Junxia Ruan, Xiuping Zhang, Shaobo Yao+4 more · 2021 · Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology · added 2026-04-24
Objective To investigate the mechanism underlying the immunosuppressive effect and its reverse of γδ1 T cells derived from breast cancer tissues by inducing immunosenescence. Methods After γδ1 T cells Show more
Objective To investigate the mechanism underlying the immunosuppressive effect and its reverse of γδ1 T cells derived from breast cancer tissues by inducing immunosenescence. Methods After γδ1 T cells isolated from breast cancer tissues were co-cultured with peripheral blood-derived naive CD4 Show less
Ming Yi, Lin-Jie Zhang, Xiao-Jiao Liu+6 more · 2021 · Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · Elsevier · added 2026-04-24
This study aims to explore the serum levels of IL-27 and the percentages of IL-27-producing cells in MG patients with positive acetylcholine receptor antibody (AChR-MG). A total of 17 AChR-MG patients Show more
This study aims to explore the serum levels of IL-27 and the percentages of IL-27-producing cells in MG patients with positive acetylcholine receptor antibody (AChR-MG). A total of 17 AChR-MG patients and 22 sex- and age- matched healthy controls (HCs) were recruited. Serum IL-27 levels were determined by enzyme linked immunosorbent assay. The percentages of IL-27 Serum IL-27 levels in AChR-MG were significantly higher than those in HCs (13.44 ± 0.89 vs 7.14 ± 0.75 pg/mL, P < 0.0001), and were decreased after intravenous immunoglobulin (IVIG) treatment (P = 0.004). Moreover, the frequencies of IL-27 IL-27 may play an important role in the pathological process in AChR-MG patients, and the frequencies of IL-27-producing (CD3 Show less
Physiological modulation of melanocortin-4 receptor (MC4R) signaling by MRAP2 proteins plays an indispensable role in appetite control and energy homeostasis in the central nervous system. Great inter Show more
Physiological modulation of melanocortin-4 receptor (MC4R) signaling by MRAP2 proteins plays an indispensable role in appetite control and energy homeostasis in the central nervous system. Great interspecies differences of the interaction and regulation of melanocortin receptors by MRAP protein family have been reported in several diploid vertebrates but never been investigated in the tetrapod amphibian Xenopus laevis. Here, we performed phylogenetic and synteny-based analyses to explore the evolutionary aspects of dual copies of X. laevis MC4R (xlMC4R) and MRAP2 (xlMRAP2) proteins. Our data showed that xlMRAPs directly interacted with xlMC4Rs on the cell surface as a functional antiparallel dimeric topology and pharmacological studies suggested a homology specific regulatory pattern of the melanocortin system in X. laevis. Show less
Patients with non-small cell lung cancer (NSCLC) initially responding to tyrosine kinase inhibitors (TKIs) eventually develop resistance due to accumulating mutations in the EGFR and additional lesser Show more
Patients with non-small cell lung cancer (NSCLC) initially responding to tyrosine kinase inhibitors (TKIs) eventually develop resistance due to accumulating mutations in the EGFR and additional lesser investigated mechanisms such as the participation of the tumor microenvironment (TME). Here, we examined the potential for MET inhibitor capmatinib for the treatment of osimertinib-resistant NSCLCs and normalizing the TME. We first established that HCC827 and H1975 cells showed increased resistance against osimertinib when co-cultured with CAFs isolated from osimertinib-resistant patients. Additionally, we showed that CAFs promoted epithelial-mesenchymal transition (EMT) and self-renewal ability in both HCC827 and H1975 cells. We subsequently found that both CAF-cultured HCC827 and H1975 showed a significantly higher expression of MET, Akt, Snail and IL-1β, which were associated with survival and inflammatory responses. These cells in turn, promoted the generation of CAFs from normal lung fibroblasts. Subsequently, we observed that the treatment of capmatinib resulted in the re-sensitization of CAF-co-cultured H1975 and HCC827 to osimertinib, in association with reduced EMT and self-renewal ability. MET-silencing experiment using siRNA supported the observations made with capmatinib while with a greater magnitude. MET-silenced cell exhibited a severely hindered expression of inflammatory markers, IL-1β and NF-κB; EMT markers, Snail and Vimentin, while increased E-cadherin. Finally, we demonstrated that the combination of capmatinib and osimertinib led to an increased tumor inhibition and significantly lower number of CAFs within the patient derived xenograft (PDX) model. Taken together, our findings suggested that an increased MET/Akt/Snail signaling was induced between the NSCLC cells and their TME (CAFs), resulting in osimertinib resistance. Suppression of this pathway by capmatinib may bypass the EGFR activating mutation and overcomes osimertinib resistance by targeting both tumor cells and CAFs. Show less
Traumatic brain injury (TBI) is a highly lethal event with a poor prognosis. Recovering residual neuronal function in the intermediate stage of TBI is important for treatment; however, neuroinflammati Show more
Traumatic brain injury (TBI) is a highly lethal event with a poor prognosis. Recovering residual neuronal function in the intermediate stage of TBI is important for treatment; however, neuroinflammation and neuronal apoptosis impede residual neuronal repair processes. Considering that hyperglycemia influences inflammatory processes and neuronal survival, we examined the effects of high glucose on neuroinflammation and neuronal death during the intermediate phase of TBI. Rat models of type 2 diabetes mellitus and/or TBI were developed and behaviorally assessed. Neurological function and cognitive abilities were impaired in TBI rats and worsened by type 2 diabetes mellitus. Histopathological staining and analyses of serum and hippocampal mRNA and protein levels indicated that neuroinflammation and apoptosis were induced in TBI rats and exacerbated by hyperglycemia. Hyperglycemia inhibited hippocampal mitogen-activated protein kinase kinase 5 (MEK5) phosphorylation in TBI rats. Show less
Immune disorders play an important role in the pathogenesis of Crohn's disease (CD). Notably, the increased immune response of Th1 cells and related cytokines is associated with the onset of CD. IL-27 Show more
Immune disorders play an important role in the pathogenesis of Crohn's disease (CD). Notably, the increased immune response of Th1 cells and related cytokines is associated with the onset of CD. IL-27 is a newly discovered IL-12-related cytokine, but its expression and clinical significance in CD patients are still controversial. This study is aimed at evaluating the serum levels of IL-27 in CD patients and analyzing their clinical significance. The results indicated that serum levels of IL-27 in CD patients were significantly higher than those in control subjects (median (interquartile range (IQR)): 110.0 (95.0, 145.0) vs. 85.0 (80.0, 95.0) pg/ml, Show less
Cardiovascular diseases (CVDs) are seriously threatening to human life and health. Polyunsaturated fatty acids (PUFAs) are known for their role in preventing CVDs. It is beneficial to population healt Show more
Cardiovascular diseases (CVDs) are seriously threatening to human life and health. Polyunsaturated fatty acids (PUFAs) are known for their role in preventing CVDs. It is beneficial to population health to promote the content of PUFAs in bovine milk. In recent years, limited research based on molecular mechanisms has focused on this field. The biological roles of numerous microRNAs (miRNAs) remain unknown. In this study, a promising and negatively correlated pair of the miRNA (miRNA-193a-5p) and a fatty acid desaturase 1 ( Show less
Sleeve gastrectomy (SG) is the most widely used bariatric procedures globally, which could improve glucose and lipid metabolism dramatically. Circular RNAs (circRNAs) are being increasingly implicated Show more
Sleeve gastrectomy (SG) is the most widely used bariatric procedures globally, which could improve glucose and lipid metabolism dramatically. Circular RNAs (circRNAs) are being increasingly implicated in numerous pathophysiological processes. However, for diabetes mellitus (DM), the expression and function of circRNAs remain largely undetermined, in particular, whether circRNAs mediate the amelioration of DM observed after SG. Using a diabetic rat model, we subjected liver tissue from SG and sham-operated rats to RNA sequencing. Amongst the 103 differentially regulated circRNAs identified in diabetic rats after SG, we focused on circDOCK7, a highly expressed circRNA derived from the back-splicing of the DOCK7 gene. Silencing of circDOCK7 significantly inhibited cellular proliferation and induction of apoptosis in insulin-resistant rat hepatocytes. Further analysis indicated circDOCK7 harbored binding sites for miR-139-3p and regulated the expression of minichromosome maintenance 3 (MCM3) through sequestration of miR-139-3p. Our findings therefore demonstrate a novel regulatory pathway involving circDOCK7 that regulates cellular proliferation and apoptosis through increasing the expression of MCM3. Overall, our study establishes a list of specific circRNAs expressed in diabetic rat liver after SG including circDOCK7 which serve as potential biomarkers and treatment targets for DM patients. Show less
Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurre Show more
Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m Show less
Vitamin E (VE) is an essential fat-soluble nutrient for dairy cows. Vitamin E deficiency leads to immune suppression and oxidative stress and increases the susceptibility of cows to reproductive disor Show more
Vitamin E (VE) is an essential fat-soluble nutrient for dairy cows. Vitamin E deficiency leads to immune suppression and oxidative stress and increases the susceptibility of cows to reproductive disorders in the early post-partum period. However, studies on plasma proteomics of VE deficiency have not been reported so far. Therefore, the purpose of this study was to understand the changes of blood protein profile in cows with subclinical VE deficiency in the early post-partum period. In this study, plasma protein levels of 14 healthy cows (>4 μg/ml α-tocopherol) and 13 subclinical VE-deficient cows (2-3 μg/ml α-tocopherol) were analyzed by tandem mass tag (TMT). The results showed that there were 26 differentially expressed proteins (DEPs) in the plasma of cows with subclinical VE deficiency compared with healthy controls. Twenty-one kinds of proteins were downregulated, and five kinds were upregulated, among which eight proteins in protein-protein interactions (PPI) network had direct interaction. These proteins are mainly involved in the MAPK signaling pathway, pantothenic acid and coenzyme A (CoA) biosynthesis, PPAR signaling pathway, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The top four DEPs in PPI (APOC3, APOC4, SAA4, PHLD) and one important protein (VNN1) by literature review were further verified by ELISA and Western blot. The expression levels of APOC3, VNN1, and SAA4 were significantly lower than those of healthy controls by ELISA. VNN1 was significantly lower than those of healthy controls by Western blot. VNN1 is closely related to dairy cow subclinical VE deficiency and can be a potential biomarker. It lays a foundation for further research on the lack of pathological mechanism and antioxidative stress of VE. Show less
Previous genotyping-based assays have identified non-coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of Show more
Previous genotyping-based assays have identified non-coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of coding variants within all IL family genes in leprosy was still limited. To obtain the full mutation spectrum of all ILs in leprosy, we performed a targeted deep sequencing of coding regions of 58 ILs genes in 798 leprosy patients (age 56.2 ± 14.4; female 31.5%) and 990 healthy controls (age 38.1 ± 14.0; female 44.3%) from Yunnan, Southwest China. mRNA expression alterations of ILs in leprosy skin lesions or in response to M. leprae treatment were estimated by using publicly available expression datasets. Two coding variants in IL27 (rs17855750, p.S59A, p = 4.02 × 10 Show less
Ageing-related osteoporosis is becoming an emerging threat to human health along with the ageing of human population. The decreased rate of osteogenic differentiation and bone formation is the major c Show more
Ageing-related osteoporosis is becoming an emerging threat to human health along with the ageing of human population. The decreased rate of osteogenic differentiation and bone formation is the major cause of ageing-related osteoporosis. Microtubule actin cross-linking factor 1 (MACF1) is an important cytoskeletal factor that promotes osteogenic differentiation and bone formation. However, the relationship between MACF1 expression and ageing-related osteoporosis remains unclear. This study has investigated the expression pattern of MACF1 in bone tissues of ageing-related osteoporosis patients and ageing mice. The study has further elucidated the mechanism of MACF1 promoting bone formation by inhibiting HES1 expression and activity. Moreover, the therapeutic effect of MACF1 on ageing-related osteoporosis and post-menopausal osteoporosis was evaluated through in situ injection of the MACF1 overexpression plasmid. The study supplemented the molecular mechanisms between ageing and bone formation, and provided novel targets and potential therapeutic strategy for ageing-related osteoporosis. Show less
Global knockout of the BK channel has been proven to affect bone formation; however, whether it directly affects osteoblast differentiation and the mechanism are elusive. In the current study, we furt Show more
Global knockout of the BK channel has been proven to affect bone formation; however, whether it directly affects osteoblast differentiation and the mechanism are elusive. In the current study, we further investigated the role of BK channels in bone development and explored whether BK channels impacted the differentiation and proliferation of osteoblasts via the canonical Wnt signaling pathway. Our findings demonstrated that knockout of Kcnma1 disrupted the osteogenesis of osteoblasts and inhibited the stabilization of β-catenin. Western blot analysis showed that the protein levels of Axin1 and USP7 increased when Kcnma1 was deficient. Together, this study confirmed that BK ablation decreased bone mass via the Wnt/β-catenin signaling pathway. Our findings also showed that USP7 might have the ability to stabilize the activity of Axin1, which would increase the degradation of β-catenin in osteoblasts. Show less
Preterm birth (PTB) is an immune-inflammatory disease that needs to be resolved. This study aimed to identify the role of interleukin-27 (IL-27), an immunomodulatory factor, in PTB and its associated Show more
Preterm birth (PTB) is an immune-inflammatory disease that needs to be resolved. This study aimed to identify the role of interleukin-27 (IL-27), an immunomodulatory factor, in PTB and its associated mechanisms. Here, we analyzed the high-throughput of samples data from the maternal-fetal interface to the peripheral circulation obtained from public databases and reported that the elevated IL-27 was involved with the onset of PTB. Further bioinformatics analyses (e.g. GeneMANIA and GSEA) revealed that IL-27 overexpression in the peripheral circulation as well as maternal-fetal interface is related to the activation of the immune-inflammatory process represented by IFN-γ signaling, etc. In addition, IL-27 and immune infiltration correlation analysis demonstrated that IL-27 mediates this immune-inflammatory imbalance, plausibly mainly through monocyte-macrophage and neutrophils. This finding was further validated by analyzing additional datasets. Overall, this is the first study to elaborate on the role of IL-27-mediated immuno-inflammation in PTB from the perspective of bioinformatics, which may provide a novel strategy for the prevention and treatment of PTB. Show less
The tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with the occurrence and development of various diseases, including inflammation and cancer. However, the role and mechanis Show more
The tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with the occurrence and development of various diseases, including inflammation and cancer. However, the role and mechanism of TRAP1 in the development of lung cancer need to be further explored. Therefore, the purpose of this study is to investigate the role of TRAP1 in the regulation of apoptosis by cisplatin and its special mechanism. The RT-qPCR and Western blot were used to detect the mRNA and protein expression of ANGPTL4 in A549 and H1299 cells, respectively. And the cell apoptosis and cell cycle were measured by flow cytometry (FCM). The expression of genes related to apoptosis and drug resistance as well as the cell cycle regulators, including MDM2, CyclinB1, and CDK1, were detected by Western blot. Finally, the reactive oxygen species (ROS) indicator DCFH-DA was performed to detect the generation of ROS, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. The results showed that the expression of TRAP1 was significantly increased in A549/DDP and H1299/DDP than A549 and H1299 cells. Further research found that knockdown of TRAP1 induced apoptosis and caused G2/M cell cycle arrest in A549/DDP and H1299/DDP cells. What is more, siTRAP1 reduced the relative JC-1 polymer monomer fluorescence ratio and decreased the ΔΨm, up-regulated the expression of Cytochrome C. Importantly, siTRAP1 induces ROS-dependent mitochondrial dysfunction. It is suggested that that TRAP1 suppresses cisplatin-induced apoptosis by promoting ROS-dependent mitochondrial dysfunction. Show less
Dingxin Recipe (DXR) is a traditional Chinese medicine formula that has been reported to be effective and safe treatment for cardiovascular diseases, such as arrhythmias, coronary heart disease. Dingx Show more
Dingxin Recipe (DXR) is a traditional Chinese medicine formula that has been reported to be effective and safe treatment for cardiovascular diseases, such as arrhythmias, coronary heart disease. Dingxin Recipe IV (DXR IV) was further improved from the DXR according to the traditional use. However, the mechanism of DXR IV in atherosclerosis is unclear. This study aimed to illustrate whether DXR IV improve atherosclerosis through modulating the lipid metabolism and gut microbiota in atherosclerosis mice. 40 male ApoE DXR IV exerted the anti-atherosclerosis effect by inhibiting the excessive cholesterol deposition in aorta and regulating the level of TG, TC, LDL-C and HDL-C. The composition of gut microbiota was changed. Interestingly, the relative abundance of Muribaculaceae and Ruminococcaceae increased after DXR IV administration, whereas the abundance of Erysipelotrichaceae decreased, which have been beneficial to lipid metabolism. Nine potential metabolic biomarkers, including acetate, butyrate, propionate, alanine, succinate, valerate, xylose, choline, glutamate, were identified, which were related to fatty acid metabolism. Further, the pathway of fatty acid was detected by the RT-qPCR and western blotting. Compared with model group, the level of LXR-α and SREBP1 decreased significantly in DXR IV group while LXR-β, SREBP2 showed no statistical significance. It indicated that DXR IV modulated lipid metabolism by LXR-α/SREBP1 but not LXRβ and SREBP2. DXR IV exhibits potential anti-atherosclerosis effect, which is closely related to lipid metabolism and the gut microbiota. This study may provide novel insights into the mechanism of DXR IV on atherosclerosis and a basis for promising clinical usage. Show less
Atrial fibrillation (AF) is the more significant portion of arrhythmia in clinical practice, with inflammation and fibrosis as its central pathological mechanisms. This study aimed to investigate angi Show more
Atrial fibrillation (AF) is the more significant portion of arrhythmia in clinical practice, with inflammation and fibrosis as its central pathological mechanisms. This study aimed to investigate angiopoietin-like 4 (ANGPTL4) effects on angiotensin II- (Ang II-) induced AF and its related pathophysiological mechanisms. C57BL/6J mice were randomized and divided into three groups: the control group, the Ang II group, and the ANGPTL4 group (Ang II with ANGPTL4 treatment). Mice were infused with Ang II (2000 ng/kg/min) and were administrated with recombinant human ANGPTL4 (rhANGPTL4, 20 Show less
RNA editing is a feature of RNA maturation resulting in the formation of transcripts whose sequence differs from the genome template. Brain RNA editing may be altered in Alzheimer's disease (AD). Here Show more
RNA editing is a feature of RNA maturation resulting in the formation of transcripts whose sequence differs from the genome template. Brain RNA editing may be altered in Alzheimer's disease (AD). Here, we analyzed data from 1,865 brain samples covering 9 brain regions from 1,074 unrelated subjects on a transcriptome-wide scale to identify inter-regional differences in RNA editing. We expand the list of known brain editing events by identifying 58,761 previously unreported events. We note that only a small proportion of these editing events are found at the protein level in our proteome-wide validation effort. We also identified the occurrence of editing events associated with AD dementia, neuropathological measures and longitudinal cognitive decline in: SYT11, MCUR1, SOD2, ORAI2, HSDL2, PFKP, and GPRC5B. Thus, we present an extended reference set of brain RNA editing events, identify a subset that are found to be expressed at the protein level, and extend the narrative of transcriptomic perturbation in AD to RNA editing. Show less
Age-related macular degeneration (AMD) is a common cause of vision loss. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, accompanied by oxidative damage, plays a Show more
Age-related macular degeneration (AMD) is a common cause of vision loss. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, accompanied by oxidative damage, plays a crucial role in AMD. It is well known that manganese superoxide dismutase (MnSOD) encoded by SOD2 is a critical molecule in fighting against oxidative stress, and Snail encoded by SNAI1 is the essential transcription factor for EMT. However, the effect of MnSOD on EMT and the underlying mechanism in RPE cells remains unknown. In this study, we found that MnSOD knockdown triggered the EMT by upregulating Snail, while MnSOD overexpression reversed EMT even with TGFβ treatment in RPE cells, and the anti-oxidative stress activity of MnSOD mediated this observation. In addition, Snail depletion increased both expression and activity of MnSOD while Snail overexpression decreased MnSOD expression and activity, and Dual-luciferase reporter and ChIP assays showed that Snail directly bound to E-box (CACCTG) in the SOD2 promoter. Moreover, MnSOD over-expression and Snail interference co-treatment strengthened the anti-oxidation and EMT reversing. Therefore, our findings demonstrate that MnSOD prevents EMT of RPE cells in AMD through inhibiting oxidative injury to RPE. Moreover, a critical EMT transcription factor, Snail, functions as a new negative transcriptional factor of SOD2. Herein, the Snail-MnSOD axis forms a mutual loop in the development of AMD, which may be a novel systemic treatment target for preventing AMD. Show less
Poly(ADP-ribose) polymerase 1 (PARP1) has a major regulatory role in cardiovascular disease. However, inhibiting PARP1 activity does not significantly improve clinical outcomes of cardiovascular disea Show more
Poly(ADP-ribose) polymerase 1 (PARP1) has a major regulatory role in cardiovascular disease. However, inhibiting PARP1 activity does not significantly improve clinical outcomes of cardiovascular disease, which suggests that the regulatory mechanism of PARP1 in cardiovascular disease is unclear. Here, we focused on deacetylation regulatory mechanisms of PARP1 and crosstalk of PARP1 post-translational modifications. We uncovered the crucial molecular interactions and protein modifications of deacetylase Sirtuin 2 (SIRT2) and PARP1 in vascular damage. The results showed that SIRT2 was involved in this process and oxidative stress damage factor PARP1 was a novel physiological substrate of SIRT2. SIRT2 interacted with PARP1 at the PARP-A-helical domain and deacetylated the K249 residue of PARP1. Furthermore, SIRT2 promoted ubiquitination of the K249 residue of PARP1 via mobilization of the E3 ubiquitin ligase WW domain-containing protein 2 (WWP2), which led to proteasome-mediated degradation of PARP1. Knockout of SIRT2 in mice and cells increased PARP1 acetylation and decreased PARP1 ubiquitination, which in turn aggravated oxidative stress-induced vascular injury and remodeling. Conversely, overexpression of SIRT2 in mice and cells decreased PARP1 acetylation, increased PARP1 ubiquitination, and relieved oxidative stress-induced vascular injury and remodeling. Overall, this study revealed a previously unrecognized mechanistic link between SIRT2 and PARP1 in the regulation of oxidative stress-induced vascular injury. Show less
Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer Show more
Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro. Show less
Currently, a comprehensive method for exploration of transcriptional regulation has not been well established. We explored a novel pipeline to analyze transcriptional regulation using co-analysis of R Show more
Currently, a comprehensive method for exploration of transcriptional regulation has not been well established. We explored a novel pipeline to analyze transcriptional regulation using co-analysis of RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq). The G protein-coupled receptors (GPCRs) possibly associated with macrophages were further filtered using a reduced-Cox regression model. ATAC-seq profiles were used to map the chromatin accessibility of the GPRC5B promoter region. Pearson analysis was performed to identify the transcription factor (TF) whose expression was correlated with open chromatin regions of GPRC5B promoter. ChIP-seq profiles were obtained to confirm the physical binding of GATA4 and its predicted binding regions. For verification, quantitative polymerase chain reaction (qPCR) and multidimensional database validations were performed. The reduced-Cox regression model revealed the prognostic value of GPRC5B. A novel pipeline for TF exploration was proposed. With our novel pipeline, we first identified chr16:19884686-19885185 as a reproducible open chromatin region in the GPRC5B promoter. Thereafter, we confirmed the correlation between GATA4 expression and the accessibility of this region, confirmed its physical binding, and proved GPRC5B, correlated with macrophages, was a key GPCR affecting COAD prognosis. Further, with our novel pipeline, TF GATA4 was identified as a direct upstream of GPRC5B. This study proposed a novel pipeline for TF exploration and provided a theoretical basis for COAD therapy. Show less
Atherosclerosis, as a chronic inflammatory disease within the arterial wall, is a leading cause of morbidity and mortality worldwide due to its role in myocardial infarction, stroke and peripheral art Show more
Atherosclerosis, as a chronic inflammatory disease within the arterial wall, is a leading cause of morbidity and mortality worldwide due to its role in myocardial infarction, stroke and peripheral artery disease. Additional evidence is emerging that the angiopoietin-like (ANGPTL) family of proteins participate in the pathology of this disease process via endothelial dysfunction, inflammation, dyslipidemia, calcification, foam cell formation and platelet activation. This review summarizes current knowledge on the ANGPTL family of proteins in atherosclerosis related pathological processes. Moreover, the potential value of ANGPTL family proteins as predictive biomarkers in atherosclerosis is discussed. Given the attractive role of ANGPTL3, ANGPTL4, ANGPTL8 in atherosclerotic dyslipidemia via regulation of lipoprotein lipase (LPL), antisense oligonucleotide or/and monoclonal antibody-based inactivation of these proteins represent potential atherosclerotic therapies. Show less
Increasing evidence has suggested that T helper 17 (Th17) cells play a central role in the pathogenesis of ocular immune disease. The association between pathogenic Th17 cells and the development of u Show more
Increasing evidence has suggested that T helper 17 (Th17) cells play a central role in the pathogenesis of ocular immune disease. The association between pathogenic Th17 cells and the development of uveitis has been confirmed in experimental and clinical studies. Several cytokines affect the initiation and stabilization of the differentiation of Th17 cells. Therefore, understanding the mechanism of related cytokines in the differentiation of Th17 cells is important for exploring the pathogenesis and the potential therapeutic targets of uveitis. This article briefly describes the structures, mechanisms, and targeted drugs of cytokines-including interleukin (IL)-6, transforming growth factor- Show less
Post-synaptic density 93 (PSD-93) mediates glutamate excitotoxicity induced by ischemic brain injury, which then induces microglial inflammatory response. However, the underlying mechanisms of how PSD Show more
Post-synaptic density 93 (PSD-93) mediates glutamate excitotoxicity induced by ischemic brain injury, which then induces microglial inflammatory response. However, the underlying mechanisms of how PSD-93 mediates the crosstalk between neurons and microglia in the post-synaptic dense region remain elusive. CX3 chemokine ligand 1 (CX3CL1) is a chemokine specifically expressed in neurons while its receptor CX3CR1 is highly expressed in microglia. In this study, we examined the interaction of PSD-93 and CX3CL1 in the crosstalk between neurons and microglia in acute ischemic stroke. We utilized male C57BL/6 mice to establish the middle cerebral artery occlusion model (MCAO) and designed a fusion small peptide Tat-CX3CL1 (357-395aa) to inhibit PSD-93 and CX3CL1 interaction. The combination peaks of PSD-93 and CX3CL1 at 6 hr after I/R were observed. The binding sites were located at the 420-535 amino acid sequence of PSD-93 and 357-395 amino acid sequence of CX3CL1. Tat-CX3CL1 (357-395aa) could inhibit the interaction of PSD-93 and CX3CL1 and inhibited the pro-inflammatory cytokine IL-1β and TNF-α expression and provided neuroprotection following reperfusion. Together, these data suggest that PSD-93 binds CX3CL1 to activate microglia and initiate neuroinflammation. Specific blockade of PSD-93-CX3CL1 interaction reduces I/R induced neuronal cell death, and provides a new therapeutic target for ischemic stroke. Show less
Histone deacetylases (HDACs) engage in the regulation of various cellular processes by controlling global gene expression. The dysregulation of HDACs leads to carcinogenesis, making HDACs ideal target Show more
Histone deacetylases (HDACs) engage in the regulation of various cellular processes by controlling global gene expression. The dysregulation of HDACs leads to carcinogenesis, making HDACs ideal targets for cancer therapy. However, the use of HDAC inhibitors (HDACi) as single agents has been shown to have limited success in treating solid tumors in clinical studies. This study aimed to identify a novel downstream effector of HDACs to provide a potential target for combination therapy. Transcriptome sequencing and bioinformatics analysis were performed to screen for genes responsive to HDACi in breast cancer cells. The effects of HDACi on cell viability were detected using the MTT assay. The mRNA and protein levels of genes were determined by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The binding of CREB1 (cAMP-response element binding protein 1) to the promoter of the KDELR (The KDEL (Lys-Asp-Glu-Leu) receptor) gene was validated by the ChIP (chromatin immunoprecipitation assay). The association between KDELR2 and protein of centriole 5 (POC5) was detected by immunoprecipitation. A breast cancer-bearing mouse model was employed to analyze the effect of the HDAC3-KDELR2 axis on tumor growth. KDELR2 was identified as a novel target of HDAC3, and its aberrant expression indicated the poor prognosis of breast cancer patients. We found a strong correlation between the protein expression patterns of HADC3 and KDELR2 in tumor tissues from breast cancer patients. The results of the ChIP assay and qRT-PCR analysis validated that HDAC3 transactivated KDELR2 via CREB1. The HDAC3-KDELR2 axis accelerated the cell cycle progression of cancer cells by protecting the centrosomal protein POC5 from proteasomal degradation. Moreover, the HDAC3-KDELR2 axis promoted breast cancer cell proliferation and tumorigenesis in vitro and in vivo. Our results uncovered a previously unappreciated function of KDELR2 in tumorigenesis, linking a critical Golgi-the endoplasmic reticulum traffic transport protein to HDAC-controlled cell cycle progression on the path of cancer development and thus revealing a potential therapeutical target for breast cancer. Show less