RESUMO
Neurovascular coupling (NVC) provides new insights into migraine, a neurological disorder impacting over one billion people worldwide. This study compared NVC and cerebral blood flow (CBF) in patients with migraine without aura (MwoA) and healthy controls. About 55 MwoA patients in the interictal phase and 40 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging and arterial spin-labeling perfusion imaging scans. The CBF and resting-state neuronal activity indicators, including the amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC), were calculated for each participant. The global and regional NVCs were assessed using cross-voxel CBF-neuronal activity correlations and CBF/neuronal activity ratios. Patients with MwoA showed increased CBF/ALFF ratios in the left media, superior and inferior frontal gyri, and anterior cingulate gyrus, increased CBF/DC ratios in the left middle and inferior frontal gyri, and increased CBF/ReHo ratios in the right corpus callosum and right posterior cingulate gyrus. Lower CBF/ALFF ratios in the right rectal gyrus, the left orbital gyrus, the right inferior frontal gyrus, and the right superior temporal gyrus were also found in the MwoA patients. Furthermore, the CBF/ALFF ratios in the inferior frontal and superior temporal gyri were positively correlated with the Headache Impact Test scores and Hamilton anxiety scale scores in the MwoA patients. These findings provide evidence for the theory that abnormal NVC contributes to MwoA.
Assuntos
Enxaqueca sem Aura , Acoplamento Neurovascular , Humanos , Enxaqueca sem Aura/diagnóstico por imagem , Circulação Cerebrovascular , Lobo Frontal , Corpo CalosoRESUMO
Somatic symp tom disorders (SSDs) are a group of psychiatric disorders characterized by persistent disproportionate concern and obsessive behaviors regarding physical conditions. Currently, SSDs lack effective treatments and their pathophysiology is unclear. In this paper, we aimed to examine microstructural abnormalities in the brains of patients with SSD using diffusion kurtosis imaging (DKI) and to investigate the correlation between these abnormalities and clinical indicators. Diffusion kurtosis images were acquired from 30 patients with SSD and 30 healthy controls (HCs). Whole-brain maps of multiple diffusion measures, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), mean kurtosis (MK), radial kurtosis (RK), and axial kurtosis (AK), were calculated. To analyze differences between the two groups, nonparametric permutation testing with 10,000 randomized permutations and threshold-free cluster enhancement was used with family-wise error-corrected p values < 0.05 as the threshold for statistical significance. Then, the correlations between significant changes in these diffusion measures and clinical factors were examined. Compared to HCs, patients with SSD had significantly higher FA, MK, and RK and significantly lower MD and RD in the cerebellum, thalamus, basal ganglia, and limbic cortex. The FA in the left caudate and the pontine crossing tract were negatively correlated with disease duration; the MD and the RD in the genu of the corpus callosum were positively correlated with disease duration. Our findings highlight the role of the cerebellum-thalamus-basal ganglia-limbic cortex pathway, especially the cerebellum, in SSDs and enhance our understanding of the pathogenesis of SSDs.
Assuntos
Sintomas Inexplicáveis , Transtornos Mentais , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Cerebelo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Gânglios da Base/diagnóstico por imagemRESUMO
BACKGROUND: The trigeminal vascular system is an important part of the anatomical and physiological basis of migraine. The effective connectivity (EC) among the regions of interest (ROIs) in the trigeminal vascular system involved in migraine without aura (MWoA) remains unclear. METHODS: In this cross-sectional study, 48 patients (mean [SD] age 38.06 [10.35] years; male, 14/48 [29%]) with MWoA during the interictal phase and 48 healthy controls of similar age and sex (mean [SD] age 38.96 [10.96] years; male, 14/48 [29%]) underwent resting-state functional magnetic resonance imaging (fMRI). Dynamic causal modeling analysis was conducted to investigate directional EC among ROIs in the trigeminal vascular system including the bilateral brainstem, the primary somatosensory cortex (S1), the thalamus, and the insula. RESULTS: Compared with the healthy control group, MWoA represented significantly reduced EC from the left brainstem (Brainstem.L) to the left insula (MWoA: mean [SD] -0.16 [0.36]; healthy controls: mean [SD] 0.11 [0.41]; Pcorrected = 0.021), reduced EC from the Brainstem.L to the right insula (MWoA: mean [SD] -0.15 [0.39]; healthy controls: mean [SD] 0.03 [0.35]; Pcorrected = 0.021), and decreased EC from the left thalamus (Thalamus.L) to the Brainstem.L (MWoA: mean [SD] -0.13 [0.56]; healthy controls: mean [SD] 0.10 [0.45]; Pcorrected = 0.021). Altered EC parameters were not significantly correlated with MWoA clinical data. CONCLUSION: These results further provide increasing evidence that disturbed homeostasis of the trigeminovascular nociceptive pathway is involved in the pathophysiological mechanisms of migraine. Patients with MWoA exhibited a regional interaction distinct from healthy controls in the neural pathway of the Bilateral Insula-Brainstem.L-Thalamus.L, which may shed light on the future understanding of brain mechanisms for MWoA. Future brain-based interventions are suggested to consider the dysregulation in the Bilateral Insula-Brainstem.L-Thalamus.L circuits.
Assuntos
Enxaqueca sem Aura , Humanos , Masculino , Adulto , Enxaqueca sem Aura/diagnóstico por imagem , Estudos Transversais , Imageamento por Ressonância Magnética/métodos , Encéfalo , Tronco Encefálico/diagnóstico por imagemRESUMO
Background: There are limited studies exploring the relationship between physical activity (PA), cognitive function, and the brain processing characteristics in healthy older adults. Methods: A total of 41 participants (42.7 ± 20.5 years, 56.1% males) were included in the data analysis. The International Physical Activity Questionnaire Short Form was used to assess PA levels, and the Chinese version of the Montreal Cognitive Assessment-Basic and the Flanker task were employed to evaluate cognitive function. Furthermore, fMRI technology was utilized to examine brain activation patterns. Results: The cognitive function of the older adults was found to be significantly lower compared to the young adults. Within the older adults, those with high levels of PA exhibited significantly higher cognitive function than those with low and medium PA levels. The fMRI data showed significant differences in brain activation patterns among young adults across the different PA levels. However, such difference was not observed among older adults. Conclusion: A decline in cognitive function was observed among older adults. There was a significant correlation between the levels of PA and cognitive function in healthy older adults. The study demonstrated significant effects of PA levels on brain activation patterns in inhibitory control-related regions among young adults, while not significant among older adults. The findings suggest that neurological mechanisms driving the relationship between PA and cognitive function may differ between older and young adults.
Assuntos
Cognição , Exercício Físico , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Cognição/fisiologia , Projetos Piloto , Exercício Físico/fisiologia , Adulto , Pessoa de Meia-Idade , Idoso , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Inquéritos e Questionários , Adulto Jovem , Fatores EtáriosRESUMO
The emergence of resistance to PARP1 inhibitors poses a current therapeutic challenge, necessitating the development of novel strategies to overcome this obstacle. The present study describes the design and synthesis of a series of small molecules that target both PARP1 and c-Met. Among them, compound 16 is identified as a highly potent dual inhibitor, exhibiting excellent inhibitory activities against PARP1 (IC50 = 3.3 nM) and c-Met (IC50 = 32.2 nM), as well as demonstrating good antiproliferative effects on HR-proficient cancer cell lines and those resistant to PARP1 inhibitors. Importantly, compound 16 demonstrates superior antitumor potency compared to the PARP1 inhibitor Olaparib and the c-Met inhibitor Crizotinib, either alone or in combination, in MDA-MB-231 and HCT116OR xenograft models. These findings highlight the potential of PARP1/c-Met dual inhibitors for expanding the indications of PARP1 inhibitors and overcoming tumor cells' resistance to them.
Assuntos
Antineoplásicos , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Linhagem Celular Tumoral , Poli(ADP-Ribose) Polimerase-1 , Crizotinibe/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proliferação de Células , Antineoplásicos/farmacologiaRESUMO
INTRODUCTION: Drug dependence causes an overestimation of drug-related stimuli and an underestimation of non-drug-related stimuli, such as food. The purpose of this study was to investigate the effects of acute moderate-intensity dance and aerobic exercise on drug craving, appetite, prefrontal neural activation to food cues, and food reward in women with methamphetamine MA dependence. METHODS: Thirty-nine women who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition MA dependence criteria participated in the experiment and were randomly assigned to either a dance (n = 20) or exercise (n = 19) group. A moderate-intensity (65%-75% maximum heart rate) 35-min dance or treadmill intervention counterbalanced with a reading control session was conducted. After the intervention or control, subjective drug craving was measured before and after exposure to drug-related cues. Visual analog scales were used to measure subjective feelings of appetite. Participants then completed a visual food cue paradigm while using functional near-infrared spectroscopy to monitor prefrontal blood oxygen changes. Finally, the Leeds Food Preference Questionnaire was used to measure reward responses to different categories of food. RESULTS: The results showed that the dance and exercise interventions reduced subjective craving for drugs after being exposed to drug cues (P = 0.019). Implicit wanting (P < 0.001) and relative preferences (P = 0.001) for high-calorie savory foods were all increased after interventions relative to control. Compared with the control session, the left dorsolateral prefrontal cortex (P = 0.020) was activated when viewing high-calorie foods after moderate-intensity aerobic exercise. CONCLUSIONS: The current results support the use of moderate-intensity exercise as a therapeutic intervention to restore the balance between drug and nondrug rewards by decreasing cue-induced MA craving and increasing food reward.