keyword
https://read.qxmd.com/read/38361405/autophagy-inhibitors-3-ma-and-baf-may-attenuate-hippocampal-neuronal-necroptosis-after-global-cerebral-ischemia-reperfusion-injury-in-male-rats-by-inhibiting-the-interaction-of-the-rip3-aif-cypa-complex
#21
JOURNAL ARTICLE
Chen Zhang, Renhui Liu, Mengmeng Chen, Yang Xu, Xiaoqin Jin, Bing Shen, Jingye Wang
Our previous study found that receptor interacting protein 3 (RIP3) and apoptosis-inducing factor (AIF) were involved in neuronal programmed necrosis during global cerebral ischemia-reperfusion (I/R) injury. Here, we further studied its downstream mechanisms and the role of the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (BAF). A 20-min global cerebral I/R injury model was constructed using the 4-vessel occlusion (4-VO) method in male rats. 3-MA and BAF were injected into the lateral ventricle 1 h before ischemia...
February 2024: Journal of Neuroscience Research
https://read.qxmd.com/read/38358974/arid1a-loss-is-associated-with-increased-nrf2-signaling-in-human-head-and-neck-squamous-cell-carcinomas
#22
JOURNAL ARTICLE
Vinh Nguyen, Travis P Schrank, Michael B Major, Bernard E Weissman
Prior to the next generation sequencing and characterization of the tumor genome landscape, mutations in the SWI/SNF chromatin remodeling complex and the KEAP1-NRF2 signaling pathway were underappreciated. While these two classes of mutations appeared to independently contribute to tumor development, recent reports have demonstrated a mechanistic link between these two regulatory mechanisms in specific cancer types and cell models. In this work, we expand upon these data by exploring the relationship between mutations in BAF and PBAF subunits of the SWI/SNF complex and activation of NRF2 signal transduction across many cancer types...
2024: PloS One
https://read.qxmd.com/read/38357971/mutation-of-the-swi-snf-complex-component-smarce1-decreases-nucleosome-stability-in-es-cells-and-impairs-differentiation
#23
JOURNAL ARTICLE
Katsunobu Kashiwagi, Junko Yoshida, Hiroshi Kimura, Keiko Shinjo, Yutaka Kondo, Kyoji Horie
The SWI/SNF chromatin remodeling complex consists of more than 10 component proteins that form a large protein complex of>1 MDa. The catalytic proteins Smarca4 or Smarca2 work in concert with the component proteins to form a chromatin platform suitable for transcriptional regulation. However, the mechanism by which each component protein works synergistically with the catalytic proteins remains largely unknown. Here, we report on the function of Smarce1, a component of the SWI/SNF complex, through the phenotypic analysis of homozygous mutant embryonic stem (ES) cells...
February 15, 2024: Journal of Cell Science
https://read.qxmd.com/read/38355080/organophosphate-esters-in-edible-marine-fish-tissue-specific-distribution-species-specific-bioaccumulation-and-human-exposure
#24
JOURNAL ARTICLE
Li Zhang, Cheng Yan, Jiaxin Ma, Rui Hou, Lu Lu
Although growing evidences have proved the wide presence of organophosphate esters (OPEs) in marine environments, information on the tissue- and species-specific accumulation characteristics of these emerging pollutants in wild marine fish and the associated human exposure risks are currently lacking. Eleven OPEs were comprehensively investigated for their occurrence and tissue accumulation in 15 marine fish species and their living environment matrices (seawater and sediment) from the Beibu Gulf. The OPE concentrations were statistically higher in the liver (17...
February 12, 2024: Environmental Pollution
https://read.qxmd.com/read/38352517/single-molecule-chromatin-configurations-link-transcription-factor-binding-to-expression-in-human-cells
#25
Benjamin R Doughty, Michaela M Hinks, Julia M Schaepe, Georgi K Marinov, Abby R Thurm, Carolina Rios-Martinez, Benjamin E Parks, Yingxuan Tan, Emil Marklund, Danilo Dubocanin, Lacramioara Bintu, William J Greenleaf
The binding of multiple transcription factors (TFs) to genomic enhancers activates gene expression in mammalian cells. However, the molecular details that link enhancer sequence to TF binding, promoter state, and gene expression levels remain opaque. We applied single-molecule footprinting (SMF) to measure the simultaneous occupancy of TFs, nucleosomes, and components of the transcription machinery on engineered enhancer/promoter constructs with variable numbers of TF binding sites for both a synthetic and an endogenous TF...
February 4, 2024: bioRxiv
https://read.qxmd.com/read/38349514/ripks-and-neuroinflammation
#26
REVIEW
Yue Xu, Feng Lin, Guolei Liao, Jiaxing Sun, Wenli Chen, Lei Zhang
Neuroinflammation is an immune response in the central nervous system and poses a significant threat to human health. Studies have shown that the receptor serine/threonine protein kinase family (RIPK) family, a popular research target in inflammation, has been shown to play an essential role in neuroinflammation. It is significant to note that the previous reviews have only examined the link between RIPK1 and neuroinflammation. However, it has yet to systematically analyze the relationship between the RIPK family and neuroinflammation...
February 13, 2024: Molecular Neurobiology
https://read.qxmd.com/read/38329694/targeting-cholesterol-biosynthesis-for-at-rt-comprehensive-expression-analysis-and-validation-in-newly-established-at-rt-cell-line
#27
JOURNAL ARTICLE
Fumitaka Matsumoto, Kiyotaka Yokogami, Ai Yamada, Hiroshi Moritake, Takashi Watanabe, Shinji Yamashita, Yuichiro Sato, Hideo Takeshima
Atypical teratoid/rhabdoid (AT/RT) is a rare and highly malignant tumor of the central nervous system (CNS). It is most commonly found in children less than 5 years of age and is associated with inactivation of loss of function of SMARCB1/INI1. An experimental model for AT/RT is necessary to develop new and effective therapies. We established a patient-derived new cell line (MZ611ATRT), which showed loss of BAF-47. MZ611ATRT genetically features somatic heterozygous deletion of SMARCB1 and single nucleotide deletion of the residual allele, exon 5 ([c...
February 8, 2024: Human Cell
https://read.qxmd.com/read/38328828/berberine-alleviates-ischemic-brain-injury-by-enhancing-autophagic-flux-via-facilitation-of-tfeb-nuclear-translocation
#28
JOURNAL ARTICLE
Yi-Li Liu, Tao Guo, Yong-Jie Zhang, Shun-Cong Tang, Xiao-Ming Zhao, Hong-Yun He, Chun-Lei Yu, Yi-Hao Deng
Berberine has been demonstrated to alleviate cerebral ischemia/reperfusion injury, but its neuroprotective mechanism has yet to be understood. Studies have indicated that ischemic neuronal damage was frequently driven by autophagic/lysosomal dysfunction, which could be restored by boosting transcription factor EB (TFEB) nuclear translocation. Therefore, this study investigated the pharmacological effects of berberine on TFEB-regulated autophagic/lysosomal signaling in neurons after cerebral stroke. A rat model of ischemic stroke and a neuronal ischemia model in HT22 cells were prepared using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD), respectively...
February 7, 2024: American Journal of Chinese Medicine
https://read.qxmd.com/read/38328215/mammalian-swi-snf-complex-activity-regulates-pou2f3-and-constitutes-a-targetable-dependency-in-small-cell-lung-cancer
#29
Leslie Duplaquet, Kevin So, Alexander W Ying, Xinyue Li, Yixiang Li, Xintao Qiu, Rong Li, Shilpa Singh, Xiaoli S Wu, Qi Liu, Jun Qi, Tim D D Somerville, Hillary Heiling, Emanuele Mazzola, Yenarae Lee, Thomas Zoller, Christopher R Vakoc, John G Doench, William C Forrester, Tinya Abrams, Henry W Long, Matthew J Niederst, Cigall Kadoch, Matthew G Oser
Small cell lung cancers (SCLC) are comprised of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLC, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes, including non-canonical BAF (ncBAF) complexes, as top dependencies specific to POU2F3-positive SCLC...
January 24, 2024: bioRxiv
https://read.qxmd.com/read/38315003/overcoming-clinical-resistance-to-ezh2-inhibition-using-rational-epigenetic-combination-therapy
#30
JOURNAL ARTICLE
Yaniv Kazansky, Daniel Cameron, Helen S Mueller, Phillip Demarest, Nadia Zaffaroni, Noemi Arrighetti, Valentina Zuco, Yasumichi Kuwahara, Romel Somwar, Marc Ladanyi, Rui Qu, Elisa de Stanchina, Filemon S Dela Cruz, Andrew L Kung, Mrinal M Gounder, Alex Kentsis
Epigenetic dependencies have become evident in many cancers. Based on antagonism between BAF/SWI/SNF and PRC2 in SMARCB1-deficient sarcomas, we recently completed the clinical trial of the EZH2 inhibitor tazemetostat. However, the principles of tumor response to epigenetic therapy in general, and tazemetostat in particular, remain unknown. Using functional genomics and diverse experimental models, we define molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors. We found distinct acquired mutations that converge on the RB1/E2F axis and decouple EZH2-dependent differentiation and cell cycle control...
February 5, 2024: Cancer Discovery
https://read.qxmd.com/read/38313908/imaging-features-of-biliary-adenofibroma-with-malignant-transformation-a-case-report-and-literature-review
#31
Yuanyuan Zhang, Qingqing Chen, Yue Shi, Fang Wang, Hongjie Hu
Biliary adenofibroma (BAF) is a rare benign tumor, but it has the potential for malignant transformation. The differentiation between benign and malignant forms of BAF before surgery is of great importance for clinical decision-making. We report a case of BAF with invasive carcinoma. The patient did not present any clinical symptoms but had a history of hepatitis B virus infection for more than twenty years. Magnetic resonance imaging (MRI) revealed a solid and cystic 4 cm mass in segment II of the liver exhibiting hypointense signals on T1-weighted images and intermediate-to-high intensity signals on T2-weighted images...
January 2024: Curēus
https://read.qxmd.com/read/38313292/arid1a-dependent-canonical-baf-complex-suppresses-inflammatory-programs-to-drive-efficient-germinal-center-b-cell-responses
#32
Vipul Shukla, Ajay Abraham, Daniela Samaniego-Castruita, Jillian Paladino, Isabella Han, Prathyaya Ramesh, Mi Thao Tran, Rebecca M Southern, Ashima Shukla
Differentiating B cells in germinal centers (GC) require tightly coordinated transcriptional and epigenetic transitions to generate efficient humoral immune responses. The mammalian Brg1/Brm-associated factor (BAF) complexes are major regulators of nucleosomal remodeling, crucial for cellular differentiation and development, and are commonly mutated in several cancers, including GC-derived B cell lymphomas. However, the specific roles of distinct BAF complexes in GC B cell biology and generation of functional humoral immune responses are not well understood...
January 18, 2024: Research Square
https://read.qxmd.com/read/38301943/antibiotics-and-antibiotic-resistance-genes-removal-in-biological-aerated-filter
#33
JOURNAL ARTICLE
Xiangkun Li, Ziyi Lu, Baoli Wu, Hongwei Xie, Gaige Liu
Two laboratory-level biological aerated filters (BAF) were constructed to explore their treatment capacity for simulated antibiotic wastewater at high (1---16 mg/L) and low (0---0.5 mg/L) concentrations. Results showed that BAF was capable of removing both sulfonamides and tetracyclines with an efficiency of over 90 % at 16 mg/L. The main mechanism for removing antibiotics was found to be biodegradation followed by adsorption. Paenarthrobacter was identified as the key genus in sulfonamides degradation, while Hydrogenophaga played a crucial role in tetracyclines degradation...
January 30, 2024: Bioresource Technology
https://read.qxmd.com/read/38294656/phytoremediation-of-heavy-metals-spiked-soil-by-celosia-argentea-l-effect-on-plant-growth-and-metal-stabilization
#34
JOURNAL ARTICLE
Umer Hussain, Rabia Afza, Iram Gul, Muhammad Anwar Sajad, Ghulam Mujtaba Shah, Zahir Muhammad, Shujaul Mulk Khan
Soil contaminated with heavy metals cause serious threat to the soil quality, biota, and human. The removal or stabilization of heavy metals through plants is an environment friendly approach. The aim of study was to assess the potential of Celosia argentea L. for the phytoremediation of heavy metals contaminated soil. Soil was spiked with different levels (0, 100, 200, 300, and 400 mg/kg) of chromium (Cr), copper (Cu), lead (Pb), and Zn (Zn). Experiment was carried out in greenhouse and impact of heavy metals was evaluated on plant by assessing the germination rate and plant growth...
January 31, 2024: Environmental Science and Pollution Research International
https://read.qxmd.com/read/38293113/utilizing-a-dual-endogenous-reporter-system-to-identify-functional-regulators-of-aberrant-stem-cell-and-differentiation-activity-in-colorectal-cancer
#35
Sandor Spisak, David Chen, Pornlada Likasitwatanakul, Paul Doan, Zhixin Li, Pratyusha Bala, Laura Vizkeleti, Viktoria Tisza, Pushpamail De Silva, Marios Giannakis, Brian Wolpin, Jun Qi, Nilay S Sethi
Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators that regulate these key cellular programs in CRC, we developed an endogenous reporter system by genome-editing human CRC cell lines with knock-in fluorescent reporters at the SOX9 and KRT20 locus to report aberrant stem cell-like activity and differentiation, respectively, and then performed pooled genetic perturbation screens. Constructing a dual reporter system that simultaneously monitored aberrant stem cell-like and differentiation activity in the same CRC cell line improved our signal to noise discrimination...
January 17, 2024: bioRxiv
https://read.qxmd.com/read/38275587/the-role-of-the-at-rich-interaction-domain-1a-gene-arid1a-in-human-carcinogenesis
#36
REVIEW
Jing Jing Li, Cheok Soon Lee
The switch/sucrose non-fermentable (SWI/SNF) (SWI/SNF) complex uses energy from ATP hydrolysis to mobilise nucleosomes on chromatin. Components of SWI/SNF are mutated in 20% of all human cancers, of which mutations in AT-rich binding domain protein 1A ( ARID1A ) are the most common. ARID1A is mutated in nearly half of ovarian clear cell carcinoma and around one-third of endometrial and ovarian carcinomas of the endometrioid type. This review will examine in detail the molecular functions of ARID1A, including its role in cell cycle control, enhancer regulation, and the prevention of telomerase activity...
December 19, 2023: Genes
https://read.qxmd.com/read/38262318/global-environmental-and-toxicological-impacts-of-polybrominated-diphenyl-ethers-versus-organophosphate-esters-a-comparative-analysis-and-regrettable-substitution-dilemma
#37
JOURNAL ARTICLE
Abdul Qadeer, Sidra Mubeen, Mengyang Liu, Tadiyose Girma Bekele, Chinemerem R Ohoro, Abiodun O Adeniji, Alhafez M Alraih, Zeeshan Ajmal, Ahmad S Alshammari, Yas Al-Hadeethi, Denisse Archundia, Shengwu Yuan, Xia Jiang, Shuhang Wang, Xixi Li, Sébastien Sauvé
The prevalence of organophosphate esters (OPEs) in the global environment is increasing, which aligns with the decline in the usage of polybrominated diphenyl ethers (PBDEs). PBDEs, a category of flame retardants, were banned and classified as persistent organic pollutants (POPs) through the Stockholm Convention due to their toxic and persistent properties. Despite a lack of comprehensive understanding of their ecological and health consequences, OPEs were adopted as replacements for PBDEs. This research aims to offer a comparative assessment of PBDEs and OPEs in various domains, specifically focusing on their persistence, bioaccumulation, and toxicity (PBT) properties...
January 17, 2024: Journal of Hazardous Materials
https://read.qxmd.com/read/38262111/lysosomal-alkalinization-in-nutrient-restricted-cancer-cells-activates-cytoskeletal-rearrangement-to-enhance-partial-epithelial-to-mesenchymal-transition
#38
JOURNAL ARTICLE
H Hazal Hüsnügil, Aliye Ezgi Güleç Taşkıran, Ismail Güderer, Leman Nur Nehri, Göksu Oral, Nazlı Şevval Menemenli, Özün Özcan, Ariana Noghreh, Aytekin Akyol, Sreeparna Banerjee
INTRODUCTION: Nutrient restriction in cancer cells can activate a number of stress response pathways for cell survival. We aimed to determine mechanistically how nutrient depletion in colorectal cancer (CRC) cells leads to cellular adaptation. MATERIALS AND METHODS: Cell survival under nutrient depletion (ND) was evaluated by colony formation and in vivo tumor formation assays. Lysosomes are activated with ND; therefore, we incubated the ND cells with the V-ATPase inhibitor Bafilomycin A1 (ND+Baf)...
January 22, 2024: Translational Oncology
https://read.qxmd.com/read/38256867/hiv-1-transcription-inhibition-using-small-rna-binding-molecules
#39
JOURNAL ARTICLE
Pooja Khatkar, Gifty Mensah, Shangbo Ning, Maria Cowen, Yuriy Kim, Anastasia Williams, Fardokht A Abulwerdi, Yunjie Zhao, Chen Zeng, Stuart F J Le Grice, Fatah Kashanchi
The HIV-1 transactivator protein Tat interacts with the transactivation response element (TAR) at the three-nucleotide UCU bulge to facilitate the recruitment of transcription elongation factor-b (P-TEFb) and induce the transcription of the integrated proviral genome. Therefore, the Tat-TAR interaction, unique to the virus, is a promising target for developing antiviral therapeutics. Currently, there are no FDA-approved drugs against HIV-1 transcription, suggesting the need to develop novel inhibitors that specifically target HIV-1 transcription...
December 25, 2023: Pharmaceuticals
https://read.qxmd.com/read/38246388/exploration-and-comparison-of-the-relationship-between-pahs-and-ros-in-pm-2-5-emitted-from-multiple-anthropogenic-sources-in-the-guanzhong-plain-china
#40
JOURNAL ARTICLE
Hongmei Xu, Yunxuan Gu, Yunlong Bai, Dan Li, Meixuan Liu, Zexuan Wang, Qian Zhang, Jian Sun, Zhenxing Shen
Anthropogenic emissions have emerged as an important source of urban atmospheric PM2.5 , exacerbating air pollution and the associated health implications. This study analyses PM2.5 , originating from major anthropogenic sources (industries, motor vehicles, and solid-fuel combustion for domestic applications) in the Guanzhong Plain in China, along with the parent- (p-), alkylated- (a-), and oxygenated- (o-) polycyclic aromatic hydrocarbons (PAHs) and reactive oxygen species (ROS) levels in PM2.5 . Industrial emissions are mainly characterised by high abundances of benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), and benz[a]fluoranthene (BaF)...
January 19, 2024: Science of the Total Environment
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