tough luminescent hydrogel with Europium is fabricated using a facile copolymerization process by introducing 2,2':6',2-terpyridine (TPy) into a dual physical cross-linked hydrogel. The obtained P(NAGA-co-MAAc)/Eu/TPy (x) (x refers to the feed ratio of NAGA to MAAc) hydrogels not only show outstanding mechanical performances (fracture strength, ≈2.5 MPa), but also give a special ability of rapid detection to low concentrations of zinc ions. Attractively, the theoretical limits of detection (LOD) of the hydrogel sensors are calculated as 1.6 µm, which is acceptable within the WHO limit. Furthermore, the continuous change in fluorescence of P(NAGA-co-MAAc)/Eu/TPy (10) strips upon contact with Zn2+ can be clearly observed by the naked eyes with the aid of a portable UV lamp, resulting in semi-quantitative naked-eyes detection through a standard colorimetric card. Moreover, by identifying the RGB value of the hydrogel sensor, it can also realize quantitative analysis. Therefore, excellence in sensing, simplicity in structure, and convenience in using make P(NAGA-co-MAAc)/Eu/TPy (10) hydrogel as a superior fluorescent chemosensor of Zn2+ ions.


Assuntos
Hidrogéis , Luminescência , Hidrogéis/química , Íons/química , Fluorescência , Zinco/química
11.
Biol Reprod ; 108(6): 902-911, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-36917263

RESUMO

N6-methyladenosine (m6A), an epigenetic modification on RNAs, plays an important role in many physiological and pathological processes. However, the involvement of m6A in goat uterus during early pregnancy remains largely unknown. In this study, we found that the total m6A level was increasing in goat uterus as early pregnancy progressed. Methyltransferase-like 3 (METTL3) is a core catalytic subunit of the m6A methyltransferase. We thus determined the expression and regulation of METTL3 in goat uterus. METTL3 was highly expressed in the luminal and glandular epithelia from day 16 (D16) to D25 of pregnancy, and it could be up-regulated by estrogen and progesterone in goat uterus and primary endometrial epithelial cells (EECs). In EECs, knockdown or overexpression of METTL3 resulted in a significant decrease or increase of cell proliferation, respectively. METTL3 knockdown reduced the m6A level of not only total RNA but also connective tissue growth factor (CTGF) mRNA. Luciferase assay suggested that METTL3 might target the potential m6A sites in the 3'untranslated region (3'UTR) of CTGF mRNA. Moreover, METTL3 positively regulated CTGF expression, and CTGF knockdown significantly counteracted the promoting effect of METTL3 overexpression on EEC proliferation. Collectively, METTL3 is dynamically expressed in goat uterus and can affect EEC proliferation by regulating CTGF in an m6A-dependent manner. Our results will lay a foundation for further studying the crucial mechanism of METTL3-mediated m6A modification in goat uterus during early pregnancy.


Assuntos
Fator de Crescimento do Tecido Conjuntivo , Cabras , Animais , Feminino , Fator de Crescimento do Tecido Conjuntivo/genética , Cabras/genética , Metiltransferases/genética , Metiltransferases/metabolismo , Células Epiteliais/metabolismo , RNA Mensageiro/metabolismo , Proliferação de Células/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-36763047

RESUMO

Silicone elastomers, such as poly(dimethylsiloxane) (PDMS), have a broad range of applications in basic biomedical research and clinical medicine, ranging from the preparation of microfluidic devices for organs-on-chips and ventriculoperitoneal shunts for the treatment of hydrocephalus to implantable neural probes for neuropharmacology. Despite the importance, the protein adsorptions on silicone elastomers in these application environments represent a significant challenge. Surface coatings with slippery lubricants, inspired by the Nepenthes pitcher plants, have recently received much attention for reducing protein adsorptions. Nevertheless, the depletion of the physically infused lubricants limits their broad applications. In this study, we report a covalently attached slippery surface coating to reduce protein adsorptions on PDMS surfaces. As demonstrations, we show that the adsorption of serum proteins, human fibrinogen and albumin, can be significantly reduced by the slippery surface coating in both planar PDMS surfaces and 3D microfluidic channels. The preparation of slippery surface coatings relies on the acid-catalyzed polycondensation reaction of dimethyldimethoxysilane, which utilizes a low-cost and scalable dip-coating method. Furthermore, cell metabolic activity and viability studies demonstrate the biocompatibility of the surface coating. These results suggest the potential applications of slippery surface coatings to reduce protein adsorptions for implantable medical devices, organs-on-chips, and many others.

13.
Mol Ther ; 31(5): 1313-1331, 2023 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-36739479

RESUMO

Astrocyte-microglial interaction plays a crucial role in brain injury-associated neuroinflammation. Our previous data illustrated that astrocytes secrete microRNA, leading to anti-inflammatory effects on microglia. Long non-coding RNAs participate in neuroinflammation regulation after traumatic brain injury. However, the effect of astrocytes on microglial phenotype via long non-coding RNAs and the underlying molecular mechanisms remain elusive. We used long non-coding RNA sequencing on murine astrocytes and found that exosomal long non-coding RNA 4933431K23Rik attenuated traumatic brain injury-induced microglial activation in vitro and in vivo and ameliorated cognitive function deficiency. Furthermore, microRNA and messenger RNA sequencing together with binding prediction illustrated that exosomal long non-coding RNA 4933431K23Rik up-regulates E2F7 and TFAP2C expression by sponging miR-10a-5p. Additionally, E2F7 and TFAP2C, as transcription factors, regulated microglial Smad7 expression. Using Cx3cr1-Smad7 overexpression of adeno-associated virus, microglia specifically overexpressed Smad7 in the attenuation of neuroinflammation, resulting in less cognitive deficiency after traumatic brain injury. Mechanically, overexpressed Smad7 physically binds to IκBα and inhibits its ubiquitination, preventing NF-κB signaling activation. The Smad7 activator asiaticoside alleviates neuroinflammation and protects neuronal function in traumatic brain injury mice. This study revealed that an exosomal long non-coding RNA from astrocytes attenuates microglial activation after traumatic brain injury by up-regulating Smad7, providing a potential therapeutic target.


Assuntos
Lesões Encefálicas Traumáticas , MicroRNAs , RNA Longo não Codificante , Camundongos , Animais , Microglia/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Astrócitos/metabolismo , Doenças Neuroinflamatórias , MicroRNAs/metabolismo , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo , Fenótipo , Camundongos Endogâmicos C57BL
14.
Transl Stroke Res ; 14(4): 608-623, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36181627

RESUMO

Moyamoya disease (MMD) is characterized by frequent migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) in the intima layer of blood vessels. However, the underlying mechanism is unclear. Toll-like receptor (TLR) 7 is abundantly expressed in smooth muscle cells (SMCs) in multiple vascular diseases, which might be linked to the disease-associated vascular remodeling. In the present study, the expression of TLR7 in MMD vessels was examined using the superficial temporal artery (STA) and middle cerebral artery (MCA) from MMD patients. Furthermore, the effect of TLR7 activation on the VSMC phenotype switch in vitro and vascular remodeling in vivo was assessed using a 9.4Tesla MRI. Our results demonstrated that the TLR7 and microRNA Let-7c expression are upregulated in VSMCs and the plasma of MMD patients, respectively. Additionally, TLR7 stimulation by Let-7c or Imiquimod induces a synthetic phenotype switch in VSMCs. Mechanistic studies revealed that Akt/mTOR signaling is responsible for this TLR-induced VSMC phenotypic switch. The Let-7c or Imiquimod treatment also resulted in reduced blood flow of internal carotid arteries (ICAs) in an in vivo model, while TLR7 inhibition attenuated the ICA stenosis. Besides, Let-7c was also found to be elevated in the hypoxic endothelial cells. Taken together, our study demonstrates that Let-7c released by endothelial cells under hypoxic conditions may activate TLR7 on VSMCs, ultimately leading to the phenotype switch and vascular wall remodeling. These findings thus elucidate the putative mechanisms underlying progressive stenosis of blood vessels in MMD and provide prospective therapeutic targets for further exploration.


Assuntos
Doença de Moyamoya , Humanos , Doença de Moyamoya/genética , Remodelação Vascular/fisiologia , Constrição Patológica/metabolismo , Células Endoteliais/metabolismo , Imiquimode/metabolismo , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Miócitos de Músculo Liso/metabolismo , Proliferação de Células , Fenótipo
15.
Cells ; 11(23)2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36497052

RESUMO

Moyamoya disease (MMD) is an occlusive, chronic cerebrovascular disease affected by genetic mutation and the immune response. Furthermore, vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) participate in the neointima of MMD, but the etiology and pathophysiological changes in MMD vessels remain largely unknown. Therefore, we established the circZXDC (ZXD family zinc finger C)-miR-125a-3p-ABCC6 (ATP-binding cassette subfamily C member 6) axis from public datasets and online tools based on "sponge-like" interaction mechanisms to investigate its possible role in VSMCs. The results from a series of in vitro experiments, such as dual luciferase reporter assays, cell transfection, CCK-8 assays, Transwell assays, and Western blotting, indicate a higher level of circZXDC in the MMD plasma, especially in those MMD patients with the RNF213 mutation. Moreover, circZXDC overexpression results in a VSMC phenotype switching toward a synthetic status, with increased proliferation and migration activity. CircZXDC sponges miR-125a-3p to increase ABCC6 expression, which induces ERS (endoplasmic reticulum stress), and subsequently regulates VSMC transdifferentiation from the contractive phenotype to the synthetic phenotype, contributing to the intima thickness of MMD vessels. Our findings provide insight into the pathophysiological mechanisms of MMD and indicate that the circZXDC-miR-125a-3p-ABCC6 axis plays a pivotal role in the progression of MMD. Furthermore, circZXDC might be a diagnostic biomarker and an ABCC6-specific inhibitor and has the potential to become a promising therapeutic option for MMD.


Assuntos
MicroRNAs , Doença de Moyamoya , Proteínas Associadas à Resistência a Múltiplos Medicamentos , RNA Circular , Humanos , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Proliferação de Células/genética , Transdiferenciação Celular , Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Doença de Moyamoya/genética , Doença de Moyamoya/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Músculo Liso Vascular/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , RNA Circular/genética
16.
Brain Sci ; 12(10)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36291219

RESUMO

OBJECTIVE: To analyze the risk factors of transient neurological deficits (TND) and perioperative stroke in patients with MMD after extracranial-intracranial revascularization. METHODS: A retrospective analysis of the clinical data of 183 patients with MMD undergoing 203 EC-IC bypass operation procedures from January 2018 to August 2020. According to whether TND and stroke occurred within 14 days after operation, univariate analysis and multivariate logistic regression were used. RESULTS: TND occurred in 26 cases (12.8%) of revascularization. The results of the univariate analysis showed that history of diabetes, multiple episodes of preoperative symptoms, lesions involving the posterior circulation, and high postoperative blood pressure are the risk factors of TND. Further multivariate logistic regression analysis showed that multiple episodes of preoperative symptoms (p = 0.016) and lesions involving the posterior circulation (p = 0.014) are the independent risk factors for TND. Perioperative stroke occurred in 12 cases (5.9%). The results of the univariate analysis showed that older age, history of hypertension, preoperative cerebral infarction as the main symptom, lesions involving the posterior circulation, and high perioperative blood pressure are the risk factors of perioperative stroke. The results of multivariate logistic regression analysis showed that preoperative cerebral infarction as the main symptom (p = 0.015) is an independent risk factor for perioperative stroke. The occurrence of perioperative complications was not related to the improvement of follow-up mRS (Modified Rankin Scale) score and long-term cerebral rehemorrhage. CONCLUSIONS: Clinically, patients with MMD have multiple episodes of preoperative symptoms, lesions involving the posterior circulation, and preoperative cerebral infarction and should be attached when undergoing revascularization.

17.
J Hazard Mater ; 439: 129654, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35908401

RESUMO

Oil-water emulsions separation is frequently required considering the production and environmental issues. Herein, a nano-modification strategy has been proposed for carboxylated poly(propylene oxide)-poly(ethylene oxide) block polyether (mANP) using epoxy-functionalized magnetic nanoparticles (Fe3O4@SiO2-GPTMS), achieving the construction of a highly efficient demulsifier (M-mANP). Bottle tests showed that M-mANP could separate over 98.5% of water from the asphaltene-stabilized water-in-oil (W/O) emulsion at mANP concentration of 150 ppm within 2 min at room temperature. The demulsification efficiency for crude oil-in-water emulsion was nearly 100%. According to interfacial tension and wettability tests, the nano-modification endows M-mANP with good amphiphilicity and high interfacial activity, which enables M-mANP to rapidly adsorb at the oil-water interface. Molecular dynamics simulation shows that abundant oxygen-containing groups (hydroxyl, ether bond, ester and carboxyl groups, Fe-O and Si-O bond) in M-mANP could strengthen the interaction with water, facilitating the replacement of asphaltene molecules at interfacial film. Observation of demulsification process by microscope reveals that the nano-size promotes M-mANP to bridge small dispersed droplets, enhancing the flocculation and coalescence of droplets. The nano-modified carboxylated polyether with outstanding demulsification ability shows a promising application for the treatment of different oil-water emulsions.

18.
Nano Lett ; 22(9): 3668-3677, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35439419

RESUMO

The real-time monitoring of neurochemical release in vivo plays a critical role in understanding the biochemical process of the complex nervous system. Current technologies for such applications, including microdialysis and fast-scan cyclic voltammetry, suffer from limited spatiotemporal resolution or poor selectivity. Here, we report a soft implantable aptamer-graphene microtransistor probe for real-time monitoring of neurochemical release. As a demonstration, we show the monitoring of dopamine with nearly cellular-scale spatial resolution, high selectivity (dopamine sensor >19-fold over norepinephrine), and picomolar sensitivity, simultaneously. Systematic benchtop evaluations, ex vivo experiments, and in vivo studies in mice models highlight the key features and demonstrate the capability of capturing the dopamine release dynamics evoked by pharmacological stimulation, suggesting the potential applications in basic neuroscience studies and studying neurological disease-related processes. The developed system can be easily adapted for monitoring other neurochemicals and drugs by simply replacing the aptamers functionalized on the graphene microtransistors.


Assuntos
Dopamina , Grafite , Animais , Camundongos , Norepinefrina , Oligonucleotídeos
19.
Sci Adv ; 8(8): eabn2277, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35196090

RESUMO

Extensive studies in both animals and humans have demonstrated that high molecular weight neurochemicals, such as neuropeptides and other polypeptide neurochemicals, play critical roles in various neurological disorders. Despite many attempts, existing methods are constrained by detecting neuropeptide release in small animal models during behavior tasks, which leaves the molecular mechanisms underlying many neurological and psychological disorders unresolved. Here, we report a wireless, programmable push-pull microsystem for membrane-free neurochemical sampling with cellular spatial resolution in freely moving animals. In vitro studies demonstrate the sampling of various neurochemicals with high recovery (>80%). Open-field tests reveal that the device implantation does not affect the natural behavior of mice. The probe successfully captures the pharmacologically evoked release of neuropeptide Y in freely moving mice. This wireless push-pull microsystem creates opportunities for neuroscientists to understand where, when, and how the release of neuropeptides modulates diverse behavioral outputs of the brain.

20.
Adv Healthc Mater ; 11(10): e2101667, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35108456

RESUMO

The efficient regeneration of corneal nerves is of limited success in the field of ophthalmology. This work reports the use of a non-invasive electrical stimulation technique that uses a transparent graphene-based corneal stimulation electrode and that can achieve efficient regeneration of corneal nerves. The corneal stimulation electrode is prepared using electroactive nitrogen-containing conducting polymers such as polyaniline functionalized graphene (PAG). This composite can carry a high capacitive current. It can be used to tune transmembrane signaling pathways including calcium channels and the MAPK signaling pathway. Tuning can lead to the efficient regeneration of corneal damaged nerves after the surgery of laser in-situ keratomileusis (LASIK). The composite and its application reported have the potential to provide a new way to treat nerve-related injuries.


Assuntos
Grafite , Córnea/cirurgia , Eletrodos , Regeneração Nervosa/fisiologia , Transdução de Sinais
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