scholarly journals Agomelatine Softens Depressive-Like Behavior through the Regulation of Autophagy and Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Fengpei Chen ◽  
Shijia Chen ◽  
Jie Liu ◽  
Nashwa Amin ◽  
Weidong Jin ◽  
...  
Keyword(s):  
Short Chain Fatty Acids ◽  
Underlying Mechanism ◽  
Primary Objective ◽  
High Recurrence Rate ◽  
Pharmacological Effects ◽  
Chronic Restraint Stress ◽  
Protein Markers ◽  
Inflammatory Protein ◽  
Antidepressant Effects ◽  
Activity Marker

Depression is a common and disabling mental disorder with high recurrence rate. Searching for more effective treatments for depression is a long-standing primary objective in neuroscience. Agomelatine (AGO) was reported as an antidepressant with unique pharmacological effects. However, its effects and the underlying mechanism are still unclear. In this study, we sought to evaluate the antidepressant effects of AGO on the chronic restraint stress (CRS) mouse model and preliminarily investigate its effects on the gut microbial metabolites. The CRS model mice were established in 28 days with AGO (60 mg/kg/day, by oral) or fluoxetine (15 mg/kg/day, by oral) administration. The number of behavioral tests was conducted to evaluate the effect of AGO on depression-like behavior alleviation. Meanwhile, the expression of the BDNF/TrkB/pERK signaling pathway, apoptosis, autophagy, and inflammatory protein markers were assessed using western blot and immunofluorescence. Our findings show that AGO can attenuate the depressive-like behavior that significantly appeared in both sucrose preference and forced swimming tests. Additionally, a noticeable upregulation of autophagy including Beclin1 and LC3II, microglial activity marker Iba-1, and BDNF/TrkB/pERK signaling pathways are indicated. An obvious decreased expression of NF-κB, iNOS, and nNOS as well as apoptosis including Bax is observed in AGO administration mice. On the other hand, we found that AGO impacted the rebalancing of short-chain fatty acids (SCFAs) in mouse feces. Altogether, these findings suggest that AGO can exert antidepressant effects in a different molecular mechanism.

scholarly journals PCDHGB7 Increases Chemosensitivity to Carboplatin by Inhibiting HSPA9 via Inducing Apoptosis in Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Siqi Hou ◽  
Ming Shan ◽  
Chunyang Gao ◽  
Xinxin Feng ◽  
Yongheng Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Caspase 3 ◽  
Triple Negative ◽  
Chemotherapy Resistance ◽  
Underlying Mechanism ◽  
High Recurrence Rate ◽  
Tnbc Cell ◽  
Resistance To Chemotherapy

Breast cancer is one of the most serious cancers worldwide, and chemotherapy resistance frequently drives cancer progression. Triple-negative breast cancer (TNBC) has a high recurrence rate and poor prognosis given its resistance to chemotherapy. In our previous study, we found a remarkable abnormal methylation modification of the PCDHGB7 gene in breast cancer. However, the roles of PCDHGB7 in the progression and treatment of breast cancer are unclear. In this study, we examined the effects of PCDHGB7 on the sensitivity of TNBC cells to carboplatin and investigated the underlying mechanism. By knocking down and overexpressing PCDHGB7 in HS578T and BT549 cells, we confirmed that PCDHGB7 increases TNBC cell chemosensitivity to carboplatin. Mechanistically, we found that PCDHGB7 negatively regulates the expression of HSPA9, uplifting its inhibition on P53 translocation and caspase-3 activation. Thus, we demonstrated that PCDHGB7 increases chemosensitivity of TNBC cells to carboplatin by inhibiting HSPA9 via inducing apoptosis. PCDHGB7 and HSPA9 represent potential therapeutic targets for chemosensitivity in breast cancer.

Metformin potentiates cognitive and antidepressant effects of fluoxetine in rats exposed to chronic restraint stress and high fat diet: potential involvement of hippocampal c-Jun repression

2018 ◽  
Vol 391 (4) ◽  
pp. 407-422 ◽  
Author(s):  
Sara A. Khedr ◽  
Ahmed A. Elmelgy ◽  
Omnyah A. El-Kharashi ◽  
Hadwa A. Abd-Alkhalek ◽  
Manal L. Louka ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Restraint Stress ◽  
Chronic Restraint Stress ◽  
High Fat ◽  
Antidepressant Effects

scholarly journals Therapeutic Duration and Extent Affect the Effect of Moxibustion on Depression-Like Behaviour in Rats via Regulating the Brain Tryptophan Transport and Metabolism

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Hao Li ◽  
Lan Sang ◽  
Xing Xia ◽  
Ruirui Zhao ◽  
Mingyue Wang ◽  
...  
Keyword(s):  
Forced Swimming Test ◽  
Open Field Test ◽  
Alternative Therapy ◽  
Underlying Mechanism ◽  
Depression Effect ◽  
Major Depressive ◽  
Antidepressant Effects ◽  
Swimming Test ◽  
The Brain ◽  
Complex Influence

Moxibustion has been widely accepted as an alternative therapy for major depressive disease (MDD). However, the efficacy of moxibustion treatment on MDD is highly variable because of its irregular operation. This study was designed to investigate how therapeutic duration and extent influence the anti-depression effect of moxibustion and the underlying mechanism involved. Rats with lipopolysaccharide-induced depression-like behavior were treated by moxibustion treatment. The anti-depression effect was determined by forced swimming test and open field test. Tryptophan (Trp) transport and its metabolism to serotonin (5-HT) and kynurenine (Kyn) were evaluated to explore the anti-depression mechanism. The results showed that moxibustion treatment could alleviate the depression-like behavior in rats. Trp transport and 5-HT generation were significantly increased, and the Trp-Kyn pathway was moderately inhibited by moxibustion. Prolonged therapy could be beneficial to the anti-depression effect by promoting the brain uptake of Trp and shifting the Trp metabolism to 5-HT. An enhanced therapeutic extent could increase 5-HT generation. In conclusion, this study determined that the anti-depression effect of moxibustion involves improved Trp transport and metabolism. The therapeutic duration benefits antidepressant effects, but the complex influence of the therapeutic extent on moxibustion efficacy requires further studies.

scholarly journals Metformin Ameliorates Lipopolysaccharide-Induced Depressive-Like Behaviors and Abnormal Glutamatergic Transmission

2020 ◽  
Author(s):  
Jiang Chen ◽  
Tian Zhou ◽  
Wen-Bin Chen ◽  
Dong Lin ◽  
A-Min Guo ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Tail Suspension Test ◽  
Underlying Mechanism ◽  
Glutamatergic Transmission ◽  
Patch Clamp Recording ◽  
Hippocampal Pyramidal Neurons ◽  
Whole Cell Patch Clamp ◽  
Antidepressant Effects ◽  
Swimming Test

Abstract BackgroundMetformin, a first-line drug for type 2 diabetes mellitus (T2DM), has been found to reduce depressive symptoms in patients comorbid depression with other diseases. However, it is largely unclear that how metformin ameliorates the depressive-like behaviors. MethodsLipopolysaccharide (LPS) was injected intraperitoneally into C57BL/6 mice to induce depressive-like behaviors, and metformin was administrated in LPS-induced depression mouse model. Forced swimming test (FST) and tail suspension test (TST) were employed to detect the depressive-like behaviors. Whole-cell patch clamp recording in the hippocampal pyramidal neurons was adopted to record the miniature excitatory postsynaptic currents (mEPSCs) and paired-pulse ratios (PPR). ResultsWe found LPS-treated mice exhibited increased immobility in FST and TST, and elevated glutamatergic transmission. Furthermore, metformin administration in the LPS-treated mice ameliorated depressive-like behaviors and abnormal glutamatergic transmission. ConclusionOur results suggest that metformin have antidepressant effects and can correct abnormal glutamatergic transmission, providing an insight to the underlying mechanism of metformin on depression.

Randomized, open-label, perioperative phase II study evaluating nivolumab alone or nivolumab plus ipilimumab in patients with resectable HCC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4098-4098
Author(s):  
Ahmed Omar Kaseb ◽  
Roberto Carmagnani Pestana ◽  
Luis M. Vence ◽  
Jorge M. Blando ◽  
Shalini Singh ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Phase Ii ◽  
Interim Analysis ◽  
Response Rate ◽  
Pilot Trial ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Primary Objective ◽  
High Recurrence Rate ◽  
Open Label

4098 Background: In HCC, surgical resection is associated with high recurrence rate, and no effective neoadjuvant or adjuvant therapies currently exist. On the basis of of previous reports on the efficacy and safety of anti–PD-1 (nivolumab) and anti–CTLA-4 (ipilimumab) antibodies against HCC, we initiated a randomized pilot trial of perioperative immunotherapy for resectable HCC. Methods: This is a randomized, phase II pilot trial of nivolumab (Arm A) or nivolumab + ipilimumab (Arm B) as pre-operative treatment for patients (pt) with HCC who are eligible for surgical resection. Pt are given nivolumab 240 mg every 2 weeks (wk) for a total of 6 wk. Pt in Arm B are treated concurrently with ipilimumab 1 mg/kg every 6 wk. Surgical resection occurs within 4 weeks after last cycle of therapy. Pt continue adjuvant immunotherapy for up to 2 years after resection. Primary objective is the safety and tolerability of nivolumab +/- ipilimumab. Secondary objectives include overall response rate, complete response rate and time to progression. Exploratory objectives include evaluating the pre- and post-treatment immunological changes in tumor tissues and peripheral blood. Results: 17 pt were enrolled at the time of interim analysis (8 in Arm A, 9 in Arm B) and 14 were evaluable. Most pt (53%) were 60-70yo, and males (70%). 6 pt were HCV-positive and 4 had chronic hepatitis B. 14 pt proceeded with resection as planned; surgery was aborted for 2 pt (1 for frozen abdomen and 1 for development of contralateral liver nodule). One is still receiving preoperative therapy. Pathologic complete response (pCR) was observed in 4/14 evaluable pt – 2 in Arm A and 2 Arm B (29% pCR rate). 4 pt in Arm B and 1 in Arm A experienced grade 3 or higher toxicity prior to surgery. Conclusions: We report a pCR rate of 29% in an interim analysis of a phase II pilot trial of perioperative immunotherapy for resectable HCC. Treatment was safe and surgical resection was not delayed. The study is ongoing and results may contribute to a paradigm shift in the perioperative treatment of HCC. Clinical trial information: NCT03222076.

scholarly journals Angiotensin‐(1‐7) Alleviates Autophagy Response Through the PI3K/Akt/mTOR Signaling Pathway in Severe Acute Pancreatitis

2021 ◽  
Author(s):  
Chunyun Li ◽  
Xiaozheng Yu ◽  
Yinan Guo ◽  
Xueyan Wang ◽  
Ruixia Liu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Signaling Pathway ◽  
Severe Acute Pancreatitis ◽  
Underlying Mechanism ◽  
Mtor Signaling ◽  
Medical Emergency ◽  
Protein Markers ◽  
Mtor Signaling Pathway ◽  
Ar42j Cells ◽  
The Impact

Abstract Background: Severe acute pancreatitis (SAP) is a fatal medical emergency. The autophagy response is essential for cellular homeostasis, and plays an important role in SAP. We aimed to determine if angiotensin‐(1‐7), abbreviated as Ang1‐7, regulates the autophagy response in SAP and to elucidate the underlying mechanism.Methods: We used a rat model to investigate the effects of Ang1-7 on pancreatic pathomorphological damage and the autophagy response, which were evaluated using histological scoring and the quantification of the autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and p62/SQSTM (p62) by western blotting and immunohistochemistry. We treated rat pancreatic acinar AR42J cells with caerulein (CAE) to build an in vitro model. To prevent degradation of the autophagy markers, so that we could determine the increase in autophagic vacuolization, we used chloroquine to inhibit autophagosome and lysosome fusion. The PI3K inhibitor BEZ235 was used to suppress PI3K/Akt/mTOR signaling. We observed the impact of Ang1-7 on the autophagy response and evaluated the underlying mechanism by detecting protein expressions of LC3 and p62.Results: In the rat SAP model, Ang1-7 significantly relieved pancreatic pathological damage. Ang1-7 also reduced autophagy protein markers, including the LC3-Ⅱ to LC3-Ⅰ ratio and the p62 level. In AR42J cells, the autophagy markers significantly increased after treatment with CAE and chloroquine. The autophagy response was significantly alleviated after treatment of the cells with Ang1-7, while blocking the PI3K/Akt/mTOR pathway remarkably counteracted this effect.Conclusions: Our results indicated that Ang1-7 alleviated the autophagy response in SAP via the PI3K/Akt/mTOR signaling pathway.

scholarly journals Meta-Analysis of Sleep Deprivation Effects on Patients With Depression

2021 ◽  
Vol 12 ◽  
Author(s):  
Baiqi Hu ◽  
Chunyan Liu ◽  
Tingting Mou ◽  
Fangyi Luo ◽  
Tingting Lv ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Subgroup Analysis ◽  
Web Of Science ◽  
Meta Analysis ◽  
Comprehensive Analysis ◽  
Cochrane Library ◽  
High Recurrence Rate ◽  
Antidepressant Effects ◽  
Participant Characteristics ◽  
The Cochrane Library

Objective: Depression is a common disorder with a high recurrence rate. Since the effect of sleep deprivation on depression in existing studies were inconsistent, the present study aimed to reassess the effects of SD on patients by performing a meta-analysis of updated research.Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles before January 20th, 2021. Data on participant characteristics, SD characteristics, adjunctive method and tests for depression were extracted. A comprehensive analysis was conducted to assess the effect of SD on depression and subgroup analysis was used to determine the sources of heterogeneity.Results: In total, 8 articles were included. An SD time of <7 days slightly worsened depression levels [0.24 (−0.21, 0.69); I2 = 0%; P = 0.43], a time of 7–14 days had antidepressant effects [−1.52 (−2.07, −0.97); I2 = 19.6%; P = 0.288], and a time of more than 14 days also worsened depression [0.76 (0.12, 1.40); I2 = 43.7%; P = 0.169].Conclusion: SD may serve as an effective antidepressant measure in humans when the time was 7–14 days, while a time of <7 days and more than 14 days worsened depression.

scholarly journals Butyrate Emerges as a Crucial Effector of Zhi-Zi-Chi Decoctions to Ameliorate Depression via Multiple Pathways of Brain-gut Axis

2022 ◽  
Author(s):  
Jialin Liu ◽  
Yichao Fang ◽  
Lixun Cui ◽  
Zhongzhao Wang ◽  
Yusha Luo ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Antidepressant Activity ◽  
Short Chain Fatty Acids ◽  
Underlying Mechanism ◽  
Short Chain ◽  
Antidepressant Effect ◽  
Sequencing Analysis ◽  
Bioactive Constituents ◽  
Ameliorative Effect ◽  
The Brain

Abstract Background: Gut microbiota has emerged as a crucial target of gut-brain axis to influence brain and behavior and also has been closely connected with depression. Zhi-Zi-Chi decoctions (ZZCD), as a classic oral formula in clinic prescribed to clear heat and relieve restlessness traditionally, is widely applied in depression treatment nowadays. However, the underlying mechanism in the antidepressant activity of ZZCD remains largely unknown. Our previous study revealed that isoflavones, the bioactive constituents of Semen Sojae Praeparatum, benefited health by regulating the gut microbiota, which introduced the gut microbiota into understanding the mechanism of Traditional Chinese Medicine (TCM). Hence, in the present study, we aimed to investigate the antidepressant mechanism of ZZCD by focusing on the gut microbiota. Results: A classic depression model of chronic mild unpredictable stress (CUMS) was established in rats based on the results of behavioral tests and hippocampal histomorphology. 16S rRNA sequencing analysis indicated that ZZCD could increase short-chain fatty acid-producing and anti-inflammatory bacteria and reduce inflammatory and tryptophan-metabolizing bacteria, which reflected the changes of short-chain fatty acids (SCFAs), inflammation and tryptophan metabolism from the perspective of the gut microbiota. Furthermore, ZZCD reversed the alterations of BDNF, TNF-α, pro-inflammatory cytokines and neurotransmitters in the gut, blood and brain along the brain-gut axis and restored the decrease of butyrate in cecal content caused by CUMS. Then, butyrate was utilized to validate its ameliorative effect on pathological characteristics of depressive rats. Conclusions: Taken together, these results show that ZZCD exhibits antidepressant effect through modulating gut microbiota to facilitate the production of butyrate, which further regulate anti-inflammation, neurotransmitters, endocrine and BDNF along the gut-brain axis. Hence, this study fills the gap of the antidepressive mechanism of ZZCD in the light of the brain-gut axis and established a multi-targets and multi-levels platform eventually for further research into the mechanism of other TCM efficacy.

scholarly journals The N-terminal polypeptide derived from vMIP-II exerts its anti-tumor activity in human breast cancer by regulating lncRNA SPRY4-IT1

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Haihua Wu ◽  
Yueyue Wang ◽  
Tiantian Chen ◽  
Yu Li ◽  
Haifeng Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Biological Effects ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Inflammatory Protein ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Anti Tumor Activity

Accumulating evidence demonstrates that long non-coding RNA (lncRNA) sprouty4-intron transcript 1 (lncRNA SPRY4-IT1) plays a vital role in the development of breast cancer. However, the underlying mechanism has not been eventually illuminated. We aimed to explore the biological activity of lncRNA SPRY4-IT1 in breast cancer cells and whether N-terminal polypeptide derived from viral macrophage inflammatory protein II (NT21MP) could exert its anti-tumor effect by regulating lncRNA SPRY4-IT1 and its target gene SKA2. Real-time RT-PCR, Western blotting, wound healing, and invasion assays were used to achieve this goal. We found that lncRNA SPRY4-IT1 was highly expressed in breast cancer cells. Moreover, NT21MP markedly inhibited biological effects of breast cancer cells by regulating lncRNA SPRY4-IT1, which was partially achieved through SKA2. Our findings suggested that lncRNA SPRY4-IT1 could serve as a novel biomarker by NT21MP for breast cancer.

scholarly journals Metformin Ameliorates Lipopolysaccharide-Induced Depressive-Like Behaviors and Abnormal Glutamatergic Transmission

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 359
Author(s):  
Jiang Chen ◽  
Tian Zhou ◽  
A-Min Guo ◽  
Wen-Bing Chen ◽  
Dong Lin ◽  
...  
Keyword(s):  
Tail Suspension Test ◽  
Underlying Mechanism ◽  
Glutamatergic Transmission ◽  
Comorbid Depression ◽  
First Line ◽  
Antidepressant Effects ◽  
Swimming Test ◽  
Insight Into ◽  
Line Drug

Metformin, a first-line drug for type 2 diabetes mellitus (T2DM), has been found to reduce depressive symptoms in patients with comorbid depression and other diseases. However, it is largely unclear how metformin ameliorates depressive-like behaviors. Here, we used lipopolysaccharide (LPS) to induce depressive-like behaviors in mice and found that LPS-treated mice exhibited increased immobility in the forced swimming test (FST) and tail suspension test (TST), as well as increased glutamatergic transmission. Furthermore, metformin administration in the LPS-treated mice ameliorated depressive-like behaviors and elevated glutamatergic transmission. Our results suggest that metformin has antidepressant effects and can correct abnormal glutamatergic transmission, providing an insight into the underlying mechanism by which metformin acts against depression.

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