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1.
Front Psychiatry ; 15: 1433239, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39252757

RESUMEN

Objective: Previous studies have found that patients with Major Depressive Disorder (MDD) exhibit impaired visual motion perception capabilities, and multi-level abnormalities in the human middle temporal complex (MT+), a key brain area for processing visual motion information. However, the brain activity pattern of MDD patients during the perception of visual motion information is currently unclear. In order to study the effect of depression on the activity and functional connectivity (FC) of MT+ during the perception of visual motion information, we conducted a study combining task-state fMRI and psychophysical paradigm to compare MDD patients and healthy control (HC). Methods: Duration threshold was examined through a visual motion perception psychophysical experiment. In addition, a classic block-design grating motion task was utilized for fMRI scanning of 24 MDD patients and 25 HC. The grating moved randomly in one of eight directions. We examined the neural activation under visual stimulation conditions compared to the baseline and FC. Results: Compared to HC group, MDD patients exhibited increased duration threshold. During the task, MDD patients showed decreased beta value and percent signal change in left and right MT+. In the sample comprising MDD and HC, there was a significant negative correlation between beta value in right MT+ and duration threshold. And in MDD group, activation in MT+ were significantly correlated with retardation score. Notably, no such differences in activation were observed in primary visual cortex (V1). Furthermore, when left MT+ served as the seed region, compared to the HC, MDD group showed increased FC with right calcarine fissure and surrounding cortex and decreased FC with left precuneus. Conclusion: Overall, the findings of this study highlight that the visual motion perception function impairment in MDD patients relates to abnormal activation patterns in MT+, and task-related activity are significantly connected to the retardation symptoms of the disease. This not only provides insights into the potential neurobiological mechanisms behind visual motion perception disorder in MDD patients from the aspect of task-related brain activity, but also supports the importance of MT+ as a candidate biomarker region for MDD.

2.
Integr Cancer Ther ; 23: 15347354241273962, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39223822

RESUMEN

BACKGROUND: The traditional Chinese medicine (TCM) Xiaoliu Pingyi recipe (XLPYR) has been clinically used for several decades, demonstrating favorable therapeutic effects. However, the underlying regulatory mechanisms remain unclear. The aim of this study was to explore the anti-tumor effects of XLPYR and its regulatory role in the vascular microenvironment through in vivo and in vitro experiment. MATERIALS AND METHODS: In the in vivo study, a C57BL/6J mouse model of lung adenocarcinoma (LUAD) allografts was established, and various interventions were administered for 14 days (Model group: administered normal saline via oral gavage; Pemetrexed (PEM) group: intraperitoneally injected with a solution of pemetrexed, once every 3d; XLPYR group: administered XLPYR via oral gavage; Combination (COMBI) group: received XLPYR via oral gavage simultaneously with intraperitoneal injection of pemetrexed solution). Tumor volume and weight were then compared among the groups. The impact of XLPYR on the tumor vascular microenvironment was assessed using immunohistochemistry staining. In the in vitro study, XLPYR-containing serum was prepared by oral administration to SD rats. The CCK-8 assay evaluated the effect of the serum on the proliferation of normal lung epithelial BEAS-2B cells and LUAD A549 cells, determining the optimal intervention concentrations. The cell migration and invasion abilities were evaluated using the wound-healing assay and Transwell assay, respectively. Finally, ELISA assay measured VEGF secretion levels in the LUAD cell supernatant, and RT-qPCR and Western Blot were employed to detect differences in HIF-1α, VEGFA, Ang-2, and PI3K/Akt mRNA and protein expression levels in both in vivo and in vitro experiments. RESULTS: In the in vivo study, XLPYR significantly inhibited the growth of mice LUAD allografts, with enhanced anti-tumor effects observed with prolonged drug intervention. Immunohistochemistry staining revealed reduced MVD and increased pericyte coverage in all intervention groups. Regarding vascular function, FITC-Dextran extravasation in the tumor tissues of the Model group was significantly higher than in the intervention groups, particularly with lower extravasation in the COMBI group compared to the PEM group. In the in vitro study, XLPYR demonstrated a time- and concentration-dependent inhibitory effect on LUAD cells, and with greater sensitivity in inhibiting LUAD cells compared to BEAS-2B cells. The wound-healing assay and Transwell assay confirmed that XLPYR significantly suppressed the migration and invasion abilities of LUAD cells. ELISA experiments further revealed a significant decrease in VEGF expression in the supernatant of each intervention group. RT-qPCR and Western Blot results showed consistent findings between the in vivo and in vitro experiments. HIF-1α, VEGFA, and Ang-2 mRNA and protein expression levels were significantly downregulated in the PEM group, XLPYR group, and COMBI group. There were no significant differences in the expression of PI3K and Akt mRNA and total protein, but the expression levels of phosphorylated p-PI3K and p-Akt were notably downregulated. CONCLUSION: XLPYR significantly inhibited C57BL/6J mouse LUAD allograft growth and improved the vascular microenvironment, thereby intervening in tumor angiogenesis and inducing vascular normalization. It suppressed LUAD cell proliferation, migration, and invasion, while reducing VEGF concentration in the cell supernatant. The regulatory mechanism may involve inhibiting PI3K/Akt protein phosphorylation and downregulating angiogenesis-related factors, such as HIF-1α, VEGF, and Ang-2.


Asunto(s)
Adenocarcinoma del Pulmón , Medicamentos Herbarios Chinos , Neoplasias Pulmonares , Ratones Endogámicos C57BL , Microambiente Tumoral , Animales , Medicamentos Herbarios Chinos/farmacología , Microambiente Tumoral/efectos de los fármacos , Ratones , Adenocarcinoma del Pulmón/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Humanos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Masculino , Pemetrexed/farmacología , Neovascularización Patológica/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Medicina Tradicional China/métodos
3.
Adv Mater ; 36(40): e2406618, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39205536

RESUMEN

Stimuli-responsive ultralong organic phosphorescence (UOP) materials that in response to external factors such as light, heat, and atmosphere have raised a tremendous research interest in fields of optoelectronics, anticounterfeiting labeling, biosensing, and bioimaging. However, for practical applications in life and health fields, some fundamental requirements such as biocompatibility and biodegradability are still challenging for conventional inorganic and aromatic-based stimuli-responsive UOP systems. Herein, an edible excipient, sodium carboxymethyl cellulose (SCC), of which UOP properties exhibit intrinsically multistimuli responses to excited wavelength, pressure, and moisture, is reported. Impressively, as a UOP probe, SCC enables nondestructive detection of hardness with superb contrast (signal-to-background ratio up to 120), while exhibiting a response sensitivity to moisture that is more than 5.0 times higher than that observed in conventional fluorescence. Additionally, its applicability for hardness monitoring and high-moisture warning for tablets containing a moisture-sensitive drug, with the quality of the drug being determinable through the naked-eye visible UOP, is demonstrated. This work not only elucidates the reason for stimulative corresponding properties in SCC but also makes a major step forward in extending the potential applications of stimuli-responsive UOP materials in manufacturing high-quality and safe medicine.


Asunto(s)
Carboximetilcelulosa de Sodio , Excipientes , Comprimidos , Comprimidos/química , Carboximetilcelulosa de Sodio/química , Excipientes/química , Dureza , Sustancias Luminiscentes/química
4.
Adv Sci (Weinh) ; 11(40): e2403063, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39207086

RESUMEN

Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local-to-global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local-to-local BA4 - MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local-to-global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD.


Asunto(s)
Trastorno Depresivo Mayor , Imagen por Resonancia Magnética , Corteza Motora , Humanos , Femenino , Adulto , Imagen por Resonancia Magnética/métodos , Masculino , Corteza Motora/fisiopatología , Corteza Motora/diagnóstico por imagen , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/diagnóstico por imagen , Desempeño Psicomotor/fisiología , Corteza Visual/fisiopatología , Corteza Visual/diagnóstico por imagen , Trastornos Psicomotores/fisiopatología , Persona de Mediana Edad , Mapeo Encefálico/métodos
5.
Drug Resist Updat ; 74: 101085, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38636338

RESUMEN

Enhanced DNA repair is an important mechanism of inherent and acquired resistance to DNA targeted therapies, including poly ADP ribose polymerase (PARP) inhibition. Spleen associated tyrosine kinase (Syk) is a non-receptor tyrosine kinase acknowledged for its regulatory roles in immune cell function, cell adhesion, and vascular development. This study presents evidence indicating that Syk expression in high-grade serous ovarian cancer and triple-negative breast cancers promotes DNA double-strand break resection, homologous recombination (HR), and subsequent therapeutic resistance. Our investigations reveal that Syk is activated by ATM following DNA damage and is recruited to DNA double-strand breaks by NBS1. Once localized to the break site, Syk phosphorylates CtIP, a pivotal mediator of resection and HR, at Thr-847 to promote repair activity, particularly in Syk-expressing cancer cells. Inhibition of Syk or its genetic deletion impedes CtIP Thr-847 phosphorylation and overcomes the resistant phenotype. Collectively, our findings suggest a model wherein Syk fosters therapeutic resistance by promoting DNA resection and HR through a hitherto uncharacterized ATM-Syk-CtIP pathway. Moreover, Syk emerges as a promising tumor-specific target to sensitize Syk-expressing tumors to PARP inhibitors, radiation and other DNA-targeted therapies.


Asunto(s)
Roturas del ADN de Doble Cadena , Resistencia a Antineoplásicos , Recombinación Homóloga , Quinasa Syk , Quinasa Syk/metabolismo , Quinasa Syk/genética , Quinasa Syk/antagonistas & inhibidores , Humanos , Roturas del ADN de Doble Cadena/efectos de los fármacos , Femenino , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Fosforilación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Reparación del ADN/efectos de los fármacos , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/antagonistas & inhibidores , Proteínas de la Ataxia Telangiectasia Mutada/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Animales , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos
6.
Artículo en Inglés | MEDLINE | ID: mdl-38320861

RESUMEN

AIM: Selective serotonin reuptake inhibitors (SSRIs) are among the most important antidepressants. However, there is limited research on predicting the occurrence of treatment-resistant depression (TRD) after 5 years. Examining the predictive effect of TRD occurrence using resting-state fMRI in patients initiating SSRIs treatment at the onset of major depressive disorder (MDD) could potentially enhance TRD management. METHODS: A total of 60 first-episode drug-naive MDD patients who met the criteria, along with 41 healthy controls of Han Chinese ethnicity, were recruited. All MDD patients received SSRIs as the initial treatment for relieving depressive symptoms. Resting-state fMRI scans were conducted for all subjects. Follow-up assessments were conducted over a period of five years, during which MDD patients were categorized into treatment-resistant depression (TRD) and non-treatment-resistant depression (NRD) groups based on disease progression. Amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and Regional Homogeneity (ReHo) values were calculated and compared among the three groups. Additionally, receiver operating characteristic (ROC) curves were employed to identify potential predictors. RESULTS: After 5 years of follow-up, it was found that 43 MDD patients were classified as NRD, while 17 were classified as TRD. In comparison to TRD, NRD exhibited decreased ALFF in the left middle cingulum gyrus (MCG.L) and in the right middle frontal gyrus (MFG.R), as well as decreased ReHo in MCG.L. Furthermore, NRD showed increased fALFF in the left precuneus (PCUN.L). The area under the curve (AUC) values were as follows: 0.724 (MCG.L by ALFF), 0.732 (MFG.R), 0.767 (PCUN.L), 0.774 (MCG.L by ReHo), 0.878 (combined), 0.547 (HAMD), and 0.408 (HAMA) respectively. CONCLUSION: The findings suggest that PCUN.L, MFG.R, MCG.L, and the combined measures may indicate the possibility of developing TRD after 5 years when SSRIs are used as the initial therapy for relieving depressive symptoms in MDD patients.

7.
World J Clin Cases ; 12(2): 314-321, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38313633

RESUMEN

BACKGROUND: Despite sharing similar pathogenic factors, cancer and coronary heart disease (CHD) occur in comparable populations at similar ages and possess similar susceptibility factors. Consequently, it is increasingly commonplace for patients to experience the simultaneous occurrence of cancer and CHD, a trend that is steadily rising. AIM: To determine the impacts of continuing care on lung cancer patients with CHD following percutaneous coronary intervention (PCI). METHODS: There were 94 lung cancer patients with CHD following PCI who were randomly assigned to the intervention group (n = 38) and the control group (n = 41). In the intervention group, continuing care was provided, while in the control group, routine care was provided. An evaluation of cardiac and pulmonary function, medication compliance, a 6-min walk test, and patient quality of life was performed. RESULTS: Differences between the two groups were significant in left ventricular ejection fraction, 6-min walk test, oxygen uptake, quality of life and medication compliance (P < 0.05). In comparison with the control group, the enhancement in the intervention group was more significant. The intervention group had more patients with high medication compliance than the control group, with a statistically significant difference (P < 0.05). CONCLUSION: After undergoing PCI, lung patients with CHD could benefit from continued care in terms of cardiac and pulmonary function, medications compliance, and quality of life.

8.
World J Clin Cases ; 12(1): 59-67, 2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38292645

RESUMEN

BACKGROUND: Cardiovascular disease, particularly myocardial infarction (MI) profound impact on patients' quality of life and places a substantial burden on the healthcare and economy systems. Developments in medical technology have led to the emergence of coronary intervention as an essential method for treating MI. AIM: To assess the effects of cardiac rehabilitation care on cardiac function recovery and negative emotions in MI after coronary intervention. METHODS: This study included a total of 180 patients with MI during the period from June 2022 to July 2023. Selected patients were divided into two groups: An observation group, which receiving cardiac rehabilitation care; a control group, which receiving conventional care. By comparing multiple observation indicators such as cardiac function indicators, blood pressure, exercise tolerance, occurrence of adverse cardiac events, and negative emotion scores between the two groups of patients. All the data were analyzed and compared between two groups. RESULTS: There were 44 males and 46 females in the observation group with an average age of 36.26 ± 9.88 yr; there were 43 males and 47 females in the control group, with an average age of 40.87 ± 10.5 yr. After receiving the appropriate postoperative nursing measures, the results of the observation group showed significant improvement in several indicators compared with the control group. Indicators of cardiac function, such as left ventricular end-diastolic internal diameter and left ventricular ejection fraction were significantly better in the observation group than in the control group (P < 0.05). Exercise endurance assessment showed that the 6-minute walking test distance was significantly increased in the patients of the observation group (P < 0.01). In addition, the incidence of adverse cardiac events was significantly lower in the observation group, and negative mood scores were significantly reduced (P < 0.05). CONCLUSION: Cardiac rehabilitation care after coronary intervention has a significant positive impact on functional recovery. This emphasizes the importance of cardiac rehabilitation care to improve patient recovery.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38270690

RESUMEN

PURPOSE: Although a number of studies involving small-vessel de novo coronary disease showed clinical benefits of drug-coated balloons (DCB), the role of DCB in large vessel lesions is still unclear. METHODS: We searched main electronic databases for randomized controlled trials (RCTs) comparing DCB with stents for large vessel de novo coronary artery disease. The primary endpoint was major cardiovascular adverse events (MACE), composite cardiovascular death (CD), myocardial infarction (MI), or target lesion revascularization (TLR). RESULTS: This study included 7 RCTs with 770 participants. DCB were associated with a marked risk reduction in MACE [Risk Ratio (RR): 0.48; 95% confidence interval [CI]: 0.24 to 0.97; P = 0.04], TLR (RR: 0.53; 95% CI: 0.25 to 1.14; P = 0.10), and late lumen loss [standard mean difference (SMD): -0.57; 95% CI: -1.09 to -0.05; P = 0.03] as compared with stents. There is no significant difference in MI (RR: 0.58; 95% CI: 0.21 to 1.54; P = 0.27), CD (RR: 0.33; 95% CI: 0.06 to 1.78; P = 0.19), and minimal lumen diameter (SMD: -0.34; 95% CI: -0.72 to 0.05; P = 0.08) between groups. In subgroup analyses, the risk reduction of MACE persisted in patients with chronic coronary syndrome (RR: 0.25; 95% CI: 0.07 to 0.89; P = 0.03), and patients receiving DCB vs. bare metal stent (RR: 0.19; 95% CI: 0.05 to 0.73; P = 0.01). In addition, there was no significant difference between the DCB group and the drug eluting stent group for MACE (RR: 0.69; 95% CI: 0.30 to 1.60; P = 0.38). CONCLUSION: DCB may be an effective therapeutic option in patients with large vessel de novo coronary artery disease.

10.
Alpha Psychiatry ; 24(5): 217-225, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38105781

RESUMEN

Objective: The aim of this study was to identify regions with altered degrees of centrality (DC) and changes in their functional connectivity (FC) in first-episode drug-naïve major depressive disorder (FEDN-MDD) patients using resting-state functional magnetic resonance imaging (fMRI). Methods: The study included 74 FEDN-MDD patients who met the study criteria and 41 healthy controls (HCs). All had undergone fMRI scanning in the resting condition. To evaluate differences between FEDN-MDD patients and HCs, we first compared the DC between the 2 groups. The DC regions with the most significant differences were then taken as seeds, and their FC was calculated. Results: Right posterior cingulum cortex (PCC.R), right precuneus (PCUN.R), and right putamen (PUT.R) all showed significantly different DC values (P < .001) between FEDN-MDD patients and HC groups, which helped in distinguishing these groups. The PUT.R in FEDN-MDD patients showed increased FC (P < .001) with the right inferior temporal gyrus and right inferior occipital gyrus compared to HC. Moreover, the PCUN.R in FEDN-MDD patients showed decreased FC (P < .001) with bilateral cerebellum crus I, left cerebellum crus II, bilateral orbital medial frontal gyrus, right superior medial frontal gyrus, left precuneus, left posterior cingulum cortex, right superior frontal gyrus, and PCC.R compared with the HC group. The P-values for cluster testing were .050, while for voxel testing they were .001. Conclusion: These findings imply that PUT.R, PCUN.R, and PCC.R serve as the core brain net hub in FEDN-MDD patients, and their FC displays aberrant function. This may involve a specific psychiatric neuropathology associated with FEDN-MDD.

12.
Sci Rep ; 13(1): 18643, 2023 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-37903974

RESUMEN

Treatment is challenging due to the heterogeneity of hepatocellular carcinoma (HCC). Chromatin regulators (CRs) are important in epigenetics and are closely associated with HCC. We obtained HCC-related expression data and relevant clinical data from The Cancer Genome Atlas (TCGA) databases. Then, we crossed the differentially expressed genes (DEGs), immune-related genes and CRs to obtain immune-related chromatin regulators differentially expressed genes (IRCR DEGs). Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to select the prognostic gene and construct a risk model for predicting prognosis in HCC, followed by a correlation analysis of risk scores with clinical characteristics. Finally, we also carried out immune microenvironment analysis and drug sensitivity analysis, the correlation between risk score and clinical characteristics was analyzed. In addition, we carried out immune microenvironment analysis and drug sensitivity analysis. Functional analysis suggested that IRCR DEGs was mainly enriched in chromatin-related biological processes. We identified and validated PPARGC1A, DUSP1, APOBEC3A, AIRE, HDAC11, HMGB2 and APOBEC3B as prognostic biomarkers for the risk model construction. The model was also related to immune cell infiltration, and the expression of CD48, CTLA4, HHLA2, TNFSF9 and TNFSF15 was higher in high-risk group. HCC patients in the high-risk group were more sensitive to Axitinib, Docetaxel, Erlotinib, and Metformin. In this study, we construct a prognostic model of immune-associated chromatin regulators, which provides new ideas and research directions for the accurate treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Cromatina/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Biomarcadores , Biomarcadores de Tumor/genética , Pronóstico , Microambiente Tumoral/genética , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Inmunoglobulinas , Citidina Desaminasa , Antígenos de Histocompatibilidad Menor
13.
Molecules ; 28(12)2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37375374

RESUMEN

Leishmaniasis is a neglected tropical disease, and there is an emerging need for the development of effective drugs to treat it. To identify novel compounds with antileishmanial properties, a novel series of functionalized spiro[indoline-3,2'-pyrrolidin]-2-one/spiro[indoline-3,3'-pyrrolizin]-2-one 23a-f, 24a-f, and 25a-g were prepared from natural-product-inspired pharmaceutically privileged bioactive sub-structures, i.e., isatins 20a-h, various substituted chalcones 21a-f, and 22a-c amino acids, via 1,3-dipolar cycloaddition reactions in MeOH at 80 °C using a microwave-assisted approach. Compared to traditional methods, microwave-assisted synthesis produces higher yields and better quality, and it takes less time. We report here the in vitro antileishmanial activity against Leishmania donovani and SAR studies. The analogues 24a, 24e, 24f, and 25d were found to be the most active compounds of the series and showed IC50 values of 2.43 µM, 0.96 µM, 1.62 µM, and 3.55 µM, respectively, compared to the standard reference drug Amphotericin B (IC50 = 0.060 µM). All compounds were assessed for Leishmania DNA topoisomerase type IB inhibition activity using the standard drug Camptothecin, and 24a, 24e, 24f, and 25d showed potential results. In order to further validate the experimental results and gain a deeper understanding of the binding manner of such compounds, molecular docking studies were also performed. The stereochemistry of the novel functionalized spirooxindole derivatives was confirmed by single-crystal X-ray crystallography studies.


Asunto(s)
Antiprotozoarios , Leishmania donovani , Simulación del Acoplamiento Molecular , Microondas , Antiprotozoarios/química , Camptotecina/farmacología , Relación Estructura-Actividad
14.
Front Psychiatry ; 14: 1170890, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37333925

RESUMEN

Cushing's syndrome (CS) is a rare disease with multiple somatic signs and a high prevalence of co-occurring depression. However, the characteristics of depression secondary to CS and the differences from major depression have not been described in detail. In this case, we report a 17-year-old girl with treatment-resistant depression with a series of atypical features and acute psychotic episodes, which is a rare condition secondary to CS. This case showed a more detailed profile of depression secondary to CS and highlighted the differences with major depression in clinical features, and it will improve insight into the differential diagnosis especially when the symptoms are not typical.

15.
Medicine (Baltimore) ; 102(15): e33439, 2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37058046

RESUMEN

We aimed to investigate the differential diagnosis of depressive episodes in patients with major depressive disorder (MDD) and bipolar disorder (BD) using peripheral blood cytokine expression levels. The levels of interleukin (IL)-2, IL-6, IL-10, IL-17, IL4, and IL-12; interferon (IFN)-γ; and tumor necrosis factor (TNF)-α were measured in patients with MDD and BD presenting acute episodes in an inpatient psychiatric setting. The expression levels of IL-6, IL-10, IL-17, and IFN-γ in the MDD and BD groups were higher than those in the control group (P < .05), but there was no significant difference between the patient groups and control group. Only the expression levels of TNF-α and IL-4 were higher in both groups than in the control group, and the BD group had higher levels than the MDD group (P < .05). The expression levels of IL-17, IFN-γ, IL-10, and IL-4 were significantly higher in BD-related manic episodes than in BD-related depressive episodes (P < .05). IL-6, IFN-γ, TNF-α, IL-10, and IL-4 levels were higher in BD-related depressive episodes than in MDD-related depressive episodes (P < .05). The receiver operating characteristic curve test for MDD and BD and the area under the curve for IL-4 revealed good clinical predictability. Patients with MDD and BD exhibited different cytokine profiles when experiencing acute episodes; patients with BD exhibited a more severe immune-inflammatory response system-compensatory immunoregulatory response system (CIRS) imbalance. IL-4 was found to have diagnostic value in differentiating between active depressive episodes in MDD and BD.


Asunto(s)
Trastorno Bipolar , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/psicología , Trastorno Bipolar/diagnóstico , Interleucina-4 , Interleucina-10 , Interleucina-17 , Interleucina-6 , Factor de Necrosis Tumoral alfa , Biomarcadores , Citocinas
16.
Drug Des Devel Ther ; 16: 2365-2382, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35910781

RESUMEN

Background: As the main component of turmeric (Curcuma longa L.), curcumin is widely used in the treatment of various diseases. Previous studies have demonstrated that curcumin has great potential as a therapeutic agent, but the lack of understanding of the functional mechanism of the drug has hindered the widespread use of the natural product. In the present study, we used comprehensive bioinformatics analysis and in vitro experiments to explore the anti-tumor mechanism of curcumin. Materials and Methods: LUAD mRNA expression data were obtained from TCGA database and differentially expressed genes (DEGs) were identified using R software. Functional enrichment analysis was conducted to further clarify its biological properties and hub genes were identified by a protein-protein interaction (PPI) network analysis. Survival analysis and molecular docking were used to analyze the effectiveness of the hub genes. By an in vitro study, we evaluated whether curcumin could influence the proliferation, migration, and invasion activities of LUAD cells. Results: In this study, 1783 DEGs from LUAD tissue samples compared to normal samples were evaluated. Functional enrichment analysis and the PPI network revealed the characteristics of the DEGs. We performed a topological analysis and identified 10 hub genes. Of these, six genes (INS, GCG, SST, F2, AHSG, and NPY) were identified as potentially effective biomarkers of LUAD. The molecular docking results indicated that curcumin targets in regulating lung cancer may be INS and GCG. We found that curcumin significantly inhibited the proliferation, migration, and invasion of LUAD cells and significantly decreased the expression of the INS and GCG genes. Conclusion: The results of this study suggest that the therapeutic effects of curcumin on LUAD may be achieved through the intervention of INS and GCG, which may act as potential biomarkers for LUAD prevention and treatment.


Asunto(s)
Adenocarcinoma del Pulmón , Curcumina , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Biomarcadores de Tumor , Biología Computacional , Curcumina/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Simulación del Acoplamiento Molecular
17.
Front Pharmacol ; 13: 827710, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35928272

RESUMEN

Background: Leukopenia is one of the side effects of radiotherapy and chemotherapy. Diyushengbai tablet (DYT) is used to prevent and treat leukopenia caused by various reasons. A meta-analysis was performed to systematically analyze the therapeutic effects of DYT on preventing and treating leukopenia caused by radiotherapy and chemotherapy. Objectives: This study aimed to systematically evaluate the efficacy and safety of DYT in preventing and treating leukopenia caused by radiotherapy and chemotherapy. Methods: We performed a comprehensive literature search of electronic databases such as PubMed, The Cochrane Library, China Knowledge Network (CNKI), China Biomedical Literature Database (CBM), Wanfang Data Knowledge Service Platform, and VIP, through November of 2021. The scanning reports deadline is until November 2021. The bias risk evaluation criteria developed by the Cochrane collaborative organization were used to evaluate the literature quality of the included studies. The RevMan5.4 software was used to analyze the data, and the Stata16.0 was used to perform the Egger test. Results: After selecting all the databases, a total of 41 reports which involved 3,793 cases were analyzed. Meta-analysis showed that DYT could significantly reduce the white blood cell (WBC) suppression caused by radiotherapy and chemotherapy and improve the patients' WBC counts and neutrophils, compared with the efficacy of other oral WBC-elevating drugs such as Leucogen tablets and Batilol tablets and additional utilization of granulocyte colony-stimulating factor (G-CSF). The results of meta-analysis showed that for preventive medication purpose, the overall incidence of leukocyte suppression was [RR = 0.74, 95%CI (0.59, 0.92), p = 0.006], and the white blood cell count was [MD = 1.12, 95%CI (0.95, 1.29), p < 0.00001]; while for therapeutic purpose, the incidence of overall leukocyte suppression was [RR = 0.61, 95%CI (0.38, 0.95), p = 0.03], and the white blood cell count was [MD = 1.20, 95%CI (0.77, 1.62), p < 0.00001]. More importantly, the additional use of DYT can reduce the application amount of G-CSF. The results showed that the application of G-CSF can be reduced by an average of 1.57 from the beginning of treatment to return normal white blood cells around 2.23 in two cycles of chemotherapy. Conclusion: DYT is more effective in preventing and treating leukopenia caused by radiotherapy and chemotherapy than other oral WBC-elevating drugs, which have a high clinical value.

18.
Front Psychiatry ; 13: 853961, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35928782

RESUMEN

Background: Adolescence is a period of high incidence for depression. However, there is a limited treatment option for the adolescent depression. For treatment-resistant major depressive disorder, HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) appears therapeutically effective. The aim of the study is to explore the early effects of repetitive transcranial magnetic stimulation in combination with sertraline in adolescents with first-episode major depressive disorder. Methods: A total of 100 teenage patients with first-episode depression were randomly divided into the study groups. Both groups were treated with sertraline. In addition, the study group was treated with ten sessions of add-on rTMS. The control group was given sertraline only. The depressive symptom and cognitive function were assessed by the Hamilton depression rating scale 17 version (HAMD-17), Children's Depression Rating Scale-Revised (CDRS-R), Integrated visual and auditory continuous performance test (IVA-CPT), and THINC-it. Results: The number of early improvers after 2 weeks of treatment in the study group was statistically significant higher compared to the control group (95.83% vs 73.47%, χ2 = 9.277, P = 0.002). There was significant difference observed in responder rates (62.50% vs. 28.57%, χ2 = 11.262, P = 0.001) or in remission rates (31.25% vs. 6.12%, χ2 = 10.130, P = 0.001) between the two groups at 4 weeks. The score of HAMD-17 and CDRS-R in the study group were significantly lower than the control group (Fgroup = 12.91 vs 10.21, P < 0.05). Attention Quotient (listening, visual and full-scale) attention quotient of IVA-CPT in the study group were higher than those in the control group after treatment, and the differences were statistically significant(P < 0.05). The study group showed higher score in Spotter than the control group after treatment (P < 0.05). Discussion: This is the most extensive blinded, randomized clinical study to date examining the efficacy of 10-Hz add-on rTMS for first-onset adolescent depression. Our results support that add-on rTMS accelerates the efficacy of the antidepressants, improving the depressive symptoms and cold cognitive function in first-episode adolescent depression. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100048534].

19.
Cereb Cortex ; 32(10): 2129-2139, 2022 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-34613359

RESUMEN

Medial prefrontal cortex (MPFC) and other regions like the occipital cortex (OC) exhibit abnormal neural activity in major depressive disorder (MDD). Their relationship to specific biochemical, psychophysical, and psychopathological changes remains unclear, though. For that purpose, we focus on a particular subregion in OC, namely middle temporal (MT) visual area that is known to mediate the perception of visual motion. Using high-field 7 T magnetic resonance imaging (MRI), including resting state functional MRI and proton magnetic resonance spectroscopy, the amplitude of low-frequency fluctuations (ALFF) of the blood oxygen level-dependent signal in MT, MT-seeded functional connectivity (FC), and gamma-aminobutyric acid (GABA) in MT were investigated. Applying the vision motion psychophysical task, the motion suppression index of subjects was also examined. We demonstrate significantly elevated neural variability (as measured by ALFF) in MT together with decreases in both MT GABA and motion suppression in our MDD sample. Unlike in healthy subjects, MT neural variability no longer modulates the relationship of MT GABA and motion suppression in MDD. MT also exhibits reduction in global inter-regional FC to MPFC in MDD. Finally, elevated MT ALFF relates to specifically retardation in behavior as measured by the Hamilton subscore. Together, MT provides a strong candidate for biomarker in MDD.


Asunto(s)
Trastorno Depresivo Mayor , Trastorno Depresivo Mayor/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Lóbulo Occipital/diagnóstico por imagen , Espectroscopía de Protones por Resonancia Magnética , Ácido gamma-Aminobutírico
20.
Artículo en Inglés | MEDLINE | ID: mdl-34745279

RESUMEN

BACKGROUND: To date, around 4 per 100,000 adolescents committed suicide within the 29 OECD countries. The suicidal behavior is related to psychological factors, genetics, neurobiology, and other biomarkers. The aim of this study was to examine risk factors for the development of suicidal ideation in adolescent females with depression, focusing on the relationship between different testosterone levels and suicidal ideation, in order to help develop strategies to intervene in suicidal behavior in female adolescents with depression. METHOD: In this single-center prospective cohort study, we enrolled adolescent females with depression. We collected information on their baseline data, testosterone levels, symptom self-rating scale scores, suicidal ideation, non-suicidal self-injurious (NSSI) behaviours, and suicide attempts. We used multivariate logistic regression to identify risk factors for the development of suicidal ideation in adolescent females with depression. RESULTS: A total of 113 hospitalized adolescent females were enrolled with a mean age of 13.5 (1.20). Among these patients, there were 86 (76.11%) subjects who suffered from suicidal ideation, 59 (52.21%) had NSSI and 23 (20.35%) had suicide attempt behavior. In the final model, higher level of testosterone (p=0.04) and higher age (p=0.02) were associated with the higher odds of having suicidal ideation. CONCLUSION: In this exploratory cohort study, the emergence of suicidal ideation was common among adolescent females with depression. This study is consistent with the other studies. It shows that the age is a potential predictor for suicidal ideation in hospitalized adolescent females with depression.

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