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The first paired electrolysis-enabled arylation of quinoxalin-2(1H)-ones was achieved using cyanoarenes as the arylation reagents. A variety of 3-arylquinoxalin-2(1H)-ones with various important functional groups were obtained in moderate to good yields under metal- and chemical oxidant-free conditions. With a pair of reductive and oxidative processes occurring among the substrates and reaction intermediates, the power consumption can be dramatically reduced.
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OBJECTIVE: To evaluate the therapeutic efficacy and safety of agomelatine for treating the sleep and mood disorders in epilepsy patients. METHODS: Retrospective data were derived from 113 epilepsy patients for at least 8 weeks. All the subjects were divided into two groups, one was treated with agomelatine, the other was treated with escitalopram. Their depression and anxiety states were assessed by Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Scales. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The HAMA, HAMD and PSQI scores in both groups significantly declined after the treatments with agomelatine and escitalopram. However, the agomelatine group exhibited greater improvement in terms of HAMA and PSQI scores compared to the escitalopram group. No severe adverse events were observed in agomelatine group. SIGNIFICANCE: Agomelatine performed better in HAMA and PSQI scores compared to escitalopram, where no significant increase in seizure frequency or side effects were observed. Possibly, agomelatine presents a promising therapeutic option for treating the sleep or mood disorders in epilepsy patients.
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Transtorno Depressivo Maior , Epilepsia , Humanos , Estudos Retrospectivos , Escitalopram , Resultado do Tratamento , Sono , Transtornos do Humor/etiologia , Transtornos do Humor/induzido quimicamente , Acetamidas/efeitos adversos , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamenteRESUMO
AIMS: Abuse of methamphetamine has aroused concern worldwide. Stimulant use and sexual behaviours have been linked in behavioural and epidemiological studies. Although methamphetamine-related neurofunctional differences are reported in previous studies, only few studies have examined neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence. METHODS: Neurofunctional changes were measured using a cue-reactivity task involving methamphetamine, sexual, and neutral cues in 20 methamphetamine abusers who were evaluated after a short- (1 week to 3 months) and long-term (10-15 months) abstinence. RESULTS: Five brain regions mainly involved in the occipital lobe and the parietal lobe were found with the group-by-condition interaction. Region-of-interest analyses found higher sexual-cue-related activation than other two activations in all five brain regions in the long-term methamphetamine abstinence group while no group differences were found. Negative relationships between motor impulsivity and methamphetamine- or sexual-cue-related activations in the left middle occipital gyrus, the superior parietal gyrus and the right angular gyrus were found. CONCLUSIONS: The findings suggested that methamphetamine abstinence may change the neural response of methamphetamine abusers to methamphetamine and sexual cues, and the neurofunction of the five brain regions reported in this study may partly recover with long-term methamphetamine abstinence. Given the use and relapse of methamphetamine for sexual purposes, the findings of this study may have particular clinical relevance.
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Transtornos Relacionados ao Uso de Anfetaminas , Sinais (Psicologia) , Metanfetamina , Comportamento Sexual , Humanos , Transtornos Relacionados ao Uso de Anfetaminas/fisiopatologia , Masculino , Adulto , Comportamento Sexual/efeitos dos fármacos , Imageamento por Ressonância Magnética , Lobo Parietal/fisiopatologia , Lobo Parietal/efeitos dos fármacos , Feminino , Lobo Occipital/fisiopatologia , Encéfalo/fisiopatologia , Encéfalo/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Adulto Jovem , Comportamento Impulsivo/efeitos dos fármacos , Mapeamento Encefálico/métodos , Fatores de TempoRESUMO
BACKGROUND: As a medicinal and food homologous plant, Rosa damascena is not only highly ornamental, but also rich in a variety of active ingredients such as polyphenols and flavonoids. It is widely used in cosmetics, food and pharmaceutical industries. OBJECTIVE: To study the in vitro efficacy of Rosa damascena solid state fermentation liquid (RDF) and water extract (RDE). METHODS: Firstly, the effect of RDF and RDE on the proliferation rate of B16F10 cells was detected by CCK-8 method, and the melanin content was measured by sodium hydroxide lysis method to evaluate the whitening effect of them. Finally, the antioxidant, anti-wrinkling and soothing effects of RDF and RDE were evaluated by biochemical methods in vitro. RESULTS: RDF and RDE within a certain concentration range (0.05%-0.5%) had no effect on the proliferation of B16F10 cells. Compared with Rosa damascena extract (RDE), RDF showed significant effects on bleaching, antioxidant, anti-wrinkling and soothing, among which 0.5% RDF showed the best effect. CONCLUSION: Both RDF and RDE at a certain concentration have effect on skin care in vitro, but the effect of RDF is more significant than that of RDE.
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Antioxidantes , Proliferação de Células , Fermentação , Extratos Vegetais , Rosa , Rosa/química , Extratos Vegetais/farmacologia , Camundongos , Animais , Proliferação de Células/efeitos dos fármacos , Antioxidantes/farmacologia , Higiene da Pele/métodos , Água/química , Envelhecimento da Pele/efeitos dos fármacos , Melaninas , Linhagem Celular Tumoral , Humanos , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologiaRESUMO
BACKGROUND: Increasing amounts of ultraviolet radiation occur as ozone depletion causes the earth's ozone layer to be destroyed, making antioxidant efficacy a research hotspot. Previous studies on plum blossom have mostly focused on Volatile Oils, Flavonoids, Phenylpropanoids, and other compounds, whereas few studies have focused on low molecular weight polypeptide (LMWP) of plum blossom. This research provides a reference for the deep processing and utilization of plum blossom. OBJECTIVES: (a) Plum blossom low molecular weight polypeptides protect HaCaT cells against UVB-induced oxidative damage in vitro and the underlying mechanism. (b) Improve the theoretical basis for the intense processing and utilization of plum blossom. METHODS: The safe concentration of LMWP and the survival rate of HaCaT cells were determined using the CCK-8 experiment. The fluorescence intensity of reactive oxygen species (ROS) was identified using the dichlorofluorescin diacetate (DCFH-DA) method; Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were measured in ruptured cells; Western blot analysis was used to examine the expression levels of three proteins: nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and benzoquinone oxidoreductase 1 (NQO-1). RESULTS: It was noted that a certain concentration of LMWP could promote cell proliferation. In oxidatively damaged HaCaT cells, SOD levels and survival rates were markedly reduced, but ROS and MDA levels were elevated. However, after treatment with LMWP, the survival rate of the cells and SOD levels were markedly increased, and the levels of ROS and MDA were markedly decreased. As shown by Western blotting, the model group exhibited lower levels of Nrf2, HO-1, and NQO-1 expression than the control group, whereas LMWP-treated cells had significantly higher levels of Nrf2, HO-1, and NQO-1 expression than their model-treated counterparts. CONCLUSIONS: LMMP can effectively protect HaCaT cells against oxidative damage in vitro induced by UVB, and the underlying mechanism is linked to the activation of the transcription factor Nrf2.
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Células HaCaT , Prunus domestica , Humanos , Espécies Reativas de Oxigênio , Prunus domestica/metabolismo , Raios Ultravioleta/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Peso Molecular , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Peptídeos/metabolismoRESUMO
The current research leverages the structural features and property superiorities along with benefits in protecting cardiovascular system of gallic acid (GLC) and gentisic acid (HGA) to optimize in vitro/vivo peculiarities of cardiotonic drug milrinone (MIL) through developing a stratagem of cocrystallization-driven double-optimized ternary salt cocrystal. This strategy assembles MIL ternary salt cocrystal by shaping a cocrystallization moiety relying on noncovalent interplays with GLC to obtain permeability advancement and molding a salt segment via the salification of proton transfer between HGA and MIL molecules to facilitate solubility enhancement. While the ameliorative in vitro properties further modulate the in vivo pharmacokinetic behaviors, thus fulfilling a dual optimization of MIL's biopharmaceutical characteristics on both in vitro and in vivo aspects. Along this line, the first MIL ternary salt cocrystal, viz., [HMIL+-GA-]-MIL-GLC-H2O (denoted as MTSC hereinafter), has been satisfactorily constructed and precisely structurally identified by diversified techniques. The single-crystal X-ray diffraction experiment validates that a molecular salt [HMIL+-GA-] species cocrystallizes with one neutral MIL, two GLC, and five solvent water molecules, among which the organic constituents compose laminated hydrogen bond networks, and then are self-assembled by water molecules to a 3D supramolecular structure. The unique structural feature and stacking pattern of MTSC make both the permeability and solubility be respectively enhanced by 9.69 times and 5.17- to 6.03-fold compared with the parent drug per se. The experimental outcomes are powerfully supported by associated calculations based on density functional theory. Intriguingly, these optimal in vitro physicochemical natures of MTSC have been potently converted into strengths of in vivo pharmacokinetics, showcasing the elevated drug plasma concentration, elongated half-life, alongside advanced bioavailability. Consequently, this presentation not just contributes a brand-new crystalline form with utility values, but ushers in a new dimension of ternary salt cocrystals for improving in vitro/vivo limitations of poor drug bioavailability.
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Produtos Biológicos , Cardiotônicos , Milrinona , Cristalização/métodos , Solubilidade , Cloreto de Sódio , Água/químicaRESUMO
Correction for 'Supramolecular self-assembly of amantadine hydrochloride with ferulic acid via dual optimization strategy establishes a precedent of synergistic antiviral drug-phenolic acid nutraceutical cocrystal' by Ling-Yang Wang et al., Analyst, 2021, 146, 3988-3999, https://doi.org/10.1039/D1AN00478F.
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Compared with healthy controls, heroin users (HUs) show evidence of structural and functional brain alterations. However, little is known about the possibility of brain recovery after protracted heroin abstinence. The purpose of this study was to investigate whether brain recovery is possible after protracted abstinence in HUs. A total of 108 subjects with heroin addiction completed structural and functional scans, and 61 of those subjects completed 8-month follow-up scans. Resting-state data and 3D-T1 MR images were collected for all participants, first at baseline and again after 8 months. Cognitive function and craving were measured by the Trail Making Test-A (TMT-A) and Visual Analog Scale for Craving, respectively. The cortical thickness and resting-state functional connectivity (RSFC) differences were then analyzed and compared between baseline and follow-up, and correlations were obtained between neuroimaging and behavioral changes. HUs demonstrated improved cognition (shorter TMT-A time) and reduced craving at the follow-up (HU2) relative to baseline (HU1), and the cortical thickness in the bilateral superior frontal gyrus (SFG) was significantly greater at HU2 than at HU1. Additionally, the RSFC of the left SFG with the inferior frontal gyrus (IFG), insula, and nucleus accumbens and that of the right SFG with the IFG, insula and orbitofrontal cortex (OFC) were increased at HU2. The changes in TMT-A time were negatively correlated with the RSFC changes between the left SFG and the bilateral IFG, the bilateral caudate, and the right insula. The changes in craving were negatively correlated with the RSFC changes between the left OFC and the bilateral SFG. Our results demonstrated that impaired frontal-limbic neurocircuitry can be partially restored, which might enable improved cognition as well as reduced craving in substance-abusing individuals. We provided novel scientific evidence for the partial recovery of brain circuits implicated in cognition and craving after protracted abstinence.
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Dependência de Heroína , Mapeamento Encefálico , Seguimentos , Dependência de Heroína/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Córtex Pré-FrontalRESUMO
To display the capability of the phenolic acid nutraceutical ferulic acid (FLA) in optimizing the in vitro/in vivo properties of the antiviral drug amantadine hydrochloride (AMH) and achieve synergistically enhanced antiviral effects, thereby gaining some new insights into pharmaceutical cocrystals of antiviral drugs with phenolic acid nutraceuticals, a cocrystallization strategy of dual optimization was created. Based on this strategy, the first drug-phenolic acid nutraceutical cocrystal of AMH with FLA, namely AMH-FLA-H2O, was successfully assembled and completely characterized by employing single-crystal X-ray diffraction and other analytical techniques. The cocrystal was revealed to be composed of AMH, FLA, and water molecules in the ratio of 3 : 1 : 1.5, and charge-assisted hydrogen bonds containing chloride ions crucially maintained the crystal lattice together with water molecules. The in vitro/in vivo properties of the cocrystal were systematically evaluated via both theoretical and experimental methods, and the results indicate that the dissolubility of AMH is down-regulated by two-thirds in the cocrystal, resulting in its potential for sustained pharmacokinetic release and the elimination of the adverse effects of AMH. More importantly, the enhanced antiviral effects of the current cocrystal were proven against four viral strains, and the pharmaceutical synergy between AMH and FLA was realized with a combination index (CI) of less than 1. Thus, the present work provides a novel crystalline product with bright commercial prospect for the classical antiviral drug AMH and also establishes an avenue for the synergetic antiviral application of nutraceutical phenolic acids via the cocrystallization strategy of dual optimization.
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Amantadina , Antivirais , Antivirais/farmacologia , Ácidos Cumáricos , Cristalização , Suplementos Nutricionais , Hidroxibenzoatos , SolubilidadeRESUMO
For highlighting the predominance of phenolic acid nutraceutical ferulic acid (FR) in regulating the in vivo/vitro performances of anticancer drug 5-fluorouracil (Flu) and strengthening their cooperativity in antitumor effect, thus achieving a major breakthrough in the development of drug-nutraceutical cocrystal with synergistic antitumor action, a cocrystallization strategy of dual optimization is created, in which both the in vivo and vitro natures of Flu are improved by exploiting the FR's excellent physicochemical property. Moreover, Flu's anticancer effects were promoted by exerting the assistant antitumor peculiarity of FR. Such dual optimization of FR for Flu in physicochemical properties and anticancer activities is beneficial for realizing synergistic augmentation effect by taking the benefit of the cooperativeness of Flu and FR in the anticancer ability. Based on this idea, a novel cocrystal of Flu and FR, namely, Flu-FR-H2O, is successfully assembled as the first 5-fluorouracil-nutraceutical cocrystal with synergistic antitumor effect and its explicit structure is resolved. The single-crystal X-ray diffraction demonstrates that Flu and FR have a ratio of 1 : 1 with one equivalent of solvent water in the cocrystal, where one-dimensional hydrogen-bonding helices and FR-Flu hydrogen-bonding pairs, together construct a three-dimensional supramolecular network. By combining experimental evaluation with theoretical analysis, in vitro/vivo pharmaceutical properties are scientifically investigated. Results show that the permeability and aqueous solubility of Flu are respectively elevated by 5.08 and 1.64 folds, which has brought about ameliorated pharmacokinetics, thus providing prolonged retention time and increased oral bioavailability. More interestingly, the cocrystal shows synergistic inhibition ability of Flu and FR against tested tumor cell strains, hence laying the groundwork for reducing the dosage and even the toxic side effects of Flu. As a result of this, the present research not only provides a new strategy for Flu to optimize its physicochemical properties and antitumor activities simultaneously but also offers some opinions for the development of synergistic antitumor pharmaceutical cocrystals.
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Suplementos Nutricionais , Fluoruracila , Ácidos Cumáricos , Cristalização , Fluoruracila/farmacologia , Hidroxibenzoatos , SolubilidadeRESUMO
BACKGROUND: Bone cement leakage is a major complication in the treatment of percutaneous vertebroplasty for Kümmell's disease, and the focus of close attention during the surgery. The purpose of this article was to investigate the clinical outcomes of Kümmell's disease treated by percutaneous vertebroplasty with or without bone cement leakage. METHODS: A total of 64 patients with Kümmell's disease from December 2016 to February 2018 treated by percutaneous vertebroplasty were included in the study. After the treatment, 32 cases were respectively divided into two groups according to X-ray examination of bone cement leakage: leakage group and non-leakage group. Preoperative course, age, sex, bone mineral density, damaged segment, anterior vertebral height, vertebral compression rate, Cobb angle, visual analogue scale and Oswestry dysfunction index were compared between the two groups. After surgery, the amount of bone cement injected, operation time, adjacent vertebral refracture rate, visual analogue scale, Oswestry dysfunction index, the recovery value of vertebral anterior height and the improvement value of Cobb angle were compared between the two groups. RESULTS: The course, age and Cobb angle of the leakage group were significantly greater than those of the non-leakage group (P< 0.05, respectively). The height of anterior vertebral margin and bone mineral density in the leakage group were significantly lower than those in the non-leakage group (P< 0.05, respectively). The two groups were followed up for at least 24 months. The amount of bone cement injected was significantly greater in the leakage group than in the non-leakage group (P=0.000). Visual analogue scale and Oswestry dysfunction index of the two groups on the second day after surgery and at the last follow-up were significantly lower than these before surgery (P< 0.05, respectively), but there was no significant difference between the two groups. In the leakage group, the recovery value of the anterior edge height of the injured vertebra and the improvement value of the Cobb angle on the second day after surgery and at the last follow-up were significantly improved compared with the non-leakage group (P< 0.05, respectively). CONCLUSION: Percutaneous vertebroplasty is an effective and minimally invasive treatment for Kümmell's disease. The leakage group had longer course, older age, more serious kyphotic deformity, vertebral compression and osteoporosis, and higher amount of bone cement injected than these of the non-leakage group. However, there were not significant differences in the rate of adjacent vertebral refractures, visual analogue scale and Oswestry dysfunction index between the two groups. Therefore, the bone cement leakage does not affect the surgical effect.
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Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Idoso , Cimentos Ósseos/efeitos adversos , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento , Vertebroplastia/efeitos adversosRESUMO
Bromhexine is an expectorant drug repurposing as a TMPRSS2 inhibitor, which has also been proposed for potential treatment in COVID-19 infection. Multicomponent crystal strategy has been applied in bromhexine to improve its poor solubility, which limits its bioavailability and efficacy. A new bromhexine crystal and its fumarate salt crystal have been successfully obtained by slow evaporation technique. Both compounds have been characterized by X-ray single-crystal diffraction, TGA and FT-IR spectroscopy. Hirshfeld surface analysis has been carried out to further quantify the patterns of intermolecular interactions. Compared with bromhexine, the multicomponent crystal with pharmaceutically acceptable conformer of fumaric acid shows improved thermal stability and solubility in water.
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Objective: With the aim of surmounting the severe hepatotoxicity induced by antituberculosis drug isoniazid (INH), a novel cocrystal of INH with hepatoprotective nutraceutical syringic acid (SYA), namely INH-SYA, was designed and prepared through cocrystallization strategy, which is an intriguing attempt to reduce the toxic side effects of INH.Significance: The study not only provides new thinking for inhibiting toxic side effects of drugs through cocrystallization strategy, but also opens a new pathway for the application of nutraceuticals in the pharmacy.Methods: INH and SYA were successfully crystallized into the same crystal lattice through combining volatilization with solvent assisted methods. The resulting cocrystal was structurally characterized by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC).Results: The SCXRD analysis for the present cocrystal revealed that it has a 1:1 ratio of INH to SYA with two molecules INH homodimers and two SYA molecules, in which they are arranged alternately linked by hydrogen bonds to form a six molecules ring structure (R66(40)) in crystal. The systematic evaluation of the in vitro/in vivo suggested that, owing to the formation of cocrystal, the dissolution efficiency of SYA was increased 5.85-fold compared with that of coarse SYA, and the oral bioavailability of the cocrystal in rats was enhanced by 3.66 times. As a result, the present INH-SYA cocrystal almost removed INH induced serious hepatotoxicity, which was further demonstrated by the hepatotoxicity studies in rats.Conclusion: INH-SYA cocrystal could effectively reduce the hepatotoxicity of INH.
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Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Isoniazida/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cristalização , Ácido Gálico/análogos & derivados , Ácido Gálico/química , RatosRESUMO
Three new compounds, namely massonside C (1), massonianoside F (2), and 3, 8-dimethyl- herbacetin-7-O-ß-D-glucopyranoside (3), together with five known compounds (4-8), were isolated from the fresh needles of Pinus massoniana. Their structures were established by 1D, 2D NMR, HRMS and comparison with the literature data. The absolute configuration of 1 was confirmed by a combination of X-ray single crystal analysis. All isolated compounds were evaluated for the protective effect of human umbilical vein endothelial cells against oxidative damage.
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Diterpenos , Lignanas , Pinus , Células Endoteliais , Flavonoides , Humanos , Estrutura Molecular , Folhas de Planta , Raios XRESUMO
Marine-derived fungi are considered to be valuable producers of bioactive secondary metabolites used as lead compounds with medicinal importance. In this study, chemical investigation of the seawater-derived fungus Aspergillus sydowii SW9 led to the isolation and identification of one new quinazolinone alkaloid, 2-(4-hydroxybenzyl)-4-(3-acetyl)quinazolin-one (1), one new aromatic bisabolene-type sesquiterpenoid, (2) and one new chorismic acid analogue (3), as well as two known alkaloids (compounds 4 and 5). Their structures were determined by extensive 1D/2D NMR and mass spectrometric data, and the absolute configurations of 2 and 3 were assigned by the analysis of ECD spectra aided by quantum chemical computations. Compounds 1, 2, and 4 exhibited selective inhibitory activities against the human pathogenic bacteria Escherichia coli, Staphylococcus aureus, S. epidermidis, and Streptococcus pneumoniae, with MIC values ranging from 2.0 to 16 µg/mL.
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Anti-Infecciosos/química , Organismos Aquáticos , Aspergillus/química , Aspergillus/metabolismo , Água do Mar/microbiologia , Metabolismo Secundário , Microbiologia da Água , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Fermentação , Humanos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura MolecularRESUMO
We present the case of a 28 year old patient with an incomplete tear of the tunica albuginea occurred after having sexual intercourse in the female superior position. The diagnostic assessment was performed first clinically, then with CT, owing to its high resolution, allowed to exactly detect the tear location leading to precise preoperative planning. After adequate diagnosis through imaging and proper planning, the patient was performed a selective minimally invasive surgical approach to repair the lesion. The patient had good erection with no angular deformity or plaque formation after a 3-month follow-up.
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Doenças do Pênis/cirurgia , Pênis/lesões , Ruptura/cirurgia , Adulto , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , Doenças do Pênis/diagnóstico por imagem , Pênis/diagnóstico por imagem , Pênis/cirurgia , Ruptura/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
A new tetracopper(II) complex bridged both by oxamido and carboxylato groups, namely [Cu4 (dmaepox)2 (bpy)2 ](NO3 )2 ·2H2 O, where H3 dmaepox and bpy represent N-benzoato-N'- (3-methylaminopropyl)oxamide and 2,2'-bipyridine, was synthesized, and its structure reveals the presence of a centrosymmetric cyclic tetracopper(II) cation assembled by a pair of cis-dmaepox3- - bridged dicopper(II) units through the carboxylato groups, in which the endo- and exo-copper(II) ions bridged by the oxamido group have a square-planar and a square-pyramidal coordination geometries, respectively. The aromatic packing interactions assemble the complex molecules to a two-dimensional supramolecular structure. The reactivity toward DNA and protein bovine serum albumin (BSA) indicates that the complex can interact with herring sperm DNA through the intercalation mode and the binding affinity is dominated by the hydrophobicity and chelate ring arrangement around copper(II) ions and quenches the intrinsic fluorescence of BSA via a static process. The cytotoxicity of the complex shows selective cancer cell antiproliferative activity.
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Antineoplásicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Cobre/farmacologia , Desenho de Fármacos , Hepatócitos/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Compostos Organometálicos/farmacologia , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/metabolismo , Sítios de Ligação , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobre/efeitos adversos , Cobre/química , Cobre/metabolismo , Cristalografia por Raios X , Hepatócitos/patologia , Humanos , Substâncias Intercalantes/efeitos adversos , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Cinética , Ligantes , Neoplasias Hepáticas/patologia , Estrutura Molecular , Compostos Organometálicos/efeitos adversos , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , SolubilidadeRESUMO
Six new phragmalin limonoids, named moluccensin Z1 (1), moluccensin Z2 (2), carapanolide Y (3), tabulalin N (4), chukvelutilide A1 (5), and velutinasin J (6), as well as two known compounds, chukvelutilide A (7) and velutinasin D (8) were isolated from the stems of Chukrasia tabularis A. Juss. The structures of the new compounds 1â»6 were confirmed by spectroscopic methods, including IR and HRESIMS, as well as 1D and 2D NMR, and by comparisons with the data of known analogues. All compounds were tested for α-glucosidase and acetylcholinesterase inhibitory activities. However, none of the compounds was active against α-glucosidase and acetylcholinesterase in vitro.
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Limoninas/isolamento & purificação , Meliaceae/química , Limoninas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/química , Caules de Planta/químicaRESUMO
Lentiviral vectors are now widely considered as one of the most common gene delivery tools for dividing and non-dividing cells. However, insertional mutagenesis has been found in clinical trials with retroviral vectors, which poses a safety risk. The use of non-integrating lentiviral (NIL) vectors, which avoid integration, eliminates the insertional mutagenesis problem. These NIL vectors are unable to mediate stable gene delivery into dividing cells, which makes them of limited use in the clinical practice of gene therapy. In this study, we constructed a NIL vector which harbors the scaffold/matrix attachment region (S/MAR) sequence and a therapeutic gene. NIL retained episomal erythropoietin (EPO) gene expression for 74days in dividing cells both with and without selection. Furthermore, Southern blot analysis showed that the NIL vector was retained extrachromosomally in CHO cells. In conclusion, the NIL vector based on an S/MAR sequence retained the extrachromosomal expression of a therapeutic gene in dividing cells. Our results show that NIL vectors maybe a safe and effective means of gene delivery, which is of potential clinical significance.
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Eritropoetina/genética , Técnicas de Transferência de Genes , Vetores Genéticos/metabolismo , Lentivirus/genética , Plasmídeos/metabolismo , Animais , Células CHO , Divisão Celular , Cricetulus , Eritropoetina/metabolismo , Expressão Gênica , Vetores Genéticos/química , Células HEK293 , Humanos , Lentivirus/metabolismo , Fator 1 de Elongação de Peptídeos/genética , Fator 1 de Elongação de Peptídeos/metabolismo , Plasmídeos/química , Regiões Promotoras Genéticas , TransgenesRESUMO
A new trinickel(II) complex bridged by N-[3-(dimethylamino)propyl]- N'-(2-hydroxylphenyl)oxamido (H3 pdmapo), namely [Ni3 (pdmapo)2 (H2 O)2 ]â 4CH3 OH, was synthesized and characterized by X-ray single-crystal diffraction and other methods. In the molecule, two symmetric cis-pdmapo3- mononickel(II) complexes as a "complex ligand" using the carbonyl oxygen atoms coordinate to the center nickel(II) ion situated on an inversion point. The Ni···Ni distance through the oxamido bridge is 5.2624(4) Å. The center nickel(II) ion and the lateral ones have octahedral and square-planar coordination geometries, respectively. In the crystal, a three-dimensional supramolecular network dominated by hydrogen bonds is observed. The reactivity toward DNA/protein bovine serum albumin (BSA) revealed that the complex could interact with herring sperm DNA (HS-DNA) through the intercalation mode and quench the intrinsic fluorescence of BSA via a static mechanism. The in vitro anticancer activities suggested that the complex is active against the selected tumor cell lines.