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BACKGROUND: Little is understood about the association between psychosomatic symptoms and advanced cancer among older Chinese patients. METHODS: This secondary analysis was part of a multicenter cross-sectional study based on an electronic patient-reported outcome platform. Patients with advanced cancer were included between August 2019 and December 2020 in China. Participants (over 60 years) completed the MD Anderson Symptom Inventory (MDASI) and Hospital Anxiety and Depression Scale (HADS) to measure symptom burden. Network analysis was also conducted to investigate the network structure, centrality indices (strength, closeness, and betweenness) and network stability. RESULTS: A total of 1022 patients with a mean age of 66 (60-88) years were included; 727 (71.1%) were males, and 295 (28.9%) were females. A total of 64.9% of older patients with advanced cancer had one or more symptoms, and up to 80% had anxiety and depression. The generated network indicated that the physical symptoms, anxiety and depression symptom communities were well connected with each other. Based on an evaluation of the centrality indices, 'distress/feeling upset' (MDASI 5) appears to be a structurally important node in all three networks, and 'I lost interest in my own appearance' (HADS-D4) had the lowest centrality indices. The network stability was relatively high (> 0.7). CONCLUSION: The symptom burden remains high in older patients with advanced cancer in China. Psychosomatic symptoms are highly interactive and often present as comorbidities. This network can be used to provide targeted interventions to optimize symptom management in older patients with advanced cancer in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024957), registered on 06/12/2020.
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Depressão , Neoplasias , Masculino , Feminino , Humanos , Idoso , Depressão/diagnóstico , Depressão/epidemiologia , Estudos Transversais , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Transtornos de AnsiedadeRESUMO
OBJECTIVE: The aims of this study were to explore the frequency of somatic symptom disorder (SSD) and the relationship between SSD and somatic, psychological, and social factors in Chinese patients with breast cancer. METHODS: This multicenter cross-sectional study enrolled 264 patients with breast cancer from three different departments in Beijing. The structured clinical interview for fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (SCID-5) for SSD. Standardized questionnaires and clinical data were used to compare patients with and without SSD. RESULTS: Somatic symptom disorder was diagnosed in 21.6% (57/264) of all enrolled patients. No differences were found between SSD patients and non-SSD patients in terms of sociodemographic characteristics and tumor-specific variables, except radiotherapy. However, patients with SSD reported higher levels of depression, anxiety and cancer-related worry. They also showed a longer duration of symptoms, greater impairment in daily life, more concern over their physical complaints and more doctor visits. In a stepwise binary logistic regression analysis, among others, higher health anxiety (WI-8, Exp(B) = 0.107, p = 0.009) and more doctor visits (OR = -1.841, p < 0.001) showed a significant association with SSD; the model explained 53.7% of the variance. CONCLUSIONS: Similar to other physical diseases, there is a high prevalence of SSD in patients with breast cancer. Somatic symptom disorder patients differ from non-SSD patients by exhibiting higher cancer-related emotional distress and dysfunctional illness perception and behavior. There remain substantial challenges in the diagnosis of SSD in patients with cancer and other medical conditions. CLINICAL TRIAL REGISTRATION: ChiCTR2100051525.
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Neoplasias da Mama , Sintomas Inexplicáveis , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/psicologia , China/epidemiologia , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Prevalência , Transtornos Somatoformes/psicologia , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Major depressive disorder (MDD) is associated with an increased risk of suicide and suicide attempt among cancer patients. However, we do not know how many cancer patients without MDD have suicidal ideation (SI). OBJECTIVES: This study aimed to investigate the prevalence, characteristics and correlated factors of SI among advanced cancer patients without MDD. METHODS: This is a multi-center, cross-sectional study based on an electronic patient-reported outcome systems in patients who were diagnosed with advanced lung, liver, gastric, esophageal, colorectal or breast cancer, the top six prevalent cancers in China. A total of 2930 advanced cancer patients were recruited from 10 regional representative cancer centers across China from August 2019 to December 2020. Patients completed the Patient Health Questionnaire-9 regarding if they had thoughts of being better off dead or of hurting themselves in some way in the previous 2 weeks. Patients also completed the symptom inventory and quality of life assessment. Generalized estimating equation model was performed to explore the correlated factors associated with SI among the patients without MDD. RESULTS: The overall prevalence of SI among advanced cancer patients without MDD was 13.1%. The prevalence was higher in older patients. After adjusted for existing conditions, patients with vomiting symptom (p < 0.001), poorer life quality (p < 0.001), and middle education level (p = 0.031) were correlated factors of SI. CONCLUSIONS: The suicidal ideation is common in advanced cancer patients without MDD. Patients with vomiting, poor quality of life, and middle education level should be screened and monitored for suicidal ideation even without MDD. CLINICAL TRIAL INFORMATION: ChiCTR1900024957.
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Transtorno Depressivo Maior , Neoplasias , Humanos , Idoso , Ideação Suicida , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Estudos Transversais , Qualidade de Vida , Vômito , Neoplasias/epidemiologiaRESUMO
BACKGROUND: To identify candidate key genes and pathways related to resting mast cells in meningioma and the underlying molecular mechanisms of meningioma. METHODS: Gene expression profiles of the used microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. GO and KEGG pathway enrichments of DEGs were analyzed using the ClusterProfiler package in R. The protein-protein interaction network (PPI), and TF-miRNA- mRNA co-expression networks were constructed. Further, the difference in immune infiltration was investigated using the CIBERSORT algorithm. RESULTS: A total of 1499 DEGs were identified between tumor and normal controls. The analysis of the immune cell infiltration landscape showed that the probability of distribution of memory B cells, regulatory T cells (Tregs), and resting mast cells in tumor samples were significantly higher than those in the controls. Moreover, through WGCNA analysis, the module related to resting mast cells contained 158 DEGs, and KEGG pathway analysis revealed that the DEGs were dominant in the TNF signaling pathway, cytokine-cytokine receptor interaction, and IL-17 signaling pathway. Survival analysis of hub genes related to resting mast cells showed that the risk model was constructed based on 9 key genes. The TF-miRNA- mRNA co-regulation network, including MYC-miR-145-5p, TNFAIP3-miR-29c-3p, and TNFAIP3-hsa-miR-335-3p, were obtained. Further, 36 nodes and 197 interactions in the PPI network were identified. CONCLUSION: The results of this study revealed candidate key genes, miRNAs, and pathways related to resting mast cells involved in meningioma development, providing potential therapeutic targets for meningioma treatment.
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Perfilação da Expressão Gênica , Mastócitos/citologia , Neoplasias Meníngeas/genética , Meningioma/genética , Algoritmos , Bases de Dados Genéticas , Humanos , Imunidade Celular , Interleucina-17/metabolismo , Células B de Memória/citologia , Neoplasias Meníngeas/imunologia , Neoplasias Meníngeas/patologia , Meningioma/imunologia , Meningioma/patologia , MicroRNAs/metabolismo , Mapas de Interação de Proteínas , Transdução de Sinais , Linfócitos T Reguladores/citologiaRESUMO
BACKGROUND: This study was intended to investigate the genomic landscape of the immune microenvironments of brain metastases in breast cancer. METHODS: Three gene expression profile datasets (GSE76714, GSE125989 and GSE43837) of breast cancer with brain metastases were downloaded from Gene Expression Omnibus (GEO) database. After differential expression analysis, the tumor immune microenvironment and immune cell infiltration were analyzed. Then immune-related genes were identified, followed by function analysis, transcription factor (TF)-miRNA-mRNA co-regulatory network analysis, and survival analysis of metastatic recurrence. RESULTS: The present results showed that the tumor immune microenvironment in brain metastases was immunosuppressed compared with primary caner. Compared with primary cancer samples, the infiltration ratio of plasma cells in brain metastases samples was significantly higher, while the infiltration ratio of macrophages M2 cells in brain metastases samples was significantly lower. Total 42 immune-related genes were identified, such as THY1 and NEU2. CD1B, THY1 and DOCK2 were found to be implicated in the metastatic recurrence of breast cancer. CONCLUSIONS: Targeting macrophages or plasma cells may be new strategies for immunotherapy of breast cancer with brain metastases. THY1 and NEU2 may be potential therapeutic targets for breast cancer with brain metastases, and THY1, CD1B and DOCK2 may serve as potential prognostic markers for improvement of brain metastases survival.
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Neoplasias Encefálicas , Neoplasias da Mama , Neoplasias Encefálicas/genética , Mama , Neoplasias da Mama/genética , Genômica , Humanos , Microambiente TumoralRESUMO
BACKGROUND AND AIMS: Glioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor. This study aimed to identify the key genes associated with the development of GBM and provide new diagnostic and therapies for GBM. METHODS: Three microarray datasets (GSE111260, GSE103227, and GSE104267) were selected from Gene Expression Omnibus (GEO) database for integrated analysis. The differential expressed genes (DEGs) between GBM and normal tissues were identified. Then, prognosis-related DEGs were screened by survival analysis, followed by functional enrichment analysis. The protein-protein interaction (PPI) network was constructed to explore the hub genes associated with GBM. The mRNA and protein expression levels of hub genes were respectively validated in silico using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. Subsequently, the small molecule drugs of GBM were predicted by using Connectivity Map (CMAP) database. RESULTS: A total of 78 prognosis-related DEGs were identified, of which10 hub genes with higher degree were obtained by PPI analysis. The mRNA expression and protein expression levels of CETN2, MKI67, ARL13B, and SETDB1 were overexpressed in GBM tissues, while the expression levels of CALN1, ELAVL3, ADCY3, SYN2, SLC12A5, and SOD1 were down-regulated in GBM tissues. Additionally, these genes were significantly associated with the prognosis of GBM. We eventually predicted the 10 most vital small molecule drugs, which potentially imitate or reverse GBM carcinogenic status. Cycloserine and 11-deoxy-16,16-dimethylprostaglandin E2 might be considered as potential therapeutic drugs of GBM. CONCLUSIONS: Our study provided 10 key genes for diagnosis, prognosis, and therapy for GBM. These findings might contribute to a better comprehension of molecular mechanisms of GBM development, and provide new perspective for further GBM research. However, specific regulatory mechanism of these genes needed further elaboration.
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In this paper, the physical layer security (PLS) of fractional orbital angular momentum (OAM) multiplexing under atmospheric turbulence channels is studied. Based on the PLS theory, the secrecy capacities and the probabilities of positive secrecy capacities of fractional OAM (FrOAM) multiplexing systems with different topological charge intervals are analyzed. The influence of the eavesdropping ratio and the power allocation on secrecy capacities are compared. The simulation results show that, under the finite aperture limitation, the FrOAM multiplexing technique provides higher security over the integer OAM multiplexing in terms of the total secrecy capacities under weak and medium turbulence.
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BMS-830216 is a diprotic acid prodrug of two pKa values (<2 and 6.8) with high apparent solubility at pH ≥ 7. At â¼ pH 4 solutions of BMS-830216 appear to be surface active, in which their surface tension can be reduced from 72 to 65 dynes when its concentrations is above the critical aggregation concentration (CACâ¼0.2 mM). Additionally, at this pH, BMS-830216 tends to form liquid crystalline phases (at ≥ 2 mg/mL) in acetate buffer when using tris salt. Furthermore, after raising the concentration beyond 20 mg/g, formation of gel-like dispersions was noted. These gel-like dispersions exhibited a strong elastic strength, significantly impacting the dissolution behavior of the tris salt. Mechanistically, it is likely that BMS-830216 tris salt in solution first forms a lamellar phase followed by formation of a gel phase at higher concentrations (≥20 mg/mL). As indicated by SAXS, the lamellar phase formed seems to have two d-spacing values (â¼5 nm and â¼10 nm (weak), which seems to correspond to two molecules connected tail by tail (5 nm). Further investigation is needed for phase identification, as their properties can affect the physical behavior of BMS-830216 in the development of pharmaceutical dosage forms.
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Pró-Fármacos/química , Receptores de Somatostatina/antagonistas & inibidores , Varredura Diferencial de Calorimetria , Química Farmacêutica , Liberação Controlada de Fármacos , Géis , Cristais Líquidos , Pró-Fármacos/farmacologia , Espalhamento a Baixo Ângulo , Solubilidade , Tensão Superficial , Difração de Raios X/métodosRESUMO
Protein therapeutics are exposed to various surfaces during product development, where their adsorption possibly causes unfolding, denaturation, and aggregation. In this paper, we aim to characterize four types of typical surfaces used in the development of biologics: polycarbonate, polyethersulfone, borosilicate glass, and cellulose. Contact angles of these surfaces were measured using three probing liquids: water, formamide, and diidomethane, from which acid/base (AB) and Lifshitz-van der Waals (LW) interaction components were derived. To explore the interactions of surfactants of Pluronics/Poloxamers (PEO-PPO-PEO copolymers) with these surfaces, the adsorption of three Pluronics (F68, F127, and L44) at these surfaces was determined using a quartz crystal microbalance with dissipation technique (QCM-D). For hydrophobic surfaces without AB component (polycarbonate and polyethersulfone), these copolymers exhibited significant adsorption with a little dissipation at low concentrations. For hydrophilic surfaces with AB component (cellulose and borosilicate), the adsorption at low-surfactant concentration is low while dissipation is relatively high. Additionally, the chemical properties of Pluronics such as the ratio of PPO to PEO, along with the interaction of PPO with surfaces were observed to play a critical role in adsorption. Furthermore, the interfacial structure of the adsorbed layer was affected by both AB interaction and the presence of PEO block.
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Poloxâmero/química , Polietilenoglicóis/química , Propilenoglicóis/química , Proteínas/química , Tensoativos/química , Adsorção , Celulose/química , Química Farmacêutica/métodos , Vidro/química , Interações Hidrofóbicas e Hidrofílicas , Cimento de Policarboxilato/química , Polímeros/química , Sulfonas/química , Propriedades de SuperfícieRESUMO
Liquid crystal lipid-based formulations are an effective approach to prolong pharmacokinetics and reduce burst release of a drug on subcutaneous delivery. The objective of this paper was to investigate the influence of phase structures of a lipid-based liquid crystal delivery system and its associated mechanical properties on the release profile of a peptide. It was hypothesized that release of drug molecules are closely related to the mechanical properties that are controlled by phase structures. Experimentally, the relationship between phase structures of lipid liquid crystal system-soy phosphatidyl choline (SPC) and glycerol dioleate (GDO) in water were characterized by polarized light microscopy and small angle X-ray diffraction. Their rheological properties were evaluated with a rheometer and the in vitro release of the peptide as a measure drug release from the LC-depot injection. Three phases: disordered phase, lamellar phase, mixtures of cubic, lamellar, and hexagonal phases were detected by varying formulation compositions. A significant difference in rheological behavior was observed. The disordered phase displayed some attributes of typical Newtonian fluid with lowest viscosity while the lamellar phase showed a shear thinning behavior. Regarding the mechanical strength, the lamellar phase presents the highest storage modulus due to its layer structure followed by mixed phases. Comparing release profiles, the lamellar phase produced a fast release followed by the mixture of phases. In conclusion, this study demonstrates the ability to characterize LC phase structures with microscopy, small angle X-ray diffraction, and rheological measurements and their link to modulating a peptide release profile.
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Cristais Líquidos/química , Oligopeptídeos/administração & dosagem , Preparações de Ação Retardada , Diglicerídeos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Excipientes , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Lipídeos/química , Oligopeptídeos/química , Fosfatidilcolinas , Reologia , Solubilidade , Viscosidade , ÁguaRESUMO
We study two-dimensional sub-wavelength atom localization based on the microwave coupling field controlling and spontaneously generated coherence (SGC) effect. For a five-level M-type atom, introducing a microwave coupling field between two upper levels and considering the quantum interference between two transitions from two upper levels to lower levels, the analytical expression of conditional position probability (CPP) distribution is obtained using the iterative method. The influence of the detuning of a spontaneously emitted photon, Rabi frequency of the microwave field, and the SGC effect on the CPP are discussed. The two-dimensional sub-half-wavelength atom localization with high-precision and high spatial resolution is achieved by adjusting the detuning and the Rabi frequency, where the atom can be localized in a region smaller thanλ/10×λ/10. The spatial resolution is improved significantly compared with the case without the microwave field.
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OBJECTIVE: We researched associations between somatic symptom severity (SSS), and physical and psychological factors in Chinese breast cancer patients. METHODS: This multicenter cross-sectional study enrolled 255 Chinese breast cancer patients of different stages and treatment phases. They answered standard instruments assessing SSS (Patient Health Questionnaire [PHQ]-15), depression (PHQ-9), anxiety (General Anxiety Disorder [GAD]-7), health anxiety (Whiteley-7 [WI-7]), illness perception (Brief-Illness Perception Questionnaire [IPQ]), illness attribution (Illness Perception Questionnaire-Revised [IPQ-R]), and sense of coherence (Sense of Coherence [SOC]-9). Logistic regression was applied to identify the strongest correlates with SSS. RESULTS: Our sample of high (PHQ-15 ≥ 10) and low SSS differed significantly in the following physical and psychological variables: symptom duration (r = 0.339, P < .001), symptom-related disability (Karnofsky Index) (r = 0.182, P < .001), depression (r = 0.556, P < .001), anxiety (r = 0.433, P < .001), health anxiety (r = 0.400, P < .001), illness perception (r = 0.349, P < .001), psychological illness attributions (r = 0.217, P < .01), and sense of coherence (r = -0.254, P < .001). In an adjusted stepwise multiple binary logistic regression analysis, higher health anxiety (WI-7, B = 0.388, P = .002), higher depression (PHQ-9, B = 0.158, P < .001), younger age (B = -0.042, P = .048), higher impairment in daily life (B = 1.098, P = .010), and longer symptom duration (Wald = 18.487, P = .001) showed a significant association with high SSS; the model explained 55.1% of the variance. CONCLUSIONS: High somatic symptom burden in breast cancer is associated with physical and psychosocial features. The results are a basis for further research to evaluate the new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, SSD concept in cancer patients and to better operationalize psychobehavioral factors in this patient group.
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Neoplasias da Mama/psicologia , Transtornos Psicofisiológicos/psicologia , Senso de Coerência , Adaptação Psicológica , Adulto , Idoso , Ansiedade/psicologia , Povo Asiático , Neoplasias da Mama/complicações , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Transtornos Psicofisiológicos/etiologia , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: To evaluate the relationship between quality of life (QOL) and physical as well as psychological variables in Chinese breast cancer patients. METHODS: This multicenter cross-sectional study enrolled 254 Chinese breast cancer patients in different stages and treatment phases. They answered standard instruments assessing QOL (EORTC), somatic symptom severity (PHQ-15), depression (PHQ-9), anxiety (GAD-7), health-related anxiety (WI-7), illness perception (BIPQ), and sense of coherence (SOC-9). Canonical correlation was applied to identify the strongest correlates between the physical, emotional and social QOL scales and the physical and psychological variables. RESULTS: In our sample, a low global QOL was significantly associated with the following physical and psychological variables: symptom-related disability (Karnofsky Index) (r = .211, p < .01), somatic symptom severity (r = -.391, p < .001), depression (r = -.488, p < .001), anxiety (r = -.439, p < .001), health-related anxiety (r = -.398, p < .001), dysfunctional illness perception (r = -.411, p < .001), and sense of coherence (r = .371, p < .001). In the canonical correlation analysis, high somatic symptom severity, depression, anxiety, dysfunctional illness perception, and low sense of coherence showed the strongest correlations with low physical, emotional and social functioning. The first three significant canonical correlations between these two sets of variables were .78, .56, and .45. CONCLUSIONS: QOL in Chinese breast cancer patients is strongly associated with psychological factors. Our results suggest that Chinese physicians and nurses should incorporate these factors into their care for women with breast cancer to improve patients' QOL.
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Neoplasias da Mama/psicologia , Qualidade de Vida/psicologia , Estresse Psicológico/psicologia , Adulto , Ansiedade/psicologia , China , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Percepção , Senso de Coerência , Inquéritos e QuestionáriosRESUMO
This study aimed in understanding the degradation behaviors of an IgG 1 subtype therapeutic monoclonal antibody A (mAb-A) associated with pH and buffer species. The information obtained in this study can augment conventional, stability-based screening paradigms by providing the direction necessary for efficient experimental design. Differential scanning calorimetry (DSC) was used for studying conformational stability. Dynamic light scattering (DLS) was utilized to generate B 22*, a modified second virial coefficient for the character of protein-protein interaction. Size-exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC) were employed to separate degradation products. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for determining the molecular size and liquid chromatography mass spectrometry (LC-MS) were used for identifying the sequence of the separated fragments. The results showed that both pH and buffer species played the roles in controlling the degradation behaviors of mAb-A, but the pH was more significant. In particular, pH 4.5 induced additional thermal transition peaks occurring at a low temperature compared with pH 6.5. A continual temperature-stress study illustrated that the additional thermal transition peaks related to the least stable structure and a greater fragmentation. Although mAb-A showed the comparable conformational structures and an identical amount of aggregates at time zero between the different types of buffer species at pH 6.5, the aggregation formation rate showed a buffer species-dependent discrepancy over a temperature-stress period. It was found that the levels of aggregations associated with the magnitudes of protein-protein interaction forces.
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Anticorpos Monoclonais/química , Imunoglobulina G/química , Soluções Tampão , Varredura Diferencial de Calorimetria/métodos , Cromatografia em Gel/métodos , Eletroforese em Gel de Poliacrilamida/métodos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Espectrometria de Massas/métodos , Conformação Proteica , TemperaturaRESUMO
Recent studies have shown that histone acetylation is involved with the regulation of enzyme glutamate decarboxylases (GADs), including GAD67 and GAD65. Here, we investigated the histone acetylation modifications of GADs in the pathogenesis of epilepsy and explored the therapeutic effect of a novel second-generation histone deacetylase inhibitor (HDACi) JNJ-26481585 in epilepsy animals. We revealed the suppression of GADs protein and mRNA level, and histone hypoacetylation in patients with temporal lobe epilepsy and pilocarpine-induced epilepsy mice model. Double-immunofluorescence also indicated that the hypoacetyl-H3 was located in hippocampal GAD67/GAD65 positive neurons in epilepsy mice. JNJ-26481585 significantly reversed the decrease of the GAD67/GAD65 both protein and mRNA levels, and the histone hypoacetylation of GABAergic neurons in epilepsy mice. Meanwhile, single-cell real-time PCR performed in GFP-GAD67/GAD65 transgenic mice demonstrated that JNJ-26481585 induced increase of GAD67/GAD65 mRNA level in GABAergic neurons. Furthermore, JNJ-26481585 significantly alleviated the epileptic seizures in mice model. Together, our findings demonstrate inhibition of GADs gene via histone acetylation plays an important role in the pathgenesis of epilepsy, and suggest JNJ-26481585 as a promising therapeutic strategy for epilepsy.
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Epigênese Genética/fisiologia , Epilepsia do Lobo Temporal/enzimologia , Regulação Enzimológica da Expressão Gênica , Glutamato Descarboxilase/biossíntese , Pilocarpina/toxicidade , Adolescente , Adulto , Animais , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/genética , Feminino , Glutamato Descarboxilase/genética , Humanos , Ácidos Hidroxâmicos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Adulto JovemRESUMO
The impact of pepsin on the maintenance of supersaturated solution of the HCl salt of a weakly basic drug was evaluated in simulated gastric fluid by monitoring the drug solubility in the absence and presence of pepsin. In the presence of pepsin, the HCl salt maintained its apparent solubility through 24 h, whereas, no such solubility advantage was seen in the absence of pepsin. Consequently, a minimum inhibitory concentration of pepsin is required for maintenance of supersaturation. In addition, NMR study seems to indicate a molecular level interaction between pepsin and HCl salt leading to a weak binding between the two. Therefore, for the HCl salts of weak bases having disproportionation potential, it is preferred that preformulation solubility studies are conducted in the presence of pepsin to reflect their in vivo behavior in maintaining supersaturation solubility.
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Ácido Clorídrico/química , Pepsina A/química , Soluções Farmacêuticas/química , Química Farmacêutica/métodos , Concentração de Íons de Hidrogênio , SolubilidadeRESUMO
PURPOSE: To investigate the structural effect of polymeric excipients on the behavior of free volume of drug-polymer dispersions in relation to glass transition. METHODS: Two drugs (indomethacin and ketoconazole) were selected to prepare amorphous dispersions with PVP, PVPVA, HPC, and HPMCAS through spray drying. The physical attributes of the dispersions were characterized using SEM and PXRD. The free volume (hole-size) of the dispersions along with drugs and polymers was measured using positron annihilation lifetime spectroscopy (PALS). Their glass transition temperatures (Tgs) were determined using DSC and DMA. FTIR spectra were recorded to identify hydrogen bonding in the dispersions. RESULTS: The chain structural difference-flexible (PVP and PVPVA) vs. inflexible (HPC and HPMCAS)-significantly impacts the free volume and Tgs of the dispersions as well as their deviation from ideality. Relative to Tg, free volume seems to be a better measure of hydrogen bonding interaction for the dispersions of PVP, HPC, and HPMCAS. The free volume of polymers and their dispersions in general appears to be related to their conformations in solution. CONCLUSIONS: Both the backbone chain rigidity of polymers as well as drug-polymer interaction can impact the free volume and glass transition behaviors of the dispersions.
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Excipientes/química , Vidro/química , Indometacina/química , Cetoconazol/química , Polímeros/química , Temperatura de Transição , Excipientes/análise , Indometacina/análise , Cetoconazol/análise , Polímeros/análiseRESUMO
In the real world, the object does not exist in isolation, and it always appears in a certain scene. Usually the object is fixed in a particular scene and even in special spatial location. In this paper, we propose a method for judging scene consistency effectively. Scene semantics and geometry relation play a key role. In this paper, we use PatchNet to deal with these high-level scene structures. We construct a consistent scene database, using semantic information of PatchNet to determine whether the scene is consistent. The effectiveness of the proposed algorithm is verified by a lot of experiments.
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Modelos Teóricos , Reconhecimento Visual de Modelos , AlgoritmosRESUMO
In the current era, diffusion models have emerged as a groundbreaking force in the realm of medical image segmentation. Against this backdrop, we introduce the Diffusion Text-Attention Network (DTAN), a pioneering segmentation framework that amalgamates the principles of text attention with diffusion models to enhance the precision and integrity of medical image segmentation. Our proposed DTAN architecture is designed to steer the segmentation process towards areas of interest by leveraging a text attention mechanism. This mechanism is adept at identifying and zeroing in on the regions of significance, thus improving the accuracy and robustness of the segmentation. In parallel, the integration of a diffusion model serves to diminish the influence of noise and irrelevant background data in medical images, thereby improving the quality of the segmentation results. The diffusion model is instrumental in filtering out extraneous factors, allowing the network to more effectively capture the nuances and characteristics of the target regions, which in turn enhances segmentation precision. We have subjected DTAN to rigorous evaluation across three datasets: Kvasir-Sessile, Kvasir-SEG, and GlaS. Our focus was particularly drawn to the Kvasir-Sessile dataset due to its relevance to clinical applications. When benchmarked against other state-of-the-art methods, our approach demonstrated significant improvements on the Kvasir-Sessile dataset, with a 2.77% increase in mean Intersection over Union (mIoU) and a 3.06% increase in mean Dice Similarity Coefficient (mDSC). These results provide strong evidence of the DTAN's generalizability and robustness, and its distinct advantages in the task of medical image segmentation.