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Article: Transcription Factor KLF14 and Metabolic Syndrome.

Yang, Qianyi / Civelek, Mete

2020 Volume 7, Page(s) 91

Abstract: Metabolic syndrome (MetSyn) is a combination of metabolic abnormalities that lead to the development of cardiovascular disease (CVD) and Type 2 Diabetes (T2D). Although various criteria for defining MetSyn exist, common abnormalities include abdominal ... ...

Abstract	Metabolic syndrome (MetSyn) is a combination of metabolic abnormalities that lead to the development of cardiovascular disease (CVD) and Type 2 Diabetes (T2D). Although various criteria for defining MetSyn exist, common abnormalities include abdominal obesity, elevated serum triglyceride, insulin resistance, and blood glucose, decreased high-density lipoprotein cholesterol (HDL-C), and hypertension. MetSyn prevalence has been increasing with the rise of obesity worldwide, with significantly higher prevalence in women compared with men and in Hispanics compared with Whites. Affected individuals are at a higher risk of developing T2D (5-fold) and CVD (2-fold). Heritability estimates for individual components of MetSyn vary between 40 and 70%, suggesting a strong contribution of an individual's genetic makeup to disease pathology. The advent of next-generation sequencing technologies has enabled large-scale genome-wide association studies (GWAS) into the genetics underlying MetSyn pathogenesis. Several such studies have implicated the transcription factor KLF14, a member of the Krüpple-like factor family (KLF), in the development of metabolic diseases, including obesity, insulin resistance, and T2D. How KLF14 regulates these metabolic traits and increases the risk of developing T2D, atherosclerosis, and liver dysfunction is still unknown. There have been some debate and controversial results with regards to its expression profile and functionality in various tissues, and a systematic review of current knowledge on KLF14 is lacking. Here, we summarize the research progress made in understanding the function of KLF14 and describe common attributes of its biochemical, physiological, and pathophysiological roles. We also discuss the current challenges in understanding the role of KLF14 in metabolism and provide suggestions for future directions.
Language	English
Publishing date	2020-05-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2020.00091
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Modeling and analyzing an opinion network dynamics considering the environmental factor.

Yin, Fulian / Wang, Jinxia / Jiang, Xinyi / Huang, Yanjing / Yang, Qianyi / Wu, Jianhong

Mathematical biosciences and engineering : MBE

2023 Volume 20, Issue 9, Page(s) 16866–16885

Abstract: With the development of Internet technology, social media has gradually become an important platform where users can express opinions about hot events. Research on the mechanism of public opinion evolution is beneficial to guide the trend of opinions, ... ...

Abstract	With the development of Internet technology, social media has gradually become an important platform where users can express opinions about hot events. Research on the mechanism of public opinion evolution is beneficial to guide the trend of opinions, making users' opinions change in a positive direction or reach a consensus among controversial crowds. To design effective strategies for public opinion management, we propose a dynamic opinion network susceptible-forwarding-immune model considering environmental factors (NET-OE-SFI), which divides the forwarding nodes into two types: support and opposition based on the real data of users. The NET-OE-SFI model introduces environmental factors from infectious diseases into the study of network information transmission, which aims to explore the evolution law of users' opinions affected by the environment. We attempt to combine the complex media environmental factors in social networks with users' opinion information to study the influence of environmental factors on the evolution of public opinion. Data fitting of real information transmission data fully demonstrates the validity of this model. We have also made a variety of sensitivity analysis experiments to study the influence of model parameters, contributing to the design of reasonable and effective strategies for public opinion guidance.
Language	English
Publishing date	2023-08-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2265126-3
ISSN	1551-0018 ; 1551-0018
ISSN (online)	1551-0018
ISSN	1551-0018
DOI	10.3934/mbe.2023752
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Article ; Online: PKC signal amplification suppresses non-small cell lung cancer growth by promoting p21 expression and phosphorylation

Liu, Shuyan / Zhang, Yayun / Yang, Qianyi / Zhang, Yingqiu / Liu, Han / Huang, Mu-Hua / Wang, Ruoyu / Lu, Faqiang

Heliyon. 2022 Sept., v. 8, no. 9 p.e10657-

2022

Abstract: Protein kinase C (PKC) activation was previously associated with oncogenic features. However, small molecule inhibitors targeting PKC have so far proved ineffective in a number of clinical trials for cancer treatment. Recent progresses have revealed that ...

Abstract	Protein kinase C (PKC) activation was previously associated with oncogenic features. However, small molecule inhibitors targeting PKC have so far proved ineffective in a number of clinical trials for cancer treatment. Recent progresses have revealed that most PKC mutations detected in diverse cancers actually lead to loss-of-function, thus suggesting the tumor-suppressive roles of PKC proteins. Unfortunately, the development of chemicals to enhance PKC activity is lagging behind relative to its small molecular inhibitors. Here, we report that a bisindolylmaleimide derivative (3,4-bis(1-(prop-2-ynyl)-1H-indol-3-yl)-1 H-pyrrole-2,5-dione, BD-15) significantly inhibited cell growth in non-small cell lung cancer (NSCLC). Mechanistically, BD-15 treatment resulted in markedly enhanced phosphorylation of PKC substrates and led to cell cycle arrest in G2/M. Further, BD-15 treatment upregulated p21 protein levels and enhanced p21 phosphorylation. BD-15 also promoted caspase3 cleavage and triggered cellular apoptosis. In xenograft mouse models, BD-15 exerted anti-tumor effects to suppress in vivo tumor formation. Collectively, our findings revealed the tumor-suppressive roles of BD-15 through enhancing PKC signaling and thus leading to upregulation of p21 expression and phosphorylation.
Keywords	apoptosis ; cancer therapy ; cell cycle checkpoints ; cell growth ; loss-of-function mutation ; lung neoplasms ; mice ; phosphorylation ; protein kinase C ; xenotransplantation ; PKC ; Bisindolylmaleimide derivative ; BD-15 ; p21 ; NSCLC
Language	English
Dates of publication	2022-09
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e10657
Database	NAL-Catalogue (AGRICOLA)

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Article: Li

Yang, Qianyi / Lu, Fuqiang / Liu, Yulin / Zhang, Yijie / Wang, Xiujuan / Pang, Yuepeng / Zheng, Shiyou

Nanomaterials (Basel, Switzerland)

2021 Volume 11, Issue 4

Abstract: Solid electrolytes with high Li-ion conductivity and electrochemical stability are very important for developing high-performance all-solid-state batteries. In this work, ... ...

Abstract	Solid electrolytes with high Li-ion conductivity and electrochemical stability are very important for developing high-performance all-solid-state batteries. In this work, Li
Language	English
Publishing date	2021-04-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662255-5
ISSN	2079-4991
ISSN	2079-4991
DOI	10.3390/nano11040946
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Article ; Online: Genetic polymorphism of IL36RN in Han patients with generalized pustular psoriasis in Sichuan region of China: A case-control study.

Li, Zhongtao / Yang, Qianyi / Wang, Sheng

Medicine

2018 Volume 97, Issue 31, Page(s) e11741

Abstract: The aim of this study was to detect IL36RN variant types and frequency in Han patients with generalized pustular psoriasis (GPP) in Sichuan region of China, reveal the difference of variant frequency between GPP alone and GPP + PV (psoriasis vulgaris), ... ...

Abstract	The aim of this study was to detect IL36RN variant types and frequency in Han patients with generalized pustular psoriasis (GPP) in Sichuan region of China, reveal the difference of variant frequency between GPP alone and GPP + PV (psoriasis vulgaris), and preliminarily clarify the pathogenesis of GPP in this region.Genomic DNA was extracted and subjected to polymerase chain reaction (PCR) for the amplification of the entire encoding and splice sites of the IL36RN gene followed by bidirectional sequencing. Differences in frequencies of IL36RN variants between groups were analyzed by SPSS Statistics 17.0 software. Meanwhile, the IL36RN variant frequency between GPP alone and GPP + PV was compared.The total IL36RN variant frequency was 60.47% in Han GPP patients from Sichuan region of China. Three variant types (c.115 + 6T > C, c.140A > G, c.227C > T) were identified, among which c.115 + 6T > C exhibited the highest frequency (55.81%). All the 3 variants' frequency of GPP alone group had statistical significance when compared with PV patients and normal controls (P < .05). The IL36RN variant frequency of GPP alone group was statistically higher than that of GPP + PV group (79.17% vs 36.84%, P < .05).IL36RN may be the major disease-causing gene in GPP patients in Han population in Sichuan region of China. c.115 + 6T > C is a possible hot-spot mutation within the IL36RN gene. In contrast to GPP + PV, IL36RN mutations possibly play a more important role in the development of GPP alone.
MeSH term(s)	Adolescent ; Adult ; Aged ; Asians/genetics ; Case-Control Studies ; Child ; Child, Preschool ; China/epidemiology ; Female ; Humans ; Infant ; Interleukins/genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Psoriasis/ethnology ; Young Adult
Chemical Substances	IL36RN protein, human ; Interleukins
Language	English
Publishing date	2018-08-16
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000011741
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Article: PKC signal amplification suppresses non-small cell lung cancer growth by promoting p21 expression and phosphorylation.

Liu, Shuyan / Zhang, Yayun / Yang, Qianyi / Zhang, Yingqiu / Liu, Han / Huang, Mu-Hua / Wang, Ruoyu / Lu, Faqiang

Heliyon

2022 Volume 8, Issue 9, Page(s) e10657

Abstract	Protein kinase C (PKC) activation was previously associated with oncogenic features. However, small molecule inhibitors targeting PKC have so far proved ineffective in a number of clinical trials for cancer treatment. Recent progresses have revealed that most PKC mutations detected in diverse cancers actually lead to loss-of-function, thus suggesting the tumor-suppressive roles of PKC proteins. Unfortunately, the development of chemicals to enhance PKC activity is lagging behind relative to its small molecular inhibitors. Here, we report that a bisindolylmaleimide derivative (3,4-bis(1-(prop-2-ynyl)-1
Language	English
Publishing date	2022-09-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e10657
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Robust Threshold-Switching Behavior Assisted by Cu Migration in a Ferroionic CuInP

Zhong, Zhipeng / Wu, Shuaiqin / Li, Xiang / Wang, Zhiqiang / Yang, Qianyi / Huang, Bangchi / Chen, Yan / Wang, Xudong / Lin, Tie / Shen, Hong / Meng, Xiangjian / Wang, Ming / Shi, Wu / Wang, Jianlu / Chu, Junhao / Huang, Hai

ACS nano

2023 Volume 17, Issue 13, Page(s) 12563–12572

Abstract: The two-dimensional layered material ... ...

Abstract	The two-dimensional layered material CuInP
Language	English
Publishing date	2023-05-15
Publishing country	United States
Document type	Journal Article
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.3c02406
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Article ; Online: The Bi-Functional Paxilline Enriched in Skin Secretion of Tree Frogs (

Yin, Chuanling / Zeng, Fanpeng / Huang, Puyi / Shi, Zhengqi / Yang, Qianyi / Pei, Zhenduo / Wang, Xin / Chai, Longhui / Zhang, Shipei / Yang, Shilong / Dong, Wenqi / Lu, Xiancui / Wang, Yunfei

Toxins

2023 Volume 15, Issue 1

Abstract: The skin secretion of tree frogs contains a vast array of bioactive chemicals for repelling predators, but their structural and functional diversity is not fully understood. Paxilline (PAX), a compound synthesized ... ...

Abstract	The skin secretion of tree frogs contains a vast array of bioactive chemicals for repelling predators, but their structural and functional diversity is not fully understood. Paxilline (PAX), a compound synthesized by
MeSH term(s)	Animals ; Rats ; Anura ; Indoles/pharmacology ; Potassium Channels/metabolism
Chemical Substances	Indoles ; paxilline (3T9U9Z96L7) ; Potassium Channels
Language	English
Publishing date	2023-01-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins15010070
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Article ; Online: Proteasomal deubiquitylase activity enhances cell surface recycling of the epidermal growth factor receptor in non-small cell lung cancer.

Wang, Shanshan / Wang, Taishu / Yang, Qianyi / Cheng, Shaoxuan / Liu, Fang / Yang, Guoheng / Wang, Fuqiang / Wang, Ruilin / Yang, Dian / Zhou, Mingyu / Duan, Chengen / Zhang, Yingqiu / Liu, Han / Dai, Zhaoxia / Tian, Kang / Liu, Shuyan

Cellular oncology (Dordrecht)

2022 Volume 45, Issue 5, Page(s) 951–965

Abstract: Purpose: The epidermal growth factor receptor (EGFR) represents a top therapeutic target in the treatment of non-small cell lung cancer. EGFR expression is intricately modulated by receptor endocytosis, during which EGFR ubiquitylation and ... ...

Abstract	Purpose: The epidermal growth factor receptor (EGFR) represents a top therapeutic target in the treatment of non-small cell lung cancer. EGFR expression is intricately modulated by receptor endocytosis, during which EGFR ubiquitylation and deubiquitylation play fundamental roles to govern receptor fate. This study aims to uncover novel aspects of the endocytic regulation of EGFR trafficking by deubiquitylases. Methods: The expression and ubiquitylation of EGFR in non-small cell lung cancer cells treated with deubiquitylase inhibitors were assessed by immunoblotting, immunoprecipitation and mass spectrometry analyses. The intracellular EGFR distribution was investigated using immunofluorescence and confocal microscopy assays, and colocalizations with endocytic compartments were examined using GFP-tagged Rab proteins as markers. The influence of the proteasomal deubiquitylase inhibitor b-AP15 on EGF- and HSP90 inhibitor-induced EGFR downregulation was evaluated by immunoblotting. The anticancer effects of b-AP15 were assessed by cell proliferation, colony formation and flow cytometry assays, as well as xenograft animal models. Results: We found that b-AP15 caused a dramatically enhanced ubiquitylation of EGFR in lung cancer cells. Treatment with b-AP15 decreased cell surface EGFR levels and accumulated EGFR on recycling endosomes marked with Rab4A and Rab11A. b-AP15 effectively repressed EGF- and HSP90 inhibitor-induced EGFR degradation. Lung cancer cells exposed to b-AP15 showed markedly reduced cell propagation and significantly increased cell apoptosis. Furthermore, b-AP15 effectively inhibited tumor xenograft growth in nude mice. Conclusion: Proteasomal USP14 and UCHL5 act collectively to promote cell surface recovery of EGFR. Inhibition of proteasomal deubiquitylase activity induces increased EGFR ubiquitylation and retention on recycling endosomes. The USP14 and UCHL5 dual inhibitor b-AP15 elicits potent tumor-suppressive effects to deter cell proliferation and induce apoptotic cell death in lung cancer.
MeSH term(s)	Animals ; Humans ; Mice ; Antineoplastic Agents/pharmacology ; Apoptosis ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Line, Tumor ; Epidermal Growth Factor/pharmacology ; ErbB Receptors/metabolism ; Lung Neoplasms/pathology ; Mice, Nude ; Proteasome Inhibitors/pharmacology ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	Antineoplastic Agents ; Epidermal Growth Factor (62229-50-9) ; ErbB Receptors (EC 2.7.10.1) ; Proteasome Inhibitors ; Ubiquitin Thiolesterase (EC 3.4.19.12) ; USP14 protein, human ; EGFR protein, human (EC 2.7.10.1)
Language	English
Publishing date	2022-09-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2595109-9
ISSN	2211-3436 ; 1875-8606 ; 2211-3428
ISSN (online)	2211-3436
ISSN	1875-8606 ; 2211-3428
DOI	10.1007/s13402-022-00699-0
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Article ; Online: Adipocyte-Specific Modulation of KLF14 Expression in Mice Leads to Sex-Dependent Impacts on Adiposity and Lipid Metabolism.

Yang, Qianyi / Hinkle, Jameson / Reed, Jordan N / Aherrahrou, Redouane / Xu, Zhiwen / Harris, Thurl E / Stephenson, Erin J / Musunuru, Kiran / Keller, Susanna R / Civelek, Mete

Diabetes

2022 Volume 71, Issue 4, Page(s) 677–693

Abstract: Genome-wide association studies identified single nucleotide polymorphisms on chromosome 7 upstream of KLF14 to be associated with metabolic syndrome traits and increased risk for type 2 diabetes (T2D). The associations were more significant in women ... ...

Abstract	Genome-wide association studies identified single nucleotide polymorphisms on chromosome 7 upstream of KLF14 to be associated with metabolic syndrome traits and increased risk for type 2 diabetes (T2D). The associations were more significant in women than in men. The risk allele carriers expressed lower levels of the transcription factor KLF14 in adipose tissues than nonrisk allele carriers. To investigate how adipocyte KLF14 regulates metabolic traits in a sex-dependent manner, we characterized high-fat diet-fed male and female mice with adipocyte-specific Klf14 deletion or overexpression. Klf14 deletion resulted in increased fat mass in female mice and decreased fat mass in male mice. Female Klf14-deficient mice had overall smaller adipocytes in subcutaneous fat depots but larger adipocytes in parametrial depots, indicating a shift in lipid storage from subcutaneous to visceral fat depots. They had reduced metabolic rates and increased respiratory exchange ratios consistent with increased use of carbohydrates as an energy source. Fasting- and isoproterenol-induced adipocyte lipolysis was defective in female Klf14-deficient mice, and concomitantly, adipocyte triglycerides lipase mRNA levels were downregulated. Female Klf14-deficient mice cleared blood triglyceride and nonesterified fatty acid less efficiently than wild-type. Finally, adipocyte-specific overexpression of Klf14 resulted in lower total body fat in female but not male mice. Taken together, consistent with human studies, adipocyte KLF14 deficiency in female but not in male mice causes increased adiposity and redistribution of lipid storage from subcutaneous to visceral adipose tissues. Increasing KLF14 abundance in adipocytes of females with obesity and T2D may provide a novel treatment option to alleviate metabolic abnormalities.
MeSH term(s)	Adipocytes/metabolism ; Adiposity/genetics ; Animals ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Female ; Genome-Wide Association Study ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism ; Lipid Metabolism/genetics ; Male ; Mice ; Obesity/genetics ; Obesity/metabolism ; Sex Factors
Chemical Substances	Klf14 protein, mouse ; Kruppel-Like Transcription Factors
Language	English
Publishing date	2022-01-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db21-0674
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