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1.
BMC Med Imaging ; 24(1): 162, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38956470

ABSTRACT

BACKGROUND: The image quality of computed tomography angiography (CTA) images following endovascular aneurysm repair (EVAR) is not satisfactory, since artifacts resulting from metallic implants obstruct the clear depiction of stent and isolation lumens, and also adjacent soft tissues. However, current techniques to reduce these artifacts still need further advancements due to higher radiation doses, longer processing times and so on. Thus, the aim of this study is to assess the impact of utilizing Single-Energy Metal Artifact Reduction (SEMAR) alongside a novel deep learning image reconstruction technique, known as the Advanced Intelligent Clear-IQ Engine (AiCE), on image quality of CTA follow-ups conducted after EVAR. MATERIALS: This retrospective study included 47 patients (mean age ± standard deviation: 68.6 ± 7.8 years; 37 males) who underwent CTA examinations following EVAR. Images were reconstructed using four different methods: hybrid iterative reconstruction (HIR), AiCE, the combination of HIR and SEMAR (HIR + SEMAR), and the combination of AiCE and SEMAR (AiCE + SEMAR). Two radiologists, blinded to the reconstruction techniques, independently evaluated the images. Quantitative assessments included measurements of image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), the longest length of artifacts (AL), and artifact index (AI). These parameters were subsequently compared across different reconstruction methods. RESULTS: The subjective results indicated that AiCE + SEMAR performed the best in terms of image quality. The mean image noise intensity was significantly lower in the AiCE + SEMAR group (25.35 ± 6.51 HU) than in the HIR (47.77 ± 8.76 HU), AiCE (42.93 ± 10.61 HU), and HIR + SEMAR (30.34 ± 4.87 HU) groups (p < 0.001). Additionally, AiCE + SEMAR exhibited the highest SNRs and CNRs, as well as the lowest AIs and ALs. Importantly, endoleaks and thrombi were most clearly visualized using AiCE + SEMAR. CONCLUSIONS: In comparison to other reconstruction methods, the combination of AiCE + SEMAR demonstrates superior image quality, thereby enhancing the detection capabilities and diagnostic confidence of potential complications such as early minor endleaks and thrombi following EVAR. This improvement in image quality could lead to more accurate diagnoses and better patient outcomes.


Subject(s)
Artifacts , Computed Tomography Angiography , Endovascular Procedures , Humans , Retrospective Studies , Female , Computed Tomography Angiography/methods , Aged , Male , Endovascular Procedures/methods , Middle Aged , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/diagnostic imaging , Deep Learning , Radiographic Image Interpretation, Computer-Assisted/methods , Stents , Endovascular Aneurysm Repair
2.
Int J Biol Macromol ; 274(Pt 1): 133306, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909729

ABSTRACT

Condensed tannins were isolated from the bark of Ficus altissima and fractionated into four subcomponents on a Sephadex LH-20 column with 60 %, 80 %, 100 % methanol, and 70 % acetone, separately. Their structures were characterized by MALDI-TOF MS coupled with HPLC-ESI-MS and confirmed to be polymers of B-type procyanidin glucosides, procyanidins, and prodelphinidin glucosides. The degree of polymerization (DP) of these polymers was as high as 21, and the mDPs of the four subcomponents were calculated as 2.4, 6.6, 10.5 and 13.4, respectively. They competitively or noncompetitively suppressed the activities of tyrosinase and α-glucosidase through hydrogen bonding and hydrophobic interaction. And they also showed a powerful antioxidative activity. Correlation analyses verified that the anti-tyrosinase capacity exhibited a significant positive correlation (R2monophenolase = 0.9167 and R2diphenolase = 0.9302) with mDP within the methanol-water system, and the anti-α-glucosidase activity also showed a significant positive correlation with the mDP (R2 = 0.9187). In contrast, the antioxidant capability showed a significant negative correlation with the mDP (R2DPPH = 0.9258, R2ABTS = 0.9372). This study confirmed that condensed tannins from the bark of F. altissima were desirable anti-tyrosinase, anti-α-glucosidase, and antioxidant agents, and elucidated the relationships of their mDP (molecular weight) and activities, which provided a scientific basis for the comprehensive utilization of these polymers in the food, cosmetics, medicine and other fields.

3.
Neuroradiology ; 66(5): 785-796, 2024 May.
Article in English | MEDLINE | ID: mdl-38478062

ABSTRACT

PURPOSE: This study aimed to investigate the diagnostic performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in identifying aberrations in the corticospinal tract (CST), whilst elucidating the relationship between abnormalities of CST and patients' motor function. METHODS: Altogether 21 patients with WHO grade II or grade IV glioma were enrolled and divided into Group 1 and Group 2, according to the presence or absence of preoperative paralysis. DKI and DTI metrics were generated and projected onto the CST. Histograms of the CST along x, y, and z axes were developed based on DKI and DTI metrics, and compared subsequently to determine regions of aberrations on the fibers. The receiver operating characteristic curve was performed to investigate the diagnostic efficacy of DKI and DTI metrics. RESULTS: In Group 1, a significantly lower fractional anisotropy, radial kurtosis and mean kurtosis, and a higher mean diffusivity were found in the ipsilateral CST as compared to the contralateral CST. Significantly higher relative axial diffusivity, relative radial diffusivity, and relative mean diffusivity (rMD) were found in Group 1, as compared to Group 2. The relative volume of ipsilateral CST abnormalities higher than the maximum value of mean kurtosis combined with rMD exhibited the best diagnostic performance in distinguishing dysfunction of CST with an AUC of 0.93. CONCLUSION: DKI is sensitive in detecting subtle changes of CST distal from the tumor. The combination of DKI and DTI is feasible for evaluating the impairment of the CST.


Subject(s)
Diffusion Tensor Imaging , Glioma , Humans , Diffusion Tensor Imaging/methods , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/pathology , Diffusion Magnetic Resonance Imaging , Glioma/diagnostic imaging , Glioma/pathology , ROC Curve
4.
Radiol Oncol ; 58(1): 23-32, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38378035

ABSTRACT

BACKGROUND: The aim of the study was to investigate the diagnostic value of imaging necrosis (Imnecrosis) in grading, predict the genotype and prognosis of gliomas, and further assess tumor necrosis by dynamic contrast-enhanced MR perfusion imaging (DCE-MRI). PATIENTS AND METHODS: We retrospectively included 150 patients (104 males, mean age: 46 years old) pathologically proved as adult diffuse gliomas and all diagnosis was based on the 2021 WHO central nervous system (CNS) classification. The pathological necrosis (Panecrosis) and gene mutation information were collected. All patients underwent conventional and DCE-MRI examinations and had been followed until May 31, 2021. The Imnecrosis was determined by two experienced neuroradiologists. DCE-MRI derived metric maps have been post-processed, and the mean value of each metric in the tumor parenchyma, peritumoral and contralateral area were recorded. RESULTS: There was a strong degree of inter-observer agreement in defining Imnecrosis (Kappa = 0.668, p < 0.001) and a strong degree of agreement between Imnecrosis and Panecrosis (Kappa = 0.767, p < 0.001). Compared to low-grade gliomas, high-grade gliomas had more Imnecrosis (85.37%, p < 0.001), and Imnecrosis significantly increased with the grade of gliomas increasing. And Imnecrosis was significantly more identified in IDH-wildtype, 1p19q-non-codeletion, and CDKN2A/B-homozygous-deletion gliomas. Using multivariate Cox regression analysis, Imnecrosis was an independent and unfavorable prognosis factor (Hazard Ratio = 2.113, p = 0.046) in gliomas. Additionally, extravascular extracellular volume fraction (ve) in tumor parenchyma derived from DCE-MRI demonstrated the highest diagnostic efficiency in identifying Panecrosis and Imnecrosis with high specificity (83.3% and 91.9%, respectively). CONCLUSIONS: Imnecrosis can provide supplementary evidence beyond Panecrosis in grading, predicting the genotype and prognosis of gliomas, and ve in tumor parenchyma can help to predict tumor necrosis with high specificity.


Subject(s)
Brain Neoplasms , Glioma , Adult , Male , Humans , Middle Aged , Brain Neoplasms/pathology , Prognosis , Retrospective Studies , Neoplasm Grading , Glioma/diagnostic imaging , Glioma/genetics , Glioma/pathology , Necrosis
5.
J Magn Reson Imaging ; 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38131220

ABSTRACT

BACKGROUND: Glioma classification affects treatment and prognosis. Reliable imaging methods for preoperatively evaluating gliomas are essential. PURPOSE: To evaluate tumor multiregional mean apparent propagator (MAP) features in glioma diagnosis and to compare those with diffusion-kurtosis imaging (DKI). STUDY TYPE: Retrospective study. SUBJECTS: 70 untreated glioma patients (31 LGGs (low-grade gliomas), 34 women; mean age, 47 ± 12 years, training (60%, n = 42) and testing cohorts (40%, n = 28)). FIELD STRENGTH/SEQUENCE: 3-T, diffusion-MRI using q-space Cartesian grid sampling with 11 different b-values. ASSESSMENT: Tumor multiregional MAP (mean squared displacement (MSD); q-space inverse variance (QIV); non-Gaussianity (NG); axial/radial non-Gaussianity (NGAx, NGRad); return-to-origin/axis/plane probability (RTOP, RTAP, and RTPP)); and DKI metrics (axial/mean/radial kurtosis (AK, MK, and RK)) on tumor parenchyma (TP) and peritumoral areas (PT) in histopathologically gliomas grading and genotyping were assessed. STATISTICAL TESTS: Mann-Whitney U; Kruskal-Wallis; Benjamini-Hochberg; Bonferroni-correction; receiver operating curve (ROC) and area under curve (AUC); DeLong's test; Random Forest (RF). P value<0.05 was considered statistically significant after multiple comparisons correction. RESULTS: Compared with LGGs, MSD, and QIV were significantly lower in TP, whereas NG, NGAx, NGRad, RTOP, RTAP, RTPP, and DKI metrics were significantly higher in HGGs (high-grade gliomas) (P ≤ 0.007), as well as in isocitrate-dehydrogenase (IDH)-mutated than IDH-wildtype gliomas (P ≤ 0.039). These trends were reversed for PT (tumor grades, P ≤ 0.011; IDH-mutation status, P ≤ 0.012). ROC analysis showed that, in TP, DKI metrics performed best in TP (AUC 0.83), whereas in PT, RTPP performed best (AUC 0.77) in glioma grading. AK performed best in TP (AUC 0.77), whereas MSD and RTPP performed best in PT (AUC 0.73) in IDH genotyping. Further RF analysis with DKI and MAP demonstrated good performance in grading (AUC 0.91, Accuracy 82%) and IDH genotyping (AUC 0.87, Accuracy 79%). DATA CONCLUSION: Tumor multiregional MAP features could effectively evaluate gliomas. The performance of MAP may be similar to DKI in TP, while in PT, MAP may outperform DKI. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

6.
Eur Radiol ; 33(10): 6636-6647, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37095360

ABSTRACT

OBJECTIVES: To comprehensively evaluate the glioma using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Forty-two patients (18 women; mean age, 45 years) with pathologically confirmed gliomas were retrospectively included. All the patients underwent conventional and advanced MRI examinations (QSM, DWI, MRS, etc.). Five patients underwent paired QSM (pre- and post-enhancement). Four Visually Accessible Rembrandt Image (VASARI) features and intratumoural susceptibility signal (ITSS) were observed. Three ROIs each were manually drawn separately in the tumour parenchyma with relatively high and low magnetic susceptibility. The association between the tumour's magnetic susceptibility and other MRI parameters was also analysed. RESULTS: Morphologically, gliomas with heterogeneous ITSS were more similar to high-grade gliomas (p = 0.006, AUC: 0.72, sensitivity: 70%, and specificity: 73%). Heterogeneous ITSS was significantly associated with tumour haemorrhage, necrosis, diffusion restriction, and avid enhancement but did not change between pre- and post-enhanced QSM. Quantitatively, tumour parenchyma magnetic susceptibility had limited value in grading gliomas and identifying IDH mutation status, whereas the relatively low magnetic susceptibility of the tumour parenchyma helped identify oligodendrogliomas in IDH mutated gliomas (AUC = 0.78) with high specificity (100%). The relatively high tumour magnetic susceptibility significantly increased after enhancement (p = 0.039). Additionally, we found that the magnetic susceptibility of the tumour parenchyma was significantly correlated with ADC (r = 0.61) and Cho/NAA (r = 0.40). CONCLUSIONS: QSM is a promising candidate for the comprehensive evaluation of gliomas, except for IDH mutation status. The magnetic susceptibility of tumour parenchyma may be affected by tumour cell proliferation. KEY POINTS: • Morphologically, gliomas with a heterogeneous intratumoural susceptibility signal (ITSS) are more similar to high-grade gliomas (p = 0.006; AUC, 0.72; sensitivity, 70%; and specificity, 73%). Heterogeneous ITSS was significantly associated with tumour haemorrhage, necrosis, diffusion restriction, and avid enhancement but did not change between pre- and post-enhanced QSM. • Tumour parenchyma's relatively low magnetic susceptibility helped identify oligodendroglioma with high specificity. • Tumour parenchyma magnetic susceptibility was significantly correlated with ADC (r = 0.61) and Cho/NAA (r = 0.40).


Subject(s)
Brain Neoplasms , Glioma , Oligodendroglioma , Humans , Female , Middle Aged , Brain Neoplasms/pathology , Retrospective Studies , Sensitivity and Specificity , Glioma/pathology , Magnetic Resonance Imaging/methods , Oligodendroglioma/diagnostic imaging , Hemorrhage , Neoplasm Grading , Diffusion Magnetic Resonance Imaging/methods
7.
Cancer Sci ; 113(5): 1739-1751, 2022 May.
Article in English | MEDLINE | ID: mdl-35238098

ABSTRACT

Obesity increases the risk of colorectal cancer (CRC) by 30%. The obese tumor microenvironment compromises antitumor immunity by eliciting exhausted T cells (Tex). Hypothesizing that Dahuang Fuzi Baijiang decoction (DFB) is a combined classical prescription from the "Synopsis of Prescriptions of the Golden Chamber". We first determined that DFB regresses tumor growth in high-fat diet-induced obese mice by expanding the TIM3- subset with intermediate expression of programmed cell death-1 (PD-1int TIM3- ) and restricting the PD-1hi TIM3+ subset. Transcription factor 1 (TCF1) is highly expressed in the PD-1int TIM3- subset but is absent in PD-1hi TIM3+ cells. We next confirmed that progenitor PD-1int TCF+ cells robustly produce tumor necrosis factor-α (TNFα) and interferon-γ, whereas terminally differentiated PD-1int TCF+ cells have defects in generating TNFα. With transgenic ob/ob mice, we found that DFB produces cooperative efficacy with anti-PD-1 (αPD-1) by limiting the PD-1hi Tim3+ subset and amplifying the PD-1int TCF+ population. Finally, we defined the recombinant chemokine C-C-motif receptor 2 (CCR2)+ CD8+ subset as terminal Tex and identified that the differentiation from progenitor to terminal Tex is driven, at least in part, by the chemokine (C-C motif) ligand 2 (CCL2)/CCR2 axis. The CCR2 inhibitor enhances the response to αPD-1 by promoting the counts of progenitor Tex. Altogether, DFB dampens CCL2 and preserves progenitor Tex in the obese microenvironment to restrain CRC progression. These findings provide unambiguous evidence that the traditional Chinese formula DFB can prevent tumor progression by modulating adaptive immunity and establish a strong rationale for further clinical verification.


Subject(s)
Colorectal Neoplasms , Hepatitis A Virus Cellular Receptor 2 , Animals , CD8-Positive T-Lymphocytes , Cell Differentiation , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Diterpenes , Drugs, Chinese Herbal , Hepatitis A Virus Cellular Receptor 2/metabolism , Humans , Mice , Obesity/metabolism , Programmed Cell Death 1 Receptor/metabolism , Tumor Microenvironment , Tumor Necrosis Factor-alpha/metabolism
8.
Front Radiol ; 1: 704888, 2021.
Article in English | MEDLINE | ID: mdl-37492172

ABSTRACT

Glioma is a type of severe brain tumor, and its accurate segmentation is useful in surgery planning and progression evaluation. Based on different biological properties, the glioma can be divided into three partially-overlapping regions of interest, including whole tumor (WT), tumor core (TC), and enhancing tumor (ET). Recently, UNet has identified its effectiveness in automatically segmenting brain tumor from multi-modal magnetic resonance (MR) images. In this work, instead of network architecture, we focus on making use of prior knowledge (brain parcellation), training and testing strategy (joint 3D+2D), ensemble and post-processing to improve the brain tumor segmentation performance. We explore the accuracy of three UNets with different inputs, and then ensemble the corresponding three outputs, followed by post-processing to achieve the final segmentation. Similar to most existing works, the first UNet uses 3D patches of multi-modal MR images as the input. The second UNet uses brain parcellation as an additional input. And the third UNet is inputted by 2D slices of multi-modal MR images, brain parcellation, and probability maps of WT, TC, and ET obtained from the second UNet. Then, we sequentially unify the WT segmentation from the third UNet and the fused TC and ET segmentation from the first and the second UNets as the complete tumor segmentation. Finally, we adopt a post-processing strategy by labeling small ET as non-enhancing tumor to correct some false-positive ET segmentation. On one publicly-available challenge validation dataset (BraTS2018), the proposed segmentation pipeline yielded average Dice scores of 91.03/86.44/80.58% and average 95% Hausdorff distances of 3.76/6.73/2.51 mm for WT/TC/ET, exhibiting superior segmentation performance over other state-of-the-art methods. We then evaluated the proposed method on the BraTS2020 training data through five-fold cross validation, with similar performance having also been observed. The proposed method was finally evaluated on 10 in-house data, the effectiveness of which has been established qualitatively by professional radiologists.

9.
Neural Plast ; 2020: 8830670, 2020.
Article in English | MEDLINE | ID: mdl-32952549

ABSTRACT

Background: Previous researches indicate that Itpr2 -/- mice (inositol 1,4,5-trisphosphate receptor type 2 knockout mice) show depressive-like symptoms; however, little is known regarding the in vivo neurobiological effect of Itpr2 as well as the specific pattern of brain abnormalities in Itpr2 -/- mice. Methods/Materials. First, behavioral tests, structural magnetic resonance imaging (MRI), and resting-state functional MRI were performed on Itpr2 -/- mice and matched healthy controls. Voxel-based morphometry and seed-based voxel-wise functional connectivity (FC) were, respectively, calculated to assess the gray matter volume and the functional activities of the brain in vivo. Second, the sample of relevant changed brain regions was extracted to detect the expression of BDNF. Finally, to further validate the relationship between Itpr2 deficiency and the observed brain abnormalities, we performed Western blotting to detect the expression of pro-BDNF and mBDNF in Itpr2 -/- C8-D1A (a type of astrocyte). Results: Compared with controls, Itpr2 -/- mice showed depressive-like behaviors as well as significantly lower gray matter volume in striatums mainly, periaqueductal GM, and the right frontoparietal cortices as well as lower striatal-hippocampal and striatal-right parietal cortex (mainly for the primary and secondary somatosensory cortex) FC. Moreover, decreased expression of mBDNF was found in both sample tissues of the striatum in Itpr2 -/- mice and Itpr2 -/- C8-D1A. Conclusion: By combining biochemistry and MR analyses, this study provides evidences to support that the Itpr2-related neuropathological effect is possibly mediated by the striatal abnormality associated with dysfunctional astrocytes in Itpr2 -/- mice in vivo, thus may help us better understand underlying mechanisms of Itpr2 deficiency as well as its relation to depressive-like behavior.


Subject(s)
Astrocytes/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Corpus Striatum/pathology , Corpus Striatum/physiopathology , Depression/pathology , Depression/physiopathology , Inositol 1,4,5-Trisphosphate Receptors/genetics , Inositol 1,4,5-Trisphosphate Receptors/physiology , Animals , Cell Line , Depression/metabolism , Gray Matter/pathology , Mice, Knockout
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 56-60, 2020 Jan 30.
Article in Chinese | MEDLINE | ID: mdl-32376566

ABSTRACT

OBJECTIVE: To study the behavioral changes of inositol 1, 4, 5-trisphosphate receptor type 2 knockout (Itpr2-/- mice) and investigate the blood perfusion changes in the hippocampus using three-dimensional arterial spin labeling (3D-ASL). METHODS: 28 Itpr2-/- mice and 20 wild-type mice were assessed for depressive phenotype using behavioral tests (including sucrose consumption test, tail suspension test, forced swimming test and open field test). 15 Itpr2-/- mice and 14 wild-type mice were randomly selected for 3D-T2WI imaging of the whole brain and 3D-ASL imaging of the middle hippocampal layer, and cerebral blood flow (CBF) of the middle hippocampal layer was calculated. ITK-SNAP was used to delineate the bilateral hippocampal area and measure the average CBF value. RESULTS: Compared with the wild-type mice, Itpr2-/- mice exhibited a distinct depressive phenotype with significantly decreased sucrose preference (P < 0.05) and increased immobile time in tail suspension test (P < 0.05) and forced swimming test (P < 0.01), without obvious changes in the performance in open field test (P > 0.05). Significantly decreased mean CBF values were found in the left and right hippocampus of Itpr2-/- mice as compared with the wild-type mice (left: 73.30 ±5.609 vs 95.77±5.095; right: 73.53±5.700 vs 100.5±4.696; bilateral means: 73.42±5.607 vs98.12±4.754; P < 0.01). CONCLUSIONS: Itpr2 deficiency can cause depressive phenotype and affect the cerebral blood flow in the hippocampus of mice.


Subject(s)
Cerebrovascular Circulation , Depression/genetics , Hippocampus/diagnostic imaging , Imaging, Three-Dimensional , Animals , Hippocampus/blood supply , Inositol 1,4,5-Trisphosphate Receptors/genetics , Mice , Mice, Knockout , Perfusion Imaging , Spin Labels
11.
Aquat Toxicol ; 224: 105480, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32417752

ABSTRACT

The calanoid copepod, Acartia tonsa, is relatively sensitive to marine pollution. Glutathione S-transferase (GST) multifunctional enzyme, as a biomarker, play an important role in detoxification metabolism of exogenous substances. In the present study, GST-theta and GST-mu class homology genes (designated as AtGSTT1 and AtGSTM2) were identified and characterized from A. tonsa. The coding sequence of AtGSTT1 comprised 726 bp and encoded a putative protein of 241 amino acid residues. AtGSTM2 contained an open reading frame of 678 bp that encoded a putative 227 amino acid polypeptide. Both proteins contained a conserved GST-N domain and a GST-C domain. Structural analysis revealed the characteristic N-terminal G-site. Three-dimensional structure analysis showed that AtGSTT1 and AtGSTM2 have two typical domains of GST family: The ßαßαßßα topology structure at the N- terminus and the superhelical structure at the C- terminus. Subsequently, the expression levels of the two GST genes were detected in A. tonsa using real-time quantitative PCR after exposure to 1,2-dimethylnaphthalene (C2-NAPH) at different concentrations (0.574, 5.736 and 57.358 µg/L) for 24, 48, 72, and 96 h. AtGSTT1 mRNA expression was significantly up-regulated in a time-dependent manner and the highest mRNA expression occurred at 5.736 µg/L C2-NAPH exposure for 96 h. AtGSTM2 mRNA expression peaked at 72 h in 0.574 µg/L and 5.736 µg/L dose groups. The expression level of AtGSTM2 showed an increasing trend in a time-dependent manner at 57.358 µg/L of C2-NAPH. These results suggested that GST genes may play an important role in protecting A. tonsa from C2-NAPH pollution, and provide a theoretical basis for further study on the molecular mechanism of polycyclic aromatic hydrocarbon (PAHs) pollution on zooplankton.


Subject(s)
Copepoda/drug effects , Environmental Monitoring/methods , Glutathione Transferase/genetics , Naphthalenes/toxicity , Water Pollutants, Chemical/toxicity , Animals , Base Sequence , Cloning, Molecular , Copepoda/enzymology , Copepoda/genetics , DNA, Complementary/genetics , Dose-Response Relationship, Drug , Glutathione Transferase/metabolism , High-Throughput Nucleotide Sequencing , RNA, Messenger/genetics , Toxicity Tests, Acute
12.
Biomed Pharmacother ; 111: 1057-1065, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30841419

ABSTRACT

Major depressive disorder (MDD) affects ˜16% of the world population. Chronic stressors contribute to reduced hippocampal volumes and increase the risk of developing MDD. Our previous work showed that XYS ameliorates social isolation and chronic unpredictable mild stress (CUMS) induced depressive-like behaviors in rats by regulating hypothalamic-pituitary-adrenal hyperactivation, locus coeruleus -norepinephrine activity and kynurenine/5-hydroxytryptamin balance. Here, we report that CUMS & isolation-treated mice exhibit depressive-like behaviors and show a phenotype of mixed apoptosis/autophagy characteristic in mice hippocampus in vivo. Modified Xiaoyao San (MXS) significantly ameliorates CUMS & social isolation-induced anhedonia, loss of interests, psychomotor retardation and behavioral despair. It suppresses the apoptosis by downregulaing condensation of heterochromatin and reducing hippocampal TdT-mediated dUTP Nick-End Labeling (TUNEL)-positive cells. MSX significantly inhibits mitochondrial outer membrane permeabilization (MOMP) reduces the release of cytochrome C and the shift of apoptosis inducing factor (AIF) from mitochondria to nucleus. Further, it stimulates the formation of autophagosomes and activates the expression of Atg5 and LC3II. Combined silencing of Atg5 and Atg7 dampens MOMP and impaired the anti-apoptotic effects of MXS. In conclusion, MXS ameliorates depressive-like behaviors by triggering autophagy to alleviate neuronal apoptosis. MXS is an effective supplement for MDD treatment, and can be harnessed to enhance autophagy and synergize with antidepressant action.


Subject(s)
Antidepressive Agents/pharmacology , Apoptosis/drug effects , Autophagosomes/drug effects , Depression/drug therapy , Depressive Disorder, Major/drug therapy , Drugs, Chinese Herbal/pharmacology , Neurons/drug effects , Animals , Apoptosis Inducing Factor/metabolism , Autophagosomes/metabolism , Autophagy/drug effects , Depression/metabolism , Depressive Disorder, Major/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Male , Mice , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/metabolism , Neurons/metabolism , Permeability/drug effects , Signal Transduction/drug effects , Stress, Psychological/drug therapy , Stress, Psychological/metabolism
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