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An intelligent delivery nanoformulation could enhance the utilization efficacy, uptake, and translocation of pesticides in plants. Herein, a redox/pH-triggered and fluorescent smart delivery nanoformulation was designed and constructed by using hollow mesoporous organosilica nanoparticles (HMONs) and ZnO quantum dots as the nanocarrier and capping agent, respectively. Boscalid was further loaded to generate Boscalid@HMONs@ZnO with a loading rate of 9.8% for controlling Botrytis cinerea (B. cinerea). The quantity of boscalid released by Boscalid@HMONs@ZnO in a glutathione environment or at pH 3.0 was 1.3-fold and 1.9-fold higher than that in a neutral condition. Boscalid@HMONs@ZnO has 1.7-fold the toxicity index of boscalid technical against B. cinerea in antifungal experiments. Pot experiments revealed that the efficacy of Boscalid@HMONs@ZnO was significantly enhanced more than 1.27-fold compared to commercially available water-dispersible granules of boscalid. Due to the fluorescence properties of Boscalid@HMONs@ZnO, pesticide transport's real-time monitoring of pesticide translocation in tomato plants could be observed by confocal laser scanning microscopy. Fluorescence images revealed that HMONs@ZnO had been effectively transported via treated leaves or roots in tomato plants. This research showed the successful application of HMONs@ZnO as a nanocarrier for controlling disease and offered an effective avenue to explore the real-time tracking of pesticide translocation in plants.
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Botrytis , Nanopartículas , Oxirredução , Óxido de Zinco , Botrytis/efeitos dos fármacos , Nanopartículas/química , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Concentração de Íons de Hidrogênio , Corantes Fluorescentes/química , Compostos de Bifenilo/química , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Solanum lycopersicum/química , Praguicidas/química , Praguicidas/toxicidade , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Liberação Controlada de Fármacos , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Niacinamida/análogos & derivadosRESUMO
This study systematically explored the transdermal diffusion law of functional substances of Jingu Zhitong Gel(JGZTG). The transdermal diffusion research methods of JGZTG were investigated by single factor trial with the automated transdermal(dry-heat) sampling system. High performance liquid chromatography(HPLC) content determination method was established to determine the contents of ferulic acid, senkyunolide I, cinnamic acid, hydroxy-ε-xanthoxylin, hydroxy-α-xanthoxylin, and hydroxy-ß-xanthoxylin in the transdermal diffusion solution of JGZTG. The transdermal diffusion law of the components within 16 h was investigated. The results showed that the optimal transdermal diffusion method of JGZTG was as follows: Rat skin was used as the transdermal barrier; normal saline was used as the receiving medium; the dosage of JGZTG was 0.3 g, and the receiving solution was extracted by ethyl acetate. The results of transdermal diffusion showed that the release of ferulic acid, cinnamic acid, and senkyunolide I increased significantly at 0-8 h and slowed down at 8-16 h. The drug release was a synergic process of diffusion and dissolution, in which ferulic acid and cinnamic acid followed Higuchi and Ritger-Peppas equations, and liguolactone I followed Higuchi equation. The transdermal diffusion curves of hydroxy-ε-zanthoxylin, hydroxy-α-zanthoxylin, and hydroxy-ß-zanthoxylin showed continuous release within 16 h, and the drug release was skeleton dissolution. The diffusion law followed zero-order equation, first-order equation, and Ritger-Peppas equation. In clonclusion, it is a controlled release of ferulic acid, ligustrone I, cinnamic acid, hydroxy-ε-pyrroxylin, hydroxy-α-pyrroxylin, and hydroxy-ß-pyrroxylin in JGZTG, which can maintain stable blood drug concentration with 16 h, and the cumulative transmittance of each component with 12 h can reach 80% of cumulative transmittance with 24 h, which is in line with the clinical drug use law of bis in die.
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Medicamentos de Ervas Chinesas , Absorção Cutânea , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Ratos , Animais , Difusão , Administração Cutânea , Pele/metabolismo , Pele/química , Géis/química , Masculino , Ratos Sprague-Dawley , Cromatografia Líquida de Alta Pressão , Cinamatos/farmacocinética , Cinamatos/análise , Cinamatos/química , Ácidos Cumáricos/farmacocinética , Ácidos Cumáricos/análiseRESUMO
Extremely inefficient utilization of pesticides has prompted a study of low-cost, sustainable, and smart application systems. Herein, as a promising pesticide nanocarrier, hollow mesoporous organosilica nanoparticles (HMONs) were first synthesized by using inexpensive CaCO3 nanoparticles as the hollow templates. A redox/near-infrared light dual-triggered pesticide release system was further achieved via loading avermectin (AVM) into the HMONs and coating a layer of polydopamine (PDA). The as-prepared AVM@HMONs@PDA displays a favorable pesticide load capability (24.8 wt %), outstanding photothermal performance, and high adhesion to leaves. In addition, with glutathione (GSH), the AVM cumulative release from AVM@HMONs@PDA was 3.5 times higher than that without GSH. Under ultraviolet light irradiation, the half-life of AVM@HMONs@PDA was prolonged by 17.0-fold compared to that of the AVM technical. At day 21 after treatment in the insecticidal activity, the median lethal concentrations (LC50) values displayed that the toxicity of AVM@HMONs@PDA for Panonychus citri (McGregor) was enhanced 4.0-fold compared with the commercial emulsifiable concentrate. In the field trial, at day 28 after spraying, AVM@HMONs@PDA was significantly more control effective than AVM-EC in controlling the P. citri (McGregor), even at a 50% reduced dosage. Moreover, HMONs@PDA was safe for crops. This research presents a novel preparation approach for HMONs, and it also offers a promising nanoplatform for the precise release of pesticides.
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Nanopartículas , Praguicidas , Praguicidas/toxicidade , Nanopartículas/toxicidade , Ivermectina/toxicidade , Raios UltravioletaRESUMO
Most endometrial cancers (EC) are diagnosed at an early stage with a favorable prognosis. However, for patients with advanced or recurrent disease, the chemotherapy response rate and overall survival remain poor. A novel in vitro model, tumor organoids, has important value in providing a more individualized treatment plan for tumor patients. However, the slow growth of the established EC organoid seriously hinders the application of EC organoids. Cancer-associated fibroblasts (CAFs), the main component of tumor stroma, have been reported to promote the proliferation of endometrial cancer cell lines and primary endometrial cancer cells in vivo and in vitro. Therefore, we optimized the current endometrial cancer organoid by introducing CAFs isolated from EC lesions. Here we developed long-term expandable organoids from endometrial cancer lesions, which show disease-associated traits and cancer-linked mutations. Based on the co-culture of CAFs and endometrial cancer organoids, we found that CAFs could promote the growth of endometrial cancer organoids, might by secreting factors according to the result that CAFs could also promote the growth. Our research provided a more promising model for the basic and preclinical study of endometrial cancer.
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Fibroblastos Associados a Câncer , Neoplasias do Endométrio , Fibroblastos Associados a Câncer/patologia , Proliferação de Células/genética , Neoplasias do Endométrio/metabolismo , Endométrio/metabolismo , Endométrio/patologia , Feminino , Fibroblastos/metabolismo , Humanos , OrganoidesRESUMO
This study aims to explore the key factors influencing the processing of braised Rehmanniae Radix, optimize the processing, and determine the correlation between the components in different processed products and chroma values, which is expected to add quantitative indexes for the processing of braised Rehmanniae Radix and better control the processing. The weights of the indexes catalpol, rehmannioside D, verbascoside, isoacteoside, 5-hydroxymethylfurfural, reducing sugar, and appearance were calculated based on analytic hierarchy process(AHP) in combination with coefficient of variation, and the overall desirability(OD) was obtained. Box-Behnken design was used to explore the optimal amount of water added, time for soaking with rice wine, and steaming time in the processing of braised Rehmanniae Radix. Colorimeter was employed to determine the chroma of 17 samples and raw samples, and SPSS, Prism, and other software to investigate the correlation between the components in braised Rehmanniae Radix and the chroma values. The results showed that each factor influenced the processing, and the influence followed the order of steaming time>amount of water added>time for soaking with rice wine. The optimal processing process is as below: A total of 100 g medicinal material was added with 7 times of water, followed by soaking with rice wine for 5 h and steaming in a pot for 6 h. The correlation analysis suggested the extremely significantly positive correlation between L~* and content of catalpol, between a~* and 5-hydroxymethylfurfural content, and between b~* and catalpol content, and the extremely significantly negative correlation between L~* and the content of 5-hydroxymethylfurfural and reducing sugar, and between b~* and the content of 5-hydroxymethylfural and reducing sugar. In this experiment, response surface methodology was used to optimize the processing technology of braised Rehmanniae Radix and the optimized process was rational and feasible. The content of chemical components in braised Rehmanniae Radix was significantly correlated with the chroma. This study provided a new method for the quality evaluation of braised Rehmanniae Radix.
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Medicamentos de Ervas Chinesas , Rehmannia , Medicamentos de Ervas Chinesas/química , Furaldeído/análogos & derivados , Glucosídeos Iridoides , Extratos Vegetais , Rehmannia/química , Açúcares , Tecnologia , ÁguaRESUMO
To discover novel dihydropyridin-2-one derivatives with higher HDAC inhibitory activity and subtype selectivity, twenty-seven dihydropyridin-2-one derivatives containing triazole unit were synthesized via click chemistry. The structures of these compounds have been confirmed by IR, 1H NMR and HR-MS spectra. Preliminary in vitro pharmacological tests showed that these compounds potently inhibited HDAC1 and HDAC6, which also displayed significant antiproliferative effect on five cancer cells, and most of them were better than that of the parent compound 1A and drug SAHA. Specifically, compound 18g exhibited most potent anti-HDAC1 activity, and also showed the greatest potency against PC-3 and Hep G2. Additionally, all compounds were nontoxic to health RWPE-1 and VERO cells, while SAHA showed essential toxicity.
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Antineoplásicos/farmacologia , Di-Hidropiridinas/química , Inibidores de Histona Desacetilases/farmacologia , Animais , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células , Chlorocebus aethiops , Química Click , Células Hep G2 , Inibidores de Histona Desacetilases/síntese química , Histona Desacetilases/metabolismo , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/química , Células VeroRESUMO
The binding interactions between the cyclohexanocucurbit[6]uril (Cy6CB6) host and a series of dialkyl-4,4'-bipyridinium (viologen) dicationic guests were investigated in the solution phase, using (1)H NMR spectroscopy, and in the solid phase, using X-ray diffraction methods. In D2O solution, methyl viologen (MV(2+)) and ethyl viologen (EV(2+)) form 1:1 complexes in which the bipyridinium aromatic nucleus is partially included inside the Cy6CB6 cavity. Propyl viologen (PV(2+)), butyl viologen (BV(2+)), pentyl viologen (FV(2+)), and heptyl viologen (HV(2+)) form 2:1 complexes with Cy6CB6, in which each of the viologen aliphatic chains is included by a host molecule. In the solid state, EV(2+) forms a polypseudorotaxane via pseudorotaxane interdigitation of Cy6CB6 hosts. The PV(2+) guest forms a dumbbell-shaped structure with a Cy6CB6 host residing over each of the terminal propyl groups of the guest. In contrast to this, the BV(2+) guest and Cy6CB6 form a different polypseudorotaxane structure in which dumbbell-shaped structures, formed by two host molecules interacting with a single guest, are interconnected through metal-host coordination.
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AIM: To investigate the clinical characteristics, treatment methods and outcomes of rhegmatogenous retinal detachment (RRD) in highly myopic eyes with implantable collamer lens (ICL). METHODS: High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were reviewed. Comprehensive ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each patient. RESULTS: A total of nine RRD eyes from nine patients who received V4c-ICL implantation were included. The mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo (range, 1-60mo). At the initial visit for RRD, giant retinal tear (GRT), horseshoe tear, simple round hole, and horseshoe tear combined with round hole were detected in 3, 3, 2, and 1 eye(s), respectively, with macula-off in eyes. Eight patients received surgical treatment, and one patient was treated by retinal laser photocoagulation alone. The ICL was preserved in 7 eyes. At the last follow-up, the mean best corrected visual acuity (BCVA) improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR (P=0.035), and no case of recurrent retinal detachment was found. CONCLUSION: The morphological presentation of retinal breaks is diverse in this study. The ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data, companied with acceptable visual and anatomical outcomes.
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PURPOSE: To investigate the influence of transarterial embolization (TAE) on programmed cell death-ligand 1(PD-L1) expression and CD8+T tumour infiltrative lymphocyte cytotoxicity in the Sprague-Dawley (SD) rat model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: An orthotopic HCC model was established in twenty SD rats treated with TAE (lipiodol, n = 10) or sham (normal saline, n = 10) using homologous N1S1 hepatoma cells. Rats were euthanized 1 week after embolization. Flow cytometry was used to assess the proportion of CD4+T, CD8+T and programmed cell death-1+(PD-1+) CD8+T lymphocytes in the spleens and tumours. Distribution of CD8+T, granzyme-B+CD8+T lymphocytes and PD-L1+ cells was assessed by immunohistochemistry (IHC) or multiplex IHC. p value < 0.05 was considered statistically significant. RESULTS: The CD4/CD8 ratio and PD-1+CD8+ T lymphocytes exhibited higher values in TAE-treated tumours compared to sham-treated tumours (p = 0.021 and p = 0.071, respectively). Conversely, the number of CD8+T lymphocytes was decreased in TAE-treated tumours (p = 0.043), especially in the central region (p = 0.045). However, more CD8+T lymphocytes were found infiltrating the marginal region than central region in TAE-treated tumours (p = 0.046). The proportion of granzyme-B+CD8+T lymphocytes and the PD-L1 positive areas was elevated in tumours that treated with TAE (p all < 0.05). There was a negative correlation between PD-L1 expression and the number of infiltration of CD8+ T lymphocytes (p = 0.036). CONCLUSIONS: Immune cells are distributed unevenly in the tumours after TAE. The intrinsic induction state of the tumour after embolization may be insufficient to elicit a maximal response to PD-1/PD-L1 inhibitors.
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BACKGROUND: Electroacupuncture (EA) is effective in relieving pain in patients with postherpetic neuralgia (PHN). However, the mechanism underlying the therapeutic effect of EA in PHN is still unclear. Systemic injection of resiniferatoxin (RTX), an ultrapotent analog of TRPV1 agonist, in adult rats can reproduce the clinical symptoms of PHN by ablating TRPV1-expressing sensory neurons. In this study, we determined the beneficial effect of EA and the potential mechanisms in this rat model of PHN. METHODS: PHN was induced in rats by a single injection of RTX. Thermal hyperalgesia was tested with a radiant heat stimulus, and mechanical allodynia was quantified with von Frey filaments. TRPV1 receptors were shown by using immunofluorescence labeling. The ultrastructural changes of the sciatic nerve were assessed by electron microscopic examination. The sprouting of myelinated primary afferent terminals into the spinal dorsal horn was mapped by using the transganglionic tracer cholera toxin B-subunit (CTB). RESULTS: RTX injection diminished thermal sensitivity and gradually induced tactile allodynia within 3 weeks. EA applied to GB30 and GB34 at 2 and 15 Hz, but not 100 Hz, significantly increased the thermal sensitivity 4 weeks after treatment and decreased the tactile allodynia 2 weeks after treatment in RTX-treated rats. EA treatment at 2 and 15 Hz recovered the loss of TRPV1-positive dorsal root ganglion neurons and their central terminals of afferent fibers in the spinal superficial dorsal horn of RTX-treated rats. Moreover, EA significantly reduced the loss of unmyelinated fibers and the damage of the myelinated nerve fibers of RTX-treated rats. Furthermore, EA at 2 and 15 Hz inhibited the sprouting of myelinated primary afferent terminals into the spinal lamina II of RTX-treated rats. CONCLUSIONS: EA treatment improves thermal perception by recovering TRPV1-positive sensory neurons and nerve terminals damaged by RTX. EA Also reduces RTX-induced tactile allodynia by attenuating the damage of myelinated afferent nerves and their abnormal sprouting into the spinal lamina II. Our study provides new information about the mechanisms of the therapeutic actions of EA in the treatment of PHN.
Assuntos
Eletroacupuntura , Hiperalgesia/patologia , Hiperalgesia/terapia , Neuralgia Pós-Herpética/patologia , Neuralgia Pós-Herpética/terapia , Temperatura , Animais , Toxina da Cólera/metabolismo , Modelos Animais de Doenças , Diterpenos , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Masculino , Bainha de Mielina/metabolismo , Neurônios Aferentes/metabolismo , Neurônios Aferentes/patologia , Células do Corno Posterior/metabolismo , Células do Corno Posterior/patologia , Subunidades Proteicas/metabolismo , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/patologia , Nervo Isquiático/ultraestrutura , Canais de Cátion TRPV/metabolismo , Fatores de TempoRESUMO
OBJECTIVE: To observe the choroidal thickness in eyes with chronic central serous chorioretinopathy(CSC) after half-dose photodynamic therapy(PDT). METHODS: Case series study. Consecutive 30 patients (35 eyes) with chronic CSC admitted from October 2010 to October 2011 in Zhongshan Ophthalmic Center were recruited in this study. Optical coherence tomography(OCT),fundus fluorescein angiography, indocyanine green angiography (ICGA) were performed in each patient to confirm the diagnosis. ICGA-guided PDT was performed in each patient. Choroidal thickness at subfoveal and 1500 µm superior, inferior, nasal and temporal to the fovea were measured before PDT, 1, 3 and 6 months after PDT using enhanced depth imaging OCT. Data were analyzed with one-way repeated measures ANOVA and LSD-t test when pairwise comparison was needed. RESULTS: Thirty patients, aged from 33 to 66 years old, including 26 males and 4 females (gender ratio 6.5: 1) were recruited. Subfoveal choroidal thickness (SFCT) in chronic CSC eyes was (435.54 ± 102.91) µm at baseline,which decreased significantly to (373.63 ± 106.01) µm, (360.69 ± 111.06) µm and (369.00 ± 108.12) µm at 1 month, 3 months and 6 months after PDT respectively (F = 108.34, P < 0.01). At 6 months after PDT, SFCT was slightly thicker than that at the 3(rd) month,but no statistical significance was noted (LSD-t test: P > 0.05). The changing trends of choroidal thickness at the other 4 measuring points were similar to that of the SFCT. CONCLUSION: Choroidal thickness is reduced within 6 months post PDT in chronic CSC eyes.
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Coriorretinopatia Serosa Central/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Adulto , Idoso , Coriorretinopatia Serosa Central/patologia , Corioide/patologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Tomografia de Coerência Óptica , VerteporfinaRESUMO
BACKGROUND: Weeds grow aggressively in agricultural fields, leading to reduced crop yields and an inability to meet the growing demand for food. Herbicides are currently the most effective method for weed control. However, the overuse of herbicides has resulted in the evolution of resistance mutants and has caused environmental pollution. Therefore, new technologies are urgently required to address this global challenge. RESULTS: We report a copper-benzene-1,4-dicarboxylate metal organic framework (Cu-BDC MOF)-functionalized carboxyl hollow mesoporous silica (HMS-COOH) delivery system for the pH-controlled release of the acetyl-CoA carboxylase (ACCase)-inhibiting herbicide quizalofop-p-ethyl (QE). The delivery system (QE@HMS@Cu-BDC) enabled the efficient control of barnyard grasses that are susceptible and resistant to ACCase-inhibiting herbicides, which showed 93.33% and 88.33% FW control efficacy at 67.5 g ha-1 , respectively. With the lowest pH value (3), QE and copper ion were released slowly to total 70.30% and 78.55% levels (respectively) from QE@HMS@Cu-BDC after 89 h. QE@HMS@Cu-BDC showed better absorption, conduction, transportation and ACCase activity inhibition performance than that of QE emulsifiable concentrate (EC) in both susceptible and ACCase-herbicide resistant barnyard grasses. In addition, with the safener effect of carrier HMS@Cu-BDC and the aid of the safener fenchlorazole-ethyl (FE), the application of QE@HMS@Cu-BDC was shown to mitigate the damage caused by QE to rice plants. CONCLUSION: This work found that the new material HMS-COOH@Cu-BDC can be used to mitigate herbicide-induced oxidative stress and improve rice plant safety. Futhermore, the QE@HMS-COOH@Cu-BDC constructed in this research might be used as an efficient nanopesticide formulation for weed controls in paddy rice fields. © 2023 Society of Chemical Industry.
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Herbicidas , Oryza , Herbicidas/farmacologia , Acetil-CoA Carboxilase/genética , Cobre/farmacologia , Dióxido de Silício/farmacologia , Plantas Daninhas , Concentração de Íons de Hidrogênio , Resistência a HerbicidasRESUMO
OBJECTIVE: To investigate and compare the choroidal thickness between healthy male and female subjects. METHOD: Six-hundred and twenty eyes of 310 healthy volunteers with no ophthalmic disease history were recruited, including 152 males and 158 females. All volunteers were subgrouped into Group A to F according to their ages. Enhanced depth imaging choroidal scans were obtained in all eyes by using spectral-domain optical coherence tomography. Subfoveal choroidal thickness (SFCT) and choroidal thickness at 1 mm/3 mm superior, inferior, nasal and temporal to the fovea were measured. Choroidal thickness was compared between male and female in the subgroups with different age. RESULTS: Mean SFCT was higher in 152 males (298.02 ± 101.47) µm than that in 158 females (256.28 ± 90.87) µm with statistically significant difference (t' = 4.853, P < 0.05). Choroid at 1 mm and 3 mm from the fovea were also thicker in the male (t' = 5.050, t = 4.597, t = 5.225, t = 5.363, t = 5.608, t' = 4.239, t = 4.108, t' = 5.589; P < 0.05). In any subgroup from A to E, SFCT in male was significantly thicker than female, after adjusted for refractive error (t = 2.343, t' = 2.163, t = 3.239, t = 2.181, t' = 2.982; P < 0.05). In Group F, mean SFCT in male was thicker than female, but without statistical significance (t' = 0.681, P > 0.05). CONCLUSIONS: Gender was one of the factors that affect the choroid thickness in healthy populations. In subjects under 70, male have thicker choroid than female. This result at least partially explained the gender predilection of macular diseases, such as central serous chorioretinopathy and idiopathic macular hole.
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Corioide/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , Corioide/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Radiografia , Fatores Sexuais , Tomografia de Coerência Óptica , Adulto JovemAssuntos
Descolamento Retiniano/cirurgia , Recurvamento da Esclera/métodos , Técnicas de Sutura , Adulto , Câmara Anterior/patologia , Comprimento Axial do Olho/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/fisiopatologia , Estudos Prospectivos , Descolamento Retiniano/patologia , Descolamento Retiniano/fisiopatologiaRESUMO
Montan wax is a mineral wax extracted from lignite type coal. It has been registered as a food additive in Japan though there have been no reports of toxicological evaluation, mainly due to the fact that it is considered a natural product. As part of a general safety assessment of montan wax, we have performed a 90-day toxicity study in Fisher 344 (F344) rats. Groups of 10 males and 10 females were given the material at dose levels of 0 (Group 1), 0.56 (Group 2), 1.67 (Group 3), or 5% (Group 4) in the diet for 90 days. During the experiment, there were no remarkable changes in general conditions and no deaths occurred in any group. On hematological examination, Hb, Ht, MCV and MCH were significantly decreased and WBC was significantly increased in all treated rats. On serum biochemical examination, AST and ALT were found to be elevated more than four fold in all treated groups as compared to the respective control group values in both sexes. Furthermore, relative organ weights for the liver, spleen, lung and kidneys were increased in all treated groups of both sexes. Histopathological examination revealed diffuse multiple granulomas in the livers with severe hepatocyte damage and lymphocytic infiltration. Granulomatous lesions were also apparent in the mesenteric lymph nodes in all treated males and females. These findings clearly demonstrate that montan wax, at doses of more than 0.56% in the diet, induces multiple granulomas with severe inflammation in the liver. Because pathological, hematological and serum biochemical changes were observed in the lowest dose group, a no-observed-adverse-effect level (NOAEL) could not be determined in the present study.
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Aditivos Alimentares/toxicidade , Granuloma/etiologia , Hepatócitos/patologia , Hepatopatias/etiologia , Ceras/toxicidade , Animais , Dieta , Relação Dose-Resposta a Droga , Feminino , Granuloma/sangue , Granuloma/patologia , Hepatócitos/efeitos dos fármacos , Hepatopatias/sangue , Hepatopatias/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344RESUMO
Knowledge of intrinsic tumor heterogeneity is vital for understanding of tumor progression mechanisms as well as for providing efficient treatments. In situ proteomic profiling of tumors is a powerful technology with potential to enhance our understanding of tumor biology, but sources of variability due to patient and tumor heterogeneity are poorly understood and are the topic of this investigation. Clarification of variability within case and between cases is also important for designing future studies. Direct protein profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a sensitive and powerful technology for obtaining hundreds of protein expression peaks from a thin tissue section. By combining robotic microspotting and laser capture microdissection with MALDI MS, we acquired multiple spectra per case to evaluate inter- and intra-case variability in human colorectal tumor and murine cecal carcinoma. We detected 256 peaks from 164 samples of 111 patients, which consisted of 55 normal colorectal mucosal samples, 24 adenomas, 71 primary carcinomas, and 14 hepatic metastases. In addition, we detected 291 peptide/protein peaks from 34 orthotopically transplanted murine cecal carcinomas and 14 hepatic metastases. In human colorectal samples, we observed that proteomic profiling in adenomas was more homogeneous across patients than in normal mucosa specimens (p=0.0008), but primary carcinoma exhibited greater heterogeneity than normal mucosa and adenomas (both p<0.0001). Murine cecal carcinomas were homogeneous within and between carcinomas, while their hepatic metastases tended toward greater intra-tumor differences (p<0.0001). Inter- and intra-case variability was approximately equal for many protein peaks. Acquiring up to 5 subsamples per case could reduce the total number of cases required, but further reduction from additional subsampling was modest unless intra-case variability comprises a greater proportion of total variation (e.g. >70%). In summary, this study characterizes intra- and inter-case variability of high-throughput protein expression in colorectal tumors, and provides guidance for the sample numbers required for in situ proteomic studies.
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Carcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas de Neoplasias/análise , Análise Serial de Proteínas , Proteômica , Animais , Carcinoma/patologia , Neoplasias Colorretais/patologia , Humanos , Camundongos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Arctiin, a plant lignan that can be extracted from the Arctium lappa (burdock) seeds, is a possible environmental endocrine disruptor compounds and have been shown to influence sex hormone metabolism as well as protein synthesis, steroid biosynthesis. Modifying effects of arctiin on prostate carcinogenesis in probasin/SV 40 T antigen (Tag) transgenic (TG) rats were examined. A total of 64 male TG rats, 6 weeks old, were randomly divided to three experimental groups (soybean free Oriental MF diet with 0.1, 0.02, or 0.004% arctiin) and a control group (soybean free Oriental MF diet). Animals were killed at the end of week 18. Histopathological evaluation of prostate revealed that all the rats in any group developed adenocarcinoma in dorsolateral lobe of prostate, except two rats in 0.1% arctiin treated and one rat in 0.002% arctiin treated groups without prostate adenocarcinoma development. However, there were no definite treatment-related changes with statistical significance in all parameters for prostate carcinomas measured in this experiment. These results indicated that arctiin might not exert significant modifying effect on prostate carcinogenesis in SV 40 Tag TG rats at least under the present experiment.
Assuntos
Adenoma/fisiopatologia , Furanos/farmacologia , Glucosídeos/farmacologia , Neoplasias da Próstata/fisiopatologia , Adenoma/veterinária , Administração Oral , Proteína de Ligação a Androgênios/genética , Ração Animal , Animais , Animais Geneticamente Modificados , Antígenos Transformantes de Poliomavirus/genética , Transformação Celular Neoplásica , Medicamentos de Ervas Chinesas , Masculino , Neoplasias da Próstata/veterinária , Distribuição Aleatória , Ratos , SementesRESUMO
PURPOSE: To modify an infusion cannula for vitreous surgery and decrease cannula-related complications. DESIGN: New surgical instrument. METHODS: A conventional 20-gauge infusion cannula was modified by forming a 135-degree angle at the joint of the flange between the cannula adapter and the needle. The sloped plane of the needle tip was opposite the bent adapter. The cannula was routinely fastened with a 7-0 absorbable suture after insertion into the eye. RESULTS: We used the modified infusion cannula in 50 consecutive phakic eyes (48 patients). Intraoperatively, the cannula remained attached to the globe surface; it did not tilt anteriorly and damage the lens when touched inadvertently. No suprachoroidal or subretinal infusion was observed. Neither the lens nor the retina was damaged. There were no cannula-related retinal detachments or breaks during follow-up. CONCLUSIONS: The modified infusion cannula is more effective and safer during pars plana vitrectomy in phakic eyes compared with a conventional cannula.
Assuntos
Cateterismo/instrumentação , Vitrectomia/instrumentação , Corpo Vítreo/cirurgia , Desenho de Equipamento , Humanos , Complicações Intraoperatórias/prevenção & controleRESUMO
The expression and significance of p57KIP2, an important inhibitor of the cell cycle, remain unclear during carcinogenesis and during late metastasis to lymph nodes of tumors. To detail changes of p57KIP2 during colorectal carcinogenesis and during late metastasis to lymph nodes, p57KIP2, cyclin A, cyclin B1, cyclin E, CDK2, and Ki67 were immunohistochemically investigated in 22 specimens of normal mucosa, 62 of adenomas, 17 of carcinomas in adenomas, 189 of primary carcinomas, and 23 of lymph node metastases. Situated in nuclei, p57KIP2 expression increased significantly from normal mucosa to adenomas (p=0.0068), from mild through moderate to severe dysplasia in adenomas (p=0.0132). It significantly decreased from adenomas to unpaired primary carcinomas (p=0.0112) and from peripheral adenomas to paired central carcinomas (p=0.0018), but remained unchanged when primary carcinomas metastasized to lymph nodes (p=0.3401). p57KIP2 expression was not correlated with clinicopathological indices, but the patients having tumors without p57KIP2 tended to show a poor prognosis (p=0.0674). High p57KIP2 was significantly correlated with increased cyclin A (p=0.0007), elevated cyclin B1 (p=0.0007), reduced CDK2 (p=0.0021), and increased Ki67 (p=0.0013) in adenomas. Thus, loss of p57KIP2 expression appears associated with colorectal carcinogenesis.