Publications by authors named "Qi Su"

239 Publications

Development of a PCR-based dot blot assay for the detection of fowl adenovirus.

Poult Sci 2021 Oct 20;101(1):101540. Epub 2021 Oct 20.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong 271001, China. Electronic address:

Group-I Fowl adenovirus (FAdV) is still widespread in China's chicken farms, leading to huge economic losses. The traditional PCR method, which can detect all serotypes at the same time, is not sensitive enough to obtain accurate results, especially in some samples containing only a low titer of virus, such as contaminated live vaccine. In order to solve this problem, this study developed a dot blot assay based on the above PCR method. A total of 6 probes targeting the conserved region of FAdV were designed and systematically optimized through sensitivity, accuracy, and stability analyses. Results showed that it is not only suitable for 12 serotypes, but also effectively improve the sensitivity, which increased more than 100 times in comparison with PCR assay. Moreover, this sensitivity was increased 100 times when detecting contaminated live vaccine samples, showing the great prospect of this method in daily monitoring.
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http://dx.doi.org/10.1016/j.psj.2021.101540DOI Listing
October 2021

A stretchable and strain-unperturbed pressure sensor for motion interference-free tactile monitoring on skins.

Sci Adv 2021 Nov 24;7(48):eabi4563. Epub 2021 Nov 24.

Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abi4563DOI Listing
November 2021

Induction of estrogen receptor β-mediated autophagy sensitizes breast cancer cells to TAD1822-7, a novel biphenyl urea taspine derivative.

Mol Biol Rep 2021 Nov 18. Epub 2021 Nov 18.

School of Pharmacy, Health Science Center, Shaanxi Province, Xi'an Jiaotong University, No. 76, Yanta West Street, #54, Xi'an, 710061, People's Republic of China.

Background: Female breast cancer has become the most commonly diagnosed cancer worldwide. As a tumor suppressor, estrogen receptor β (ERβ) can be potentially targeted for breast cancer therapy.

Methods And Results: TAD1822-7 was evaluated for ERβ-mediated autophagy and cell death using cell proliferation assay, Annexin V/PI staining, immunofluorescence, western blotting, ERβ siRNA, ERβ plasmid transfection and hypoxia cell models. TAD1822-7 upregulated ERβ causing cell death and induced mitochondrial dysfunction and autophagy companied with mitochondrial located ERβ. Enhanced levels of microtubule associated protein1 light chain 3 (LC3)-II and p62/SQSTM1 (p62) indicated that TAD1822-7 blocked the late-stage autolysosome formation, leading to cell death. Mechanistically, TAD1822-7-induced cell death was mediated by phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathways. Moreover, TAD1822-7 modulated hypoxia inducible factor (HIF) functions and autophagy via the inhibition of HIF-1β in the context of hypoxia-induced autophagy. ERβ overexpression and ERβ agonist showed similar effects, whereas ERβ siRNA abrogated TAD1822-7-induced cell death, the inhibition of PI3K/AKT pathway and autophagy. The involvement of PI3K/AKT pathway and autophagy was also demonstrated in TAD1822-7-treated hypoxic breast cancer cells.

Conclusions: These findings provide new insight into the mechanism underlying the inhibitory effects of TAD1822-7 via ERβ-mediated pathways in breast cancer cells.
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http://dx.doi.org/10.1007/s11033-021-06950-5DOI Listing
November 2021

Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver.

iScience 2021 Nov 6;24(11):103233. Epub 2021 Oct 6.

Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591, USA.

Nonalcoholic fatty liver disease (NAFLD) is a global health-care problem with limited therapeutic options. To obtain a cellular resolution of pathogenesis, 82,168 single-cell transcriptomes (scRNA-seq) across different NAFLD stages were profiled, identifying hepatocytes and 12 other non-parenchymal cell (NPC) types. scRNA-seq revealed insights into the cellular and molecular mechanisms of the disease. We discovered a dual role for hepatic stellate cells in gene expression regulation and in the potential to trans-differentiate into myofibroblasts. We uncovered distinct expression profiles of Kupffer cells versus monocyte-derived macrophages during NAFLD progression. Kupffer cells showed stronger immune responses, while monocyte-derived macrophages demonstrated a capability for differentiation. Three chimeric NPCs were identified including endothelial-chimeric stellate cells, hepatocyte-chimeric endothelial cells, and endothelial-chimeric Kupffer cells. Our work identified unanticipated aspects of mouse with NAFLD at the single-cell level and advanced the understanding of cellular heterogeneity in NAFLD livers.
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http://dx.doi.org/10.1016/j.isci.2021.103233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560975PMC
November 2021

Sanguinarine impairs lysosomal function and induces ROS-dependent mitophagy and apoptosis in human hepatocellular carcinoma cells.

Arch Pharm Res 2021 Nov 9. Epub 2021 Nov 9.

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No.76, Yanta West Street, #54, Xi'an, 710061, Shaanxi Province, People's Republic of China.

Hepatocellular carcinoma (HCC) is one of the most common tumor types globally. Despite the progress made in surgical procedures and therapeutic options, HCC remains a considerable cause of cancer-related mortality. In this study, we investigated the antitumor effects of sanguinarine (Sang) on HCC and its potential mechanisms. Our findings showed that Sang impairs the acidic environment of lysosomes by inhibiting cathepsin D maturation. In addition, Sang inhibited the formation of autolysosomes in RFP-GFP-LC3 transfected cells, subsequently suppressing late mitophagy. Sang also induced reactive oxygen species (ROS)-dependent autophagy and apoptosis in HCC cells, which was significantly attenuated following treatment with a ROS scavenger. Further investigation using autophagy inhibitors revealed that sanguinarine-induced mitochondrial dysfunction and mitophagy led to mitochondrial apoptosis in HCC cells. Immunohistochemical staining of sanguinarine-treated xenograft samples revealed that it initiated and blocked autophagy. In summary, our findings suggest that in HCC cells, Sang impairs lysosomal function and induces ROS-dependent mitophagy and apoptosis.
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http://dx.doi.org/10.1007/s12272-021-01356-0DOI Listing
November 2021

Semen-Derived Exosomes Mediate Immune Escape and Transmission of Reticuloendotheliosis Virus.

Front Immunol 2021 1;12:735280. Epub 2021 Oct 1.

College of Veterinary Medicine, Shandong Agricultural University, Tai'an City, China.

Reticuloendotheliosis virus (REV) causes immune-suppression disease in poultry, leading to a significant economic burden worldwide. Recent evidence demonstrated that the REV can enter the semen and then induce artificial insemination, but how the virus gets into semen was little known. Accumulating studies indicated that exosomes serve as vehicles for virus transmission, but the role of exosomes in viral shedding through the semen remains unclear. In this study, exosomes purified from the REV-positive semen were shown with reverse transcription-PCR and mass spectrometry to contain viral genomic RNA and viral proteins, which could also establish productive infections both and and escape from the REV-specific neutralizing antibodies. More importantly, compared with the infection caused by free virions, the exosome is more efficient for the virus to ensure effective infection and replication, which can also help the REV compromise the efficacy of the host immune response. In summary, this study demonstrated that semen-derived exosomes can medicate the transmission and immune escape of REV, implicating a novel mechanism for REV entering the semen and leading to vertical transmission.
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http://dx.doi.org/10.3389/fimmu.2021.735280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517439PMC
October 2021

Multimodal obstruction of tumorigenic energy supply via bionic nanocarriers for effective tumor therapy.

Biomaterials 2021 11 9;278:121181. Epub 2021 Oct 9.

Department of Chemical Engineering, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an, 710049, China. Electronic address:

Sufficient energy generation based on effective transport of nutrient via abundant blood vessels in tumor tissue and subsequent oxidative metabolism in mitochondria is critical for growth, proliferation and migration of tumor. Thus the strategy to cut off this transport pathway (blood vessels) and simultaneously close the power house (mitochondria) is highly desired for tumor treatment. Herein, we fabricated a bionic nanocarrier with core-shell-corona structure to give selective and effective tumor therapy via stepwise destruction of existed tumor vessel, inhibition of tumor angiogenesis and dysfunction of tumor mitochondria. The core of this bionic nanocarrier consists of combretastatin A4 phosphate (CA4P) and vitamin K (VK) co-loaded mesoporous silica nanoparticle (MSNs), which is in charge of the vasculature destruction and mitochondrial dysfunction after cargos release. The N-tert-butylacrylamide (TBAM) and tri-sulfated N-acetylglucosamine (TSAG) shell served as artificial affinity reagent against vascular endothelial growth factor (VEGF) for angiogenesis inhibition. As to guarantee that these actions only happened in tumor, the hyaluronic acid (HA) corona was introduced to endow the nanocarrier with tumor targeting property and stimuli-responsiveness for accurate therapy. Both in vitro and in vivo results indicated that the CA4P/VK-MSNs-TBAM/TSAG-HA (CVMH for short) nanocarrier combined well-controllable manipulation of tumor vasculature and tumor mitochondria to effectivly cut off the tumorigenic energy supply, which performed significant inhibition of tumor growth, demonstrating the great candidate of our strategy for effective tumor therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121181DOI Listing
November 2021

Precisely Shaped Self-Adjuvanting Peptide Vaccines with Enhanced Immune Responses for HPV-Associated Cancer Therapy.

ACS Appl Mater Interfaces 2021 Oct 14;13(42):49737-49753. Epub 2021 Oct 14.

Key Laboratory of Functional Polymer Materials, Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, 94 Weijin Road, Tianjin 300071, China.

Peptide vaccines exhibit great potential in cancer therapy via eliciting antigen-specific host immune response and long-term immune memory to defend cancer cells. However, the low induced immune response of many developing vaccines implies the imperatives for understanding the favorable structural features of efficient cancer vaccines. Herein, we report on the two groups of self-adjuvanting peptide vaccines with distinct morphology and investigate the relationship between the morphology of peptide vaccines and the induced immune response. Two nanofibril peptide vaccines were created via co-assembly of a pentapeptide with a central 4-aminoproline residue, with its derivative functionalized with antigen epitopes derived from human papillomavirus E7 proteins, whereas utilization of a pentapeptide with a natural proline residue led to the formation of two nanoparticle peptide vaccines. The immunological results of dendritic cell (DCs) maturation and antigen presentation induced by the peptide assemblies implied the self-adjuvanting property of the resulting peptide vaccines. In particular, cellular uptake studies revealed the enhanced internalization and elongated retention of the nanofibril peptide vaccines in DCs, leading to their advanced performance in DC maturation, accumulation at lymph nodes, infiltration of cytotoxic T lymphocytes into tumor tissues, and eventually lysis of in vivo tumor cells, compared to the nanoparticle counterparts. The antitumor immune response caused by the nanofibril peptide vaccines was further augmented when simultaneously administrated with anti-PD-1 checkpoint blockades, suggesting the opportunity of the combinatorial immunotherapy by utilizing the nanofibril peptide vaccines. Our findings strongly demonstrate a robust relationship between the immune response of peptide vaccines and their morphology, thereby elucidating the critical role of morphological control in the design of efficient peptide vaccines and providing the guidance for the design of efficient peptide vaccines in the future.
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http://dx.doi.org/10.1021/acsami.1c15361DOI Listing
October 2021

The Function of SUMOylation and Its Critical Roles in Cardiovascular Diseases and Potential Clinical Implications.

Int J Mol Sci 2021 Sep 30;22(19). Epub 2021 Sep 30.

Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China.

Cardiovascular disease (CVD) is a common disease caused by many factors, including atherosclerosis, congenital heart disease, heart failure, and ischemic cardiomyopathy. CVD has been regarded as one of the most common diseases and has a severe impact on the life quality of patients. The main features of CVD include high morbidity and mortality, which seriously threaten human health. SUMO proteins covalently conjugate lysine residues with a large number of substrate proteins, and SUMOylation regulates the function of target proteins and participates in cellular activities. Under certain pathological conditions, SUMOylation of proteins related to cardiovascular development and function are greatly changed. Numerous studies have suggested that SUMOylation of substrates plays critical roles in normal cardiovascular development and function. We reviewed the research progress of SUMOylation in cardiovascular development and function, and the regulation of protein SUMOylation may be applied as a potential therapeutic strategy for CVD treatment.
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http://dx.doi.org/10.3390/ijms221910618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509021PMC
September 2021

Hyper-SUMOylation of SMN induced by SENP2 deficiency decreases its stability and leads to spinal muscular atrophy-like pathology.

J Mol Med (Berl) 2021 12 9;99(12):1797-1813. Epub 2021 Oct 9.

Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, 710119, Shaanxi, China.

Spinal muscular atrophy (SMA), a degenerative motor neuron disease and a leading cause of infant mortality, is caused by loss of functional survival motor neuron (SMN) protein due to SMN1 gene mutation. Here, using mouse and cell models for behavioral and histological studies, we found that SENP2 (SUMO/sentrin-specific protease 2)-deficient mice developed a notable SMA-like pathology phenotype with significantly decreased muscle fibers and motor neurons. At the molecular level, SENP2 deficiency in mice did not affect transcription but decreased SMN protein levels by promoting the SUMOylation of SMN. SMN was modified by SUMO2 with the E3 PIAS2α and deconjugated by SENP2. SUMOylation of SMN accelerated its degradation by the ubiquitin-proteasome degradation pathway with the ubiquitin E1 UBA1 (ubiquitin-like modifier activating enzyme 1) and E3 ITCH. SUMOylation of SMN increased its acetylation to inhibit the formation of Cajal bodies (CBs). These results showed that SENP2 deficiency induced hyper-SUMOylation of the SMN protein, which further affected the stability and functions of the SMN protein, eventually leading to the SMA-like phenotype. Thus, we uncovered the important roles for hyper-SUMOylation of SMN induced by SENP2 deficiency in motor neurons and provided a novel targeted therapeutic strategy for SMA. KEY MESSAGES: SENP2 deficiency enhanced the hyper-SUMOylation of SMN and promoted the degradation of SMN by the ubiquitin-proteasome pathway. SUMOylation increased the acetylation of SMN to inhibit CB formation. SENP2 deficiency caused hyper-SUMOylation of SMN protein, which further affected the stability and functions of SMN protein and eventually led to the occurrence of SMA-like pathology.
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http://dx.doi.org/10.1007/s00109-021-02130-xDOI Listing
December 2021

Liquid-liquid phase separation: Orchestrating cell signaling through time and space.

Mol Cell 2021 Oct 6;81(20):4137-4146. Epub 2021 Oct 6.

Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:

Cell signaling is a complex process. The faithful transduction of information into specific cellular actions depends on the synergistic effects of many regulatory molecules, nurtured by their strict spatiotemporal regulation. Over the years, we have gained copious insights into the subcellular architecture supporting this spatiotemporal control, including the roles of membrane-bound organelles and various signaling nanodomains. Recently, liquid-liquid phase separation (LLPS) has been recognized as another potentially ubiquitous framework for organizing signaling molecules with high specificity and precise spatiotemporal control in cells. Here, we review the pervasive role of LLPS in signal transduction, highlighting several key pathways that intersect with LLPS, including examples in which LLPS is controlled by signaling events. We also examine how LLPS orchestrates signaling by compartmentalizing signaling molecules, amplifying signals non-linearly, and moderating signaling dynamics. We focus on the specific molecules that drive LLPS and highlight the known functional and pathological consequences of LLPS in each pathway.
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http://dx.doi.org/10.1016/j.molcel.2021.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541918PMC
October 2021

Selenium sulfide disrupts the PLAGL2/C-MET/STAT3-induced resistance against mitochondrial apoptosis in hepatocellular carcinoma.

Clin Transl Med 2021 09;11(9):e536

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, P. R. China.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Overexpression of pleomorphic adenoma gene like-2 (PLAGL2) is associated with tumorigenesis. However, its function in HCC is unclear, and there are currently no anti-HCC drugs that target PLAGL2. Drug repositioning may facilitate the development of PLAGL2-targeted drug candidates.

Methods: The expression of PLAGL2 in HCC clinical tissue samples and HCC cell lines was analyzed by western blotting. The constructed HCC cell models were used to confirm the underlying function of PLAGL2 as a therapeutic target. Multiple in vitro and in vivo assays were conducted to determine the anti-proliferative and apoptosis-inducing effects of selenium sulfide (SeS ), which is clinically used for the treatment of seborrheic dermatitis and tinea versicolor.

Results: PLAGL2 expression was higher in HCC tumor tissues than in normal adjacent tissues. Its overexpression promoted the resistance of HCC cells of mitochondrial apoptosis through the regulation of the downstream C-MET/STAT3 signaling axis. SeS exerted significant anti-proliferative and apoptosis-inducing effects on HCC cells in a PLAGL2-dependent manner. Mechanistically, SeS suppressed C-MET/STAT3, AKT/mTOR, and MAPK signaling and triggered Bcl-2/Cyto C/Caspase-mediated intrinsic mitochondrial apoptosis both in vitro and in vivo.

Conclusions: Our data reveal an important role of PLAGL2 in apoptosis resistance in HCC and highlight the potential of using SeS as a PLAGL2 inhibitor in patients with HCC.
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http://dx.doi.org/10.1002/ctm2.536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441139PMC
September 2021

Five-in-One: Simultaneous isolation of multiple major liver cell types from livers of normal and NASH mice.

J Cell Mol Med 2021 10 23;25(20):9878-9883. Epub 2021 Sep 23.

Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.

NASH is a chronic liver disease that affects 3%-6% of individuals and requires urgent therapeutic developments. Isolating the key cell types in the liver is a necessary step towards understanding their function and roles in disease pathogenesis. However, traditional isolation methods through gradient centrifugation can only collect one or a few cell types simultaneously and pose technical difficulties when applied to NASH livers. Taking advantage of identified cell surface markers from liver single-cell RNAseq, here we established the combination of gradient centrifugation and antibody-based cell sorting techniques to isolate five key liver cell types (hepatocytes, endothelial cells, stellate cells, macrophages and other immune cells) from a single mouse liver. This method yielded high purity of each cell type from healthy and NASH livers. Our five-in-one protocol simultaneously isolates key liver cell types with high purity under normal and NASH conditions, enabling for systematic and accurate exploratory experiments such as RNA sequencing.
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http://dx.doi.org/10.1111/jcmm.16933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505823PMC
October 2021

Reconsideration of recurrence and metastasis in colorectal cancer.

World J Clin Cases 2021 Aug;9(24):6964-6968

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.

To discuss recurrence patterns and their significance in colorectal cancer. Preexisting medical hypotheses and the clinical phenomena of recurrence in colorectal cancer were evaluated and integrated. Colorectal cancer recurrence/metastasis consists of two types: recurrence from the activation of dormant cancer cells and recurrence from postoperative residual cancer cells. These two recurrences have their own unique mechanisms, biological behaviors, responses to therapy, and prognoses. For type 1 recurrences, surgical resection should be considered. Type 2 recurrences should be managed systematically in addition to surgical resection. The two types of colorectal cancer recurrence should be evaluated and managed separately.
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http://dx.doi.org/10.12998/wjcc.v9.i24.6964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409216PMC
August 2021

The SUMO-specific protease SENP2 plays an essential role in the regulation of Kv7.2 and Kv7.3 potassium channels.

J Biol Chem 2021 10 10;297(4):101183. Epub 2021 Sep 10.

Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, China. Electronic address:

Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2)-deficient mice develop spontaneous seizures in early life because of a marked reduction in M currents, which regulate neuronal membrane excitability. We have previously shown that hyper-SUMOylation of the Kv7.2 and Kv7.3 channels is critically involved in the regulation of the M currents conducted by these potassium voltage-gated channels. Here, we show that hyper-SUMOylation of the Kv7.2 and Kv7.3 proteins reduced binding to the lipid secondary messenger PIP. CaM1 has been shown to be tethered to the Kv7 subunits via hydrophobic motifs in its C termini and implicated in the channel assembly. Mutation of the SUMOylation sites on Kv7.2 and Kv7.3 specifically resulted in decreased binding to CaM1 and enhanced CaM1-mediated assembly of Kv7.2 and Kv7.3, whereas hyper-SUMOylation of Kv7.2 and Kv7.3 inhibited channel assembly. SENP2-deficient mice exhibited increased acetylcholine levels in the brain and the heart tissue because of increases in the vagal tone induced by recurrent seizures. The SENP2-deficient mice develop seizures followed by a period of sinus pauses or atrioventricular conduction blocks. Chronic administration of the parasympathetic blocker atropine or unilateral vagotomy significantly prolonged the life of the SENP2-deficient mice. Furthermore, we showed that retigabine, an M-current opener, reduced the transcription of SUMO-activating enzyme SAE1 and inhibited SUMOylation of the Kv7.2 and Kv7.3 channels, and also prolonged the life of SENP2-deficient mice. Taken together, the previously demonstrated roles of PIP2, CaM1, and retigabine on the regulation of Kv7.2 and Kv7.3 channel function can be explained by their roles in regulating SUMOylation of this critical potassium channel.
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http://dx.doi.org/10.1016/j.jbc.2021.101183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488601PMC
October 2021

Centromere Protein A (CENPA) Regulates Metabolic Reprogramming in the Colon Cancer Cells by Transcriptionally Activating Karyopherin Subunit Alpha 2 (KPNA2).

Am J Pathol 2021 12 8;191(12):2117-2132. Epub 2021 Sep 8.

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address:

The karyopherin α subunit gene (KPNA2), an oncogene, is involved in metabolic reprogramming in cancer. This study aimed to explore the function of KPNα in the growth and glycolysis in colon cancer (CC) cells. Genes from the Oncomine database that were differentially expressed in multiple CC types were screened. Bioinformatics analysis suggested that KPNA2 was highly expressed in CC, and consequently, high expression of KPNA2 was detected in the CC cell lines. Down-regulation of KPNA2 reduced viability and DNA-replication ability, and increased apoptosis of HCT116 and LoVo cells. It also reduced glucose consumption, extracellular acidification rate, and the ATP production in cells. Centromere protein A (CENPA) was confirmed as an upstream transcription activator of KPNA2. There was significant H3K27ac modification in the promoter region of KPNA2. CENPA primarily recruited histone acetyltransferase general control of amino acid synthesis (GCN)-5 to the promoter region of KPNA2 to induce transcription activation. Overexpression of either CENPA or GCN-5 blocked the role of short hairpin KPNα and restored growth and glycolysis in CC cells. To conclude, the findings from this study suggest that CENPA recruits GCN-5 to the promoter region of KPNA2 to induce KPNα activation, which strengthens growth and glycolysis in, and augments the development of, CC.
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http://dx.doi.org/10.1016/j.ajpath.2021.08.010DOI Listing
December 2021

Adversarial parameter defense by multi-step risk minimization.

Neural Netw 2021 Dec 25;144:154-163. Epub 2021 Aug 25.

MOE Key Laboratory of Computational Linguistics, School of EECS, Peking University, Beijing, China; Center for Data Science, Peking University, Beijing, China. Electronic address:

Previous studies demonstrate DNNs' vulnerability to adversarial examples and adversarial training can establish a defense to adversarial examples. In addition, recent studies show that deep neural networks also exhibit vulnerability to parameter corruptions. The vulnerability of model parameters is of crucial value to the study of model robustness and generalization. In this work, we introduce the concept of parameter corruption and propose to leverage the loss change indicators for measuring the flatness of the loss basin and the parameter robustness of neural network parameters. On such basis, we analyze parameter corruptions and propose the multi-step adversarial corruption algorithm. To enhance neural networks, we propose the adversarial parameter defense algorithm that minimizes the average risk of multiple adversarial parameter corruptions. Experimental results show that the proposed algorithm can improve both the parameter robustness and accuracy of neural networks.
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http://dx.doi.org/10.1016/j.neunet.2021.08.022DOI Listing
December 2021

Active Pressure Ripple Reduction of a Self-Supplied Variable Displacement Pump with Notch Least Mean Square Filter.

Micromachines (Basel) 2021 Aug 5;12(8). Epub 2021 Aug 5.

The State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou 310027, China.

As the power sources in hydraulic systems, variable displacement axial piston pumps generate flow fluctuation. Unfortunately, it results in pressure pulsation which excites the system vibration and emitted noise. The majority of studies try to eliminate the pulsation via a passive technique and the active control methodology has not been discussed in detail. In this research, the feasibility of reducing the pressure ripple by properly controlling the proportional valve has been investigated, which also supports the miniaturization of the active control system. A mathematical model of the self-supplied variable displacement pump including the control system has been developed. The filtered-X least mean square algorithm with time-delay compensation is utilized to calculate the active control signal. Simulation results show the effectiveness of the active control technique. The effect of the active control signal on the flow rate from different chambers of the pump has been analyzed. It demonstrates that the variation of the pressure pulsation should be ascribed to the comprehensive reaction of different flow rates. The major reason is that the flow of the actuator piston neutralizes the peak value of the flow ripple, generated by the nine pistons.
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http://dx.doi.org/10.3390/mi12080932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401920PMC
August 2021

Identification and Validation of a Novel Inflammatory Response-Related Gene Signature for the Prognosis of Colon Cancer.

J Inflamm Res 2021 11;14:3809-3821. Epub 2021 Aug 11.

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.

Purpose: The inflammatory response plays a crucial role in the occurrence and development of colon cancer. In this study, we aimed to explore a novel prognostic model for patients with colon cancer (COAD) based on inflammatory response-related genes.

Methods: Inflammatory response-related genes were obtained from Molecular Signatures database. Univariate and multivariate Cox regression analyses were used for model construction based on TCGA dataset. GSE39582 dataset and qRT-PCR dataset were used for validation. Gene set variation analysis and gene set enrichment analysis were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT. Immunohistochemistry analysis and experiments were used to explore the function of genes in model.

Results: In this study, a novel prognostic signature was identified using stepwise Cox proportional hazards regression analysis based on TCGA dataset. The results were subsequently validated in 562 patients from GSE39582 and a qRT-PCR data set from 70 tumor samples. Functional analysis indicated that the tumor microenvironment and immune cell infiltrate were different between high- and low-risk groups. Additionally, IHC results showed that the protein levels of prognostic genes were significantly different between COAD tissues and adjacent non-tumorous tissues, and prognostic genes could regulate the malignant phenotype of COAD cells.

Conclusion: Overall, the inflammation-related gene signature can be used for prognostic prediction in patients with COAD.
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http://dx.doi.org/10.2147/JIR.S321852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364916PMC
August 2021

[Risk Control of UPS Power Supply for Medical Equipment].

Zhongguo Yi Liao Qi Xie Za Zhi 2021 Jul;45(4):459-462

Medical Equipment Department, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201204.

Objective: Putting forward that the risk of using UPS for medical matching is easy to be ignored by managers.

Methods: The method of UPS inspection was designed and used in hospital.

Results: The qualified rate of UPS for equipment matching was 66.7% and the problems were corrected. Based on the Internet of Things technology, the UPS monitoring technology was prospected.

Conclusions: It is effective to control the risk of UPS by recognizing the risk of using UPS and specifying the strategy.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2021.04.024DOI Listing
July 2021

Knockdown of SFRS9 Inhibits Progression of Colorectal Cancer Through Triggering Ferroptosis Mediated by GPX4 Reduction.

Front Oncol 2021 16;11:683589. Epub 2021 Jul 16.

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

Ferroptosis, a newly discovered form of programmed cell death characterized by lipid peroxidation, crafts a new perspective on cancer treatment. Serine and arginine rich splicing factor 9 (SFRS9) is frequently described as a proto-oncogene in cervical and bladder cancer. However, the role of SFRS9 in colorectal cancer (CRC) and whether SFRS9 exerts its function associated with ferroptosis is largely unknown. Herein, we found that the expression of SFRS9 mRNA and protein in the CRC tissues was obviously higher than that in the paracancerous tissues. Function assays revealed that SFRS9 overexpression (SFRS9-OE) significantly promoted cell viability, cell cycle progression and colony formation of CRC cells. While SFRS9 knockdown by shRNAs transfection inhibited these progressions. Furthermore, cell death and lipid peroxidation induced by ferroptosis inducers erastin and sorafenib were suppressed by SFRS9-OE. Bioinformatics analysis indicated that SFRS9 can bind to peroxidase 4 (GPX4) mRNA which is a central regulator of ferroptosis. Western blot showed that GPX4 protein expression was clearly elevated upon SFRS9-OE, while it was decreased in SFRS9-inhibited CRC cells. RNA immunoprecipitation experiment was carried out in HCT116 cells to confirm the binding of SFRS9 and GPX4 mRNA specifically. SiGPX4 transfection reversed the inhibitory effects of SFRS9-OE on the erastin and sorafenib-induced ferroptosis. Consistent with our observations, SFRS9 promoted the growth of tumors while SFRS9 knockdown significantly inhibited tumor growth in nude mice. In conclusion, SFRS9 represents an obstructive factor to ferroptosis by upregulating GPX4 protein expression, and knocking down SFRS9 might be an effective treatment for CRC.
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http://dx.doi.org/10.3389/fonc.2021.683589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322952PMC
July 2021

Gene expression atlas of energy balance brain regions.

JCI Insight 2021 Aug 23;6(16). Epub 2021 Aug 23.

Naomi Berrie Diabetes Center, College of Physicians and Surgeons.

Energy balance is controlled by interconnected brain regions in the hypothalamus, brainstem, cortex, and limbic system. Gene expression signatures of these regions can help elucidate the pathophysiology underlying obesity. RNA sequencing was conducted on P56 C57BL/6NTac male mice and E14.5 C57BL/6NTac embryo punch biopsies in 16 obesity-relevant brain regions. The expression of 190 known obesity-associated genes (monogenic, rare, and low-frequency coding variants; GWAS; syndromic) was analyzed in each anatomical region. Genes associated with these genetic categories of obesity had localized expression patterns across brain regions. Known monogenic obesity causal genes were highly enriched in the arcuate nucleus of the hypothalamus and developing hypothalamus. The obesity-associated genes clustered into distinct "modules" of similar expression profile, and these were distinct from expression modules formed by similar analysis with genes known to be associated with other disease phenotypes (type 1 and type 2 diabetes, autism, breast cancer) in the same energy balance-relevant brain regions.
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http://dx.doi.org/10.1172/jci.insight.149137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409984PMC
August 2021

IDH2 contributes to tumorigenesis and poor prognosis by regulating m6A RNA methylation in multiple myeloma.

Oncogene 2021 Sep 17;40(35):5393-5402. Epub 2021 Jul 17.

Department of Cell Biology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou, China.

Epigenetic alterations have been previously shown to contribute to multiple myeloma (MM) pathogenesis via DNA methylations and histone modifications. RNA methylation, a novel epigenetic modification, is required for cancer cell survival, and targeting this pathway has been proposed as a new therapeutic strategy. The extent to the N6-methyladenosine (m6A)-regulatory pathway functions in MM remains unknown. Here, we show that an imbalance of RNA methylation may underlies the tumorigenesis of MM. Mechanistically, isocitrate dehydrogenase 2 (IDH2) is highly expressed in CD138 cells from MM and its levels appear a progressive increase in the progression of plasma cell dyscrasias. Downregulation of IDH2 increases global m6A RNA levels and reduces myeloma cell growth in vitro, decreases the burden of disease and prolongs overall survival in vivo. IDH2 regulates RNA methylation by activating the RNA demethylase FTO, which is an α-KG-dependent dioxygenase. Furthermore, IDH2-mediated FTO activation decreases the m6A level on WNT7B transcripts, then increases WNT7B expression and thus activated Wnt signaling pathway. Moreover, survival analysis indicates that the elevated expression of IDH2 predicts a poor prognosis. Higher expression of FTO is related to higher International Staging System (ISS) stage and higher Revised-ISS (R-ISS) stage of MM. Collectively, our studies reveal that IDH2 regulates global m6A RNA modification in MM via targeting RNA demethylases FTO. The imbalance of m6A methylation activates the Wnt signaling pathway by enhancing the WNT7B expression, and thus promoting tumorigenesis and progression of MM. IDH2 might be used as a therapeutic target and a possible prognostic factor for MM.
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http://dx.doi.org/10.1038/s41388-021-01939-7DOI Listing
September 2021

Photocatalytic degradation of sulfamonomethoxine by mesoporous phosphorus-doped titania under simulated solar light irradiation.

Chemosphere 2021 Dec 12;285:131553. Epub 2021 Jul 12.

College of Resources and Environmental Engineering, Key Laboratory of Karst Georesources and Environment, Ministry of Education, Guizhou University, Guiyang, Guizhou, China.

Photocatalytic degradation of sulfamonomethoxine (SMM) by mesoporous phosphorus-doped TiO (P-TiO) was studied under simulated solar light irradiation. The morphological structure and chemical composition of P-TiO were analyzed by XRD, SEM, HRTEM, BET, XPS and FTIR. Using the central composite design (CCD) of response surface methodology (RSM), the degradation of SMM was investigated with a range of antibiotic concentrations (4-8 mg L), catalyst dosages (400-900 mg L), P doping amounts (5-15 wt %) and irradiation time (90-150 min). The Ti-O-P bond formed during the calcination of TiO, thereby generating plate-like P-TiO, where P was uniformly distributed. Phosphorus doping can stabilize anatase TiO, which has a larger specific surface area and a lower average particle and pore size than bare TiO. The result obtained from the RSM model showed a significant correlation between the predicted values and the experimental results of SMM degradation (P < 0.05). Under the optimal experimental conditions (antibiotic concentration = 6 mg/L, catalyst dosage = 800 mg/L, P doping = 5 wt% and irradiation time = 90 min), the degradation rate of SMM was 99.51%, and the TOC was 50%. Toxicity showed a considerable reduction towards Vibrio-qinghaiensis sp.-Q67 after SMM photocatalytic degradation. Through free radical capture experiments, LC-MS detection and DFT calculations, the possible photocatalytic degradation mechanism of SMM using P-TiO as the catalyst was revealed.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131553DOI Listing
December 2021

Evolution of state-dependent strategies in stochastic games.

J Theor Biol 2021 10 25;527:110818. Epub 2021 Jun 25.

Center for Systems and Control, College of Engineering, Peking University, Beijing 100871, China; Center for Multi-Agent Research, Institute for Artificial Intelligence, Peking University, Beijing 100871, China. Electronic address:

In a population of interacting individuals, the environment for interactions often changes due to individuals' behaviors, which in turn drive the evolution of individuals' behaviors. The interplay between the environment and individuals' behaviors has been demonstrated to remarkably influence the evolutionary outcomes. In reality, in highly cognitive species such as social primates and human beings, individuals are often capable of perceiving the environment change and then differentiate their strategies across different environment states. We propose a model of environmental feedback with state-dependent strategies: individuals have perceptions of distinct environment states and therefore take distinct sub-strategies under each of them; based on the sub-strategy, individuals then decide their behaviors; their behaviors subsequently modify the environment state. We use the theory of stochastic games and evolutionary dynamics to analyze this idea. We find that when environment changes slower than behaviors, state-dependent strategies (i.e. taking different sub-strategies under different environment states) can outperform state-independent strategies (i.e. taking an identical sub-strategy under all environment states), such as Win-Stay, Lose-Shift, the most leading strategy among state-independent strategies. The intuition is that delayed environmental feedback provides chances for individuals with state-dependent strategies to exploit those with state-independent strategies. Our results hold (1) in both well-mixed and structured populations; (2) when the environment switches between two or more states. Furthermore, the environment changing rate decides if state-dependent strategies benefit global cooperation. The evolution sees the rise of the cooperation level for fast environment switching and the decrease otherwise. Our work stresses that individuals' perceptions of different environment states are beneficial to their survival and social prosperity in a changing world.
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http://dx.doi.org/10.1016/j.jtbi.2021.110818DOI Listing
October 2021

PolyTLR7/8a-conjugated, antigen-trapping gold nanorods elicit anticancer immunity against abscopal tumors by photothermal therapy-induced in situ vaccination.

Biomaterials 2021 08 8;275:120921. Epub 2021 Jun 8.

Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China. Electronic address:

Nanovaccine can elicit antigen-specific immune responses against tumor cells expressing homologous antigens and has attracted enormous attention in cancer immunotherapy. However, tumor heterogeneity remarkably hinders the development of nanovaccines. Here we demonstrate that PTT-induced in situ vaccination cancer therapy can elicit potent antitumor immunity against disseminated and metastatic tumors. Gold nanorods (AuNRs) covalently coupled with amphiphilic polyTLR7/8a and MMP-2-sensitive R9-PEG conjugate (AuNRs-IMQD-R9-PEG) were developed as a new biocompatible PTT agent with favorable photothermal efficiency and stability. Importantly, AuNRs-IMQD-R9-PEG can effectively absorb tumor-derived protein antigens, forming nanovaccines directly in vivo and enhance the activation of host dendritic cells (DCs), thereby amplifying adaptive antitumor T-cell responses, triggering effector memory immune responses, and activating innate antitumor immunity. Remarkably, peri-tumoral administration of low-dose multifunctional AuNRs followed by non-invasive near-infrared (NIR) laser irradiation enables efficient tandem PTT-vaccination treatment modality that can inhibit local as well as untreated distant and metastatic tumors in mice inoculated with poorly immunogenic, highly metastatic 4T1 tumors. Our findings indicate that AuNRs-IMQD-R9-PEG-mediated in situ cancer vaccination provides a powerful immunotherapy characterized by markedly increased infiltration of effector CD8 T, natural killer T (NKT) cells in tumors and long-term animal survival, thus, offering a promising therapeutic strategy for advanced, disseminated cancers.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120921DOI Listing
August 2021

Factors Affecting Gut Microbiome in Daily Diet.

Authors:
Qi Su Qin Liu

Front Nutr 2021 10;8:644138. Epub 2021 May 10.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.

There is a growing recognition that a good diet can help people maintain mental and physical health, while a bad one will cause the disorder of body function, and even lead to several diseases. A lot of attentions have been devoted to analyze every possible health-related factor in the daily diet, including food ingredients, additives, and cooking process. With the support of high-throughput sequencing technology, there is accumulating evidence gradually clarifying that most of these factors are mainly through the interactions with gut microbiome to trigger downstream effects. The gut microbiome may be able to act as a very sensitive mirror in response to human daily diet. A complex network of interactions among diet, gut microbiome, and health has been gradually depicted, but it is rarely discussed from a more comprehensive perspective. To this end, this review summarized the latest updates in diet-gut microbiome interactions, analyzed most identified factors involved in this process, showed the possibility of maintaining health or alleviating diseases by diet intervention, aiming to help people choose a suitable recipe more accurately.
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http://dx.doi.org/10.3389/fnut.2021.644138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141808PMC
May 2021

Correction: Co-delivery of anionic epitope/CpG vaccine and IDO inhibitor by self-assembled cationic liposomes for combination melanoma immunotherapy.

J Mater Chem B 2021 Jun;9(21):4412

Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.

Correction for 'Co-delivery of anionic epitope/CpG vaccine and IDO inhibitor by self-assembled cationic liposomes for combination melanoma immunotherapy' by Qi Su et al., J. Mater. Chem. B, 2021, 9, 3892-3899, DOI: 10.1039/d1tb00256b.
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http://dx.doi.org/10.1039/d1tb90081aDOI Listing
June 2021

Supramolecular co-assembly of self-adjuvanting nanofibrious peptide hydrogel enhances cancer vaccination by activating MyD88-dependent NF-κB signaling pathway without inflammation.

Bioact Mater 2021 Nov 16;6(11):3924-3934. Epub 2021 Apr 16.

Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China.

Peptide vaccine targeting tumor-specific antigens is a promising cancer treatment regimen. However, peptide vaccines are commonly low-immunogenic, leading to suboptimal antitumor T-cell responses. Current peptide vaccination approaches are challenged by the variability of peptide physicochemical characters and vaccine formulations, flexibility, and the broad feasibility. Here, the supramolecular co-assembly of antigen epitope-conjugated peptides (ECPs) targeting CD8 or CD4 T-cell receptors was used to engineer a nanofibrious hydrogel vaccine platform. This approach provided precise and tunable loading of peptide antigens in nanofibers, which notably increased the antigen uptake, cross-presentation, and activation of dendritic cells (DCs). Immunization in mice indicated that the co-assembled peptide hydrogel did not induce local inflammation responses and elicited significantly promoted T-cell immunity by activating the MyD88-dependent NF-κB signaling pathway in DCs. Vaccination of mice using co-assembled peptide vaccine stimulated both enhanced CD8 and CD4 T cells against EG.7-OVA tumors without additional immunoadjuvants or delivery systems, and resulted in a more remarkable cancer immunotherapy efficacy, compared with free peptide vaccine or aluminum-adjuvanted peptide formulation. Altogether, peptide co-assembly demonstrated by three independent pairs of ECPs is a facile, customizable, and chemically defined approach for co-delivering peptide antigens in self-adjuvanting hydrogel vaccines that could induce stronger anticancer T-cell responses.
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http://dx.doi.org/10.1016/j.bioactmat.2021.03.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080410PMC
November 2021

Cephalomannine inhibits hypoxia-induced cellular function via the suppression of APEX1/HIF-1α interaction in lung cancer.

Cell Death Dis 2021 05 14;12(5):490. Epub 2021 May 14.

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China.

Lung cancer (LC) is one of the leading causes of cancer-related death. As one of the key features of tumor microenvironment, hypoxia conditions are associated with poor prognosis in LC patients. Upregulation of hypoxic-induced factor-1α (HIF-1α) leads to the activation of various factors that contribute to the increased drug resistance, proliferation, and migration of tumor cells. Apurinic/apyrimidinic endonuclease-1 (APEX1) is a multi-functional protein that regulates several transcription factors, including HIF-1α, that contribute to tumor growth, oxidative stress responses, and DNA damage. In this study, we explored the mechanisms underlying cell responses to hypoxia and modulation of APEX1, which regulate HIF-1α and downstream pathways. We found that hypoxia-induced APEX1/HIF-1α pathways regulate several key cellular functions, including reactive oxygen species (ROS) production, carbonic anhydrase 9 (CA9)-mediated intracellular pH, migration, and angiogenesis. Cephalomannine (CPM), a natural compound, exerted inhibitory effects in hypoxic LC cells via the inhibition of APEX1/HIF-1α interaction in vitro and in vivo. CPM can significantly inhibit cell viability, ROS production, intracellular pH, and migration in hypoxic LC cells as well as angiogenesis of HUVECs under hypoxia through the inhibition of APEX1/HIF-1α interaction. Taken together, CPM could be considered as a promising compound for LC treatment.
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http://dx.doi.org/10.1038/s41419-021-03771-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121842PMC
May 2021
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