Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 165
Filtrar
1.
Histol Histopathol ; : 18384, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34693982

RESUMO

Retina remodeling is a consequence of many retinal degenerative diseases that are characterized by progressive photoreceptor death. Retina remodeling involves a series of complex pathological processes, consisting of photoreceptor degeneration and death, as well as retinal cell reprogramming and "rewiring". This rewiring alters retinal neural circuits that are centered on synaptic connections and lead to widespread death of retinal cells. Retinal remodeling, especially inner retinal remodeling, is the major factor that limits the effectiveness of various treatment strategies, including cell therapy; thus, it is important to elucidate the mechanisms involved in retinal remodeling during retinal degeneration. Microglia are the dominant immune cells in the retina. Microglia monitor the retinal microenvironment, are activated following retinal injury or degeneration, have powerful phagocytosis capabilities, and play a critical role in synaptic pruning during central neural system development. Analogously, microglia have been found to participate in the clearance of synaptic elements in a complement-dependent manner in the classic retinitis pigmentosa (RP) model, Royal College of Surgeons (RCS) rats, and retard the formation of ectopic neuritogenesis and the deterioration of visual function during retinal degeneration. Since previous research on microglia has rarely concentrated on synaptic remodeling during retinal degeneration, summarizing the microglial mechanisms involved in retinal remodeling is necessary in order to design compounds targeting microglia and retinal remodeling that might be promising therapeutic strategies for treating retinal degeneration.

2.
Bioorg Chem ; 116: 105273, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34474304

RESUMO

The ubiquitin-specific protease 7 (USP7)-murine double minute 2 (MDM2)-p53 network plays an important role in the regulation of p53, a tumor suppressor which plays critical roles in regulating cell growth, proliferation, cell cycle progression, apoptosis and immune response. The overexpression of USP7 and MDM2 in human cancers contributes to cancer initiation and progression, and their inhibition reactivates p53 signalings and causes cell cycle arrest and apoptosis. Herein, the current state of pharmacological characterization, potential applications in cancer treatment and mechanism of action of small molecules used to target and inhibit MDM2 and USP7 proteins are highlighted, along with the outcomes in clinical and preclinical settings. Moreover, challenges and advantages of these strategies, as well as perspectives in USP7-MDM2-p53 field are analyzed in detail. The investigation and application of MDM2 and USP7 inhibitors will deepen our understanding of the function of USP7-MDM2-p53 network, and feed in the development of effective and safe cancer therapies where USP7-MDM2-p53 network is implicated.

3.
Biomed Res Int ; 2021: 4822383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337012

RESUMO

Objective: Discectomy remains the classic procedure for treating lumbar intervertebral disc (IVD) herniation, but the occurrence of defects after discectomy is thought to be an important cause generating recurrent and accelerated IVD degeneration. Previous studies attempted suture of the annulus fissure, but the validity of this technique on restraining the degenerative process is controversial. On the other hand, cell therapies have been shown in multiple clinical and basic studies. Our purpose was to investigate the effectiveness of selective retention of autologous Bone Marrow Stromal Cells (BMSCs) with gelatin sponge in combination with annulus fibrosus suture (AFS) for the repair of IVD defects following mobile microendoscopic discectomy (MMED). Methods: This prospective, two-armed, and controlled clinical study was conducted from December 2016 to December 2018. Written informed consent was obtained from each patient. Forty-five patients with typical symptoms, positive signs of radiculopathy, and obvious lumbar disc herniation observed by MRI were enrolled. Patients were divided into 3 groups with different treating methods: MMED (n = 15), MMED+AFS (n = 15), and MMED+AFS+BMSCs (n = 15). A postoperative 2-year follow-up was performed to evaluate the patient-reported outcomes of VAS, ODI, and SF-36. The improvement rate of VAS and ODI was calculated as [(latest-preoperative)/preoperative] to evaluate the therapeutic effect of the three groups. Assessment parameters included Pfirrmann grade, intervertebral disc height (IDH), and disc protrusion size (DPS), as measured by MRI to evaluate the morphological changes. Results: All patients enrolled had a postoperative follow-up at 3, 6, 12, and 24 months. VAS and ODI scores were significantly improved compared to the preoperative status in all three groups with a mean DPS reduction rate over 50%. At the final follow-up, the improvement rate of the VAS score in the MMED+AFS+BMSCs group was significantly higher than the MMED+AFS and MMED groups (80.1% ± 7.6% vs. 71.3% ± 7.0% vs. 70.1% ± 7.8%), while ODI improvement showed a significant change (65.6% ± 8.8% vs. 59.9% ± 5.5% vs. 57.8% ± 8.1%). All participants showed significant improvement in SF-36 PCS and MCS; the differences between each group were not significant. The mean IDH loss rate of the MMED+AFS+BMSCs group was also significantly lower than other groups (-17.2% ± 1.3% vs. -27.6% ± 0.7% vs. -29.3% ± 2.2%). The Pfirrmann grade was aggravated in the MMED and MMED+AFS groups while maintained at the preoperative grade in the MMED+AFS+BMSCs group. No adverse events of cell transplantation or recurrence were found in all patients during the postoperative follow-up period. Conclusions: It is feasible and effective to repair lumbar IVD defects using SCR-enriched BMSCs with gelatin sponges, which warrants further study and development as a cell-based therapy for IVD repair.


Assuntos
Discotomia/efeitos adversos , Endoscopia , Gelatina/química , Degeneração do Disco Intervertebral/etiologia , Degeneração do Disco Intervertebral/terapia , Deslocamento do Disco Intervertebral/etiologia , Deslocamento do Disco Intervertebral/terapia , Células-Tronco Mesenquimais/citologia , Adulto , Anel Fibroso/diagnóstico por imagem , Anel Fibroso/cirurgia , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Estudos Prospectivos , Punções , Células Estromais/patologia , Inquéritos e Questionários , Suturas , Escala Visual Analógica , Adulto Jovem
4.
Cell Prolif ; 54(9): e13100, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34347352

RESUMO

OBJECTIVES: To evaluate the long-term biosafety and efficacy of transplantation of human embryonic stem cells-derived retinal pigment epithelial (hESC-RPE) cells in early-stage of Stargardt macular degeneration (STGD1). MATERIALS AND METHODS: Seven patients participated in this prospective clinical study, where they underwent a single subretinal transplantation of 1 × 105 hESC-RPE cells in one eye, whereas the fellow eye served as control. These patients were reassessed for a 60-month follow-up through systemic and ophthalmic examinations. RESULTS: None of the patients experienced adverse reactions systemically or locally, except for two who had transiently high intraocular pressure post-operation. Functional assessments demonstrated that all of the seven operated eyes had transiently increased or stable visual function 1-4 months after transplantation. At the last follow-up visit, two of the seven eyes showed visual function loss than the baseline; however, one of them showed a stable visual acuity when compared with the change of fellow eye. Obvious small high reflective foci in the RPE layer were displayed after the transplantation, and maintained until the last visit. Interestingly, three categories of patients who were classified based on autofluorescence, exhibited distinctive patterns of morphological and functional change. CONCLUSIONS: Subretinal transplantation of hESC-RPE in early-stage STGD1 is safe and tolerated in the long term. Further investigation is needed for choosing proper subjects according to the multi-model image and function assessments.


Assuntos
Células Epiteliais/citologia , Células-Tronco Embrionárias Humanas/citologia , Degeneração Macular/patologia , Epitélio Pigmentado da Retina/citologia , Pigmentos da Retina/fisiologia , Doença de Stargardt/patologia , Adulto , Diferenciação Celular/fisiologia , Linhagem Celular , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Transplante de Células-Tronco/métodos , Acuidade Visual/fisiologia , Adulto Jovem
5.
Biomed Res Int ; 2021: 8352683, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395625

RESUMO

Background: The competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms are known to play a pivotal role in intervertebral disc degeneration (IDD). Our research intended to establish a ceRNA regulatory network related to IDD through bioinformatics analyses. Methods: The expression profiles of circRNA, miRNA, and mRNA were obtained from the public Gene Expression Omnibus (GEO) datasets. Then, we use sequence-based bioinformatics methods to select differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs), or circRNAs (DEcircRNAs) related to IDD. We used ChEA3 to verify the targets of transcription factors (TFs). Then, we used DAVID to annotate the DEmRNAs. Finally, we constructed a potentially circRNA-miRNA-mRNA network related to IDD by predicting in the database (ENCORI, TargetScan, miRecords, miRmap, and circBank). Results: We identified 31 common DEmRNAs by Venn analysis, of which MMP2 was regarded as the key hub genes. Simultaneously, miR-423-5p and miR-185-5p were predicted as the upstream molecules of MMP2. Furthermore, a total of six DEcircRNAs were predicted as the upstream circRNAs of miR-423-5p and miR-185-5p. Then, a potential circRNA-miRNA-mRNA network related to IDD was constructed by bioinformatics analysis. Conclusion: A comprehensive ceRNA regulatory network was constructed, which was found to be significant in IDD progression.


Assuntos
Biologia Computacional/métodos , Degeneração do Disco Intervertebral/genética , Metaloproteinase 2 da Matriz/genética , MicroRNAs/genética , RNA Circular/genética , Progressão da Doença , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Anotação de Sequência Molecular , RNA Mensageiro/genética
6.
Stem Cell Reports ; 16(7): 1805-1817, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34214489

RESUMO

Stem cell transplantation shows enormous potential for treatment of incurable retinal degeneration (RD). To determine if and how grafts connect with the neural circuits of the advanced degenerative retina (ADR) and improve vision, we perform calcium imaging of GCaMP5-positive grafts in retinal slices. The organoid-derived C-Kit+/SSEA1- (C-Kit+) retinal progenitor cells (RPCs) become synaptically organized and build spontaneously active synaptic networks in three major layers of ADR. Light stimulation of the host photoreceptors elicits distinct neuronal responses throughout the graft RPCs. The graft RPCs and their differentiated offspring cells in inner nuclear layer synchronize their activities with the host cells and exhibit presynaptic calcium flux patterns that resemble intact retinal neurons. Once graft-to-host network is established, progressive vision loss is stabilized while control eyes continually lose vision. Therefore, transplantation of organoid-derived C-Kit+ RPCs can form functional synaptic networks within ADR and it holds promising avenue for advanced RD treatment.

7.
Bioorg Chem ; 114: 105120, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34216895

RESUMO

Bromodomain 4 (BRD4) proteins play an important role in histone post-translational modifications and facilitate several important physiological and pathological processes, including cancers. The inhibition of BRD4 by small molecule inhibitors shows promise as a therapeutic strategy for cancer treatment. However, their clinical applications were limited, which is largely hampered by off-target effects-induced toxicity. We herein report the design, synthesis, and cellular imaging of a set of tumor-anchored and BRD4-targeted fluorescent ligands by introducing selective and potent BRD4 inhibitor into different fluorophores via variable linkers. One of the fluorescent conjugates (compound 6) was demonstrated to be cell-permeable and low cytotoxic, preferentially accumulated in cancer cells, and display pronounced fluorescent signal. More importantly, 6 was identified to show specific BRD4 engagement in the cellular content. Collectively, this study provides a pathway for developing labeled BRD4 ligands and highlights that compound 6 may represent a valuable tool for explorative learning and target delivery study of BRD4.

8.
Eur J Med Chem ; 224: 113710, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34315039

RESUMO

Natural product andrographolide isolated from the plant Andrographis paniculata shows a plethora of biological activities, including anti-tumor, anti-bacterial, anti-inflammation, anti-virus, anti-fibrosis, anti-obesity, immunomodulatory and hypoglycemic activities. Based on extensive chemical structural modifications, a series of andrographolide derivatives with improved bioavailability and druggability has been developed. Moreover, greater understanding of their mechanisms of action at the molecular and cellular level has been thoroughly investigated. In this review, we give an outlook for the therapeutical potential of andrographolide and its derivatives in diverse diseases and highlighted the drug design, pharmacokinetic and mechanistic studies for the past ten years, together with a brief overview of the pharmacological effects. Notably, we focused to provide a critical enlightenment of the area of andrographolide and its derivatives with the intent of indicating the future perspectives, challenges and limitations. We believe that this review paper will benefit drug discovery where andrographolide was used as a template, shed light on the identification of drug targets for andrographolide and its analogs, as well as increase our knowledge for using them for therapeutic application, including the treatment for various forms of cancers.

9.
Front Genet ; 12: 656759, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178027

RESUMO

The functional alteration of nucleus pulposus cells (NPCs) exerts a crucial role in the occurrence and progression of intervertebral disk degeneration (IDD). Circular RNAs and microRNAs (miRs) are critical regulators of NPC metabolic processes such as growth and apoptosis. In this study, bioinformatics tools, encompassing Gene Ontology pathway and Venn diagrams analysis, and protein-protein interaction (PPI) network construction were used to identify functional molecules related to IDD. PPI network unveiled that ESR1 was one of the most critical genes in IDD. Then, a key IDD-related circ_0040039-miR-874-3p-ESR1 interaction network was predicted and constructed. Circ_0040039 promoted miR-874-3p and repressed ESR1 expression, and miR-874-3p repressed ESR1 expression in NPCs, suggesting ESR1 might be a direct target of miR-874-3p. Functionally, circ_0040039 could enhance NPC apoptosis and inhibit NPC growth, revealing that circ_0040039 might aggravate IDD by stabilizing miR-874-3p and further upregulating the miR-874-3p-ESR1 pathway. This signaling pathway might provide a novel therapeutic strategy and targets for the diagnosis and therapy of IDD-related diseases.

11.
Biomed Res Int ; 2021: 2545459, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104646

RESUMO

Background: Intervertebral disc degeneration (IDD) disease is a global challenge because of its predominant pathogenic factor in triggering low back pain, whereas cartilaginous endplate degeneration (CEPD) is the main cause of IDD. Accumulating evidence have indicated that the differentially expressed microRNAs (DEMs) and differentially expressed genes (DEGs) have been determined to be involved in multiple biological processes to mediate CEPD progression. However, the differentially expressed circular RNAs (DECs) and their potential biofunctions in CEPD have not been identified. Methods: GSE153761 dataset was analyzed using R software to predict DECs, DEMs, and DEGs. Pathway enrichment analysis of DEGs and host genes of DECs and protein-protein interaction network of DEGs were conducted to explore their potential biofunctions. Furthermore, we explore the potential relationship between DEGs and DECs. Results: There were 74 DECs, 17 DEMs, and 68 DEGs upregulated whereas 50 DECs, 16 DEMs, and 67 DEGs downregulated in CEPD group. Pathway analysis unveiled that these RNAs might regulate CEPD via mediating inflammatory response, ECM metabolism, chondrocytes apoptosis, and chondrocytes growth. A total of 17 overlapping genes were predicted between the host genes of DEGs and DECs, such as SDC1 and MAOA. Moreover, 6 upregulated DECs, of which hsa_circ_0052830 was the most upregulated circRNA in CEPD, were derived from the host genes SDC1, whereas 8 downregulated DECs were derived from the host genes MAOA. Conclusion: This will provide novel clues for future experimental studies to elucidate the pathomechanism of CEPD and therapeutic targets for CEPD-related diseases.


Assuntos
Degeneração do Disco Intervertebral/genética , MicroRNAs/genética , RNA Circular/genética , Biologia Computacional/métodos , Regulação para Baixo/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , Regulação para Cima/genética
12.
Front Oncol ; 11: 658608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937072

RESUMO

Gastric cancer is a global health problem. In this study, we investigate the role of a novel Indole derivative, named LCT-3d, in inhibiting the growth of gastric cancer cells by MTT assay. The Western blotting results showed that LCT-3d modulated the mitochondrial-related proteins and Cleaved-Caspases 3/9, to induce cell apoptosis. The up-regulation of Death receptor 5 (DR5) in MGC803 cells was observed with LCT-3d treatment. Knockdown of DR5 on MGC803 cells partially reversed the LCT-3d-induced mitochondrial apoptosis. The level of Reactive Oxygen Species (ROS) in MGC803 cells was increased with LCT-3d treatment and could be blocked with the pretreatment of the ROS inhibitor N-Acetylcysteine (NAC). The results demonstrate that the elevating ROS can up-regulate the expression of DR5, resulting in apoptosis via mitochondrial pathway. Although the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway served an important role in protecting gastric cancer cells against the injury of ROS, it can't reverse LCT-3d-induced cell apoptosis. Taken together, our study showed that LCT-3d induced apoptosis via DR5-mediated mitochondrial apoptotic pathway in gastric cancer cells. LCT-3d could be a novel lead compound for development of anti-cancer activity in gastric cancer.

13.
Mol Psychiatry ; 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963286

RESUMO

Astrocytes are integral components of synaptic transmission, and their dysfunction leads to neuropsychiatric disorders such as anxiety and depression. Liver X receptor ß (LXRß) is expressed in astrocytes, and LXRß global knockout mice shows impaired synaptic formation. In order to define the role of LXRß in astrocytes, we used a conditional Cre-loxP system to specifically remove LXRß from astrocytes. We found that this deletion caused anxiety-like but not depressive-like behaviors in adult male mice. This behavioral phenotype could be completely reproduced by selective deletion of LXRß in astrocytes in the medial prefrontal cortex (mPFC). Pyramidal neurons in layer V of mPFC are involved in mood behaviors. We found that there was an increased spontaneous excitatory synaptic transmission in layer V pyramidal neurons of the mPFC of these mice. This was concurrent with increased dendritic complexity, despite normal appearance and number of dendritic spines. In addition, gene ontology analysis of RNA sequencing revealed that deletion of astrocytic LXRß led to the enrichment of the process of synaptic transmission in mPFC. Finally, we also confirmed that renormalized excitatory synaptic transmission in layer V pyramidal neurons alleviated the anxiety in mice with astrocytic LXRß deletion in mPFC. Together, our findings reveal that astrocytic LXRß in mPFC is critical in the regulation of synaptic transmission, and this provides a potential new target for treatment of anxiety-like behavior.

14.
Viruses ; 13(2)2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670217

RESUMO

Influenza A virus is a highly variable and contagious respiratory pathogen that can cause annual epidemics and it poses an enormous threat to public health. Therefore, there is an urgent need for a new generation of antiviral drugs to combat the emergence of drug-resistant strains of the influenza virus. A novel series of butene lactone derivatives were screened and the compound 3D was selected, as it exhibited in vitro potential antiviral activity against A/Weiss/43 H1N1 virus with low toxicity. In addition, 3D dose-dependently inhibited the viral replication, expression of viral mRNA and viral proteins. 3D exerted a suppressive effect on A/Virginia/ATCC2/2009 H1N1 and A/California/2/2014 H3N2 in vitro. The time-of-addition analysis indicated that 3D suppressed H1N1 in the early stage of its life cycle. A/Weiss/43 H1N1-induced apoptosis in A549 cells was reduced by 3D via the mitochondrial apoptosis pathway. 3D could decrease the production of H1N1-induced pro-inflammatory cytokines that are induced by H1N1 in vitro and in vivo. The administration of 3D reduced lung lesions and virus load in vivo. These results suggest that 3D, which is a butene lactone derivative, is a promising agent for the treatment of influenza A virus infection.


Assuntos
4-Butirolactona/análogos & derivados , Antivirais/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Lactonas/química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Células A549 , Animais , Antivirais/química , Linhagem Celular , Citocinas/efeitos dos fármacos , Cães , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Lactonas/farmacologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C
15.
Front Cell Dev Biol ; 9: 607341, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33644046

RESUMO

Increasing evidence demonstrated that PM2.5 could cross the placenta and fetal blood-brain barrier, causing neurotoxicity of embryonic development. The retina, an embryologic extension of the central nervous system, is extremely sensitive and vulnerable to environmental insults. The adverse effects of PM2.5 exposure on the retina during embryonic neurodevelopment are still largely unknown. Our goal was to investigate the effect of PM2.5 on human retinal development, which was recapitulated by human embryonic stem cell (hESC)-derived retinal organoids (hEROs). In the present study, using the hEROs as the model, the influences and the mechanisms of PM2.5 on the developing retina were analyzed. It demonstrated that the formation rate of the hERO-derived neural retina (NR) was affected by PM2.5 in a concentration dosage-dependent manner. The areas of hEROs and the thickness of hERO-NRs were significantly reduced after PM2.5 exposure at the concentration of 25, 50, and 100 µg/ml, which was due to the decrease of proliferation and the increase of apoptosis. Although we did not spot significant effects on retinal differentiation, PM2.5 exposure did lead to hERO-NR cell disarranging and structural disorder, especially retinal ganglion cell dislocation. Transcriptome analysis showed that PM2.5 treatment was significantly associated with the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT pathways and reduced the level of the fibroblast growth factors (FGFs), particularly FGF8 and FGF10. These results provided evidence that PM2.5 exposure potentially inhibited proliferation and increased apoptosis at the early development stage of the human NR, probably through the MAPK and PI3K/Akt pathway. Our study suggested that exposure to PM2.5 suppressed cell proliferation and promoted cell apoptosis, thereby contributing to abnormal human retinal development.

16.
NPJ Regen Med ; 6(1): 16, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772031

RESUMO

Regeneration/repair after injury can be endowed by adult stem cells (ASCs) or lineage restricted and even terminally differentiated cells. In corneal epithelium, regeneration after a large wound depends on ASCs (limbal epithelial stem cells, LESCs), whereas repair after a small wound is LESCs-independent. Here, using rat corneal epithelial wounds with different sizes, we show that YAP activation promotes the activation and expansion of LESCs after a large wound, as well as the reprogramming of local epithelial cells (repairing epithelial cells) after a small wound, which contributes to LESCs-dependent and -independent wound healing, respectively. Mechanically, we highlight that the reciprocal regulation of YAP activity and the assembly of cell junction and cortical F-actin cytoskeleton accelerates corneal epithelial healing with different-sized wounds. Together, the common YAP activation and the underlying regulatory mechanism are harnessed by LESCs and lineage-restricted epithelial cells to cope with corneal epithelial wounds with different sizes.

17.
Anal Chim Acta ; 1143: 31-36, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33384127

RESUMO

This study demonstrated a facile, green and bioinspired approach to synthesize protein-posnjakite nanobiohybrid with rod-assembled hollow shuttle-like structure. Through the one-pot mild coprecipitation process, the inorganic mineral posnjakite (Cu4(SO4) (OH)6·H2O) served as a nanocarrier to efficient co-immobilization of recognition protein (streptavidin) and enzyme (horseradish peroxidase) for signal amplification, which avoids tedious linking or purification procedures and significantly simplifies the synthetic process. This nanobiohybrid was then utilized as the signal tag for immunoassays and presented excellent performance for the detection of insecticidal crystalline (Cry) protein Cry1Ab, in the linear range of 0.1-40 ng mL-1, with the limit of detection of 63 pg mL-1. This proposed strategy is expected to the integration of a variety of biomolecules with posnjakite to design diverse multifunctional nanobiohybrids for multiple applications extending from biosensors, catalysis and biomedicine to environmental science and energy.


Assuntos
Técnicas Biossensoriais , Catálise , Peroxidase do Rábano Silvestre , Proteínas , Estreptavidina
18.
Bioconjug Chem ; 32(1): 4-24, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33412857

RESUMO

In recent years, a variety of receptor-targeted fluorescent probes have been developed and widely used to realize the visualization of certain receptors, which facilitates the early diagnosis and treatment of diseases. In this Review, we focus on the recent achievements in design, chemical structure, imaging characterization, and potential applications of receptor-targeted fluorescent probes from the past 10 years. The development and application of receptor-targeted fluorescent probes will expand our knowledge of the distribution and function of disease-related receptors, shed light on the drug discovery for clinical diseases where receptors are implicated, and feed into the diagnosis and treatment of a plethora of diseases, including tumors.


Assuntos
Corantes Fluorescentes/química , Receptores de Superfície Celular/química , Animais , Descoberta de Drogas , Humanos , Estrutura Molecular , Imagem Óptica/métodos
19.
Mol Neurobiol ; 58(5): 2342-2361, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33417229

RESUMO

Müller glia originate from neuroepithelium and are the principal glial cells in the retina. During retinal development, Müller glia are one of the last cell types to be born. In lower vertebrates, such as zebrafish, Müller glia possess a remarkable capacity for retinal regeneration following various forms of injury through a reprogramming process in which endogenous Müller glia proliferate and differentiate into all types of retinal cells. In mammals, Müller glia become reactive in response to damage to protect or to further impair retinal function. Although mammalian Müller glia have regenerative potential, it is limited as far as repairing damaged retina. Lessons learned from zebrafish will help reveal the critical mechanisms involved in Müller glia reprogramming. Progress has been made in triggering Müller glia to reprogram and generate functional neurons to restore vision in mammals indicating that Müller glia reprogramming may be a promising therapeutic strategy for human retinal diseases. This review comprehensively summarizes the mechanisms related to retinal regeneration in model animals and the critical advanced progress made in Müller glia reprogramming in mammals.


Assuntos
Células Ependimogliais/fisiologia , Regeneração Nervosa/fisiologia , Retina/citologia , Animais , Proliferação de Células/fisiologia , Peixe-Zebra
20.
Exp Eye Res ; 202: 108305, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080300

RESUMO

The biosafety and efficiency of transplanting retinal pigment epithelial (RPE) cells derived from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been evaluated in phase I and phase II clinical trials. For further large-scale application, cryopreserved RPE cells must be used; thus, it is highly important to investigate the influence of cryopreservation and thawing on the biological characteristics of hESC-RPE cells and their post-transplantation vision-restoring function. Here, via immunofluorescence, qPCR, transmission electron microscopy, transepithelial electrical resistance, and enzyme-linked immunosorbent assays (ELISAs), we showed that cryopreserved hESC-RPE cells retained the specific gene expression profile, morphology, ultrastructure, and maturity-related functions of induced RPE cells. Additionally, cryopreserved hESC-RPE cells exhibited a polarized monolayer, tight junction, and gap junction structure and an in vitro nanoparticle phagocytosis capability similar to those of induced hESC-RPE cells. However, the level of pigment epithelium-derived factor (PEDF) secretion was significantly decreased in cryopreserved hESC-RPE cells. Royal College of Surgeons rats with cryopreserved hESC-RPE cells engrafted into the subretinal space exhibited a significant decrease in the b-wave amplitude compared with rats engrafted with induced hESC-RPE cells at 4 weeks post transplantation. However, the difference disappeared at 8 weeks and 12 weeks post operation. No significant difference in the outer nuclear layer (ONL) thickness was observed between the two groups. Our data showed that even after cryopreservation and thawing, cryopreserved hESC-RPE cells are still qualified as a donor cell source for cell-based therapy of retinal degenerative diseases.


Assuntos
Células-Tronco Embrionárias Humanas/fisiologia , Degeneração Retiniana/terapia , Epitélio Pigmentado da Retina/fisiologia , Transplante de Células-Tronco , Linhagem Celular , Polaridade Celular , Células Cultivadas , Criopreservação , Impedância Elétrica , Células-Tronco Embrionárias Humanas/ultraestrutura , Humanos , Microscopia Eletrônica de Transmissão , Degeneração Retiniana/metabolismo , Degeneração Retiniana/fisiopatologia , Epitélio Pigmentado da Retina/ultraestrutura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...