Glioblastoma (GBM) is the most common and aggressive primary brain tumor with great invasiveness and resistance to chemotherapy, which presents a treatment challenge. In this study, we investigated the antitumor effect of Cedrol, a sesquiterpene alcohol isolated from Cedrus atlantica, against GBM cells in vitro and in vivo. Cedrol was found to potently inhibit cell growth and induce intracellular ROS generation and DNA damage response. In addition, Cedrol induced significant G0/G1 cell cycle arrest and cell apoptosis via the extrinsic (Fas/FasL/Caspase-8) and intrinsic (Bax/Bcl-2/Caspase-9) pathways. In addition, Cedrol had a synergistic effect with temozolomide (TMZ) and reduced drug resistance by blockage of the AKT/mTOR pathway. Cedrol suppressed tumor growth in both orthotopic and xenograft GBM animal models with low or no short-term acute toxicity or long-term accumulative toxicity. In a molecular docking study, Cedrol targeted the androgen receptor (AR), and reduced DHT-mediated AR nuclear translocation, downstream gene KLK3/TMPRSS2 expression and cell proliferation. Our study demonstrates that Cedrol may be a potential candidate for drug development for single or combination treatment with TMZ in GBM therapy.
The question of whether there are biological differences between male and female brains is a fraught one, and political positions and prior expectations seem to have a strong influence on the interpretation of scientific data in this field. This question is relevant to issues of gender differences in the prevalence of psychiatric conditions, including autism, attention deficit hyperactivity disorder (ADHD), Tourette's syndrome, schizophrenia, dyslexia, depression, and eating disorders. Understanding how gender influences vulnerability to these conditions is significant. Diffusion magnetic resonance imaging (dMRI) provides a non-invasive method to investigate brain microstructure and the integrity of anatomical connectivity. Generalized q-sampling imaging (GQI) has been proposed to characterize complicated fiber patterns and distinguish fiber orientations, providing an opportunity for more accurate, higher-order descriptions through the water diffusion process. Therefore, we aimed to investigate differences in the brain's structural network between teenage males and females using GQI. This study included 59 (i.e., 33 males and 26 females) age- and education-matched subjects (age range: 13 to 14 years). The structural connectome was obtained by graph theoretical and network-based statistical (NBS) analyses. Our findings show that teenage male brains exhibit better intrahemispheric communication, and teenage female brains exhibit better interhemispheric communication. Our results also suggest that the network organization of teenage male brains is more local, more segregated, and more similar to small-world networks than teenage female brains. We conclude that the use of an MRI study with a GQI-based structural connectomic approach like ours presents novel insights into network-based systems of the brain and provides a new piece of the puzzle regarding gender differences.
It is estimated that at least one million people die by suicide every year, showing the importance of suicide prevention and detection. In this study, an autoencoder and machine learning model was employed to predict people with suicidal ideation based on their structural brain imaging. The subjects in our generalized q-sampling imaging (GQI) dataset consisted of three groups: 41 depressive patients with suicidal ideation (SI), 54 depressive patients without suicidal thoughts (NS), and 58 healthy controls (HC). In the GQI dataset, indices of generalized fractional anisotropy (GFA), isotropic values of the orientation distribution function (ISO), and normalized quantitative anisotropy (NQA) were separately trained in different machine learning models. A convolutional neural network (CNN)-based autoencoder model, the supervised machine learning algorithm extreme gradient boosting (XGB), and logistic regression (LR) were used to discriminate SI subjects from NS and HC subjects. After five-fold cross validation, separate data were tested to obtain the accuracy, sensitivity, specificity, and area under the curve of each result. Our results showed that the best pattern of structure across multiple brain locations can classify suicidal ideates from NS and HC with a prediction accuracy of 85%, a specificity of 100% and a sensitivity of 75%. The algorithms developed here might provide an objective tool to help identify suicidal ideation risk among depressed patients alongside clinical assessment.
Treatment modalities for breast cancer, the leading cause of cancer-related deaths in women worldwide, include surgery, radiotherapy, adjuvant chemotherapy, targeted therapy, and hormonal therapy. The advancement in medical technology has facilitated substantial reduction in breast cancer mortality. However, patients may experience cognitive impairment after chemotherapy. This phenomenon called chemotherapy-induced cognitive impairment (i.e., “chemobrain”) is common among breast cancer survivors. However, cognitive function deficits may exist before chemotherapy initiation. This study examined the functional network alterations in breast survivors by using resting-state functional magnetic resonance imaging (fMRI). We recruited 172 female participants and separated them into three groups: C+ (57 breast cancer survivors who had finished 3–12-month-long chemotherapy), C- (45 breast cancer survivors who had not undergone chemotherapy), and HC (70 participants with no breast cancer history). We analyzed mean fractional amplitudes of low-frequency fluctuation and graph theoretical topologies from resting-state fMRI and applied network-based analysis to portray functional changes among the three groups. Among the three groups, the C- group demonstrated hyperactivity in the prefrontal cortex, bilateral middle temporal gyrus, right inferior temporal gyrus and right angular gyrus. Only the left caudate demonstrated significantly more hypoactivity in the C- group than in the C+ group. Graph theoretical analysis demonstrated that the brains of the C+ group became inclined toward regular networks and the brains of the C- group became inclined toward random networks. Subtle alterations were noted in the brain activity and networks of our cancer survivors. Moreover, functional network disruptions occurred regardless of chemotherapeutic agent administration.