keyword
https://read.qxmd.com/read/38358010/still-water-run-deep-therapeutic-tp-effect-of-ucmsc-ex-via-regulating-mtor-to-enhance-autophagy
#21
JOURNAL ARTICLE
Zhirong Zhao, Li Han, Mei Xin, Lichen Zhou, Kexin Jiang, Qian Huang, Ruiwu Dai
Our previous study confirmed that umbilical cord mesenchymal stem cells-exosomes (ucMSC-Ex) inhibit apoptosis of pancreatic acinar cells to exert protective effects. However, the relationship between apoptosis and autophagy in traumatic pancreatitis (TP) has rarely been reported. We dissected the transcriptomics after pancreatic trauma and ucMSC-Ex therapy by high-throughput sequencing. Additionally, we used rapamycin and MHY1485 to regulate mTOR. HE, inflammatory factors and pancreatic enzymatic assays were used to comprehensively determine the local versus systemic injury level, fluorescence staining and electron microscopy were used to detect the effect of autophagy, and observe the expression levels of autophagy-related markers at the gene and protein levels...
February 2024: Journal of Cellular and Molecular Medicine
https://read.qxmd.com/read/38332877/corrigendum-to-bnip3-enhances-pancreatic-cancer-cell-migration-and-proliferation-via-modulating-autophagy-under-hypoxia-heliyon-8-10-october-2022-e11190
#22
Hongmei Li, Can Zhang, Qiong Zhang, Jiezhi Jia, Xiaojiao Wang
[This corrects the article DOI: 10.1016/j.heliyon.2022.e11190.].
January 15, 2024: Heliyon
https://read.qxmd.com/read/38325378/the-gator2-complex-maintains-lysosomal-autophagic-function-by-inhibiting-the-protein-degradation-of-mit-tfes
#23
JOURNAL ARTICLE
Shu Yang, Chun-Yuan Ting, Mary A Lilly
Lysosomes are central to metabolic homeostasis. The microphthalmia bHLH-LZ transcription factors (MiT/TFEs) family members MITF, TFEB, and TFE3 promote the transcription of lysosomal and autophagic genes and are often deregulated in cancer. Here, we show that the GATOR2 complex, an activator of the metabolic regulator TORC1, maintains lysosomal function by protecting MiT/TFEs from proteasomal degradation independent of TORC1, GATOR1, and the RAG GTPase. We determine that in GATOR2 knockout HeLa cells, members of the MiT/TFEs family are ubiquitylated by a trio of E3 ligases and are degraded, resulting in lysosome dysfunction...
January 31, 2024: Molecular Cell
https://read.qxmd.com/read/38324636/drak2-suppresses-autophagy-by-phosphorylating-ulk1-at-ser-56-to-diminish-pancreatic-%C3%AE-cell-function-upon-overnutrition
#24
JOURNAL ARTICLE
Yuting Lu, Junyu Xu, Yufeng Li, Ruoran Wang, Chengqiu Dai, Bingqian Zhang, Xinwen Zhang, Lei Xu, Yunhua Tao, Ming Han, Ren Guo, Qingqian Wu, Linshi Wu, Zhuoxian Meng, Minjia Tan, Jingya Li
Impeded autophagy can impair pancreatic β cell function by causing apoptosis, of which DAP-related apoptosis-inducing kinase-2 (DRAK2) is a critical regulator. Here, we identified a marked up-regulation of DRAK2 in pancreatic tissue across humans, macaques, and mice with type 2 diabetes (T2D). Further studies in mice showed that conditional knockout (cKO) of DRAK2 in pancreatic β cells protected β cell function against high-fat diet feeding along with sustained autophagy and mitochondrial function...
February 7, 2024: Science Translational Medicine
https://read.qxmd.com/read/38311244/siatg5-loaded-cancer-cell-membrane-fused-liposomes-induced-increased-uptake-of-albumin-bound-chemotherapeutics-in-pancreatic-cancer-cells
#25
JOURNAL ARTICLE
Jing Yan, Miaomiao Wang, Shunli Lv, Dagui Chen, Ziqing Wu, Dongyang Zhou, Shudong Zhang, Jiajing Lv, Ke Xu, Can Xu, Yan Wei
Chemotherapeutic efficacy for pancreatic cancer is severely compromised by limited drug availability to tumor cells. Herein, we constructed a cancer cell membrane-fused liposome containing a siATG5-loaded calcium phosphate (CaP) core, termed CLip@siATG5. Through cancer cell membrane camouflage, the liposomes evaded immune clearance, actively infiltrated tumor tissues, and were preferentially taken up by homotypic tumor cells. Then, siATG5 escaped from the endosomes and was liberated in the cytoplasm, mainly benefiting from CaP dissolution-induced endosome rupture and liposome disassembly in acidic endosomes...
February 2, 2024: Journal of Controlled Release
https://read.qxmd.com/read/38311007/bpa-and-low-se-exacerbate-apoptosis-and-mitophagy-in-chicken-pancreatic-cells-by-regulating-the-pten-pi3k-akt-mtor-pathway
#26
JOURNAL ARTICLE
Wenying Sun, Yutian Lei, Zhihui Jiang, Kun Wang, Huanyi Liu, Tong Xu
INTRODUCTION: Bisphenol A (BPA) is a widespread environmental pollutant which has serious toxic effects on organisms. One of the crucial trace elements is selenium (Se), whose shortage can harm biological tissues and enhance the toxicity of contaminants, in which apoptosis and autophagy are core events. OBJECTIVES: An in vivo model was established to investigate the effects of BPA and low-Se on chicken pancreatic tissue, and identify the possible potential molecular mechanism...
February 2, 2024: Journal of Advanced Research
https://read.qxmd.com/read/38297165/regulation-of-autophagy-by-perilysosomal-calcium-a-new-player-in-%C3%AE-cell-lipotoxicity
#27
REVIEW
Ha Thu Nguyen, Andreas Wiederkehr, Claes B Wollheim, Kyu-Sang Park
Autophagy is an essential quality control mechanism for maintaining organellar functions in eukaryotic cells. Defective autophagy in pancreatic beta cells has been shown to be involved in the progression of diabetes through impaired insulin secretion under glucolipotoxic stress. The underlying mechanism reveals the pathologic role of the hyperactivation of mechanistic target of rapamycin (mTOR), which inhibits lysosomal biogenesis and autophagic processes. Moreover, accumulating evidence suggests that oxidative stress induces Ca2+ depletion in the endoplasmic reticulum (ER) and cytosolic Ca2+ overload, which may contribute to mTOR activation in perilysosomal microdomains, leading to autophagic defects and β-cell failure due to lipotoxicity...
February 1, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38290659/csnk2a1-confers-gemcitabine-resistance-to-pancreatic-ductal-adenocarcinoma-via-inducing-autophagy
#28
JOURNAL ARTICLE
Zhi-De Liu, Yin-Hao Shi, Qiong-Cong Xu, Guang-Yin Zhao, Ying-Qin Zhu, Fu-Xi Li, Ming-Jian Ma, Jing-Yuan Ye, Xi-Tai Huang, Xi-Yu Wang, Xiang Xu, Jie-Qin Wang, Wei Zhao, Xiao-Yu Yin
Gemcitabine, a pivotal chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC), frequently encounters drug resistance, posing a significant clinical challenge with implications for PDAC patient prognosis. In this study, employing an integrated approach involving bioinformatic analyses from multiple databases, we unveil CSNK2A1 as a key regulatory factor. The patient-derived xenograft (PDX) model further substantiates the critical role of CSNK2A1 in gemcitabine resistance within the context of PDAC...
January 28, 2024: Cancer Letters
https://read.qxmd.com/read/38288023/periodontitis-promotes-the-progression-of-diabetes-mellitus-by-enhancing-autophagy
#29
JOURNAL ARTICLE
Zhiguo Cai, Shasha Du, Na Zhao, Nanqu Huang, Kun Yang, Liu Qi
OBJECTIVE: This study aims to identify the periodontitis factor that activates excessive autophagy in pancreatic β cells, resulting in organic lesions of pancreatic islet tissues and diminished insulin secretion, thereby accelerating the progression of diabetes mellitus (DM). METHODS: Sprague-Dawley (SD) rats were induced with periodontitis (PD), type 2 diabetes mellitus (T2DM), or the combination of T2DM and PD (DP) through a high-sugar/high-fat diet and ligation of the tooth neck with silk thread...
January 30, 2024: Heliyon
https://read.qxmd.com/read/38286986/correction-fisetin-induces-autophagy-in-pancreatic-cancer-cells-via-endoplasmic-reticulum-stress-and-mitochondrial-stress-dependent-pathways
#30
Shengnan Jia, Xiaodong Xu, Senhao Zhou, Yan Chen, Guoping Ding, Liping Cao
No abstract text is available yet for this article.
January 29, 2024: Cell Death & Disease
https://read.qxmd.com/read/38281991/current-status-of-stem-cell-therapy-for-type-1-diabetes-a-critique-and-a-prospective-consideration
#31
REVIEW
Mohamed A Ghoneim, Mahmoud M Gabr, Sawsan M El-Halawani, Ayman F Refaie
Over the past decade, there had been progress in the development of cell therapy for insulin-dependent diabetes. Nevertheless, important hurdles that need to be overcome still remain. Protocols for the differentiation of pluripotent stem cells into pancreatic progenitors or fully differentiated β-cells have been developed. The resulting insulin-producing cells can control chemically induced diabetes in rodents and were the subject of several clinical trials. However, these cells are immunogenic and possibly teratogenic for their transplantation, and an immunoisolation device and/or immunosuppression is needed...
January 29, 2024: Stem Cell Research & Therapy
https://read.qxmd.com/read/38267627/inhibition-of-adam9-promotes-the-selective-degradation-of-kras-and-sensitizes-pancreatic-cancers-to-chemotherapy
#32
JOURNAL ARTICLE
Yu-Kai Huang, Wei-Chung Cheng, Ting-Ting Kuo, Juan-Cheng Yang, Yang-Chang Wu, Heng-Hsiung Wu, Chia-Chien Lo, Chih-Ying Hsieh, Sze-Ching Wong, Chih-Hao Lu, Wan-Ling Wu, Shih-Jen Liu, Yi-Chuan Li, Ching-Chan Lin, Chia-Ning Shen, Mien-Chie Hung, Jaw-Town Lin, Chun-Chieh Yeh, Yuh-Pyng Sher
Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PDAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (ADAM)9 as a modulator of PDAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, ADAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS...
January 24, 2024: Nature Cancer
https://read.qxmd.com/read/38262267/igf1r-stimulates-autophagy-enhances-viability-and-promotes-insulin-secretion-in-pancreatic-%C3%AE-cells-in-gestational-diabetes-mellitus-by-upregulating-atg7
#33
JOURNAL ARTICLE
Qing Liu, Ying Han, Meng Zhang, Peng Yang, Yan Xiang, Min Chen, Fei Xu, Xiaochan Zhou, Dan Zheng, Juan Qin
Gestational diabetes mellitus (GDM) is a prevalent metabolic disturbance in pregnancy. This article investigated the correlations between serum IGF1R and ATG7 with insulin resistance (IR) in GDM patients. Firstly, 100 GDM patients and 100 healthy pregnant women were selected as study subjects. The levels of serum IGF1, IGF1R, and ATG7 and their correlations with the insulin resistance index homeostasis model assessment of insulin resistance (HOMA-IR) were measured and analyzed by ELISA and Pearson. Additionally, in mouse pancreatic β cells, IGF1R, ATG7, Beclin-1, and LC3-II/LC3-I levels, cell viability/apoptosis, and insulin level were assessed by western blot, CCK-8, flow cytometry, and ELISA...
January 22, 2024: Reproductive Biology
https://read.qxmd.com/read/38256073/gastrointestinal-cancer-therapeutics-via-triggering-unfolded-protein-response-and-endoplasmic-reticulum-stress-by-2-arylbenzofuran
#34
JOURNAL ARTICLE
Kui Zhang, Xin Hu, Jingjing Su, Dong Li, Abhimanyu Thakur, Vikramsingh Gujar, Hongjuan Cui
Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3'-Geranyl-3-prenyl-5,7,2',4'-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate significant anti-cancer properties against various gastrointestinal cancers, including colon, pancreatic, and gastric cancers...
January 13, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38254294/docosahexanoic-acid-attenuates-palmitate-induced-apoptosis-by-autophagy-upregulation-via-gpr120-mtor-axis-in-insulin-secreting-cells
#35
JOURNAL ARTICLE
Seok-Woo Hong, Jinmi Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
BACKGROUND: Polyunsaturated fatty acids (PUFAs) reportedly have protective effects on pancreatic β-cells; however, the underlying mechanisms are unknown. METHODS: To investigate the cellular mechanism of PUFA-induced cell protection, mouse insulinoma 6 (MIN6) cells were cultured with palmitic acid (PA) and/or docosahexaenoic acid (DHA), and alterations in cellular signaling and apoptosis were examined. RESULTS: DHA treatment remarkably repressed caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)-positive red dot signals in PA-treated MIN6 cells, with upregulation of autophagy, an increase in microtubule- associated protein 1-light chain 3 (LC3)-II, autophagy-related 5 (Atg5), and decreased p62...
January 23, 2024: Endocrinology and Metabolism
https://read.qxmd.com/read/38253121/dysregulation-of-autophagy-activation-induced-by-atorvastatin-contributes-to-new-onset-diabetes-mellitus-in-western-diet-fed-mice
#36
JOURNAL ARTICLE
Juhee Kim, Minjune Kim, Minjeong Kim, Young-Hye You, Youngmi Song, Byung-Wan Lee
BACKGROUND AND AIMS: The incidence of statin-induced new-onset diabetes (NOD) is increasing but its underlying mechanisms remain unclear. We aimed to investigate the effects of various doses of atorvastatin (ATO)-induced autophagy on the development of NOD. METHODS AND RESULTS: The isolated rat islets and MIN6 cells-treated with ATO, exhibited impaired glucose-stimulated insulin secretion, reduced insulin content, and induced apoptosis. Additionally, autophagy was induced at all doses (in vitro: 5, 10, 20 μM; in vivo: 10, 15, 20 mg/kg) in ATO-treated MIN6 cells or western diet (WD)-fed mice...
January 20, 2024: Metabolism: Clinical and Experimental
https://read.qxmd.com/read/38229750/discovery-of-novel-pde%C3%AE-autophagic-degraders-a-case-study-of-autophagy-tethering-compound-attec
#37
JOURNAL ARTICLE
Jingying Bao, Zhenqian Chen, Yu Li, Long Chen, Wei Wang, Chunquan Sheng, Guoqiang Dong
The autophagy-tethering compound (ATTEC) technology has emerged as a promising strategy for targeted protein degradation (TPD). Here, we report the discovery of the first generation of PDEδ autophagic degraders using an ATTEC approach. The most promising compound 12c exhibited potent PDEδ binding affinity and efficiently induced PDEδ degradation in a concentration-dependent manner. Mechanistic studies confirmed that compound 12c reduced the PDEδ protein level through lysosome-mediated autophagy without affecting the PDEδ mRNA expression...
January 11, 2024: ACS Medicinal Chemistry Letters
https://read.qxmd.com/read/38228036/ndrg1-overcomes-resistance-to-immunotherapy-of-pancreatic-ductal-adenocarcinoma-through-inhibiting-atg9a-dependent-degradation-of-mhc-1
#38
JOURNAL ARTICLE
Zhiheng Zhang, Bojiao Song, Haowei Wei, Yang Liu, Wenjie Zhang, Yuhong Yang, Beicheng Sun
AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is resistant to immune checkpoint blockade (ICB) therapies. Emerging evidence suggests that NDRG1 may be an important target for the development of new therapies for PDAC. Herein, we investigated the novel roles of NDRG1 and Combretastatin A-4 (CA-4) in the treatment of PDAC ICB resistance. METHODS: Enrichment of MHC class I was detected by RNA sequence and verified by RT-qPCR and immunoblotting in NDRG1-knockdown human pancreatic cancer cell lines...
January 9, 2024: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/38212158/mitochondrial-dysfunction-in-the-pathogenesis-of-acute-pancreatitis
#39
REVIEW
Xia Chen, Rui Zhong, Bing Hu
The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as a key event in the pathophysiology of AP. Mitochondrial dysfunction is closely related to calcium (Ca2+ ) overload, intracellular adenosine triphosphate depletion, mitochondrial permeability transition pore openings, loss of mitochondrial membrane potential, mitophagy damage and inflammatory responses...
December 30, 2023: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://read.qxmd.com/read/38186315/roles-of-rictor-alterations-in-gastrointestinal-tumors-review
#40
JOURNAL ARTICLE
Ruizhen Cao, Shuilong Guo, Li Min, Peng Li
Gastrointestinal tumors account for five of the top 10 causes of mortality from all cancers (colorectal, liver, stomach, esophageal and pancreatic cancer). Mammalian target of rapamycin (mTOR) signaling is commonly dysregulated in various human cancers. As a core component of the mTOR complex 2 (mTORC2), Rictor is a key effector molecule of the PI3K/Akt pathway. A high alteration rate of Rictor has been observed in gastrointestinal tumors, and such Rictor alterations are often associated with resistance to chemotherapy and related adverse clinical outcomes...
February 2024: Oncology Reports
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