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BACKGROUND: Disruptions in vascular formation attributable to chemical insults is a pivotal risk factor or potential etiology of developmental defects and various disease settings. Among the thousands of chemicals threatening human health, the highly concerning groups prevalent in the environment and detected in biological monitoring in the general population ought to be prioritized because of their high exposure risks. However, the impacts of a large number of environmental chemicals on vasculature are far from understood. The angioarchitecture complexity and technical limitations make it challenging to analyze the entire vasculature efficiently and identify subtle changes through a high-throughput in vivo assay. OBJECTIVES: We aimed to develop an automated morphometric approach for the vascular profile and assess the vascular morphology of health-concerning environmental chemicals. METHODS: High-resolution images of the entire vasculature in Tg(fli1a:eGFP) zebrafish were collected using a high-content imaging platform. We established a deep learning-based quantitative framework, ECA-ResXUnet, combined with MATLAB to segment the vascular networks and extract features. Vessel scores based on the rates of morphological changes were calculated to rank vascular toxicity. Potential biomarkers were identified by vessel-endothelium-gene-disease integrative analysis. RESULTS: Whole-trunk blood vessels and the cerebral vasculature in larvae exposed to 150 representative chemicals were automatically segmented as comparable to human-level accuracy, with sensitivity and specificity of 95.56% and 95.81%, respectively. Chemical treatments led to heterogeneous vascular patterns manifested by 31 architecture indexes, and the common cardinal vein (CCV) was the most affected vessel. The antipsychotic medicine haloperidol, flame retardant 2,2-bis(chloromethyl)trimethylenebis[bis(2-chloroethyl) phosphate], and tert-butylphenyl diphenyl phosphate ranked as the top three in vessel scores. Pesticides accounted for the largest group, with a vessel score of ≥1, characterized by a remarkable inhibition of subintestinal venous plexus and delayed development of CCV. Multiple-concentration evaluation of nine per- and polyfluoroalkyl substances (PFAS) indicated a low-concentration effect on vascular impairment and a positive association between carbon chain length and benchmark concentration. Target vessel-directed single-cell RNA sequencing of fli1a+ cells from larvae treated with λ-cyhalothrin, perfluorohexanesulfonic acid, or benzylbutyl phthalate, along with vessel-endothelium-gene-disease integrative analysis, uncovered potential associations with vascular disorders and identified biomarker candidates. DISCUSSION: This study provides a novel paradigm for phenotype-driven screenings of vascular-disrupting chemicals by converging morphological and transcriptomic profiles at a high-resolution level, serving as a powerful tool for large-scale toxicity tests. Our approach and the high-quality morphometric data facilitate the precise evaluation of vascular effects caused by environmental chemicals. https://doi.org/10.1289/EHP13214.
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Pez Cebra , Animales , Contaminantes Ambientales/toxicidad , Vasos Sanguíneos/efectos de los fármacosRESUMEN
Background: Post-auricular injection of lidocaine and methylprednisolone sodium succinate is a commonly used treatment for outpatient patients with tinnitus, but it is invasive, painful and has uncertain efficacy. We need to try to replace it with more non-invasive and effective treatments. The 2014 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery recommend the use of cognitive behavioral therapy (CBT) to treat tinnitus. Some clinical doctors have also attempted sound therapy for tinnitus. It is unclear whether sound therapy combined with CBT y is more effective than local injection of lidocaine and methylprednisolone sodium succinate in treating tinnitus. Objective: To evaluate the efficacy and influencing factors of refined sound therapy combined with CBT in the treatment of tinnitus and compare it with post-auricular injection of lidocaine and methylprednisolone sodium succinate. Methods: We recruited 100 patients with tinnitus; ultimately, 81 patients completed the experiment and underwent follow-up. Patients were randomly assigned to either the treatment group (refined sound therapy combined with CBT) or the control group (post-auricular injections of lidocaine and methylprednisolone sodium succinate). Data was collected from 49 patients in the treatment group and 32 patients in the control group. Pre- and post-treatment data were collected using the Self-Rating Depression Scale (SDS), Hamilton Anxiety Rating Scale (HAM-A), Visual Analogue Score (VAS), Tinnitus loudness and Tinnitus Handicap Inventory (THI) score. Comparisons between groups were performed using the chi-square test, Fisher's exact test, or Wilcoxon rank-sum test. All tests were two-sided and considered statistically significant with P < .05. Results: The THI, SDS and HAM-A scores in the treatment group decreased significantly. In the control group, there was a significant reduction in THI scores, but not in SDS and HAM-A scores. In addition, tinnitus loudness and VAS scores were significantly decreased in the 2 groups. There was a significant difference in the reduction of THI, SDS, HAM-A and VAS scores between the 2 groups; the treatment group showed a greater reduction. However, there was no significant difference in the reduction of tinnitus loudness. There was no statistical difference in the reduction of THI scores, SDS scores, VAS scores and tinnitus loudness in different frequency groups, but there was a statistical difference in the reduction of HAM-A scores. There was no statistical difference in the reduction of THI scores, SDS scores, HAM-A scores, VAS scores and tinnitus loudness between patients with and without hearing loss. Conclusions: (1) This new combination is more effective than post-auricular injection of lidocaine and methylprednisolone sodium succinate in treating tinnitus and improving psychological symptoms. The latter had no effect on improving psychological indicators. (2) With this combination, patients with different tinnitus frequencies experienced different improvements in anxiety. (3) Low-frequency tinnitus seems have been more likely to cause sound adaptation. (4) The improvement in tinnitus and anxiety was the same regardless of whether or not there was hearing loss.
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BACKGROUND: Extensive production and usage of commercially available products containing TiO2 NPs have led to accumulation in the human body. The deposition of TiO2 NPs has even been detected in the human placenta, which raises concerns regarding fetal health. Previous studies regarding developmental toxicity have frequently focused on TiO2 NPs < 50 nm, whereas the potential adverse effects of large-sized TiO2 NPs received less attention. Placental vasculature is essential for maternal-fetal circulatory exchange and ensuring fetal growth. This study explores the impacts of TiO2 NPs (100 nm in size) on the placenta and fetal development and elucidates the underlying mechanism from the perspective of placental vasculature. Pregnant C57BL/6 mice were exposed to TiO2 NPs by gavage at daily dosages of 10, 50, and 250 mg/kg from gestational day 0.5-16.5. RESULTS: TiO2 NPs penetrated the placenta and accumulated in the fetal mice. The fetuses in the TiO2 NP-exposed groups exhibited a dose-dependent decrease in body weight and length, as well as in placental weight and diameter. In vivo imaging showed an impaired placental barrier, and pathological examinations revealed a disrupted vascular network of the labyrinth upon TiO2 NP exposure. We also found an increase in gene expression related to the transforming growth factor-ß (TGF-ß) -SNAIL pathway and the upregulation of mesenchymal markers, accompanied by a reduction in endothelial markers. In addition, TiO2 NPs enhanced the gene expression responsible for the endothelial-to-mesenchymal transition (EndMT) in cultured human umbilical vein endothelial cells, whereas SNAIL knockdown attenuated the induction of EndMT phenotypes. CONCLUSION: Our study revealed that maternal exposure to 100 nm TiO2 NPs disrupts placental vascular development and fetal mice growth through aberrant activation of EndMT in the placental labyrinth. These data provide novel insight into the mechanisms of developmental toxicity posed by NPs.
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Exposición Materna , Placenta , Embarazo , Ratones , Femenino , Humanos , Animales , Placenta/metabolismo , Exposición Materna/efectos adversos , Células Endoteliales , Ratones Endogámicos C57BL , Desarrollo Fetal , Intercambio Materno-Fetal , Titanio/toxicidad , Titanio/metabolismoRESUMEN
Bisphenol-A bis(diphenyl phosphate) (BDP) has been increasingly detected in indoor environmental and human samples. Little is known about its developmental toxicity, particularly the intergenerational effects of parental exposure. In this study, adult zebrafish were exposed to BDP at 30-30,000 ng/L for 28 days, with results showing that exposure did not cause a transfer of BDP or its metabolites to offspring. Vascular morphometric profiling revealed that parental exposure to BDP at 30 and 300 ng/L exerted significant effects on the vascular development of offspring, encompassing diverse alterations in multiple types of blood vessels. N6-Methyladenosine (m6A) methylated RNA immunoprecipitation sequencing of larvae in the 300 ng/L group revealed 378 hypomethylated and 350 hypermethylated m6A peaks that were identified in mRNA transcripts of genes crucial for vascular development, including the Notch/Vegf signaling pathway. Concomitant changes in 5 methylcytosine (m5C) DNA methylation and gene expression of m6A modulators (alkbh5, kiaa1429, and ythdf1) were observed in both parental gonads and offspring exposed to BDP. These results reveal that parental exposure to low concentrations of BDP caused offspring vascular disorders by interfering with DNA and RNA methylation, uncovering a unique DNA-RNA modification pattern in the intergenerational transmission of BDP's developmental toxicity.
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Metilación de ADN , Fosfatos , Animales , Adulto , Humanos , ARN/metabolismo , Pez Cebra/genética , ADNRESUMEN
The pesticide fipronil is widely dispersed in aquatic environments and frequently detected in the general population. Although the adverse effects on embryonic growth by fipronil exposure have been extensively documented, the early responses for its developmental toxicity are largely unknown. In the present study, we explored the sensitive targets of fipronil, focusing on vascular injury using zebrafish embryos/larvae and cultured human endothelial cells. Exposure to 5-500 µg/L fipronil at the early stage impeded the growth of sub-intestinal venous plexus (SIVP), caudal vein plexus (CVP), and common cardinal veins (CCV). The damages on venous vessels occurred at exposure to the environmentally relevant concentration as low as 5 µg/L fipronil, whereas no significant change was observed in general toxicity indexes. In contrast, vascular development of the dorsal aorta (DA) or intersegmental artery (ISA) was not affected. In addition, the mRNA levels of vascular markers and vessel type-specific function genes exhibited significant decreases in venous genes, including nr2f2, ephb4a, and flt4, but no appreciable change in arterial genes. Likewise, the more pronounced changes in cell death and cytoskeleton disruption were shown in human umbilical vein endothelial cells as compared with human aortic endothelial cells. Furthermore, molecular docking supported a stronger affinity of fipronil and its metabolites to the proteins correlated with venous development, such as BMPR2 and SMARCA4. These results reveal the heterogeneity in developing vasculature responsive to fipronil's exposure. The preferential impacts on the veins confer higher sensitivity, allowing them to be appropriate targets for monitoring fipronil's developmental toxicity.
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ADN Helicasas , Pez Cebra , Animales , Humanos , Pez Cebra/metabolismo , Larva , Simulación del Acoplamiento Molecular , Células Endoteliales de la Vena Umbilical Humana , ADN Helicasas/metabolismo , Proteínas Nucleares , Factores de Transcripción/metabolismoRESUMEN
The placenta is pivotal for fetal development and maternal-fetal transfer of many substances, including per- and polyfluoroalkyl substances (PFASs). However, the intraplacental distribution of PFASs and their effects on placental vascular function remain unclear. In this study, 302 tetrads of matched subchorionic placenta (fetal-side), parabasal placenta (maternal-side), cord serum, and maternal serum samples were collected from Guangzhou, China. Eighteen emerging and legacy PFASs and five placental vascular biomarkers were measured. Results showed that higher levels of perfluorooctanoic (PFOA), perfluorooctane sulfonic acid (PFOS), and chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) were detected in subchorionic placenta compared to parabasal placenta. There were significant associations of PFASs in the subchorionic placenta, but not in the serum, with placental vascular biomarkers (up to 32.5%) and lower birth size. Birth weight was negatively associated with PFOA (ß: -103.8, 95% CI: -186.3 and -21.32) and 6:2 Cl-PFESA (ß: -80.04, 95% CI: -139.5 and -20.61), primarily in subchorionic placenta. Mediation effects of altered placental angiopoietin-2 and vascular endothelial growth factor receptor-2 were evidenced on associations of adverse birth outcomes with intraplacental PFOS and 8:2 Cl-PFESA, explaining 9.5%-32.5% of the total effect. To the best of our knowledge, this study is the first to report on differential intraplacental distribution of PFASs and placental vascular effects mediating adverse birth outcomes and provides novel insights into the placental plate-specific measurement in PFAS-associated health risk assessment.
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Ácidos Alcanesulfónicos , Fluorocarburos , Humanos , Embarazo , Femenino , Placenta/química , Factor A de Crecimiento Endotelial Vascular , China , Fluorocarburos/análisis , BiomarcadoresRESUMEN
Triphenyl phosphate (TPhP) is a non-halogenated organophosphorus flame retardant, and there is a higher exposure risk in children. TPhP has been found to be neurotoxic upon developmental exposure, yet the specific mechanism remains unclear. To characterize the cellular responses underlying TPhP-induced developmental neurotoxicity, we administered TPhP (0.5, 5 or 50 mg/kg/day) to neonatal mice from postnatal day 10 (P10)-P70. A total of 17,229 cells and 26,338 genes were identified in cortical samples from control and low-dose (the internal doses of metabolite DPhP comparable to human exposure level) groups using single-cell RNA sequencing (scRNA-seq). TPhP exposure led to heterogeneous transcriptional alterations and intercellular crosstalk among neurons, neural stem/progenitor cells (NSPCs), endothelial cells, and immunocytes. Deprivation of NSPCs, loss of mature neurons, and concomitant neuroinflammation mediated by extrinsic and intrinsic immunocytes were found in TPhP-exposed cortices. In addition, we observed blood-brain barrier destruction prior to the anxiety/depression-like neurobehavioral changes. These results reveal the distinctive cellular processes in TPhP's neurodevelopmental toxicity and uncover that the impeded neurogenesis, disrupted vascular barrier, and concomitant neuroinflammation are the sensitive responses to TPhP exposure. Our study paves the way for the application of scRNA-seq in toxicity assessments for emerging neurotoxic pollutants.
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Retardadores de Llama , Animales , Niño , Células Endoteliales/metabolismo , Retardadores de Llama/toxicidad , Humanos , Ratones , Organofosfatos/toxicidad , Compuestos OrganofosforadosRESUMEN
Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for hearing loss. After exposure, Cd accumulates in the inner ear and induces spiral ganglion neuron (SGN) degeneration; however, the underlying mechanisms are poorly understood. Dysfunctional autophagy has been implicated in many neurodegenerative diseases, including Cd-induced neurotoxicity. Metformin has been validated to confer not only anti-hyperglycaemic but also neuroprotective effects. However, the relationship between autophagy dysfunction, SGN degeneration, and the effect of metformin on Cd-induced SGN neurotoxicity has not yet been established. In this study, we demonstrate that metformin notably attenuates Cd-evoked SGN degeneration by restoring impaired autophagy flux, as evidenced by the suppression of Cd-induced elevation of autophagy markers microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and autophagy substrate protein p62 in degenerated SGN. Blockage of autophagy flux by chloroquine abolished metformin-induced neuroprotection against Cd-induced neurotoxicity in SGN. The results of this study reveal that autophagy dysfunction is an important component of Cd-induced SGN degeneration, and metformin may be a potential protective agent for attenuating SGN degeneration following Cd exposure.
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Cadmio , Metformina , Autofagia , Cadmio/metabolismo , Metformina/metabolismo , Metformina/farmacología , Proteínas Asociadas a Microtúbulos/metabolismo , Neuronas/metabolismo , Ganglio Espiral de la Cóclea/metabolismoRESUMEN
The residue of polychlorinated biphenyls (PCBs) exists throughout the environment and humans are subject to long-term exposure. As such, the potential environmental and health risk caused by low-dose exposure to PCBs has attracted much attention. 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126), the highest toxicity compound among dioxin-like-PCBs, has been widely used and mass-produced. Cardiotoxicity is PCB126's crucial adverse effect. Maintaining proper metabolism underlies heart health, whereas the impact of PCB126 exposure on cardiac metabolic patterns has yet to be elucidated. In this study, we administered 0.5 and 50 µg/kg bw of PCB126 to adult male mice weekly by gavage for eight weeks. Pathological results showed that low-dose PCB126 exposure induced heart injury. Metabolomic analysis of the heart tissue exposed to low-dose PCB126 identified 59 differential metabolites that were involved in lipid metabolism, amino acid metabolism, and the tricarboxylic acid (TCA) cycle. Typical metabolomic characteristic of cardiac hypertrophy was reflected by accumulation of fatty acids (e.g. palmitic, palmitoleic, and linoleic acid), and disturbance of carbohydrates including D-glucose and intermediates in TCA cycle (fumaric, succinic, and citric acid). Low-dose PCB126 exposure increased glycine and threonine, the amino acids necessary for the productions of collagen and elastin. Besides, PCB126-exposed mice exhibited upregulation of collagen synthesis enzymes and extracellular matrix proteins, indicative of cardiac fibrosis. Moreover, the expression of genes related to TGFß/PPARγ/MMP-2 signaling pathway was perturbed in the PCB126-treated hearts. Together, our results reveal that low-dose PCB126 exposure disrupts cardiac metabolism correlated with hypertrophy and fibrosis. This study sheds light on the underlying mechanism of PCBs' cardiotoxicity and identifies potential sensitive biomarkers for environmental monitoring.
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Bifenilos Policlorados , Dibenzodioxinas Policloradas , Animales , Fibrosis , Hipertrofia , Metabolismo de los Lípidos , Masculino , Ratones , Bifenilos Policlorados/toxicidadRESUMEN
G9a, a histone methyltransferase, has been found to be upregulated in a range of tumor tissues, and contributes to tumor growth and metastasis. However, the impact of G9a inhibition as a potential therapeutic target in nasopharyngeal carcinoma (NPC) is unclear. In the present study we aimed to investigate the anti-proliferative effect of G9a inhibition in the NPC cell lines CNE1 and CNE2, and to further elucidate the molecular mechanisms underlying these effects. The expression of G9a in NPC tumor tissues was significantly higher than that in normal nasopharyngeal tissues. The pharmacological inhibition of G9a by BIX-01294 (BIX) inhibited proliferation and induced caspase-independent apoptosis in NPC cells in vitro. Treatment with BIX induced autophagosome accumulation, which exacerbated the cytotoxic activity of BIX in NPC cells. Mechanistic studies have found that BIX impairs autophagosomes by initiating autophagy in a Beclin-1-independent way, and impairs autophagic degradation by inhibiting lysosomal cathepsin D activation, leading to lysosomal dysfunction. BIX was able to suppress tumor growth, possibly by inhibiting autophagic flux; it might therefore constitute a promising candidate for NPC therapy.
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Antineoplásicos/farmacología , Azepinas/farmacología , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Quinazolinas/farmacología , Autofagosomas/efectos de los fármacos , Línea Celular Tumoral , Fenómenos Fisiológicos Celulares/efectos de los fármacos , Antígenos de Histocompatibilidad/genética , Antígenos de Histocompatibilidad/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Proteínas de Membrana de los Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , ARN Interferente Pequeño/genéticaRESUMEN
With the spread of organophosphorus flame retardants (OPFRs), the environmental and health risks they induce are attracting attention. Triphenyl phosphate (TPHP) is a popular alternative to brominated flame retardant and halogenated OPFRs. Neurodevelopmental toxicity is TPHP's primary adverse effect, whereas the biomarkers and the modes of action have yet to be elucidated. In the present study, 0.5, 5, and 50 mg/kg of TPHP were orally administered to mice from postnatal day 10 (P10) to P70. The behavioral tests showed a compromised learning and memory capability. Proteomic analysis of the hippocampus exposed to 0.5 or 50 mg/kg of TPHP identified 531 differentially expressed proteins that were mainly involved in axon guidance, synaptic function, neurotransmitter transport, exocytosis, and energy metabolism. Immunoblot and immunofluorescence analysis showed that exposure to TPHP reduced the protein levels of TUBB3 and SYP in the synapses of hippocampal neurons. TPHP exposure also downregulated the gene expression of neurotransmitter receptors including Grins, Htr1α, and Adra1α in a dose-dependent fashion. Moreover, the calcium-dependent synaptic exocytosis governed by synaptic vesicle proteins STX1A and SYT1 was inhibited in the TPHP-treated hippocampus. Our results reveal that TPHP exposure causes abnormal learning and memory behaviors by disturbing synaptogenesis and neurotransmission.
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Retardadores de Llama , Animales , Retardadores de Llama/toxicidad , Hipocampo , Ratones , Organofosfatos/toxicidad , Proteómica , Transmisión Sináptica , Sinaptotagmina I , Pez CebraRESUMEN
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is a phosphorus-based flame retardant common in consumer goods and baby products. Concerns have been raised about TDCPP exposure and neurodevelopmental toxicity. However, the mechanism and early response for TDCPP-induced neurotoxicity are poorly understood. This study investigates the role of microglia-mediated neuroinflammation in TDCPP-induced neurotoxicity in mice and primary cells. TDCPP was administered to C57BL/6 pups (0, 5, or 50 mg/kg/day) via an oral gavage from postnatal days 10-38 (28 days). The results showed that TDCPP exposure for 28 days altered the gene expression of neuronal markers Tubb3, Nefh, and Nes, and led to apoptosis in the hippocampus. The mRNA levels of pro-inflammatory factors Il-1ß, Tnfα and Ccl2 dose dependently increased in the hippocampus at both 24 h and 28 days following exposure, accompanied by microglia activation characterized by an amoeboid-like phenotype. In in vitro studies using the primary microglia isolated from neonatal mice, exposure to TDCPP (0-100 µM) for 24 h resulted in cellular activation. It also increased the expression of genes responsible for inflammatory responses including surface markers and pro-inflammatory cytokines. These changes occurred in a dose-dependent fashion. Neurite outgrowth of primary mouse hippocampal neurons was inhibited by treatment with the conditioned medium harvested from microglia exposed to TDCPP. These results reveal that neonatal exposure to TDCPP induces neuronal damage through microglia-mediated inflammation. This provides insight into the mechanism of TDCPP's neurodevelopmental toxicity, and suggests that microglial cell is a sensitive responder for OPFRs exposure.
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Retardadores de Llama/toxicidad , Hipocampo/efectos de los fármacos , Microglía/efectos de los fármacos , Síndromes de Neurotoxicidad/patología , Compuestos Organofosforados/toxicidad , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Hipocampo/patología , Hipocampo/fisiología , Inflamación/inducido químicamente , Masculino , Ratones Endogámicos C57BL , Microglía/patología , Síndromes de Neurotoxicidad/etiología , Pruebas de Toxicidad/métodosRESUMEN
Cerebral ventricular infection (CVI) is one of the most dangerous complications in neurosurgery because of its high mortality and disability rates. Few studies have examined the application of neuroendoscopic surgical techniques (NESTs) to assess and treat CVI. This multicenter, retrospective study was conducted using clinical data of 32 patients with CVI who were assessed and treated by NESTs in China. The patients included 20 men and 12 women with a mean age of 42.97 years. NESTs were used to obliterate intraventricular debris and pus, fenestrate or incise the intraventricular compartment and reconstruct cerebrospinal fluid circulation, and remove artificial material. Intraventricular irrigation with antibiotic saline was applied after neuroendoscopic surgery (NES). Secondary hydrocephalus was treated by endoscopic third ventriculostomy or a ventriculoperitoneal shunt. Neuroendoscopic findings of CVI were used to classify patients into Grade I (n = 3), Grade II (n = 13), Grade III (n = 10), and Grade IV (n = 6) CVI. The three patients with grade I CVI underwent one NES, the 23 patients with grade II/III CVI underwent two NESs, and patients with grade IV CVI underwent two (n = 3) or three (n = 3) NESs. The imaging features and grades of neuroendoscopy results were positively related to the number of neurosurgical endoscopic procedures. Two patients died of multiple organ failure and the other 30 patients fully recovered. Among the 26 patients with secondary hydrocephalus, 18 received ventriculoperitoneal shunt and 8 underwent endoscopic third ventriculostomy. There were no recurrences of CVI during the 6- to 76-month follow-up after NES. Application of NESTs is an innovative method to assess and treat CVI, and its neuroendoscopic classification provides an objective, comprehensive assessment of CVI. The study trial was approved by the Institutional Review Board of Beijing Shijitan Hospital, Capital Medical University, China.
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Polybrominated diphenyl ethers (PBDEs) are distributed throughout the environment. Despite a moratorium on their use, concentrations of PBDEs in the atmosphere and in residential environments remain high due to their persistence. The environmental health risks remain concerning and one of the major adverse effects is neurodevelopmental toxicity. However, the early response and effects of PBDEs exposure on the developing brain remain unknown. In the present study, we investigated the impacts of 2,2',4,4',5-pentabrominated diphenyl ether (BDE-99) on vascular growth and vascular barrier function with an emphasis on cerebral blood vessels, in the early life stages, using a zebrafish model. No general toxicity was observed in exposing zebrafish larvae to 0-0.5⯵Mâ¯BDE-99 at 72 hpf. BDE-99 exposure resulted in neither general toxicity nor pronounced developmental impairment in somatic blood vessels, including intersegmental vessels (ISV) and common cardinal veins (CCV). Meanwhile, both 0.05⯵M and 0.5⯵M of BDE-99 reduced cerebrovascular density as well as down-regulation of VEGFA and VEGFR2 in the head. In addition, BDE-99 exposure increased vascular leakage, both in cerebral and truncal vasculature at 72 hpf. The accentuated vascular permeability was observed in the head. The mRNA levels of genes encoding tight junction molecules decreased in the BDE-99-exposed larvae, and more robust reductions in Cldn5, Zo1 and Jam were detected in the head than in the trunk. Moreover, proinflammatory factors including TNF-α, IL-1ß and ICAM-1 were induced, and the expression of neurodevelopment-related genes was suppressed in the head following BDE-99 exposure. Taken together, these results reveal that developmental exposure to BDE-99 impedes cerebrovascular growth and disturbs vascular barrier formation. The cerebral vasculature in developing zebrafish, a more sensitive target for BDE-99, may be a promising tool for the assessment of the early neurodevelopmental effects due to PBDEs exposure.
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Vasos Sanguíneos/efectos de los fármacos , Exposición a Riesgos Ambientales , Éteres Difenilos Halogenados/toxicidad , Pez Cebra/crecimiento & desarrollo , Animales , Encéfalo/irrigación sanguínea , Encéfalo/crecimiento & desarrollo , Permeabilidad Capilar/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Inflamación/genética , Inflamación/patología , Larva/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/genéticaRESUMEN
Biomass-derived carbon composites (e.g., metal oxide/biocarbon) have been used as promising electrode materials for energy storage devices owing to their natural abundance and simple preparation process. However, low loading content/inhomogeneous distribution of metal oxides and inefficient cracking of biocarbon (BC) are intractable obstacles that impede the efficient utilization of biomass. In this work, hierarchical porous MnO/BC composites were prepared by a facile molten-salt-assisted strategy based on the superior salt-water absorption ability of agaric. The addition of NaCl induces a liquid reaction medium by formation of a molten salt mixture at high temperature to effectively realize the activation and cracking of the bulk carbon, and it also acts as a recyclable sacrificial template to form mesopores and macropores in the as-prepared hierarchical porous MnO/BC composites. The highly porous and uniform BC framework effectively enhances ion diffusion and electron-transfer ability, serves as a protective layer to prevent fracturing and agglomeration of MnO, and thus enables superior rate performance and cycling stability of the MnO/BC composite for both supercapacitor electrodes (94 % capacity retention at 20â mA cm-2 after 5000â cycles) and lithium-ion battery anodes (783â mA h g-1 after 1000â cycles). Notably, considering the simple and low-cost preparation process, this work opens a promising avenue for the large-scale production of advanced metal oxide/BC hybrid electrode materials for electrochemical energy storage.
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Ventrículos Cerebrales/microbiología , Neuroendoscopía/métodos , Procedimientos Neuroquirúrgicos/métodos , Administración Intravenosa , Adulto , Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Encefalopatías/tratamiento farmacológico , Encefalopatías/microbiología , Femenino , Gentamicinas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vancomicina/uso terapéuticoRESUMEN
BACKGROUND: Tuberculum sellae meningiomas (TSMs) present a special symptom because of the adherence and compression to the optic nerve, optic artery, and the chiasm. A significant number of patients with TSMs appear visual deficits. This study aimed to investigate the surgical indications of exploring the optic canal and visual prognostic factors in the neurosurgical treatment of TSMs. METHODS: Totally 21 patients with TSM, who were operated from September 2007 to August 2011 in the Department of Neurosurgery, Tongren Hospital were enrolled in this study. Results of orbital computed tomography (CT) and magnetic resonance imaging (MRI), visual acuity, Goldmann visual field test, orbital color Doppler flow imaging (CDI) test in these patients were retrospectively analyzed. RESULTS: Visual deficit and optic canal involvement (OCI) were detected in all the 21 patients. Fourteen patients had bone proliferation within the area of the optic canal. After the operation, visual outcomes were improved in 13 patients, unchanged in 7 patients, and deteriorated in 1 patient. All the 21 patients performed orbital CDI test preoperatively, the results showed that if the peak systolic velocity (PSV) of central retinal artery (CRA) value was ≤ 8 cm/s, the visual outcome would be better. CONCLUSIONS: The surgical indications of exploring optic canal in TSM cases included: (1) The neuroimaging evidences of OCI (CT and/or MRI); (2) PSV of CRA in orbital CDI test was ≤ 8 cm/s; (3) visual acuity was below 0.1; (4) visual field deficit. The PSV of CRA in CDI test could be a prognostic factor for visual outcomes of TSMs.
Asunto(s)
Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Estudios Retrospectivos , Silla Turca/patología , Silla Turca/cirugía , Neoplasias de la Base del Cráneo/patología , Neoplasias de la Base del Cráneo/cirugía , Agudeza VisualRESUMEN
BACKGROUND: Nasopharygeal fibroangioma (NPF) can be approached through lateral rhinotomy, the middle skull fossa approach and the transcranial-facial combined approach. It is complicated and thus results in more insults, and when adopted, the total resection rate of tumor is still low. The nasal endoscope is minimally invasive, the dead angles of a craniotomy, such as sphenoid sinus, maxillary sinus, and nasopharynx are easily approached by an endoscope. Lateral rhinotomy have to make facial incision and affects maxillary bone development. We combined the craniotomy and endoscopic approach intending to take advantages of the two approaches. METHODS: Twelve NPF patients who underwent craniotomy with endoscopic assistance from March 2002 to July 2008 at the Beijing Tongren Hospital were selected. All patients were male. Their ages ranged from 11 to 33 years. The main symptoms were visual deterioration, exophthalmos, nasal obstruction, epistaxis and pharynx nasalis neoplasm. The diagnosis was based on CT, MRI and digital subtraction angiography (DSA). All patients had intracranial encroachment and all underwent DSA and embolism treatment were taken before surgery. Seven patients had a pterional craniotomy, five had a frontal-temporal-orbital-zygomatic craniotomy. Most of the tumor was resected piecemeal, then removed through the sphenoidal sinus. Finally, using an endoscope in the nasal cavity, tumor in nasal cavity was resected and removed through the sphenoidal sinus, observing the dead angle of the craniotomy and confirming that sinus drainage was unobstructed. RESULTS: The tumor was removed completely in 11 patients and partially resected in one patient because of hemorrhage. One patient had an infection after the operation and one patient had cerebrospinal rhinorrhea 3 years after surgery that was remediated by endoscopic repair. CONCLUSION: Craniotomy with endoscopic assistance in the treatment of NPF was minimally invasive, safe and efficient, and avoided facial incision.