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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.
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Transtorno Depressivo Maior , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Lobo Occipital/diagnóstico por imagem , Espectroscopia de Prótons por Ressonância Magnética , Ácido gama-AminobutíricoRESUMO
Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.
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Transtorno Depressivo Maior , Depressão , Humanos , Lobo Occipital/química , Espectroscopia de Prótons por Ressonância Magnética , Percepção Visual , Ácido gama-AminobutíricoRESUMO
Childhood trauma is one of the most prominent risk factors in developing major depressive disorder (MDD) and may lead to unfavorable outcomes of pharmacotherapy and psychotherapy in MDD. While how it modulates the treatment outcome of the repetitive transcranial magnetic stimulation (rTMS) and how sex difference may play a role in mediating this relationship remain unknown. To evaluate this question, 51 (37 women) MDD patients were treated with 10 Hz rTMS to the left dorsolateral prefrontal cortex (lDLPFC). The experience of childhood trauma was quantified by the Childhood Traumatic Questionnaire (CTQ). The depressive severity was assessed by Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI) as the primary and secondary assessments. Beck Hopelessness Scale (BHS) and Hamilton Anxiety Scale (HAMA) were also assessed for further confirmation. Thirty-six (70.6%) participants showed a response including 17 (33.3%) achieving remission to the rTMS treatment. The alleviation of depressive symptoms was negatively correlated with the CTQ scores, specifically in women but not men, in subjective BDI and BHS, but not objective HAMD or HAMA. We demonstrate that childhood trauma negatively affects the subjective perception of rTMS-lDLPFC treatment outcomes in female MDD patients. This highlights the importance of measuring childhood trauma-related symptoms in routine clinical rTMS treatment, as they may impact perceived efficacy.
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Experiências Adversas da Infância , Transtorno Depressivo Maior , Estimulação Magnética Transcraniana , Experiências Adversas da Infância/psicologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Córtex Pré-Frontal Dorsolateral/fisiopatologia , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Resultado do TratamentoRESUMO
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.
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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.
Assuntos
Adenocarcinoma de Pulmão , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Camundongos Endogâmicos C57BL , Microambiente Tumoral , Animais , Medicamentos de Ervas Chinesas/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Camundongos , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Humanos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Masculino , Pemetrexede/farmacologia , Neovascularização Patológica/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Medicina Tradicional Chinesa/métodosRESUMO
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.
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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.
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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.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Cromatina/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Biomarcadores , Biomarcadores Tumorais/genética , Prognóstico , Microambiente Tumoral/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Imunoglobulinas , Citidina Desaminase , Antígenos de Histocompatibilidade MenorRESUMO
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.
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Adenocarcinoma de Pulmão , Curcumina , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais , Biologia Computacional , Curcumina/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: Recent studies in cancer biology suggest that metabolic glucose reprogramming is a potential target for cancer treatment. However, little is known about drug intervention in the glucose metabolism of cancer stem cells (CSCs) and its related underlying mechanisms. METHODS: The crude realgar powder was Nano-grinded to meets the requirements of Nano-pharmaceutical preparations, and Nano-realgar solution (NRS) was prepared for subsequent experiments. Isolation and characterization of lung cancer stem cells (LCSCs) was performed by magnetic cell sorting (MACS) and immunocytochemistry, respectively. Cell viability and intracellular glucose concentration were detected by MTT assay and glucose oxidase (GOD) kit. Protein expressions related to metabolic reprogramming was detected by ELISA assay. Determination of the expression of HIF-1α and PI3K/Akt/mTOR pathways was carried out by RT-PCR and western blotting analysis. A subcutaneous tumor model in BALB/c-nu mice was successfully established to evaluate the effects of Nano-realgar on tumor growth and histological structure, and the expression of HIF-1α in tumor tissues was measured by immunofluorescence. RESULTS: Nano-realgar inhibits cell viability and induces glucose metabolism in LCSCs, and inhibits protein expression related to metabolic reprogramming in a time- and dose-dependent manner. Nano-realgar downregulated the expression of HIF-1α and PI3K/Akt/mTOR pathways in vitro and in vivo. Nano-realgar inhibits tumor growth and changes the histological structure of tumors through in vivo experiments and consequently inhibits the constitutive activation of HIF-1α signaling. CONCLUSIONS: These results reveal that Nano-realgar inhibits tumor growth in vitro and in vivo by repressing metabolic reprogramming. This inhibitory effect potentially related to the downregulation HIF-1α expression via PI3K/Akt/mTOR pathway.
Assuntos
Antineoplásicos/administração & dosagem , Arsenicais/administração & dosagem , Glucose/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Células-Tronco Neoplásicas/metabolismo , Sulfetos/administração & dosagem , Células A549 , Antígeno AC133/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Arsenicais/química , Arsenicais/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Células-Tronco Neoplásicas/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Sulfetos/química , Sulfetos/farmacologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Thermochemical and electronic trapping/detrapping mechanism-based resistance switching in TiO2 is one of the most extensively researched topics in the field of resistance-switching random access memory (ReRAM). In this study, the subtle correlation between the formation and rupture of the Magnéli-based conducting filament (CF), which is the mechanism of non-polar thermochemical-reaction-based switching, and the electron trapping/detrapping at the defect centers, which is the mechanism of bipolar electronic switching, is examined in detail. The chemical interaction between the TiN top electrode and the TiO2 layer generates a stable and immobile electron trapping layer, which is called a "switching layer", whereas the thin region between the just-mentioned switching layer and the remaining Magnéli CF after the thermochemical reset comprises a non-switching layer. The seemingly very complicated switching behavior with respect to the bias polarity, compliance current, and detailed biasing sequence could be reasonably explained by the phenomenological model based on the combined motions of the CF, switching layer, and non-switching layer. Light-induced detrapping experiments further supplement the suggested switching model.
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Many human disorders induce high salinity in tissues and organs, interfering with their normal physiological functions. Using a mouse model, we demonstrated that high salt intake caused infertility. Specifically, we established that high salinity dramatically affects ovarian follicle development and the extent of follicular atresia. However, it did not significantly influence the primordial follicles. TUNEL assays revealed that high salt intake inhibited follicle development by inducing the granulosa and theca cells that surround the oocytes to undergo apoptosis. Furthermore, immunohistological staining for the proliferation markers Ki67 and PH3 showed that high salt intake also repressed granulosa cell proliferation. In vitro testing of granulosa cells also confirmed that high salt significantly repressed cell proliferation and promoted cell apoptosis. In summary, high salt consumption negatively impacts reproductive functions in female mice by interfering with ovarian folliculogenesis.
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Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Cloreto de Sódio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Atresia Folicular/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Infertilidade Feminina/induzido quimicamente , Antígeno Ki-67/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oócitos/efeitos dos fármacos , Gravidez , Cultura Primária de Células , Células Tecais/efeitos dos fármacosRESUMO
Mac-1 (CD11b) is expressed on bone marrow-derived immune cells. CD11b binds to ligands to regulate leukocyte adhesion and migration across the endothelium or epithelium. Here, we employed CD11b knockout mice and an Apc(Min/+) spontaneous intestinal adenoma mouse model to clarify the function of CD11b in intestinal tumorigenesis. We showed that CD11b deficiency may contribute to the inhibition of myeloid cell trafficking to the tumor microenvironment and inactivated Wnt/ß-catenin pathway to suppress tumor growth. This effect was partly mediated by inhibiting the myeloid cell-mediated decrease in TNF-α secretion, which inhibits the recruitment of myeloid-derived suppressor cells to the tumor microenvironment and subsequently induces IFN-γ and CXCL9 production. This work provides evidence for the mechanism by which CD11b may function as an important oncogene and highlights the potential of CD11b as a therapeutic target in CRC.