WenQing Yang
Anna University, Microbiology, Graduate Student
Autophagy is closely associated with atherosclerosis and other cardiovascular diseases (CVD). Compound Danshen prescription is widely used as a clinical antiatherosclerotic drug. In our previous studies, we have shown that the combined... more
Autophagy is closely associated with atherosclerosis and other cardiovascular diseases (CVD). Compound Danshen prescription is widely used as a clinical antiatherosclerotic drug. In our previous studies, we have shown that the combined active component, ginsenoside Rg1-notoginsenoside R1-protocatechualdehyde (RRP), can effectively alleviate endothelial dysfunction and reduce atherosclerotic plaques. However, the association between cellular senescence, caused by reduced autophagy, and atherosclerosis remains unclear. In this study, we investigated whether RRP can enhance autophagy and alleviate cell senescence through the AMPK pathway. Our results showed that RRP reduced the secretion of inflammatory factors in the serum of atherosclerotic mice, enhanced autophagy, and alleviated aortic aging in mice, thus reducing atherosclerotic plaques. In human aortic endothelial cells (HAECs), RRP effectively enhanced autophagy and inhibited senescence by activating the AMPK pathway. When AMPKα...
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Glioma is an aggressive tumor, currently there is no satisfactory management available. Psoralen, as a natural product, has been found to have an effect of treating cancer in recent years, but its effect on glioma has not been explored.... more
Glioma is an aggressive tumor, currently there is no satisfactory management available. Psoralen, as a natural product, has been found to have an effect of treating cancer in recent years, but its effect on glioma has not been explored. In this study, we investigated the in vitro inhibition effect and potential targets of psoralen on glioma through network pharmacology and in vitro glioma treatment experiments. First, we used network pharmacology to preliminarily predict the 21 core genes of psoralen in the treatment of glioma, including PIK3CA, PIK3CB, PIK3CG, and JAK2. The CCK-8 method was used to detect the effect of psoralen on the proliferation of glioma U87 and U251 cells, and the results showed that psoralen could significantly inhibit the proliferation of U87 and U251 cells. The flow cytometry was used to detect the apoptosis and cell cycle changes, and it was found that psoralen could significantly promote the early apoptosis of U87 and U251 cells and had a significant cycl...
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Vascular endothelial injury is the initial stage of atherosclerosis (AS). Stimulating and activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway can regulate the expression of vascular endothelial... more
Vascular endothelial injury is the initial stage of atherosclerosis (AS). Stimulating and activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway can regulate the expression of vascular endothelial cytokines, thus affecting the occurrence and development of AS. In addition, the PI3K/Akt signaling pathway can regulate the polarization and survival of macrophages and the expression of inflammatory factors and platelet function, thus influencing the progression of AS. In recent years, traditional Chinese medicine (TCM) has been widely recognized for its advantages of fewer side effects, multiple pathways, and multiple targets. Also, the research of TCM regulation of AS via the PI3K/Akt signaling pathway has achieved certain results. This study aimed to analyze the characteristics of the PI3K/Akt signaling pathway and its role in the pathogenesis of AS, as well as the role of Chinese medicine in regulating the PI3K/Akt signaling pathway. The findings are...
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Traditional Chinese medicine has shown promising results in treating the symptoms of hypertension, a major global health concern not yet fully managed by modern medicine. It is, therefore, of high priority to clarify the altered... more
Traditional Chinese medicine has shown promising results in treating the symptoms of hypertension, a major global health concern not yet fully managed by modern medicine. It is, therefore, of high priority to clarify the altered pathophysiology of hypertension in individuals with liver Yang hyperactivity syndrome (HLYH) in response to effective treatments to better understand this disorder. The primary aim of this study was to construct a personalized syndrome discriminant system based on data capable of informing management strategies prior to the initiation of antihypertensive therapy or the implementation of screening strategies in at-risk HLYH. Based on the successful replication of HLYH rat models, we extracted the core discriminant factors of the disorder through the integration of physical signs, biochemical indicators, and metabolic markers. Macro and micro information was correlated to construct a syndrome discriminant system. At the macroscopic level, HLYH rat models chara...
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In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we... more
In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold-inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). Our results firstly revealed that hyperthermia significantly attenuated the stemness property of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)-like population. Moreover, hyperthermia substantially improved the sensitivity of radiation-resistant NPC cells and CSC-like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti-tumor-killing activity of hyperthermia against NPC c...
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Background: The Fufang Danshen formula is a clinically important anti-atherosclerotic preparation in traditional Chinese medicine. However, its anti-atherosclerotic effect is not well recognized, and the mechanisms of its combined active... more
Background: The Fufang Danshen formula is a clinically important anti-atherosclerotic preparation in traditional Chinese medicine. However, its anti-atherosclerotic effect is not well recognized, and the mechanisms of its combined active ingredients, namely Ginsenoside Rg1-Notoginsenoside R1-Protocatechuic aldehyde (RRP), remain unclear. The purpose of this study was to investigate the anti-atherosclerotic effects and potential mechanism of RRP in ApoE−/− mice and in low-shear stress-injured vascular endothelial cells.Methods: ApoE−/− mice were randomly divided into three groups: model group, rosuvastatin group, and RRP group, with C57BL/6J mice as the control group. Oil-red O, hematoxylin and eosin, Masson, and Movat staining were utilized for the observation of aortic plaque. Changes in the blood lipid indexes were observed with an automatic biochemistry analyzer. ET-1, eNOS, TXA2, and PGI2 levels were analyzed by enzyme-linked immunosorbent assay. In vitro, a fluid shear stress s...
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Purpose: Although platinum compounds are the first-line treatment for ovarian cancer, the majority of patients relapse and develop resistance to treatment. However, the mechanism underlying resistance is unclear. The goal of our study is... more
Purpose: Although platinum compounds are the first-line treatment for ovarian cancer, the majority of patients relapse and develop resistance to treatment. However, the mechanism underlying resistance is unclear. The goal of our study is to decipher the mechanism by which a metabolic kinase, diacylglycerol kinase alpha (DGKA), confers platinum resistance in ovarian cancer. Experimental Design: Metabolic kinase RNAi synthetic lethal screening was used to identify a cisplatin resistance driver in ovarian cancer. DGKA variants were used to demonstrate the need for DGKA activity in cisplatin resistance. Phospho-proteomic and genomic screens were performed to identify downstream effectors of DGKA. Therapeutic efficacy of targeting DGKA was confirmed and clinical relevance of DGKA signaling was validated using ovarian cancer patient-derived tumors that had different responses to platinum-based therapy. Results: We found that platinum resistance was mediated by DGKA and its product, phosph...
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Essential hypertension (EH) is a prevalent chronic medical condition and a major risk factor for cardiovascular morbidity and mortality.
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The present study aimed to investigate the intervention mechanisms of Rhizoma Coptidis using spontaneously hypertensive rats. A serum metabolomics analysis was performed with high performance liquid chromatography‑quadrupole/time of... more
The present study aimed to investigate the intervention mechanisms of Rhizoma Coptidis using spontaneously hypertensive rats. A serum metabolomics analysis was performed with high performance liquid chromatography‑quadrupole/time of flight mass spectrometer in positive mode. The obtained data were further analyzed by principal component and partial least‑squares discriminant analysis to reveal differentiating metabolites. The pattern of metabolites in the serum after Rhizoma Coptidis exhibited distinct alterations. A total of 10 potential biomarkers were significantly altered in the serum and may be associated with the underlying mechanism. Alterations were primarily associated with phospholipid metabolism, fatty acid metabolism, amino acid metabolism and arachidonic acid metabolism. In addition, biochemical alterations in potential biomarkers were associated with inflammation, nitric oxide production, platelet aggregation and endothelial function. By analyzing and verifying the spec...
Research Interests: Pharmacology, Principal Component Analysis, Mass Spectrometry, Biomarkers, Metabolomics, and 15 morePhospholipids, Inflammation, Medicine, Multivariate Analysis, Traditional Chinese Medicine, Discriminant Analysis, Hypertension, Endothelial Cells, Fatty acids, Blood Pressure, Nitric oxide, Animals, Lipid metabolism, High Pressure Liquid Chromatography, and Fatty acid metabolism
The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS)... more
The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs. Combined treatment with RTA and sinapine thiocyanate was demonstrated to reduce, to a varying extent,...
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Gene transcription is a central tenet of biology, traditionally measured by RT-PCR, microarray, or more recently, RNA sequencing. However, these measurements only provide a snapshot of the state of gene transcription and only represent an... more
Gene transcription is a central tenet of biology, traditionally measured by RT-PCR, microarray, or more recently, RNA sequencing. However, these measurements only provide a snapshot of the state of gene transcription and only represent an overall readout of complex transcriptional networks that regulate gene expression. In this report, we describe a novel strategy to dissect endogenous gene transcription regulation in live cells by knocking in a reporter gene, EGFP, under the control of the endogenous gene promoter, using the ARID1A gene as an example. The ARID1A gene, encoding a subunit of the ATP-dependent chromatin remodeling complex SNF/SWI, has recently been identified as a tumor suppressor in multiple cancers. Despite studies that elucidate the mechanism of ARID1A's tumor suppressor function, little is known of the genes/events that regulate ARID1A expression. Using the HEK293 cells as a model, we discovered novel aspects of ARID1A transcription regulation in response to c...
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Endothelial dysfunction and low-grade inflammation are closely associated with hypertension and other cardiovascular diseases. The combination of Uncaria (U) and Semen Raphani (R) is common in traditional Chinese medicine for the... more
Endothelial dysfunction and low-grade inflammation are closely associated with hypertension and other cardiovascular diseases. The combination of Uncaria (U) and Semen Raphani (R) is common in traditional Chinese medicine for the treatment of hypertension and heart diseases. We aimed to investigate the therapeutic effect of the combination of Uncaria and Semen Raphani on spontaneously hypertensive rats (SHRs), and valsartan was used as a positive control. In the present study, all extracts decreased systolic pressure, diastolic pressure, and mean arterial pressure. U alone showed antihypertensive efficacy and effectively decreased CECs count, while R alone showed efficacy in relieving inflammatory level. The combination of U and R showed enhanced effectiveness at lowering activated CECs and improving endothelial integrity of thoracic aorta and mesenteric artery and normalized the level of plasma biomarkers of endothelial damage. The combination of U and R decreased the mRNA level of...
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The aim of the present study was to investigate the ultrastructural damage and the expression of heat shock protein 70 (HSP70) in the rat adenohypophysis following pulsed electromagnetic wave (PEMW) exposure. The rats were randomly... more
The aim of the present study was to investigate the ultrastructural damage and the expression of heat shock protein 70 (HSP70) in the rat adenohypophysis following pulsed electromagnetic wave (PEMW) exposure. The rats were randomly divided into four groups: Sham PEMW exposure, 1x104 pulses of PEMW exposure, 1x105 pulses of PEMW exposure and 3x105 pulses of PEMW exposure. Whole body radiation of 1x104 pulses, 1x105 pulses and 3x105 pulses of PEMW were delivered with a field strength of 100 kV/m. The rats in each group (n=6 in each) were sacrificed 12, 24, 48 and 96 h after PEMW exposure. Transmission electron microscopy was then used to detect the ultrastructural changes and immunocytochemistry was used to examine the expression of HSP70. Cellular damage, including mitochondrial vacuolation occurred as early as 12 h after PEMW exposure.More severe cellular damages, including cell degeneration and necrosis, occurred 24 and 48 h after PEMW exposure. The PEMW‑induced cellular damage inc...
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Purpose: The graft versus leukemia effect by natural killer (NK) cells prevents relapse following hematopoietic stem cell transplantation. We determined whether a novel bispecific killer cell engager (BiKE) signaling through CD16 and... more
Purpose: The graft versus leukemia effect by natural killer (NK) cells prevents relapse following hematopoietic stem cell transplantation. We determined whether a novel bispecific killer cell engager (BiKE) signaling through CD16 and targeting CD33 could activate NK cells at high potency against acute myelogenous leukemia (AML) targets.Experimental Design: We investigated the ability of our fully humanized CD16 × CD33 (CD16 × 33) BiKE to trigger in vitro NK cell activation against HL60 (CD33+), RAJI (CD33−), and primary AML targets (de novo and refractory) to determine whether treatment with CD16 × 33 BiKE in combination with an ADAM17 inhibitor could prevent CD16 shedding (a novel inhibitory mechanism induced by NK cell activation) and overcome inhibition of class I MHC recognizing inhibitory receptors.Results: NK cell cytotoxicity and cytokine release were specifically triggered by the CD16 × 33 BiKE when cells were cultured with HL60 targets, CD33+de novo and refractory AML targe...
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Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells in culture. The purpose of this study was to determine if there was efficacy or toxicities of this oncolytic... more
Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells in culture. The purpose of this study was to determine if there was efficacy or toxicities of this oncolytic virus against experimental models of human malignant gliomas in vitro, in vivo, and ex vivo in malignant glioma specimens. In vitro, the majority of glioma cell lines tested (7 of 8, 87.5%) were fully permissive for myxoma virus replication and killed by infection. In vivo, intracerebral (i.c.) myxoma virus inoculation was well tolerated and produced only minimal focal inflammatory changes at the site of viral inoculation. U87 and U251 orthotopic xenograft models were used to assess myxoma virus efficacy in vivo. A single intratumoral injection of myxoma virus dramatically prolonged median survival compared with treatment with UV-inactivated myxoma virus. Median survival was not reached in myxoma virus-treated groups versus 47.3 days (U87; P = 0.0002) a...
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Purpose—The graft versus leukemia (GVL) effect by Natural Killer (NK) cells prevents relapse following hematopoietic stem cell transplantation. We determined whether a novel bi-specific killer cell engager (BiKE) signaling through CD16... more
Purpose—The graft versus leukemia (GVL) effect by Natural Killer (NK) cells prevents relapse following hematopoietic stem cell transplantation. We determined whether a novel bi-specific killer cell engager (BiKE) signaling through CD16 and targeting CD33 could activate NK cells at high potency against AML targets. Experimental Design—We investigated the ability of our fully humanized CD16x33 BiKE to trigger in vitro NK cell activation against HL60 (CD33 +), RAJI (CD33 −), and primary AML targets (de novo, refractory and post transplant) to determine whether treatment with CD16x33 BiKE in combination with an ADAM17 inhibitor could prevent CD16 shedding (a novel inhibitory mechanism induced by NK cell activation) and overcome inhibition of class I MHC recognizing inhibitory receptors. Results—NK cell cytotoxicity and cytokine release were specifically triggered by the CD16x33 BiKE when cells were cultured with HL60 targets, CD33 + de novo and refractory AML targets. Combination treatment with CD16x33 BiKE and ADAM17 inhibitor resulted in inhibition of CD16 shedding in NK cells, and enhanced NK cell activation. Treatment of NK cells from double umbilical cord blood transplant (UCBT) recipients with the CD16x33 BiKE resulted in activation, especially in those recipients with CMV reactivation.