Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway.

OBJECTIVE: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. METHODS: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC50), IC50, 2×IC50, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. RESULTS: Compared to the control group, the 10 (1/2 IC50), 20 (IC50) and 40 (2×IC50) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe2+, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). CONCLUSIONS: Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.

Polyphyllin II (PPII) Enhances the Sensitivity of Multidrug-resistant A549/DDP Cells to Cisplatin by Modulating Mitochondrial Energy Metabolism.

BACKGROUND/AIM: Cisplatin resistance often leads to treatment futility and elevated mortality rates in patients with lung cancer. One promising strategy to address this challenge involves the integration of traditional Chinese medicine (TCM) with chemotherapeutic drugs. Currently, the potential synergistic effect and underlying mechanism of polyphyllin II (PPII) and cisplatin combination in combating cisplatin (DDP) resistance in lung cancer remain unexplored. MATERIALS AND METHODS: In this study, we established a cisplatin resistance model using A549 cells and explored the underlying mechanisms of PPII in combination with cisplatin in A549/DDP resistant cells. Specifically, we assessed the impact of PPII combined with cisplatin on A549/DDP cell proliferation, viability, and the expression of apoptosis-related proteins. To gain deeper insights into the underlying mechanism, we examined the effects of PPII and cisplatin on mitochondrial function in A549/DDP cells. RESULTS: This combination induced cell cycle arrest at both the S phase and G2/M phase in A549/DDP cells, thereby promoting apoptosis. Western blotting confirmed that DDP acted synergistically with PPII to enhance the expression of apoptotic proteins, diminish the expression of anti-apoptotic proteins, and promote the expression of anti-proliferation proteins in the mitochondrial pathway of A549/DDP cells. CONCLUSION: The combination of PPII and cisplatin effectively modulated the mitochondrial function, thereby reversing drug resistance in A549/DDP cells. This innovative combination therapy shows significant promise as a novel strategy for overcoming cisplatin resistance in lung cancer.

Hederagenin Induces Apoptosis of Human Hepatoma HepG2 Cells via the Mitochondrial Pathway.

OBJECTIVE: The objective of this study is to assess the antitumor effects of hederagenin (HDG) in liver cancer (LC) cells and explore the related mechanisms. METHODS AND MATERIALS: HepG2 cells were treated with HDG and cisplatin, respectively. The CCK8 assay was used to detect cell activity, DAPI staining was used to detect the proportion of living cells, TUNEL assay to detect the proportion of apoptotic cells, flow cytometry to detect the membrane potential, fluoroscopic electron microscopy to detect microstructural changes to the mitochondrial, and western blot analysis and high-content screening to detect apoptosisrelated proteins. RESULTS: Treatment with HDG inhibited the growth of HepG2 cells, decreased the proportion of viable cells, increased the proportion of apoptotic cells, and significantly increased the proportion of cells in the G1 phase. Fluorescence staining showed that HDG damaged the mitochondria of HepG2 cells and significantly decreased the number of mitochondria. Flow cytometry showed that HDG decreased the mitochondrial membrane potential of HepG2 cells. Observations by electron microscopy showed that HDG caused swelling and vacuole formation of the mitochondria of HepG2 cells. HDG significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells and significantly increased that of the pro-apoptosis proteins Bax, Cytochrome-c, and Caspase-3. CONCLUSION: HDG induced apoptosis of HepG2 cells via the mitochondrial pathway.

Lipids, cholesterols, statins and liver cancer: a Mendelian randomization study.

Aim: To investigate the causal relationship of serum lipid indicators and lipid-lowering drugs with the risk of liver cancer using Mendelian randomization study. Methods: A two-sample Mendelian randomization (TSMR) study was performed to investigate the causal relationship between serum levels of lipid indicators and liver cancer, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), total cholesterol (TC), Apolipoprotein B (ApoB), and Apolipoprotein A1 (ApoA1).Furthermore, instrumental variable weighted regression (IVW) and summary data-based MR (SMR) analyses were performed to investigate the causal effects of lipid-lowering drugs, including statins and PCSK9 inhibitors, on the risk of liver cancer. Results: Serum LDL-c and serum TC levels showed negatively associated with liver cancer (n = 22 SNPs, OR = 0.363, 95% CI = 0.231 - 0.570; p = 1.070E-5) (n = 83 SNPs; OR = 0.627, 95% CI = 0.413-0.952; p = 0.028). However, serum levels of TG, HDL-c, and ApoA1 did not show any significant correlation with liver cancer. In the drug target MR (DMR) analyses, HMGCR-mediated level of LDL-c showed an inverse relationship with the risk of liver cancer in the IVW-MR analysis (n = 5 SNPs, OR = 0.201, 95% CI = 0.064 - 0.631; p = 5.95E-03) and SMR analysis (n = 20 SNPs, OR = 0.245, 95% CI = 0.065 - 0.926; p = 0.038) However, PCSK9 did not show any significant association with liver cancer based on both the IVW-MR and SMR analyses. Conclusion: Our results demonstrated that reduced levels of LDL-c and TC were associated with an increased risk of liver cancer. Furthermore, lipid-lowering drugs targeting HMGCR such as statins were associated with increased risk of liver cancer.

m6A-mediated upregulation of lncRNA-AC026356.1 promotes cancer stem cell maintenance in lung adenocarcinoma via activating Wnt signaling pathway.

LncRNA plays a pivotal role in the stemness and drug resistance of lung cancer. Here, we found that lncRNA-AC026356.1 was upregulated in stem spheres and chemo-resistant lung cancer cells. Our fish assay also shows that AC026356.1 was predominantly located in the cytoplasm of lung cancer cells and does not have protein-coding potential. Silencing AC026356.1 significantly inhibited proliferation and migration but increased apoptosis in A549-cisplatin (DDP) cells. Additionally, IGF2BP2 and the lncRNA-AC026356.1 positively regulated the proliferation and stemness of stem-like lung cancer cells. Further mechanistic investigation revealed that METTL14/IGF2BP2-mediated m6A modification and stabilization of the AC026356.1 RNA. Functional analysis corroborated that AC026356.1 acted as a downstream target of METTL14/IGF2BP2 and AC026356.1 silencing could block the oncogenicity of lung cancer stem-like cells. AC026356.1 expression was correlated with immune cell infiltration and T cell exhaustion. Compared with paired adjacent normal tissues, lung cancer specimens exhibited consistently upregulated METTL14/IGF2BP2/AC026356.1. M6A-modified METTL14/IGF2BP2/AC026356.1 loop may serve as a potential therapeutic target and prognostic predictor for lung cancer therapy and diagnosis in the clinic.

Construction and verification of a novel circadian clock related long non-coding RNA model and prediction of treatment for survival prognosis in patients with hepatocellular carcinoma.

Circadian clock genes are significant in the occurrence and development of HCC and long-non coding RNAs (lncRNAs) are closely related to HCC progression. In this study, we aimed to establish a prognostic risk model for HCC. Circadian clock-related lncRNAs expressed in HCC were extracted from The Cancer Genome Atlas. A nomogram was established to predict individual survival rate. Biological processes enriched for risk model transcripts were investigated by Gene Set Enrichment Analysis. Further, we evaluated the relationship between risk score and immune-checkpoint inhibitor-related gene expression level. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to assess the sensitivity of tumors in high- and low-risk score groups to different drugs. A total of 11 circadian clock-related lncRNAs were included in multi-Cox proportional hazards model analysis to establish a risk model. Univariate and multivariate Cox regression analysis showed that the risk model was an independent risk factor in HCC. The risk model was a significantly associated with the immune signature. Further GDSC analysis indicated that patients in each risk score group may be sensitive to different anti-cancer drugs. QRT-PCR analysis results showed that C012073.1, PRRT3-AS1, TMCC1-AS1, LINC01138, MKLN1-AS, KDM4A-AS1, AL031985.3, POLH-AS1, LINC01224, and AC099850.3 were more highly expressed in Huh-7 and HepG2, compared to LO2, while AC008549.1 were lower expressed. Our work established a prognostic model for HCC. Risk score analysis indicated that the model is significantly associated with modulation tumor immunity and could be used to guide more effective therapeutic strategies in the future.

[Molecular mechanisms of Gupi Xiaoji decoction inducing apoptosis of human hepatoma HepG2 cells].

Objective: To investigate the molecular mechanisms of Gupi Xiaoji decoction on apoptosis of human hepatoma cells HepG2. Methods: HepG2 cells were divided into 4 groups: control group (Control), blank serum group (Blank), Gupi Xiaoji Yin serum group (GPXJY) and cisplatin group (Positive). Eight duplicate holes were set in each group. After treated with Gupi Xiaoji Decoction-containing serum or cisplatin for 24 hours, the cell viability, the number of viable cells, the state of apoptosis, the cell cycle and the mitochondrial membrane potential were detected, and the level of lipid peroxidation (MDA) and glycolysis rate of the cells were detected. The expressions of apoptotic Bax, Bcl-2, and Caspase-3 proteins, and the contents of triacylglycerol (TG), cholesterol (TC), pyruvate and glucose in the cell supernatant were detected. Results: Compared with the control group, in the GPXJY group, the inhibition rate was increased (P＜0.05), the number of cells was decreased, the number of apoptosis-positive cells was increased (P＜0.01), the number of cells in the G1 phase was increased significantly (P＜0.05), and the cell membrane potential was decreased (P＜0.05,P＜0.01), the glycolytic function was inhibited significantly, the MDA level was increased, the expressions of Bax and Caspase-3 in the GPXJY group were increased, and the expression of Bcl-2 was decreased (P＜0.05, P＜0.01). In cell supernatant, the TC, TG and glucose contents were decreased significantly, and the pyruvate content was increased significantly (P＜0.05,P＜0.01). Conclusion: Gupi Xiaoji Decoction can induce apoptosis of HepG2 cells and may play a role in energy metabolism.

The association of oxytocin with major depressive disorder: role of confounding effects of antidepressants.

Major depressive disorder is a genetic susceptible disease, and a psychiatric syndrome with a high rate of incidence and recurrence. Because of its complexity concerning etiology and pathogenesis, the cure rate of first-line antidepressants is low. In recent years, accumulative evidences revealed that oxytocin act as a physiological or pathological participant in a variety of complex neuropsychological activities, including major depressive disorder. Six electronic databases (Web of Science, PubMed, Scopus, Google Scholar, CNKI, and Wanfang) were employed for researching relevant publications. At last, 226 articles were extracted. The current review addresses the correlation of the oxytocin system and major depressive disorder. Besides, we summarize the mechanisms by which the oxytocin system exerts potential antidepressant effects, including regulating neuronal activity, influencing neuroplasticity and regeneration, altering neurotransmitter release, down regulating hypothalamic-pituitary-adrenal axis, anti-inflammatory, antioxidation, and genetic effects. Increasing evidence shows that oxytocin and its receptor gene may play a potential role in major depressive disorder. Future research should focus on the predictive ability of the oxytocin system as a biomarker, as well as its role in targeted prevention and early intervention of major depressive disorder.

Defects of parvalbumin-positive interneurons in the ventral dentate gyrus region are implicated depression-like behavior in mice.

Depression is an increasingly common but extremely serve mood disorder that remains poorly understood and inadequately treated. Fast-spiking parvalbumin-positive interneurons (PVIs), a subpopulation of GABAergic interneurons (GABA, g-aminobutyric acid), exhibit a widespread distribution throughout the hippocampus, and has been reported to play an important role in a variety of mental disorders. However, the relationship between depression and hippocampal PVIs remains unclear. Here in this present study, a series of experiments were conducted to clarify the potential relationship. Here, chronic unpredicted mild stress (CUMS) and Lipopolysaccharide (LPS) injection were introduced to induce depression-like behavior in mice, and led to a clear decline in PVIs numbers in the ventral hippocampal (vHPC), particularly in the ventral dentate gyrus (vDG) subfield. After a selectively removal of the PVIs in PV-ires-Cre::Ai14 mice, we confirmed that ablation of PVIs from the vDG induced depression-like behavior. Furthermore, we found that the removal of vDG-PVIs induced depression likely to be accounted for upregulation of neuroinflammation. These findings facilitate us better understand the role of hippocampal PVIs in depression.

Hypoxia Inducible Factor-1α Attenuates Ischemic Brain Damage by Modulating Inflammatory Response and Glial Activity.

Hypoxia-inducible factor 1 can sufficiently control the progress of neurological symptoms after ischemic stroke owing to their actions associated with its downstream genes. In this study, we evaluated the role of HIF-1α in attenuating brain damage after endothelin-1 injection. Focal cerebral ischemia in mice were induced by endothelin-1 microinjection. Hypoxia-inducible factor 1 activator, dimethyloxalylglycine (DMOG), and HIF-1α inhibitor, acriflavine (ACF), were used to evaluate the hypoxia-inducible factor 1 activity during cerebral ischemia. The expression levels of HIF-1α, glial fibrillary acidic protein (GFAP), interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), phosphorylated I-kappa-B-alpha/total I-kappa-B-alpha (p-IκBα/IκBα) and nuclear factor kappa B (NF-kB) were assessed. Besides, mRNA levels of IL-10, tumor necrosis factor- alpha (TNF-α), and NF-kB were also analyzed. Results showed a noticeable increase in hypoxia-inducible factor 1 and IL-10 levels in the DMOG group with a decline in iNOS, TNF-α, and NF-kB levels, implying the anti-inflammatory role of hypoxia-inducible factor 1 activator following stroke. These findings were further corroborated by GFAP immunostaining that showed astrocytic activation to be inhibited 12 days post-ischemia, as well as histological and TEM analyses that demonstrated hypoxia-inducible factor 1 induction to alleviate neuronal soma damage and cell death. Based on our study, HIF-1α could be a potential therapeutic target for ischemic stroke.

Molecular Mechanisms of Chondrocyte Proliferation and Differentiation.

Cartilage is a kind of connective tissue that buffers pressure and is essential to protect joint movement. It is difficult to self-recover once cartilage is damaged due to the lack of blood vessels, lymph, and nerve tissues. Repair of cartilage injury is mainly achieved by stimulating chondrocyte proliferation and extracellular matrix (ECM) synthesis. Cartilage homeostasis involves the regulation of multiple growth factors and the transduction of cellular signals. It is a very complicated process that has not been elucidated in detail. In this review, we summarized a variety of signaling molecules related to chondrocytes function. Especially, we described the correlation between chondrocyte-specific regulatory factors and cell signaling molecules. It has potential significance for guiding the treatment of cartilage injury.

Optimized integration of fluoxetine and 7, 8-dihydroxyflavone as an efficient therapy for reversing depressive-like behavior in mice during the perimenopausal period.

Fluoxetine (FLX) has been considered as an effective anti-depressant drug. Besides, previous studies reported reasonable anti-depressant effects for 7, 8-dihydroxyflavone (7, 8 DHF). However, the combination of FLX and 7, 8 DHF in a well-established depression model has not been explored. In this study, we demonstrate that the 7, 8 DHF can improve the anti-depressant efficacy of FLX in a chronic unpredictable mild stress (CUMS)-induced depression during the perimenopausal period. The corresponding mechanism of FLX+7, 8 DHF therapy and the effect of ANA-12 are also investigated. Moreover, the influences of 7, 8 DHF (5 mg/kg/day), FLX (18 mg/kg/day), and ANA-12 (0.5 mg/kg/day) on a depressive-like behavior are displayed. Inflammatory, autophagic and apoptotic changes of hippocampus and cortex are examined by using western blot, immunofluorescence, and Real-Time Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) techniques. The protein levels of phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (Akt)/mechanistic target of rapamycin (mTOR)/phosphorylated extracellular signal-regulated kinase1/2 (p-ErK 1/2)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) of hippocampus and cortex are assessed by western blot. The combined FLX and 7, 8 DHF treatment can significantly improve depressive-like behavior in sucrose preference and forced swimming tests accompanied by a noticeable upregulation of autophagy, neuronal nuclei (NeuN), ionized calcium-binding adaptor molecule 1 (Iba1) expressions, and PI3K/Akt/ mTOR/ p-ErK 1/2 signaling pathways. Besides, an obvious increase of the brain-derived neurotrophic factor (BDNF) and TrkB levels are observed with down-regulated inflammation and apoptosis. These findings suggest that the integrated FLX and 7, 8 DHF holds a potential as an efficient treatment to ameliorate depressive-like behavior in perimenopausal patients.

Recent advances of induced pluripotent stem cells application in neurodegenerative diseases.

Stem cell is defined by its ability to self-renewal and generates differentiated functional cell types, which are derived from the embryo and various sources of postnatal animal. These cells can be divided according to their potential development into totipotent, unipotent, multipotent andpluripotent. Pluripotent is considered as the most important type due to its advantageous capability to create different cell types of the body in a similar behavior as embryonic stem cell. Induced pluripotent stem cells (iPSCs) are adult cells that maintain the characteristics of embryonic stem cells because it can be genetically reprogrammed to an embryonic stem cell-like state via express genes and transcription factors. Such cells provide an efficient pathway to explorehuman diseases and their corresponding therapy, particularly, neurodevelopmental disorders. Consequently, iPSCs can be investigated to check the specific mutations of neurodegenerative disease due to their unique ability to differentiate into neural cell types and/or neural organoids. The current review addresses the different neurodegenerative diseases model by using iPSCs approach such as Alzheimer's diseases (AD), Parkinson diseases (PD),multiplesclerosis(MS) and psychiatric disorders. We also highlight the importance of autophagy in neurodegenerative diseases.

Curcumin Can Improve Spinal Cord Injury by Inhibiting TGF-ß-SOX9 Signaling Pathway.

Spinal cord injury (SCI) is a severe nervous system disease with high morbidity and disability rate. Signaling pathways play a key role in the neuronal restorative mechanism following SCI. SRY-related high mobility group (HMG)-box gene 9 (SOX9) affects glial scar formation via Transforming growth factor beta (TGF-ß) signaling pathway. Activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is transferred into nucleus to upregulate TGF-ß-SOX9. Curcumin exhibits potent anti-inflammatory and anti-oxidant properties. Curcumin can play an important role in SCI recovery by inhibiting the expression of NF-κB and TGF-ß-SOX9. Herein, we review the potential mechanism of curcumin-inhibiting SOX9 signaling pathway in SCI treatment. The inhibition of NF-κB and SOX9 signaling pathway by curcumin has the potentiality of serving as neuronal regenerative mechanism following SCI.

SIRT1 Protects Against Apoptosis by Promoting Autophagy in the Oxygen Glucose Deprivation/Reperfusion-Induced Injury.

Silent information regulator 1 (SIRT1) contributes to cellular regulation. Previous studies have reported SIRT1 to be abnormally expressed in the ischemic penumbra of cerebral ischemia/reperfusion (I/R) injury rat model. We investigated the effect of SIRT1 on oxygen and glucose deprivation/reperfusion (OGD/R) cell injury. Over-expressed or silenced SIRT1 pheochromocytoma 12 (PC12) cells were exposed to an in-vitro OGD/R injury. Western blot, TUNEL staining and immunofluorescence analyses were performed to assess apoptosis and autophagy. We found autophagy and apoptosis to be up-regulated and down-regulated, respectively, following the over-expression of SIRT1 in the OGD/R-induced PC12 cells. We also found the silencing of SIRT1 to culminate in the down-regulation and up-regulation of autophagy and apoptosis, respectively. On the basis of our results, we surmise that SIRT1 can promote autophagy and inhibit apoptosis in-vitro, and thus exhibit potential neuroprotection against OGD/R-induced injury. This could facilitate in the development of therapeutic approaches for cerebral I/R injury.

Resveratrol treatment of spinal cord injury in rat model.

Spinal cord injury (SCI) is catastrophic and can culminate in disability and death. The routine therapy employed in early stages of SCI currently entails surgical procedures combined with high doses of methylprednisolone (MP). MP is highly controversial for the lack of consensus on its true therapeutic effects. Resveratrol (RES) has recently been recognized as a potential and novel therapeutic drug in SCI. Herein, we investigated the effect of RES in a SCI rat-model and found significant improvement in Basso-Beattie-Bresnahan scores. Results obtained from histological, immunohistochemistry, and ultra-structural examinations evidenced the tremendous treatment effect of RES. On the basis of our experimental results, we hypothesize that RES could serve as an effective SCI therapeutic with prolong treatment time following injury.

Highly Selective Production of Compound K from Ginsenoside Rd by Hydrolyzing Glucose at C-3 Glycoside Using ß-Glucosidase of Bifidobacterium breve ATCC 15700.

To investigate a novel ß-glucosidase from Bifidobacterium breve ATCC 15700 (BbBgl) to produce compound K (CK) via ginsenoside F2 by highly selective and efficient hydrolysis of the C-3 glycoside from ginsenoside Rd, the BbBgl gene was cloned and expressed in E. coli BL21. The recombinant BbBgl was purified by Ni-NTA magnetic beads to obtain an enzyme with specific activity of 37 U/mg protein using pNP-Glc as substrate. The enzyme activity was optimized at pH 5.0, 35°C, 2 or 6 U/ml, and its activity was enhanced by Mn2+ significantly. Under the optimal conditions, the half-life of the BbBgl is 180 h, much longer than the characterized ß-glycosidases, and the Km and Vmax values are 2.7 mM and 39.8 µmol/mg/min for ginsenoside Rd. Moreover, the enzyme exhibits strong tolerance against high substrate concentration (up to 40 g/l ginsenoside Rd) with a molar biotransformation rate of 96% within 12 h. The good enzymatic properties and gram-scale conversion capacity of BbBgl provide an attractive method for large-scale production of rare ginsenoside CK using a single enzyme or a combination of enzymes.

Inhibition of Autophagy in Microglia Alters Depressive-Like Behavior via BDNF Pathway in Postpartum Depression.

Postpartum depression (PPD) is associated with mood disorders and elevated inflammation. Studies have evidenced the activation/inhibition of autophagy and excessive activation of microglia to have a close relationship with depression. C57 and microglia-specific autophagy-deficient mice (Cx3Cr1Cre/+ATG5loxp/loxp) were employed to establish the chronic unpredicted mild stress depression mice model from embryonic day 7 (E7) to embryonic day 16 (E16). Fluoxetine was administered for 3 weeks (commencing from 1 week after birth). Behavioral tests (open field, forced swimming, and sucrose preference tests) were implemented. Western blot and immunofluorescence staining were employed to assess the brain-derived neurotrophic factor (BDNF) expression level, autophagy-associated proteins, and inflammatory factors. Depressive behavior was reversed following fluoxetine treatment; this was evidenced via open field, sucrose preference, and forced swimming tests. Both BDNF and autophagy-associated proteins (ATG5, Beclin-1, and LC3II) were upregulated following fluoxetine treatment. Inflammatory factors including nuclear factor kappa B and inducible nitric oxide synthase were reduced while anti-inflammatory factor interleukin-10 (IL-10) was increased after fluoxetine treatment. Microglia-specific autophagy-deficient mice (Cx3Cr1Cre/+ATG5loxp/loxp) showed a curtailed autophagy level, higher inflammatory level, and reduced BDNF expression when compared with C57 mice. Autophagy inhibition in microglia contributes to inflammation, which further instigates PPD. Fluoxetine might mediate its antidepressant effect in PPD through the autophagic pathway while upregulating BDNF expression. In view of this, regulating BDNF in microglia is a potential novel therapy target for PPD.