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To determine the potential causal association between serum lipid levels and sarcoidosis, and to investigate the potential impact of lipid lowering agents on sarcoidosis. Two-sample Mendelian randomization (TSMR) was used to investigate the association between lipid levels (including LDL-c, HDL-c, TG, and TC) and sarcoidosis risk. In addition, we used Mendelian drug target randomization (DMR) to analyze the relationship between drug targets for lowering LDL-c levels (HMGCR, PCSK9, and NPC1L1) and drug targets for lowering TG levels (LPL and APOC3) and the risk of sarcoidosis. According to the TSMR analysis, a positive correlation was observed between the serum LDL-c concentration and sarcoidosis incidence (n = 153 SNPs, OR = 1.232, 95% CI = 1.018–1.491; p = 0.031). Similarly, serum TG concentration was found to be positively associated with sarcoidosis (n = 52 SNPs, OR = 1.287, 95% CI = 1.024–1.617; p = 0.03). The DMR results demonstrated a positive correlation between PCSK9-mediated serum LDL-c levels and sarcoidosis (n = 35 SNPs, OR = 1.681, 95% CI = 1.220–2.315; p = 0.001). Similarly, serum TG levels mediated by LPL were positively associated with sarcoidosis (n = 28 SNPs, OR = 1.569, 95% CI = 1.223–2.012; p = 0.0003). This study suggested that elevated serum TG and LDL-c levels may increase the risk of sarcoidosis. PCSK9-mediated reduction of LDL-C levels (simulating the effects of PCSK9 inhibitors) and LPL-mediated reduction of TG levels (simulating the effects of LPL-related lipid lowering drugs) can decrease the risk of developing sarcoidosis. [ABSTRACT FROM AUTHOR]

Necroptosis is intimately associated with the initiation and progression of colon adenocarcinoma (COAD). However, studies on necroptosis-related genes (NRGs) and the regulating long non-coding RNAs (NRGlncRNAs) in the context of COAD are limited. We retrieved the cancer genome atlas (TCGA) to collect datasets of NRGs and NRGlncRNAs on COAD patients. The risk model constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression was then employed to identify NRGs and NRGlncRNAs with prognostic significance. Subsequently, we validated the results using gene expression omnibus (GEO) datasets from different populations, conducted Mendelian randomization (MR) analysis to explore the potential causal relationships between prognostic NRGs and COAD, and conducted cell experiments to verify the expression of prognostic NRGlncRNAs in COAD. Furthermore, we explored potential pathways and regulatory mechanisms of these prognostic NRGlncRNAs and NRGs in COAD through enrichment analysis, immune cell correlation analysis, tumor microenvironment analysis, immune checkpoint analysis, tumor sample clustering, and so on. We identified eight NRGlncRNAs (AC245100.5, AP001619.1, LINC01614, AC010463.3, AL162595.1, ITGB1-DT, LINC01857, and LINC00513) used for constructing the prognostic model and nine prognostic NRGs (AXL, BACH2, CFLAR, CYLD, IPMK, MAP3K7, ATRX, BRAF, and OTULIN) with regulatory relationships with them, and their validation was performed using GEO and GWAS datasets, as well as cell experiments, which showed largely consistent results. These prognostic NRGlncRNAs and NRGs modulate various biological functions, including immune inflammatory response, oxidative stress, immune escape, telomere regulation, and cytokine response, influencing the development of COAD. Additionally, stratified analysis of the high-risk and low-risk groups based on the prognostic model revealed elevated expression of immune cells, increased expression of tumor microenvironment cells, and upregulation of immune checkpoint gene expression in the high-risk group. Finally, through cluster analysis, we identified tumor subtypes, and the results of cluster analysis were essentially consistent with the analysis between risk groups. The prognostic NGRlncRNAs and NRGs identified in our study serve as prognostic indicators and potential therapeutic targets for COAD, providing a theoretical basis for the clinical diagnosis and treatment of COAD and offering guidance for further research. [ABSTRACT FROM AUTHOR]

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. • The different neurodegenerative diseases model by using iPSCs approach such as AD, PD, MS and psychiatric disorders. • Treatment of AD by using iPSCs-based regenerative medicine. • The potential of iPSC- MNs as a new path for clarifying mechanisms of ALS disease. • The important role of autophagy in stem cell. [ABSTRACT FROM AUTHOR]

Objective To study the effect of MIF in colon cancer exosomes on TGF-β1 expression in liver Kupffer cells and the intervention effect of Jianpi Xiaoai Fang (Spleen-invigorating Cancer-eliminating Formula, JPXAF) at cellular level. Methods Liver Kupffer cells were treated with exosomes of colon cancer cells; and TGF-β1 mRNA expression in liver Kupffer cells was detected by using RT-PCR. After the MIF gene expression of CT26 cells was knocked down with siRNA interference technique, the exosomes were used in the treatment of Kupffer cells; and the TGF-β1 expression level of Kupffer cells was evaluated with RT-PCR and ELISA. The expressions of MIF in CT26 cells and their exosomes were measured with RT-PCR and WR after intervention with serum containing low-, mid- and high-dose JPXAF; and TGF-β1 expression in Kupffer cells was measured by using RT-PCR and ELISA after CT26 cell exosomes were treated with serum containing JPXAF. Results TGF-β1 mRNA expression in mouse Kupffer cells was increased after CT26 exosome intervention (P < 0.05%. After knockdown of MIF gene expression in CT26 cells, the up-regulation of exosomes on TGF-β1 in Kupffer cells was weakened (P < 0.05%. 20% of the serum containing JPXAF decreased the expressions of MIF in CT26 cells and their exosomes (P < 0.05%, and reduced the up-regulation of CT26 exosomes on TGF-β1 expressions in Kupffer cells (P < 0.05%. Conclusion Exosomes of colon cancer cells could up-regulate TGF-β1 expression in liver Kupffer cells by MIF. The serum containing JPXAF could reduce the expression of TGF-β1 in liver Kupffer cells by inhibiting the expression of MIF in exosomes of colon cancer cells. [ABSTRACT FROM AUTHOR]

• LPS induced depression is accompanied with decline in the numbers of DG-PVIs. • CUMS induced depression is occurring with decrease in PVIs numbers in the vHPC. • Ablation of PVIs from the vDG induced depression-like behavior. • Removal vDG-PVIs induced depression potentially associated with neuroinflammation. 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. [ABSTRACT FROM AUTHOR]

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. • Fluoxetine and 7,8-DHF treatment might be mediated by BDNF/ TrkB and PI3K/Akt/mTOR signaling pathways. • ANA-12 can act as a therapeutic agent for patients having an increased level of BDNF-TrkB. • Fluoxetine and 7,8-DHF improve the behavioral function during the perimenopausal period. • The combined therapy could attenuate the inhibition of NeuN and Iba-1 expression in the hippocampus. [ABSTRACT FROM AUTHOR]

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-β) signaling pathway. Activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is transferred into nucleus to upregulate TGF-β-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-β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]