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A novel A2a adenosine receptor inhibitor effectively mitigates hepatic fibrosis in a metabolic dysfunction-associated steatohepatitis mouse model Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-3-3 Seojeong Park, Seohui Hwang, Jingyang Sun, Kyung-Hwa Jeon, Naeun Sheen, Sumin Shin, Tae Hyun Kim, Young-Sun Lee, Wonhyo Seo, Jae-Sang Ryu, Youngjoo Kwon
Hepatic fibrosis exacerbates mortality and complications in progressive metabolic dysfunction-associated steatohepatitis (MASH). The role of the adenosine 2A receptor (A2aAR) in hepatic fibrosis within the context of MASH remains uncertain. This study aims to elucidate the involvement of the A2aAR signaling pathway and the efficacy of a novel potent A2aAR antagonist in treating hepatic fibrosis in
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Impaired TFEB-mediated autophagy-lysosome fusion promotes tubular cell cycle G2/M arrest and renal fibrosis by suppressing ATP6V0C expression and interacting with SNAREs Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-3-3 Xiang Ren, Jing Wang, Huizhi Wei, Xing Li, Yiqun Tian, Zhixian Wang, Yisheng Yin, Zihao Guo, Zhenliang Qin, Minglong Wu, Xiaoyong Zeng
Increasing evidence suggests that autophagy plays a major role during renal fibrosis. Transcription factor EB (TFEB) is a critical regulator of autophagy- and lysosome-related gene transcription. However, the pathophysiological roles of TFEB in renal fibrosis and fine-tuned mechanisms by which TFEB regulates fibrosis remain largely unknown. Here, we found that TFEB was downregulated in unilateral ureteral
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mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-3-3 Nan-Shi-Yu Yang, Wen-Jing Zhong, Han-Xi Sha, Chen-Yu Zhang, Ling Jin, Jia-Xi Duan, Jian-Bing Xiong, Zhi-Jian You, Yong Zhou, Cha-Xiang Guan
The activation of NLRP3 inflammasome in microglia is critical for neuroinflammation during postoperative cognitive dysfunction (POCD) induced by sevoflurane. However, the molecular mechanism by which sevoflurane activates the NLRP3 inflammasome in microglia remains unclear. The cGAS-STING pathway is an evolutionarily conserved inflammatory defense mechanism. The role of the cGAS-STING pathway in sevoflurane-induced
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Histone lactylation: from tumor lactate metabolism to epigenetic regulation Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-3-3 Xiaoning Yu, Jing Yang, Jin Xu, Haoqi Pan, Wei Wang, Xianjun Yu, Si Shi
The Warburg Effect is one of the most well-known cancer hallmarks. This metabolic pattern centered on lactate has extremely complex effects on various aspects of tumor microenvironment, including metabolic remodeling, immune suppression, cancer cell migration, and drug resistance development. Based on accumulating evidence, metabolites are likely to participate in the regulation of biological processes
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The scheme, and regulative mechanism of pyroptosis, ferroptosis, and necroptosis in radiation injury Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-3-3 Jiaoyang Ning, Liu Chen, Yu Zeng, Gang Xiao, Wentao Tian, Qi Wu, Jiyuan Tang, Shuangshuang He, Guilong Tanzhu, Rongrong Zhou
Radiotherapy (RT) stands as the primary treatment for tumors, but it inevitably causes damage to normal cells. Consequently, radiation injury is a crucial consideration for radiation oncologists during therapy planning. Cell death including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis play significant roles in tumor treatment. While previous studies elucidated the induction of apoptosis
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Reprogramming of Lipid Metabolism Mediates Crosstalk, Remodeling, and Intervention of Microenvironment Components in Breast Cancer Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-3-3 Jia Wang, Wenfeng Zhang, Cun Liu, LongYun Wang, Jibiao Wu, Changgang Sun, Qibiao Wu
Due to the unique characteristics of breast cancer initiation sites and significant alterations in tumor metabolism, breast cancer cells rely on lipid metabolic reprogramming to effectively regulate metabolic programs during the disease progression cascade. This adaptation enables them to meet the energy demands required for proliferation, invasion, metastasis, and responses to signaling molecules
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Impact of KRAS mutation on the tumor microenvironment in colorectal cancer Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-3-3 Yiru Zhou, Yeye Kuang, Chan Wang, Yijian Yu, Lijuan Pan, Xiaotong Hu
Kirsten rat sarcoma viral oncogene homolog (KRAS) is an oncogene implicated in the pathophysiology of many cancers. Increasing evidence shows that KRAS mutation is correlated with poor prognosis in numerous cancers, including colorectal cancer (CRC), breast cancer, and melanoma. KRAS also participates in regulating the CRC microenvironment. However, the direct and indirect therapeutic targets of KRAS
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Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1 Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-25 Jun He, Xuyang Hou, Junyong Wu, Kunpeng Wang, Xiaoyan Qi, Zuxing Wei, Yin Sun, Cong Wang, Hongliang Yao, Kuijie Liu
Acute pancreatitis (AP) is a common abdominal disease that typically resolves on its own, but the mortality rate dramatically increases when it progresses to severe acute pancreatitis (SAP). In this study, we investigated the molecular mechanism underlying the development of SAP from AP. We utilized two SAP models induced by pancreatic duct ligation and caerulein administration. Transcriptomic and
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ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m6A-dependent manner Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-25 Hanwen Wang, Shixin Zhao, Hengdeng Liu, Yiling Liu, Zihui Zhang, Ziheng Zhou, Peng Wang, Shaohai Qi, Julin Xie
Background: N6-methyladenosine (m6A) is the most common and abundant mRNA modification, playing an essential role in biological processes and tumor development. However, the role of m6A methylation in skin cutaneous melanoma (SKCM) is not yet clear. This study analyzed the expression of m6A-related functional genes in SKCM and aimed to explore the key demethylase ALKBH5 mediated m6A modification and
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The m6A modification-mediated positive feedback between glycolytic lncRNA SLC2A1-DT and c-Myc promotes tumorigenesis of hepatocellular carcinoma Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-25 Zhu Zeng, Jie Wang, Fengyu Xu, Ping Hu, Yuhang Hu, Wenfeng Zhuo, Ding Chen, Shengbo Han, Fan Wang, Yong Zhao, Yan Huang, Gang Zhao
Glycolysis exerts a key role in the metabolic reprogramming of cancer. Specific long non-coding RNAs (lncRNAs) have been identified to exhibit oncogenic glycolysis regulation. Nevertheless, the precise mechanisms by which glycolysis-related lncRNAs control hepatocellular carcinoma (HCC) are still unknown. We profiled and analyzed glycolysis-associated lncRNA signatures using HCC specimens from The
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WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8 Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-25 Lei Zhou, Yun Zhong, Fan Wang, Yi Guo, Rui Mao, Hongfu Xie, Yiya Zhang, Ji Li
N6-methyladenosine (m6A), the most prevalent posttranscriptional RNA modification, involved in various diseases and cellular processes. However, the underlying mechanisms of m6A regulation in skin aging are still not fully understood. In this study, proteomics analysis revealed a significant correlation between Wilms' tumor 1-associating protein (WTAP) expression and cellular senescence. Next, upregulated
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Carbonic Anhydrase 3 is required for cardiac repair post myocardial infarction via Smad7-Smad2/3 signaling pathway Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-25 Yuanyuan Su, Dongmei Shi, Guofang Xia, Yujia Liu, Longwei Xu, Ling Dao, Xia Lu, Chengxing Shen, Congfeng Xu
Appropriate fibrosis is required to prevent subsequent adverse remodeling and heart failure post myocardial infarction (MI), and cardiac fibroblasts (CFs) play a critical role during the process. Carbonic anhydrase 3 (CAR3) is an important mediator in multiple biological processes besides its CO2 hydration activity; however, the role and underlying mechanism of CAR3 on cardiac repair post MI injury
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Ubiquitin specific protease 38 aggravates pathological cardiac remodeling by stabilizing phospho-TBK1 Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-25 Zheng Xiao, Chang Dai, Tingting Yu, Jun Zhu, Yucheng Pan, Wei Shuai, Bin Kong, He Huang
Chronic pressure overload can cause pathological cardiac remodeling and eventually heart failure. The ubiquitin specific protease (USP) family proteins play a prominent role in regulating substrate protein degradation and cardiac structural and functional homeostasis. Although USP38 is expressed in the heart, uncertainty exists regarding the function of USP38 in pathological cardiac remodeling. We
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Exosomes: The emerging mechanisms and potential clinical applications in dermatology Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-25 Honghao Yu, Heting Feng, Hong Zeng, Yiping Wu, Qi Zhang, Jing Yu, Kai Hou, Min Wu
Skin tissue, composed of epidermis, dermis, and subcutaneous tissue, is the largest organ of the human body. It serves as a protective barrier against pathogens and physical trauma and plays a crucial role in maintaining homeostasis. Skin diseases, such as psoriasis, dermatitis, and vitiligo, are prevalent and can seriously impact the quality of patient life. Exosomes are lipid bilayer vesicles derived
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Interruption of p38MAPK-MSK1-CREB-MITF-M pathway to prevent hyperpigmentation in the skin Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-17 Song-Hee Kim, Jiyeon Lee, Jihye Jung, Ga Hyun Kim, Cheong-Yong Yun, Sang-Hun Jung, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Jae-Kyung Jung, Youngsoo Kim
Background: Melanocortin 1 receptor (MC1R), a receptor of α-melanocyte-stimulating hormone (α-MSH), is exclusively present in melanocytes where α-MSH/MC1R stimulate melanin pigmentation through microphthalmia-associated transcription factor M (MITF-M). Toll-like receptor 4 (TLR4), a receptor of endotoxin lipopolysaccharide (LPS), is distributed in immune and other cell types including melanocytes where
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Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-12 Yi-Lin Zhang, Tao-Tao Tang, Wei-Jie Ni, Zhong-Tang Li, Liang-Yun-Zi Jiang, Yao Wang, Xuan Zhou, Jing-Yuan Cao, Qing Yin, Wei Jiang, Ya-Jie Zhao, Wei-Hua Gan, Ai-Qing Zhang, Zuo-Lin Li, Yi Wen, Lin-Li Lv, Bi-Cheng Liu, Bin Wang
Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor
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The Burgeoning Significance of Liquid-Liquid Phase Separation in the Pathogenesis and Therapeutics of Cancers Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-12 Wei-Xin Xu, Qiang Qu, Hai-Hui Zhuang, Xin-Qi Teng, Yi-Wen Wei, Jian Luo, Ying-Huan Dai, Jian Qu
Liquid-liquid phase separation (LLPS) is a physiological phenomenon that parallels the mixing of oil and water, giving rise to compartments with diverse physical properties. Biomolecular condensates, arising from LLPS, serve as critical regulators of gene expression and control, with a particular significance in the context of malignant tumors. Recent investigations have unveiled the intimate connection
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Inhibition of BRD4 Attenuates ER Stress-induced Renal Ischemic-Reperfusion Injury Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-11 Paula Diaz-Bulnes, Ramon M Rodríguez, Elisenda Banon-Maneus, María Laura Saiz, Cristian Ruiz Bernet, Viviana Corte-Iglesias, Maria Jose Ramirez-Bajo, Marta Lazo-Rodriguez, Isaac Tamargo-Gómez, Raúl R. Rodrigues-Diez, Ana B Sanz, Carmen Diaz-Corte, Marta Ruiz-Ortega, Fritz Diekmann, Ana M Aransay, Carlos Lopez-Larrea, Beatriz Suarez-Alvarez
Renal ischemia-reperfusion injury (IRI) leads to endoplasmic reticulum (ER) stress, thereby initiating the unfolded protein response (UPR). When sustained, this response may trigger the inflammation and tubular cell death that acts to aggravate the damage. Here, we show that knockdown of the BET epigenetic reader BRD4 reduces the expression of ATF4 and XBP1 transcription factors under ER stress activation
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Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-11 Man-Chen Hsu, Chia-Hui Chen, Mu-Chun Wang, Wen-Hua Chen, Po-An Hu, Bei-Chia Guo, Ru-Wen Chang, Chih-Hsien Wang, Tzong-Shyuan Lee
Fetuin-A, a hepatokine secreted by hepatocytes, binds to insulin receptors and consequently impairs the activation of the insulin signaling pathway, leading to insulin resistance. Apigenin, a flavonoid isolated from plants, has beneficial effects on insulin resistance; however, its regulatory mechanisms are not fully understood. In the present study, we investigated the molecular mechanisms underlying
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NK-92MI Cells Engineered with Anti-claudin-6 Chimeric Antigen Receptors in Immunotherapy for Ovarian Cancer Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-11 Junping Li, Hong Hu, Hui Lian, Shuo Yang, Manting Liu, Jinping He, Bihui Cao, Dongni Chen, Yuling Hu, Chen Zhi, Yan Shen, Xiaodie Ye, Bingjia He, Ming Zhao, Weijun Fan, Linfeng Xu, Rom Leidner, Qingde Wu, Lili Yang, Zhenfeng Zhang
Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to
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PARP1 Promotes Heart Regeneration and Cardiomyocyte Proliferation Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-11 Jiangcheng Shu, Shu Yan, Chenhui Ju, Long Chen, Minglu Liang, Cheng Wang, Kai Huang
Myocardial infarction causes cardiomyocyte loss, and depleted cardiomyocyte proliferative capacity after birth impinges the heart repair process, eventually leading to heart failure. This study aims to investigate the role of Poly(ADP-Ribose) Polymerase 1 (PARP1) in the regulation of cardiomyocyte proliferation and heart regeneration. Our findings demonstrated that PARP1 knockout impaired cardiomyocyte
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The FTO-CMPK2 Pathway in Fibroblast-like Synoviocytes Modulates Rheumatoid Arthritis Synovial Inflammation and Cartilage Homeostasis via mtDNA Regulation Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-11 Li Jin, Qiyue Chen, Ke Hu, Dandan Fan, Heping Zhang, Jiaxin Deng, Weizhong Qi, Qinghong Yu
In rheumatoid arthritis (RA), a debilitating autoimmune disorder marked by chronic synovial inflammation and progressive cartilage degradation, fibroblast-like synoviocytes (FLS) are key pathogenic players. Current treatments targeting these cells are limited. Our study focused on the Fat Mass and Obesity-associated protein (FTO), known for its roles in cell proliferation and inflammatory response
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Hypoxia-activated selectivity-improved anti-PKM2 antibody combined with prodrug TH-302 for potentiated targeting therapy in hepatocellular carcinoma Int. J. Biol. Sci. (IF 9.2) Pub Date : 2024-2-11 Bo Wang, Fang-Zheng Qi, Ping Chen, Luo-Meng Qian, Hui-Shan Su, Yang Wang, Chen-Hui Wang, Ya-Xin Hou, Qing Zhang, Ding Li, Zhe-Sheng Chen, Si-He Zhang
Background: Hypoxia induces hepatocellular carcinoma (HCC) malignancies; yet it also offers treatment opportunities, exemplified by developing hypoxia-activated prodrugs (HAPs). Although HAP TH-302 combined with therapeutic antibody (Ab) has synergistic effects, the clinical benefits are limited by the on-target off-tumor toxicity of Ab. Here, we sought to develop a hypoxia-activated anti-M2 splice
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What we learned from lifting COVID-19 restrictions in Macao in December 2022. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-24 Chon Lok Lei,Hoi Man Ng,Guihui Qin,Cheung Kwan Yeung,Chon Leng Lei,Ren-He Xu
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Protein arginine methylation in viral infection and antiviral immunity. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-24 Kai Zheng,Siyu Chen,Zhe Ren,Yifei Wang
Protein arginine methyltransferase (PRMT)-mediated arginine methylation is an important post-transcriptional modification that regulates various cellular processes including epigenetic gene regulation, genome stability maintenance, RNA metabolism, and stress-responsive signal transduction. The varying substrates and biological functions of arginine methylation in cancer and neurological diseases have
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XPOT Disruption Suppresses TNBC Growth through Inhibition of Specific tRNA Nuclear Exportation and TTC19 Expression to Induce Cytokinesis Failure. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-24 Huijuan Dai,Xiaomei Yang,Xiaonan Sheng,Yaohui Wang,Shan Zhang,Xueli Zhang,Lipeng Hu,Zhigang Zhang,Xinrui Dong,Wenjin Yin,Linli Yao,Jinsong Lu
Transfer RNAs (tRNAs) impact the development and progression of various cancers, but how individual tRNAs are modulated during triple-negative breast cancer (TNBC) progression remains poorly understood. Here, we found that XPOT (Exportin-T), a nuclear export protein receptor of tRNAs, is associated with poor prognosis in breast cancer and directly orchestrates the nuclear export of a subset of tRNAs
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Roles of Protein Post-Translational Modifications During Adipocyte Senescence. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-16 Min-Seon Hwang,Jingyeong Park,Yunha Ham,In Hye Lee,Kyung-Hee Chun
Adipocytes are adipose tissues that supply energy to the body through lipids. The two main types of adipocytes comprise white adipocytes (WAT) that store energy, and brown adipocytes (BAT), which generate heat by burning stored fat (thermogenesis). Emerging evidence indicates that dysregulated adipocyte senescence may disrupt metabolic homeostasis, leading to various diseases and aging. Adipocytes
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CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-16 Jingyu Liao,Zeyu Chen,Ruizhi Chang,Tong Yuan,Ganxun Li,Chang Zhu,Jingyuan Wen,Yi Wei,Zhao Huang,Zeyang Ding,Liang Chu,Junnan Liang,Bixiang Zhang
The centromere proteins (CENPs), a critical mitosis-related protein complexes, are involved in the kinetochore assembly and chromosome segregation. In this study, we identified that CENPA was significantly up-regulated in HCC and highly expressed CENPA correlated with poor prognosis for HCC patients. Knockdown of CENPA inhibited HCC cell proliferation and tumor growth in vitro and in vivo. Mechanistically
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Polyphyllin VII induces CTC anoikis to inhibit lung cancer metastasis through EGFR pathway regulation. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-16 Zujun Que,Bin Luo,Pan Yu,Dan Qi,Wenji Shangguan,Panpan Wang,Jiajun Liu,Yan Li,He Li,Ronghu Ke,Erxi Wu,Jianhui Tian
Circulating tumor cells (CTCs) are cells that detach from the primary tumor and enter the bloodstream, playing a crucial role in the metastasis of lung cancer. Unfortunately, there is currently a lack of drugs specifically designed to target CTCs and prevent tumor metastasis. In this study, we present evidence that polyphyllin VII, a potent anticancer compound, effectively inhibits the metastasis of
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Omentin-1 ameliorates the progress of osteoarthritis by promoting IL-4-dependent anti-inflammatory responses and M2 macrophage polarization. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-16 Chih-Yuan Ko,Yen-You Lin,David Achudhan,Jun-Way Chang,Shan-Chi Liu,Chao-Yang Lai,Yuan-Li Huang,Chun-Hao Tsai,Yi-Chin Fong,Hsien-Te Chen,Kun-Tsan Lee,Chien-Chung Huang,Ting-Kuo Chang,Chih-Hsin Tang
Osteoarthritis (OA) is a prevalent joint disease commonly associated with aging and obesity, which can lead to pain, stiffness, joint dysfunction, and disability. Omentin-1 (also called intelectin-1) is a newly discovered adipokine, which plays a protective role in suppressing the secretion of pro-inflammatory cytokines. Based on data from the Gene Expression Omnibus (GEO) dataset and clinical samples
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Genipin-activating PPARγ impedes CCR2-mediated macrophage infiltration into postoperative liver to suppress recurrence of hepatocellular carcinoma. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-16 Junyu Wu,Yau-Tuen Chan,Yuanjun Lu,Zixin Feng,Hongchao Yuan,Xiaoyu Xu,Lin Xu,Cheng Zhang,Yibin Feng,Hor-Yue Tan,Ning Wang
A high postoperative tumour recurrence rate has significantly rendered a poorer prognosis in hepatocellular carcinoma (HCC) patients. The aim of this study is to identify a natural compound genipin as a potential and effective candidate to suppress the postoperative recurrence of HCC. Clinical analysis revealed that infiltration of macrophage into the adjacent tissue but not HCC predicted patients'
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Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-16 Haixia Li,Dong Chen,Xiaoqin Zhang,Mingxian Chen,Yinghao Zhi,Weilu Cui,Shanshan Li,Fan Xu,Ying Tan,Hao Zhou,Xing Chang,Hengwen Chen
Apigenin is the active ingredient in Ludangshen. Although previous studies reported the cardioprotective actions of apigenin against doxorubicin (Dox)-induced cardiomyopathy, the underlying mechanisms remain incompletely understood. Since apigenin beneficially regulates various aspects of mitochondrial function and dynamics, we asked whether apigenin improves heart function in mice with Dox-induced
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Glutamine metabolism controls amphiregulin-facilitated chemoresistance to cisplatin in human chondrosarcoma. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-09 Yu-Ying Wu,Yat-Yin Law,Yu-Wen Huang,Nguyen Bao Tran,Chih-Yang Lin,Chao-Yang Lai,Yuan-Li Huang,Chun-Hao Tsai,Chih-Yuan Ko,Ming-Chih Chou,Wei-Chien Huang,Fang-Ju Cheng,Yi-Chin Fong,Chih-Hsin Tang
Chondrosarcoma is the second most common type of bone cancer. At present, the most effective clinical course of action is surgical resection. Cisplatin is the chemotherapeutic medication most widely used for the treatment of chondrosarcoma; however, its effectiveness is severely hampered by drug resistance. In the current study, we compared cisplatin-resistant chondrosarcoma SW1353 cells with their
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A novel lncRNA-mediated epigenetic regulatory mechanism in periodontitis. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-09 Zoe Xiaofang Zhu,Yao Liu,Jinghao Wang,Ying Xie,Rachel Yuantong Li,Qian Ma,Qisheng Tu,Neiman A Melhem,Sandrine Couldwell,Rady E El-Araby,Albert Tai,Thomas E Van Dyke,Nadeem Karimbux,Y Natalie Jeong,Jake Jinkun Chen
Periodontitis is a highly prevalent chronic inflammatory disease with an exaggerated host immune response, resulting in periodontal tissue destruction and potential tooth loss. The long non-coding RNA, LncR-ANRIL, located on human chromosome 9p21, is recognized as a genetic risk factor for various conditions, including atherosclerosis, periodontitis, diabetes, and cancer. LncR-APDC is an ortholog of
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Epigenetic modulations of immune cells: from normal development to tumor progression. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-02 Yuanchun Xu,Zongsheng He,Jing Du,Ziqiang Chen,John W M Creemers,Bin Wang,Fan Li,Yaling Wang
The dysfunction of immune cell development often impairs immunological homeostasis, thus causing various human diseases. Accumulating evidence shows that the development of different immune cells from hematopoietic stem cells are highly fine-tuned by different epigenetic mechanisms including DNA methylation, histone modifications, chromatin remodeling and RNA-related regulations. Understanding how
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S100a16 Deficiency Prevents Alcohol-induced Fatty Liver Injury via Inducing MANF Expression in Mice. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-02 Dan Wang,Rihua Zhang,Xiaoxuan Qin,Jizheng Wang,Yifang Hu,Shan Lu,Jingbao Kan,Yaoqi Ge,Ke Jin,Wen-Song Zhang,Yun Liu
Alcoholic liver disease (ALD) encompasses conditions ranging from simple steatosis to cirrhosis and even liver cancer. It has gained significant global attention in recent years. Despite this, effective pharmacological treatments for ALD remain elusive, and the core mechanisms underlying the disease are not yet fully comprehended. S100A16, a newly identified calcium-binding protein, is linked to lipid
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The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-02 Congkuan Song,Jinjin Zhang,Chenzhen Xu,Minglang Gao,Ning Li,Qing Geng
As a multi-substrate transmembrane protease, γ-secretase exists widely in various cells. It controls multiple important cellular activities through substrate cleavage. γ-secretase inhibitors (GSIs) play a role in cancer inhibition by blocking Notch cleavage, and are considered as potential therapeutic strategies for cancer. Currently, GSIs have encouraging performance in preclinical models, yet this
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Targeting Aquaporin-3 Attenuates Skin Inflammation in Rosacea. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-02 Mengting Chen,Qinqin Peng,Zixin Tan,San Xu,Yunying Wang,Aike Wu,Wenqin Xiao,Qian Wang,Hongfu Xie,Ji Li,Wei Shi,Zhili Deng
Rosacea is a common inflammatory skin disorder mediated by the dysregulation of both keratinocytes and T cells. Here, we report that aquaporin 3 (AQP3), a channel protein that mediates the transport of water/glycerol, was highly expressed in the epidermis and CD4+ T cells of both rosacea patients and experimental mice. Specifically, AQP3 deletion blocked the development of rosacea-like skin inflammation
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FLOT1 promotes gastric cancer progression and metastasis through BCAR1/ERK signaling. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-02 Ran Wang,Wei Huang,Kaimei Cai,Shihan Xiao,Wuming Zhang,Xianqin Hu,Jianping Guo,Linfeng Mao,Weijie Yuan,Yi Xu,Zihua Chen,Zhikang Chen,Chen Lai
Flotillin-1 (FLOT1) is a member of the flotillin family and serves as a hallmark of lipid rafts involved in the process of signaling transduction and vesicular trafficking. Here, we find FLOT1 promotes gastric cancer cell progression and metastasis by interacting with BCAR1, through ERK signaling. FLOT1 regulates BCAR1 phosphorylation and translocation. Overexpression of FLOT1 increases, while knockdown
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PTEN-induced kinase 1 exerts protective effects in diabetic kidney disease by attenuating mitochondrial dysfunction and necroptosis. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-02 Min-Ji Sung,Hyun-Ju An,Min Heui Ha,Seon Hwa Park,Hye Yun Jeong,Jihyun Baek,Sang Ho Lee,Yu Ho Lee,So-Young Lee
Mitochondrial dysfunction plays a pivotal role in diabetic kidney disease initiation and progression. PTEN-induced serine/threonine kinase 1 (PINK1) is a core organizer of mitochondrial quality control; however, its function in diabetic kidney disease remains controversial. Here, we aimed to investigate the pathophysiological roles of PINK1 in diabetic tubulopathy, focusing on its effects on mitochondrial
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Platelet-derived extracellular vesicles aggravate septic acute kidney injury via delivering ARF6. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-10-02 Xun Lu,Guiya Jiang,Yue Gao,Qi Chen,Si Sun,Weipu Mao,Nieke Zhang,Zepeng Zhu,Dong Wang,Guangyuan Zhang,Ming Chen,Lei Zhang,Shuqiu Chen
Circulating plasma extracellular vesicles (EVs) mostly originate from platelets and may promote organ dysfunction in sepsis. However, the role of platelet-derived EVs in sepsis-induced acute kidney injury (AKI) remains poorly understood. The present study extracted EVs from the supernatant of human platelets treated with phosphate buffer saline (PBS) or lipopolysaccharide (LPS). Then, we subjected
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Potential Roles of Metals in the Pathogenesis of Pulmonary and Systemic Hypertension. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-25 C Danielle Hopkins,Caitlin Wessel,Oscar Chen,Karim El-Kersh,Matthew C Cave,Lu Cai,Jiapeng Huang
Pulmonary and systemic hypertension (PH, SH) are characterized by vasoconstriction and vascular remodeling resulting in increased vascular resistance and pulmonary/aortic artery pressures. The chronic stress leads to inflammation, oxidative stress, and infiltration by immune cells. Roles of metals in these diseases, particularly PH are largely unknown. This review first discusses the pathophysiology
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Targeting HMGB1: A Potential Therapeutic Strategy for Chronic Kidney Disease. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-25 Tongtong Liu,Qian Li,Qi Jin,Liping Yang,Huimin Mao,Peng Qu,Jing Guo,Bo Zhang,Fang Ma,Yuyang Wang,Liang Peng,Ping Li,Yongli Zhan
High-mobility group protein box 1 (HMGB1) is a member of a highly conserved high-mobility group protein present in all cell types. HMGB1 plays multiple roles both inside and outside the cell, depending on its subcellular localization, context, and post-translational modifications. HMGB1 is also associated with the progression of various diseases. Particularly, HMGB1 plays a critical role in CKD progression
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High-fat diet promotes colitis-associated tumorigenesis by altering gut microbial butyrate metabolism. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-25 Xinyu Shao,Luojie Liu,Yuqing Zhou,Kaiqiang Zhong,Jinrong Gu,Tong Hu,Yizhou Yao,Chunli Zhou,Weichang Chen
Background: Dietary fat intake is associated with an increased risk of colitis associated cancer (CAC). A high-fat diet (HFD) leads to systemic low-grade inflammation. The colon is believed to be the first organ suffering from inflammation caused by the infiltration of pro-inflammatory macrophages, and promotes CAC progression. We explored the role of HFD in driving CAC by altering gut microbial butyrate
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Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-18 Kexin Jia,Yinhao Zhang,Ranyi Luo,Runping Liu,Yajing Li,Jianzhi Wu,Kaihong Xie,Jia Liu,Shuo Li,Fei Zhou,Xiaojiaoyang Li
Hepatic ischemia-reperfusion injury (HIRI), a common two-phase intersocietal reaction in liver surgery, typically leading to sustained liver dysfunction. During this process, liver sinusoidal endothelial cells (LSECs) are vulnerable to damage and exert senescence-associated secretory phenotype (SASP). However, how these SASP-LSECs secreted damage-associated molecular patterns (DAMPs) to impact the
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Enhanced tumor immunotherapy by polyfunctional CD19-CAR T cells engineered to secrete anti-CD47 single-chain variable fragment. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-18 Yingqi Qiu,Peiyun Liao,Hao Wang,Jianyu Chen,Yuxing Hu,Rong Hu,Honghao Zhang,Zhongwei Li,Manxiong Cao,Yulu Yang,Meifang Li,Xiaoling Xie,Yuhua Li
A high recurrence rate of non-Hodgkin's lymphoma (NHL) following chimeric antigen receptor T (CAR T) cell treatment remains a bottleneck, and immunosuppressive tumor microenvironment (TME) compromising CAR T cell efficacy in NHL is the primary cause of relapse. Accordingly, modifying the structure of CAR T cells to attenuate the inhibitory effect of TME thus reducing recurrence rate is a valuable research
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The emerging roles of metabolism in the crosstalk between breast cancer cells and tumor-associated macrophages. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-18 Yuxin Liang,Jun He,Xiguang Chen,Liyang Yin,Qiong Yuan,Qiting Zeng,Xuyu Zu,Yingying Shen
Breast cancer is the most common cancer affecting women worldwide. Investigating metabolism in breast cancer may accelerate the exploitation of new therapeutic options for immunotherapies. Metabolic reprogramming can confer breast cancer cells (BCCs) with a survival advantage in the tumor microenvironment (TME) and metabolic alterations in breast cancer, and the corresponding metabolic byproducts can
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Deciphering The Emerging Role of Programmed Cell Death in Diabetic Wound Healing. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-18 Jingyu Song,Keyu Zhu,Haiping Wang,Min Wu,Yiping Wu,Qi Zhang
Diabetic wounds are characterized by delayed and incomplete healing. As one of the most common complications of diabetes, diabetic wounds can be fatal in some cases. Programmed cell death (PCD) is an active and ordered cell death mode determined by genes, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis. It is currently believed that PCD plays a crucial role in
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Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-18 Haiyang Jiang,Peizhao Liu,Jiaqi Kang,Jie Wu,Wenbin Gong,Xuanheng Li,Yangguang Li,Juanhan Liu,Weizhen Li,Chujun Ni,Bo Liao,Xiuwen Wu,Yun Zhao,Jianan Ren
Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the
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The bidirectional interplay between ncRNAs and methylation modifications in gastrointestinal tumors. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-11 Minyu Kong,Xiao Yu,Wenzhi Guo,Ran Guo
The aberrant expression of methylation and ncRNAs, two crucial regulators of epigenetic modifications, has been widely demonstrated in cancer. The complex interplay between them is essential in promoting malignant phenotype, poor prognosis, and drug resistance in GI tumors (including esophageal, gastric, colorectal, liver, and pancreatic cancers). Therefore, we summarize the interrelation process between
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Inhibition of Heat Shock-Induced H3K9ac Reduction Sensitizes Cancer Cells to Hyperthermia. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-11 Huiyun Lin,Yihui Song,Lingjun Song,Zilong Geng,Runtan Cheng,Yinrui Lei,Fang Guo
Heat stress, clinically known as hyperthermia, is a promising adjunctive modality in cancer treatment. However, the efficacy of hyperthermia as a monotherapy is limited and the underlying mechanism remains poorly understood. Targeting histone modifications is an emerging strategy for cancer therapy, but little is known regarding the role of heat stress in altering these modifications. Here, we report
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Tofacitinib Promotes Functional Recovery after Spinal Cord Injury by Regulating Microglial Polarization via JAK/STAT Signaling Pathway. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-11 Hongdao Ma,Chenfeng Wang,Lin Han,Fanqi Kong,Zhixiao Liu,Bangke Zhang,Wenxiang Chu,Haibin Wang,Liang Wang,Qisheng Li,Weilin Peng,Haisong Yang,Chaofeng Han,Xuhua Lu
Background: The JAK/STAT signaling pathway is the main inflammatory signal transduction pathway, whether JAK/STAT contributes the pathology of SCI and targeting the pathway will alleviate SCI needs to be addressed. Here, we explored the therapeutic effect of pan-JAK inhibitor tofacitinib (TOF) on secondary injury after SCI and explained the underlying mechanisms. Methods: SCI model in rat was established
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SRSF1-mediated alternative splicing is required for spermatogenesis. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-11 Wen-Long Lei,Yuan-Yuan Li,Zongchang Du,Ruibao Su,Tie-Gang Meng,Yan Ning,Guanmei Hou,Heide Schatten,Zhen-Bo Wang,Zhiming Han,Fei Sun,Wei-Ping Qian,Chenli Liu,Qing-Yuan Sun
Alternative splicing (AS) plays significant roles in a multitude of fundamental biological activities. AS is prevalent in the testis, but the regulations of AS in spermatogenesis is only little explored. Here, we report that Serine/arginine-rich splicing factor 1 (SRSF1) plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf1 led to complete infertility
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Inonotus obliquus upregulates muscle regeneration and augments function through muscle oxidative metabolism. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-11 Chang-Lim You,Sang-Jin Lee,Jinwoo Lee,Tuan Anh Vuong,Hye-Young Lee,Se Yun Jeong,Akida Alishir,Allison S Walker,Gyu-Un Bae,Ki Hyun Kim,Jong-Sun Kang
Skeletal muscle wasting related to aging or pathological conditions is critically associated with the increased incidence and prevalence of secondary diseases including cardiovascular diseases, metabolic syndromes, and chronic inflammations. Much effort is made to develop agents to enhance muscle metabolism and function. Inonotus obliquus (I. obliquus; IO) is a mushroom popularly called chaga and has
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Loss of DDRGK1 impairs IRE1α UFMylation in spondyloepiphyseal dysplasia. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-04 Xiao Yang,Tangjun Zhou,Xin Wang,Ying Xia,Xiankun Cao,Xiaofei Cheng,Yu Cao,Peixiang Ma,Hui Ma,An Qin,Jie Zhao
Spondyloepiphyseal dysplasia (SEMD) is a rare disease in which cartilage growth is disrupted, and the DDRGK1 mutation is one of the causative genes. In our study, we established Ddrgk1fl/fl, Col2a1-ERT Cre mice, which showed a thickened hypertrophic zone (HZ) in the growth plate, simulating the previous reported SEMD pathology in vivo. Instead of the classical modulation mechanism towards SOX9, our
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Unraveling the Complex Interplay between Epigenetics and Immunity in Alcohol-Associated Liver Disease: A Comprehensive Review. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-04 Yali Liu,Tao Liu,Feiyu Zhang,Yanhang Gao
The mechanisms of immune dysfunction in alcohol-associated liver disease (ALD) have garnered growing research interest in recent times. Alcohol-mediated immune dysfunction has been implicated as a potential cause of ALD-associated microbial infection and inflammatory response. The immune microenvironment of an organism is essentially a complex network of interactions between immune cells, cytokines
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Novel insights from spatial transcriptome analysis in solid tumors. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-04 Jun Du,Zhi-Jie An,Zou-Fang Huang,Yu-Chen Yang,Ming-Hui Zhang,Xue-Hang Fu,Wei-Yang Shi,Jian Hou
Since its first application in 2016, spatial transcriptomics has become a rapidly evolving technology in recent years. Spatial transcriptomics enables transcriptomic data to be acquired from intact tissue sections and provides spatial distribution information and remedies the disadvantage of single-cell RNA sequencing (scRNA-seq), whose data lack spatially resolved information. Presently, spatial transcriptomics
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Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-04 Ming-Kun Chen,Zhuo-Yu Xiao,Zhi-Peng Huang,Kang-Yi Xue,Hui Xia,Jia-Wei Zhou,De-Ying Liao,Zhi-Jian Liang,Xiao Xie,Qing-Zhu Wei,Lin Zhong,Jian-Kun Yang,Cun-Dong Liu,Yang Liu,Shan-Chao Zhao
Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production
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p53 and MYC-regulated squalene epoxidase as Achilles heel in colorectal cancer. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-04 Martin Fischer
The transcription factors p53 and MYC are often considered non-druggable targets, but their dysregulation can generate new dependencies and treatment opportunities in cancer cells. The p53 and MYC-regulated squalene epoxidase (SQLE) has been identified as a potential Achilles heel in colorectal cancer. This is of great interest because the FDA-approved anti-fungal SQLE inhibitor Terbinafine could be
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COX2-ATP Synthase Regulates Spine Follicle Size in Hedgehogs. Int. J. Biol. Sci. (IF 9.2) Pub Date : 2023-09-04 Man Zhang,Mengyue Wang,Jingwei Jiang,Weiwei Liu,Siyi Zhou,Dehuan Wang,Miaomiao Wang,Zixian Zhao,Zhiling Xu,Wang Wu,Xia Lin,Jinwei Zhang,Wei Xu,Qu Tang,Rixing Zhan,Wanqian Liu,Li Yang,Xun Zhou,Wei Zhou,Mingxing Lei
Skin evolves essential appendages with adaptive patterns that synergistically insulate the body from environmental insults. How similar appendages in different animals generate diversely-sized appendages remain elusive. Here we used hedgehog spine follicles and mouse hair follicles as models to investigate how similar follicles form in different sizes postnatally. Histology and immunostaining show