Xiaoyaosan ameliorates CUMS-induced depressive-like and anorexia behaviors in mice via necroptosis related cellular senescence in hypothalamus
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Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia
Background This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. Methods 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. Results 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The β-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. Conclusion This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.
Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia
Background This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. Methods 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. Results 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The β-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. Conclusion This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.
Inhibition of necroptosis mitigates paclitaxel-induced neuronal damage and cognitive impairment
Paclitaxel (PTX) is a first-line chemotherapy agent for treating many types of cancers, induces cognitive impairment and neuronal damage. However, PTX-induced a limited apoptosis of neurons is not consistent with a wide range of neuroinflammation. Here, we demonstrated that in addition to inducing apoptosis in hippocampal neurons (HT22 cells), PTX causes necroptosis, a programmed cell death, via activation of the RIPK1-RIPK3-MLKL signaling pathway. Annexin V/PI dual labeling, flow cytometric analysis, image-based PI staining, and western blot techniques were used to evaluate PTX-induced necroptosis. Cell viability was determined using the CCK8 assay, whereas Ca2+ levels were measured using the Fluo-4 AM fluorescent probe. The number of cells that were positive for both Annexin V and PI staining was considerably higher in PTX-treated HT22 cells compared to those treated with the vehicle. Additionally, the nuclei of PTX-treated cells showed more diffuse necrotic staining with PI compared to the vehicle-treated cells. The Western blot study demonstrated a considerable increase in the expression of necroptotic proteins, including RIPK1, RIPK3, MLKL, and p-MLKL, following PTX treatment. The compound Necrotatin-1 (Nec-1), which specifically inhibits the protein RIPK1, effectively decreased the occurrence of necroptosis in HT22 cells triggered by PTX by lowering the excessive accumulation of intracellular Ca2+ overload. In addition, administration of Nec-1 in vivo rescued cognitive impairments in novel object recognition and Morris Water Maze tests in PTX-treated mice. These data suggest that PTX induces cognitive impairments through RIPK1-mediated necroptosis. Inhibition of necroptosis provided a potential therapeutic approach to reduce PTX-induced cognitive deficits.
Xiaoyaosan formula augments adjuvant therapy and enhances postoperative breast cancer care
IntroductionXiaoyaosan (XYS), a traditional Chinese formula, not only has good antitumor effects but also attenuates distress, anorexia, and quality of life (QoL) by regulating neurology, the microbiota, immunology, and oxidative stress. This study aimed to assess the effect of XYS on QoL, psychological pressure, and spiritual well-being in breast cancer patients undergoing adjuvant chemotherapy.MethodsThis prospective cohort study enrolled 176 postoperative breast cancer patients who received adjuvant chemotherapy combined with (n = 81) or without (n = 95) XYS for comparison. The Quality-of-Life Questionnaire Core-30 (QLQ-C30), Hospital Anxiety and Depression Scale (HADS), University of California Los Angeles (UCLA-LS), and Functional Assessment of Chronic Illness Therapy–Spiritual Well-being (FACIT–Sp) scores were evaluated before adjuvant chemotherapy (T0) and after the first (T1), second (T2), third (T3), and fourth cycles (T4) of adjuvant chemotherapy.ResultsXYS improved the QLQ-C30 score at T2 (p = 0.043), T3 (p = 0.021), and T4 (p = 0.040) and the QLQ-C30 score at T4 (p = 0.027); moreover, XYS attenuated the QLQ-C30 score at T2 (p = 0.040), T3 (p = 0.023), and T4 (p = 0.027). Regarding distress, XYS reduced the HADS-anxiety score at T2 (p = 0.010), T3 (p = 0.025), and T4 (p = 0.019) and the HADS-defined anxiety score at T3 (p = 0.038). XYS also decreased the HADS-depression score at T2 (p = 0.016), T3 (p = 0.018), and T4 (p = 0.017) and the HADS-defined depression rate at T2 (p = 0.047), T3 (p = 0.012), and T4 (p = 0.013). In addition, XYS decreased the UCLA-LS at T2 (p = 0.023) but enhanced the FACIT-Sp at T2 (p = 0.029) and T4 (p = 0.026). Furthermore, after adjustment via propensity score matching, most of the significant findings remained.DiscussionThe addition of XYS to adjuvant chemotherapy improved QoL, psychological health, and spiritual well-being in breast cancer patients.
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