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The impact of anthropogenic global warming has induced significant upward dispersal of trees to higher elevations at alpine treelines. Assessing vertical deviation from current uppermost tree distributions to potential treeline positions is crucial for understanding ecosystem responses to evolving global climate. However, due to data resolution constraints and research scale limitation, comprehending the global pattern of alpine treeline elevations and driving factors remains challenging. This study constructed a comprehensive quasi-observational dataset of uppermost tree distribution across global mountains using Google Earth imagery. Validating the isotherm of mean growing-season air temperature at 6.6 ± 0.3°C as the global indicator of thermal treeline, we found that around two-thirds of uppermost tree distribution records significantly deviated from it. Drought conditions constitute the primary driver in 51% of cases, followed by mountain elevation effect which indicates surface heat (27%). Our analyses underscore the multifaceted determinants of global patterns of alpine treeline, explaining divergent treeline responses to climate warming. Moisture, along with temperature and disturbance, plays the most fundamental roles in understanding global variation of alpine treeline elevation and forecasting alpine treeline response to ongoing global warming.
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Ecossistema , Árvores , Árvores/fisiologia , Temperatura , Temperatura Baixa , Clima , AltitudeRESUMO
BACKGROUND: Analyzing the glaucoma burden in "Belt and Road" (B&R) countries based on age, gender, and risk factors from 1990 to 2019 in order to provide evidence for future prevention strategies. METHODS: We applied global burden of disease(GBD) 2019 to compare glaucoma prevalence and Years lived with disabilities (YLDs) from 1990 to 2019 in the B&R countries. Trends of disease burden between 1990 and 2019 were evaluated using the average annual percent change and the 95% uncertainty interval (UI) were reported. RESULTS: From 1990 to 2019, most B&R countries showed a downward trend in age-standardized prevalence and YLDs (all P < 0.05). Additionally, only the age-standardized YLDs in males of Pakistan has a 0.35% increase (95%CI:0.19,0.50,P < 0.001), and most B&R countries has a decline(all P < 0.05) in age-standardized YLDs in every 5 years age group after 45 years old except for Pakistan(45-79 years and > 85 years), Malaysia(75-84 years), Brunei Darussalam(45-49 years), Afghanistan(70-79 years). Finally, in all Central Asian countries, the age-standardized YLDs due to glaucoma caused by fasting hyperglycemia demonstrated have an increase between 1990 and 2019 (all P < 0.05), but Armenia and Mongolia have a decrease between 2010 and 2019 (all P < 0.05). CONCLUSION: The prevalence of glaucoma continues to pose a significant burden across regions, ages, and genders in countries along the "B&R". It is imperative for the "B&R" nations to enhance health cooperation in order to collaboratively tackle the challenges associated with glaucoma.
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Glaucoma , Humanos , Glaucoma/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Prevalência , Idoso de 80 Anos ou mais , Adulto , Fatores de Risco , Distribuição por Idade , Carga Global da Doença/tendências , Distribuição por Sexo , Adulto Jovem , Adolescente , Efeitos Psicossociais da Doença , Anos de Vida Ajustados por Deficiência/tendênciasRESUMO
Triazine herbicides are common contaminants in coastal waters, and they are recognized as inhibitors of photosystem II, causing significant hinderance to the growth and reproduction of phytoplankton. However, the influence of these herbicides on microalgal toxin production remains unclear. This study aimed to examine this relationship by conducting a comprehensive physiological and 4D label-free quantitative proteomic analysis on the harmful dinoflagellate Karenia mikimotoi in the presence of the triazine herbicide dipropetryn. The findings demonstrated a significant decrease in photosynthetic activity and pigment content, as well as reduced levels of unsaturated fatty acids, reactive oxygen species (ROS), and hemolytic toxins in K. mikimotoi when exposed to dipropetryn. The proteomic analysis revealed a down-regulation in proteins associated with photosynthesis, ROS response, and energy metabolism, such as fatty acid biosynthesis, chlorophyll metabolism, and nitrogen metabolism. In contrast, an up-regulation of proteins related to energy-producing processes, such as fatty acid ß-oxidation, glycolysis, and the tricarboxylic acid cycle, was observed. This study demonstrated that dipropetryn disrupts the photosynthetic systems of K. mikimotoi, resulting in a notable decrease in algal toxin production. These findings provide valuable insights into the underlying mechanisms of toxin production in toxigenic microalgae and explore the potential effect of herbicide pollution on harmful algal blooms in coastal environments.
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Dinoflagellida , Herbicidas , Microalgas , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Dinoflagellida/metabolismo , Proliferação Nociva de Algas , Fotossíntese , Herbicidas/metabolismo , Ácidos Graxos/metabolismo , Triazinas/toxicidade , Triazinas/metabolismoRESUMO
T cell exhaustion caused by mitochondrial dysfunction is the major obstacle of T cells-based cancer immunotherapy. Besides exhausted T cells, the insufficient major histocompatibility complex class I (MHC I) on tumor cells leads to inefficient T cell recognition of tumor cells, compromising therapeutic efficacy. Therapeutic platform to regulate T cell exhaustion and MHC I expression for boosting T cells-based cancer immunotherapy has not been realized up to date. Herein, an injectable hydrogel is designed to simultaneously tune T cell exhaustion and MHC I expression for amplified cancer immunotherapy. The hydrogel is in situ constructed in tumor site by utilizing oxidized sodium alginate-modified tumor cell membrane vesicle (O-TMV) as a gelator, where axitinib is encapsulated in the lipid bilayer of O-TMV while 4-1BB antibody and proprotein convertase subtilisin/kexin type 9 inhibitor PF-06446846 nanoparticles are present in the cavities of hydrogel. After immune response trigged by O-TMV antigen, the 4-1BB antibody-promoted T cell mitochondrial biogenesis and the axitinib-lowered hypoxia synergistically reverse T cell exhaustion while the PF-06446846-amplified MHC I expression facilitates T cell recognition of tumor cells, demonstrating a powerful immunotherapeutic efficacy. This strategy on reprograming T cell exhaustion and improving T cell potency offers new concept for T cells-based cancer immunotherapy.
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Neoplasias , Linfócitos T , Anticorpos , Axitinibe , Antígenos de Histocompatibilidade Classe I , Humanos , Hidrogéis , Imunoterapia , Neoplasias/terapiaRESUMO
BACKGROUND: The purpose of this study was to compare the diagnostic performance of isolated-check visual evoked potential (icVEP) with that of retinal ganglion cell-inner plexiform layer (GCILP) analysis using optical coherence tomography (OCT). METHODS: A total of 45 patients were enrolled: 25 patients with open-angle glaucoma and 20 healthy patients. All patients underwent a complete ophthalmological examination. Moreover, the OCT examination was used to analyze the structures of the GCIPL. The icVEP technique was used to detect the transmission function of the magnocellular pathway, which is mainly managed by the retinal ganglion cells. The quantitative and qualitative comparisons between the diagnostic power of GCIPL analysis and that of icVEP were performed. The areas under the receiver operating characteristic curves (AUC) of GCIPL analysis and icVEP were compared using the Clarke-Pearson method. The sensitivity and specificity of the two techniques were analyzed and compared using the McNemar test. RESULTS: With the quantitative comparison, the AUC of icVEP (AUC = 0.892) was higher than that of GCIPL analysis (AUC = 0.814). However, there was no statistical significance between the AUCs of icVEP and GCIPL (P > 0.05). With the qualitative comparison, the sensitivity of icVEP was 80%, and its specificity was 90%. The sensitivity of GCIPL analysis was 72%, and its specificity was 85%. There was no significant difference between the sensitivitiesor specificities of icVEP and GCIPL analysis (P > 0.05). Moreover, 30 (66.67%) eyeshad similar resultsbetween icVEP and GCIPL analysis, and 15 (33.33%) eyes had different results (7 eyes had abnormal results with GCIPL analysisbut normal results with icVEP, and8 eyes had normal results with GCIPL analysisbut abnormal results with icVEP). CONCLUSIONS: The diagnostic power of icVEP was close to that of GCIPL analysis whether the comparison was based on the qualitative or quantitative data.
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Potenciais Evocados Visuais/fisiologia , Glaucoma de Ângulo Aberto/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Eletroencefalografia , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Curva ROC , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Cancer immunotherapy has received increasing attention in tumor therapy. However, insufficient infiltration of T cells and over-expressed PD-L1 checkpoint in tumor cells severely impede cancer immunotherapy. Here, an injectable hydrogel was designed to reinforce T cell infiltration and inactivate PD-L1 for powerful cancer immunotherapy. The hydrogel was created by sodium alginate (SA) as the gelator, where linagliptin particles and BMS-202 particles were present in hydrogel micropores. After gelation in the tumor site, the linagliptin powerfully suppressed chemokine CXCL10 degradation, enabling the introduced CXCL10 to realize sustainable chemotaxis towards strong T cell infiltration. Meanwhile, the BMS-202 inactivated PD-L1 of tumor cells, thereby eliminating the PD-L1-governed immune evasion. Therefore, the hydrogel in combination with CXCL10 demonstrated powerful cancer immunotherapy against primary and distant tumors, along with efficient inhibition of lung metastasis. Our study not only offers a potent platform against tumors, but also provides a conceptually new approach to reinforce cancer immunotherapy.
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Neoplasias Pulmonares , Linfócitos T , Humanos , Linfócitos T/metabolismo , Antígeno B7-H1/metabolismo , Hidrogéis , Evasão da Resposta Imune , Linagliptina , Neoplasias Pulmonares/terapia , ImunoterapiaRESUMO
The aim of this study was to investigate the effects of 7,8-dihydroxyflavone (7,8-DHF) in protecting retinal ganglion cells (RGCs) and promoting axonal regeneration, and to explore its potential molecular mechanisms. We used three-dimensional retinal culture system and optic nerve crush (ONC) rat models in this study. The pro-axonal regenerative effect of 7,8-DHF was determined with light microscopy observation and immunofluorescence staining of Thy1.1 and GAP43. The RGC protective function of 7,8-DHF was detected by RBPMS immunofluorescent staining and TUNEL staining. The inhibition effect of 7,8-DHF on astrocyte activation was measured using GFAP immunofluorescence and Western blotting. The protein levels of p-TrkB, p-AKT and p-ERK was examined by Western blotting and immunohistochemistry. Our results revealed that 7,8-DHF significantly promoted the average density and length of regenerated neurites and suppressed the apoptosis of GCL cells in three-dimensional culture system and significantly increased the number of RBPMS-positive cells and inhibited the GFAP expression and apoptosis of GCL cells in ONC rats. Our results also revealed that 7,8-DHF activates TrkB, AKT and ERK proteins in vivo, however, these activations can be inhibited byANA-12. In conclusion, 7,8-DHF protects RGCs and promotes axonal regeneration through the TrkB signaling pathway followed by AKT and ERK activation.
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Proteínas Proto-Oncogênicas c-akt , Células Ganglionares da Retina , Ratos , Animais , Células Ganglionares da Retina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neuritos , ApoptoseRESUMO
Ferroptosis has received increasing attentions in cancer therapy owing to its unique advantages over apoptosis. However, ferroptosis is governed by the efficiency of reactive oxygen species (ROS) production and the tumor cell antioxidant microenvironment that compromises therapeutic efficacy of ferroptosis. It is of great significance to develop a strategy that can both achieve high-efficiency ROS production and modulate tumor cell antioxidant microenvironment to amplify ferroptosis. However, until now, such a strategy has rarely been realized. Here, we, for the first time, reported a radiotherapy -mediated redox homeostasis-controllable nanomedicine for amplifying ferroptosis sensitivity in tumor therapy. The nanomedicine is constructed by co-assembling a ferroptosis inducer hemin and a thioredoxin 1 (Trx-1) inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) with human serum albumin. For our nanomedicine, hemin converts H2O2 to ROS via Fenton reaction to induce ferroptosis while PX-12 effectively inhibits the activity of antioxidant Trx-1 to suppress ROS depletion, resulting in amplified ferroptosis. Particularly, combining radiotherapy with the nanomedicine, radiotherapy depletes the other key antioxidant glutathione and generates additional radiotherapy-induced ROS, further boosting the ferroptosis effect. Therefore, our strategy can simultaneously ensure efficient ROS production and regulation of tumor cell antioxidant microenvironment, thereby enhancing efficacy of ferroptosis in tumor therapy. Our work offers an innovative approach to amplify ferroptosis sensitivity against tumors by simultaneously promoting ROS production and regulating redox homeostasis. STATEMENT OF SIGNIFICANCE: The antioxidants such as thioredoxin 1 (Trx-1) and glutathione (GSH) in tumor cells, are significantly upregulated by the innate cancer cellular redox homeostasis, severely restricting the reactive oxygen species (ROS)-based therapy and compromising the effect of Fenton reaction-induced ferroptosis against tumors. It is urgent to develop a strategy to simultaneously achieve Fenton reaction-induced ferroptosis and regulate the cancer cellular redox homeostasis against upregulated levels of Trx-1 and GSH. A radiotherapy-mediated redox homeostasis-regulatable nanomedicine was designed for amplifying ferroptosis sensitivity in tumor therapy, where the therapeutic efficacy of ferroptosis against tumors can be significantly amplified by integrating Fenton reaction-induced and radiotherapy-induced ferroptosis as well as PX-12-enabled inhibition of antioxidant Trx-1 and radiotherapy-induced downregulation of antioxidant GSH levels.
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Ferroptose , Neoplasias , Humanos , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Nanomedicina , Hemina/farmacologia , Peróxido de Hidrogênio/farmacologia , Oxirredução , Glutationa/metabolismo , Homeostase , Tiorredoxinas/metabolismo , Tiorredoxinas/farmacologia , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
"Glutamine addiction" is a unique feature of triple negative breast cancer (TNBC), which has a higher demand for glutamine and is more susceptible to glutamine depletion. Glutamine can be hydrolyzed to glutamate by glutaminase (GLS) for synthesis of glutathione (GSH), which is an important downstream of glutamine metabolic pathways in accelerating TNBC proliferation. Consequently, glutamine metabolic intervention suggests potential therapeutic effects against TNBC. However, the effects of GLS inhibitors are hindered by glutamine resistance and their own instability and insolubility. Therefore, it is of great interest to harmonize glutamine metabolic intervention for an amplified TNBC therapy. Unfortunately, such nanoplatform has not been realized. Herein, we reported a self-assembly nanoplatform (BCH NPs) with a core of the GLS inhibitor Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) and photosensitizer Chlorin e6 (Ce6) and a shell of human serum albumin (HSA), enabling effective harmonization of glutamine metabolic intervention for TNBC therapy. BPTES inhibited the activity of GLS to block the glutamine metabolic pathways, thereby inhibiting the production of GSH to amplify the photodynamic effect of Ce6. While Ce6 not only directly killed tumor cells by producing excessive reactive oxygen species (ROS), but also deplete GSH to destroy redox balance, thus enhancing the effects of BPTES when glutamine resistance occurred. BCH NPs effectively eradicated TNBC tumor and suppressed tumor metastasis with favorable biocompatibility. Our work provides a new insight for photodynamic-mediated glutamine metabolic intervention against TNBC.
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Polyphosphate (polyP) has long been recognized as a crucial intracellular reservoir for phosphorus in microorganisms. However, the dynamics of polyP and its regulatory mechanism in eukaryotic phytoplankton in response to variations in external phosphorus conditions remain poorly understood. A comprehensive investigation was conducted to examine the intracellular polyP-associated metabolic response of the dinoflagellate Karenia mikimotoi, a harmful algal bloom species, through integrated physiological, biochemical, and transcriptional analyses under varying external phosphorus conditions. Comparable growth curves and Fv/Fm between phosphorus-replete conditions and phosphorus-depleted conditions suggested that K. mikimotoi has a strong capability to mobilize the intracellular phosphorus pool for growth under phosphorus deficiency. Intracellular phosphate (IPi) and polyP contributed approximately 6-23 % and 1-3 %, respectively, to the overall particulate phosphorus (PP) content under different phosphorus conditions. The significant decrease in PP and increase in polyP:PP suggested that cellular phosphorus components other than polyP are preferred for utilization under phosphorus deficiency. Genes involved in polyP synthesis and hydrolysis were upregulated to maintain phosphorus homeostasis in K. mikimotoi. These findings provide novel insights into the specific cellular strategies for phosphorus storage and the transcriptional response in intracellular polyP metabolism in K. mikimotoi. Additionally, these results also indicate that polyP may not play a crucial role in cellular phosphorus storage in phytoplankton, at least in dinoflagellates.
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Dinoflagellida , Dinoflagellida/genética , Fósforo , Polifosfatos , Proliferação Nociva de Algas , Fitoplâncton , Expressão GênicaRESUMO
Purpose: To investigate the efficacy and safety of pulsed ultrasound (PUS) in enhancing fluorescein sodium (NaF) transport to the rabbit eye through the transscleral and transconjunctival routes in vivo. Methods: PUS and NaF were applied onto the supratemporal sclera/conjunctiva of healthy rabbit eyes. PUS (1 MHz, 2.37 W/cm2, 30% duty cycle, 5-min application time) was performed 3 times with a 5-min interval. In the same process, NaF was administered to the eye without PUS in the control. NaF concentrations in the vitreous and retina-choroid were determined by fluorescence measurement. The safety of PUS application was assessed based on temperature and intraocular pressure measurements, clinical observations, electroretinography, histology, and Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay. Results: In comparison to the control, higher NaF concentrations were found in the retina-choroid following transscleral (2.45-fold) and transconjunctival (2.97-fold) PUS applications (P < 0.05). NaF concentrations in the vitreous were 3.15 and 5.86 times greater in transscleral and transconjunctival PUS applications, respectively, compared with those obtained without PUS application (P < 0.05), and NaF level in the vitreous after transconjunctival PUS application was 2.61 times that of transscleral PUS application (P < 0.05). Ocular findings were transient and mild conjunctival injection, with no other structural and functional changes in PUS-treated eyes. Conclusions: PUS treatment can improve transscleral and transconjunctival delivery of NaF efficiently and safely. Transscleral and transconjunctival PUS applications offer potential clinical benefit in increasing drug penetration to the posterior segments of the eye for the noninvasive treatment of ocular diseases.
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Sistemas de Liberação de Medicamentos , Fluoresceína , Animais , Coelhos , Túnica Conjuntiva , Eletrorretinografia , Fluoresceína/administração & dosagem , Esclera , Ondas Ultrassônicas , Corpo Vítreo , OlhoRESUMO
Prophylactic tumor vaccines hold great promise against tumor occurrence. However, their clinical efficacy remains low due to inadequate activation of strong-sustainable immunity. Herein, a biomembrane hydrogel was designed as a powerful single-shot prophylactic tumor vaccine. Mannose-decorated hybrid biomembrane (MHCM) modified with oxidized sodium alginate (OSA) was designed as a gelator (O-MHCM), where the hybrid biomembrane (HCM) is a hybridization of bacterial outer membrane vesicles (OMV) and tumor cell membranes (TCM). The O-MHCM enables quick gelation subcutaneously where the cysteine protease inhibitor E64 is encapsulated in hydrogel micropores. After a single vaccination of E64@O-MHCM hydrogel, MHCM and E64 are released sustainably due to OSA moiety degradation. The MHCM enables active targeting to dendritic cells (DC) and effective DC maturation. Meanwhile, the E64 enables sufficient antigen availability for subsequent cross presentation. Ultimately, strong and sustainable T lymphocyte-mediated immunity was elicited, demonstrating a strong prophylactic effect against breast tumors. This study provides a long-lasting platform to prevent tumor occurrence, opening an innovative avenue for the design of a single-shot prophylactic tumor vaccine. STATEMENT OF SIGNIFICANCE: Developing a single-shot prophylactic tumor vaccine to elicit strong-sustainable immunity is of great interest clinically. Here, a prophylactic tumor vaccine was designed using an injectable biomembrane hydrogel for achieving strong-sustainable immunity. The mannose-tailored hybrid biomembrane was modified with oxidized sodium alginate to result in a gelator, which enabled the formation of the hydrogel after subcutaneous injection. Cysteine protease inhibitor E64 was incorporated into the micropores of the hydrogel. The hydrogel induced strong-sustainable immunity through the continuous release of active components. This was facilitated by the mannose moiety, which enabled active targeting, as well as the antigen and adjuvant function of biomembrane, and the E64-enabled suppression of antigen degradation. The biomembrane hydrogel demonstrated powerful prevention of 4T1 breast tumors. This study offers an attractive strategy for designing a single-shot prophylactic tumor vaccine.
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Neoplasias da Mama , Vacinas Anticâncer , Humanos , Feminino , Hidrogéis/farmacologia , Manose , Linfócitos T , Antígenos , Neoplasias da Mama/tratamento farmacológico , Células DendríticasRESUMO
T cell-based immunotherapy (TCBI) is an emerging approach to combat tumors. However, the outcome of TCBI is still far from satisfaction clinically, owing to stumbling blocks from insufficient immunogenicity, T cell exhaustion and immune evasion from programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway. Herein, an injectable tumor lysates-constructed hydrogel is reported to address these issues. Chemically modified tumor lysates are, for the first time, designed as the gelator to intratumorally construct hydrogel, achieving a robust antigen reservoir to induce strong immunogenicity. Meanwhile, hydrogel-encapsulated nicotinamide riboside and SB415286 enable strong mitophagy in T cells to prevent their exhaustion as well as powerfully genetical suppression of PD-1 expression to regulate immune evasion. Thus, our injectable hydrogel creates a robust immune niche within tumor, enabling to significantly potentiate TCBI. Our strategy pharmacologically regulates body's own T cells in situ, demonstrating potent immunotherapeutic effects and offering a conceptually new approach for TCBI.
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Hidrogéis , Neoplasias , Humanos , Receptor de Morte Celular Programada 1 , Linfócitos T/metabolismo , Imunoterapia , Microambiente TumoralRESUMO
Purpose: This study aimed to investigate the simultaneous neuroprotective and proangiogenic effects of 7,8-dihydroxyflavone (7,8-DHF) and explore the potential underlying molecular mechanisms. Methods: A coculture system of rat retinal explants and human umbilical vein endothelial cells (HUVECs) was established to determine the optimal concentration of 7,8-DHF, promoting neurite regeneration and HUVEC proliferation. Subsequently, the neuroprotective effect, proangiogenesis properties, and action mechanism of 7,8-DHF at an optimal concentration were investigated. Results: The cell proliferation, survival, migration, tube formation and p-tropomyosin-related kinase receptor B (TrkB)/TrkB levels in HUVECs were significantly promoted by 5 µM 7,8-DHF. The ganglion cell layer neuron survival, neurite regeneration, and p-TrkB/TrkB levels in retinal explants were also significantly promoted by 5 µM 7,8-DHF. All of these pharmacological actions of 7,8-DHF were blocked by N-[2-[(2-oxoazepan-3-yl)carbamoyl]phenyl]-1-benzothiophene-2-carboxamide. Conclusions: 7,8-DHF yields neuroprotection of retinal explants and proangiogenesis of HUVECs through the TrkB signaling pathway in vitro.
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Neuroproteção , Tropomiosina , Humanos , Ratos , Animais , Tropomiosina/farmacologia , Células Endoteliais da Veia Umbilical Humana , Transdução de SinaisRESUMO
BACKGROUND: Three-dimensional culture system of retinal explant is commonly used to study retinal ganglion cell (RGC) axon regeneration in vitro. The retinal explants fabricated by traditional procedure in culture system, however, are usually too small (merely 0.5 × 0.5 mm) to be easily detected or treated by current experimental techniques. Also, the constituents of culture medium have not been fully elucidated. NEW METHOD: A fabrication procedure was developed to enlarge the retinal explants and explore the reasonable concentration of fetal bovine serum (FBS) for evaluating axonal regeneration. RESULTS: There were no significant differences in the density or length of regenerative neurites in the retinal explants fabricated by traditional and modified procedures. Increased FBS concentrations promoted neurite regeneration, decreased RGCs apoptosis, and activated tyrosine kinase B (TrkB) receptors, all reaching a plateau at 1 % FBS. COMPARISON WITH EXISTING METHODS: Compared with traditional procedure, the modified fabrication procedure facilitates application of experimental techniques to retinal explants, increases the efficiency of obtaining observation area of regenerating neurites, and reduces the wastage of retinal tissues. The recommended FBS concentration determined in this study is shown to be more suitable for studying neuronal regeneration. CONCLUSION: The retinal explants made by the modified fabrication procedure are successfully applied to the three-dimensional culture system, and presented several advantages over the traditional one. Furthermore, a preliminary experiment must be performed to determine the suitable concentration of FBS in each study to ensure accuracy and stability of the results obtained from the three-dimension retinal culture system.
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Axônios , Regeneração Nervosa , Neuritos , Retina , Células Ganglionares da RetinaRESUMO
The Alpine Leaf-warbler (Phylloscopus occisinensis) is a small-sized and poorly-known songbird endemic to China. In this study, we sequenced and described the whole mitochondrial genome of the Alpine leaf-warbler. The entire mitochondrial sequence was determined by long-range PCR and conserved primer walking approaches. The results demonstrated that the whole mitochondrial genome of P. occisinensis was 16,879 bp in length with 53.1% A + T content; the genome harboured the same gene order as that of other passerine birds, including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and non-coding control region. The control region (D-loop) of P. rubicilloides include two portions that one was located between tRNA-Gln and tRNA-Phe (219 bp in length) and the other is between tRNA-Thr and tRNA- Pro (1087 bp in length), which is similar to other Leaf-warblers. Phylogenetic analysis indicated that the genome of Phylloscopus species clustered within a clade and is closer related to Aegithalidae species than Paridae species. These mitochondrial data are potentially important for the further studies on molecular evolution and conservation genetics on leaf warbler species.
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AIM: To compare the diagnostic performance of isolated-check visual evoked potential (icVEP) and standard automated perimetry (SAP), for evaluating the application values of icVEP in the detection of early glaucoma. METHODS: Totally 144 subjects (288 eyes) were enrolled in this study. icVEP testing was performed with the Neucodia visual electrophysiological diagnostic system. A 15% positive-contrast (bright) condition pattern was used in this device to differentiate between glaucoma patients and healthy control subjects. Signal-to-noise ratios (SNR) were derived based on a multivariate statistic. The eyes were judged as abnormal if the test yielded an SNR≤1. SAP testing was performed with the Humphrey Field Analyzer II. The visual fields were deemed as abnormality if the glaucoma hemifield test results outside normal limits; or the pattern standard deviation with P<0.05; or the cluster of three or more non-edge points on the pattern deviation plot in a single hemifield with P<0.05, one of which must have a P<0.01. Disc photographs were graded as either glaucomatous optic neuropathy or normal by two experts who were masked to all other patient information. Moorfields regression analysis (MRA) used as a separate diagnostic classification was performed by Heidelberg retina tomograph (HRT). RESULTS: When the disc photograph grader was used as diagnostic standard, the sensitivity for SAP and icVEP was 32.3% and 38.5% respectively and specificity was 82.3% and 77.8% respectively. When the MRA Classifier was used as the diagnostic standard, the sensitivity for SAP and icVEP was 48.6% and 51.4% respectively and specificity was 84.1% and 78.0% respectively. When the combined structural assessment was used as the diagnostic standard, the sensitivity for SAP and icVEP was 59.2% and 53.1% respectively and specificity was 84.2% and 84.6% respectivlely. There was no statistical significance between the sensitivity or specificity of SAP and icVEP, regardless of which diagnostic standard was based on. CONCLUSION: The diagnostic performance of icVEP is not better than that of SAP in the detection of early glaucoma.
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AIM: To quantify the association between diabetes and glaucoma using Meta-analysis. METHODS: PubMed and Embase were searched using medical subject headings and key words related to diabetes and glaucoma. The inclusion criteria were: 1) the study design was a prospective cohort study; 2) the exposure of interest was diabetes; 3) the outcome of interest was primary open angle glaucoma (POAG); 4) risk ratios (RR) and the corresponding 95% confidence interval (CI). Data were pooled using fixed effects models to take into account heterogeneity between studies. Seven prospective studies were selected. Diabetes increased the incidence of glaucoma by 36% (OR=1.36, 95% CI=1.25-1.50). There was no evidence of statistical heterogeneity (I2=0, P=0.53) or publication bias (the funnel plot did not identify obvious asymmetry). RESULTS: Seven prospective cohort studies were incorporated in this Meta-analysis. The pooled RR of the association between POAG and diabetes based on the risk estimates of the seven cohort studies was 1.36 (95%CI=1.24-1.50), with no significant heterogeneity across studies (I2=0; P=0.526). The sensitivity analysis yielded a range of RRs from 1.34 (95%CI=1.22-1.48) to1.40 (95%CI=1.18-1.67). CONCLUSION: Diabetes is associated with a significantly increased risk of glaucoma.