keyword
https://read.qxmd.com/read/38493499/dual-responsive-supramolecular-polymeric-nanomedicine-for-self-cascade-amplified-cancer-immunotherapy
#1
JOURNAL ARTICLE
Wenting Hu, Binglin Ye, Guocan Yu, Huang Yang, Hao Wu, Yuan Ding, Feihe Huang, Weilin Wang, Zhengwei Mao
Insufficient tumor immunogenicity and immune escape from tumors remain common problems in all tumor immunotherapies. Recent studies have shown that pyroptosis, a form of programmed cell death that is accompanied by immune checkpoint inhibitors, can induce effective immunogenic cell death and long-term immune activation. Therapeutic strategies to jointly induce pyroptosis and reverse immunosuppressive tumor microenvironments are promising for cancer immunotherapy. In this regard, a dual-responsive supramolecular polymeric nanomedicine (NCSNPs) to self-cascade amplify the benefits of cancer immunotherapy is designed...
March 17, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38493358/a-loss-of-function-mutation-in-cldn25-causing-pelizaeus-merzbacher-like-leukodystrophy
#2
JOURNAL ARTICLE
Yosuke Hashimoto, Claude Besmond, Nathalie Boddaert, Arnold Munnich, Matthew Campbell
Claudin-25 (CLDN-25), also known as Claudin containing domain 1, is an uncharacterized claudin family member. It has less conserved amino acid sequences when compared to other claudins. It also has a very broad tissue expression profile and there is currently a lack of functional information from murine knockout models. Here, we report a de novo missense heterozygous variant in CLDN25 (c. 745G>C, p. A249P) found in a patient diagnosed with Pelizaeus-Merzbacher-like leukodystrophy and presenting with symptoms such as delayed motor development, several episodes of tonic absent seizures and generalized dystonia...
March 17, 2024: Human Molecular Genetics
https://read.qxmd.com/read/38493346/incorporating-network-diffusion-and-peak-location-information-for-better-single-cell-atac-seq-data-analysis
#3
JOURNAL ARTICLE
Jiating Yu, Jiacheng Leng, Zhichao Hou, Duanchen Sun, Ling-Yun Wu
Single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) data provided new insights into the understanding of epigenetic heterogeneity and transcriptional regulation. With the increasing abundance of dataset resources, there is an urgent need to extract more useful information through high-quality data analysis methods specifically designed for scATAC-seq. However, analyzing scATAC-seq data poses challenges due to its near binarization, high sparsity and ultra-high dimensionality properties...
January 22, 2024: Briefings in Bioinformatics
https://read.qxmd.com/read/38493342/scencore-leveraging-single-cell-epigenetic-data-to-predict-chromatin-conformation-using-graph-embedding
#4
JOURNAL ARTICLE
Ziheng Duan, Siwei Xu, Shushrruth Sai Srinivasan, Ahyeon Hwang, Che Yu Lee, Feng Yue, Mark Gerstein, Yu Luan, Matthew Girgenti, Jing Zhang
Dynamic compartmentalization of eukaryotic DNA into active and repressed states enables diverse transcriptional programs to arise from a single genetic blueprint, whereas its dysregulation can be strongly linked to a broad spectrum of diseases. While single-cell Hi-C experiments allow for chromosome conformation profiling across many cells, they are still expensive and not widely available for most labs. Here, we propose an alternate approach, scENCORE, to computationally reconstruct chromatin compartments from the more affordable and widely accessible single-cell epigenetic data...
January 22, 2024: Briefings in Bioinformatics
https://read.qxmd.com/read/38493304/n-allyl-quinoxaline-derivative-exhibited-potent-and-selective-cytotoxicity-through-egfr-vegfr-mediated-apoptosis-in-vitro-and-in-vivo-studies
#5
JOURNAL ARTICLE
Mohamed S Nafie, Mohab A Ali, Magdy M Youssef
The cytotoxic activity, EGFR/VEGFR2 target inhibition, apoptotic activity, RT-PCR gene expression, in vivo employing a solid-Ehrlich carcinoma model, and in silico investigations for highlighting the binding affinity of eight quinoxaline derivatives were tested for anticancer activities. The results showed that compound 8 (N-allyl quinoxaline) had potent cytotoxicity against A594 and MCF-7 cancer cells with IC50 values of 0.86 and 1.06 µM, respectively, with noncytotoxic activity against WISH and MCF-10A cells having IC50 values more than 100 µM...
April 2024: Journal of Biochemical and Molecular Toxicology
https://read.qxmd.com/read/38493248/sensing-of-mitochondrial-dna-by-zbp1-promotes-ripk3-mediated-necroptosis-and-ferroptosis-in-response-to-diquat-poisoning
#6
JOURNAL ARTICLE
Kunmei Lai, Junjie Wang, Siyi Lin, Zhimin Chen, Guo Lin, Keng Ye, Ying Yuan, Yujiao Lin, Chuan-Qi Zhong, Jianfeng Wu, Huabin Ma, Yanfang Xu
Diquat (DQ) poisoning is a severe medical condition associated with life-threatening implications and multiorgan dysfunction. Despite its clinical significance, the precise underlying mechanism remains inadequately understood. This study elucidates that DQ induces instability in the mitochondrial genome of endothelial cells, resulting in the accumulation of Z-form DNA. This process activates Z-DNA binding protein 1 (ZBP1), which then interacts with receptor-interacting protein kinase 3 (RIPK3), ultimately leading to RIPK3-dependent necroptotic and ferroptotic signaling cascades...
March 16, 2024: Cell Death and Differentiation
https://read.qxmd.com/read/38493244/long-non-coding-rna-mllt4-antisense-rna-1-induces-autophagy-to-inhibit-tumorigenesis-of-cervical-cancer-through-modulating-the-myosin-9-atg14-axis
#7
JOURNAL ARTICLE
Tingting Zhang, Tiantian Ji, Zhao Duan, Yuanyuan Xue
The regulatory mechanism of long non-coding RNAs (lncRNAs) in autophagy is as yet not well established. In this research, we show that the long non-coding RNA MLLT4 antisense RNA 1 (lncRNA MLLT4-AS1) is induced by the MTORC inhibitor PP242 and rapamycin in cervical cells. Overexpression of MLLT4-AS1 promotes autophagy and inhibits tumorigenesis and the migration of cervical cancer cells, whereas knockdown of MLLT4-AS1 attenuates PP242-induced autophagy. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between MLLT4-AS1 and other associated targets, such as myosin-9 and autophagy-related 14(ATG14)...
March 16, 2024: Scientific Reports
https://read.qxmd.com/read/38493226/the-pleiotropic-nature-of-nono-a-master-regulator-of-essential-biological-pathways-in-cancers
#8
REVIEW
Domenica Ronchetti, Valentina Traini, Ilaria Silvestris, Giuseppina Fabbiano, Francesco Passamonti, Niccolò Bolli, Elisa Taiana
NONO is a member of the Drosophila behavior/human splicing (DBHS) family of proteins. NONO is a multifunctional protein that acts as a "molecular scaffold" to carry out versatile biological activities in many aspects of gene regulation, cell proliferation, apoptosis, migration, DNA damage repair, and maintaining cellular circadian rhythm coupled to the cell cycle. Besides these physiological activities, emerging evidence strongly indicates that NONO-altered expression levels promote tumorigenesis. In addition, NONO can undergo various post-transcriptional or post-translational modifications, including alternative splicing, phosphorylation, methylation, and acetylation, whose impact on cancer remains largely to be elucidated...
March 16, 2024: Cancer Gene Therapy
https://read.qxmd.com/read/38493157/the-localization-origin-and-impact-of-platelets-in-the-tumor-microenvironment-are-tumor-type-dependent
#9
JOURNAL ARTICLE
Ophélie Le Chapelain, Soumaya Jadoui, Angèle Gros, Samir Barbaria, Keltouma Benmeziane, Véronique Ollivier, Sébastien Dupont, Mialitiana Solo Nomenjanahary, Sabrina Mavouna, Jasmina Rogozarski, Marie-Anne Mawhin, Giuseppina Caligiuri, Sandrine Delbosc, Françoise Porteu, Bernhard Nieswandt, Pierre H Mangin, Yacine Boulaftali, Benoit Ho-Tin-Noé
BACKGROUND: How platelets interact with and influence the tumor microenvironment (TME) remains poorly characterized. METHODS: We compared the presence and participation of platelets in the TME of two tumors characterized by highly different TME, PyMT AT-3 mammary tumors and B16F1 melanoma. RESULTS: We show that whereas firmly adherent platelets continuously line tumor vessels of both AT-3 and B16F1 tumors, abundant extravascular stromal clusters of platelets from thrombopoietin-independent origin were present only in AT-3 mammary tumors...
March 16, 2024: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/38493150/nek2a-prevents-centrosome-clustering-and-induces-cell-death-in-cancer-cells-via-kif2c-interaction
#10
JOURNAL ARTICLE
Batuhan Mert Kalkan, Selahattin Can Ozcan, Enes Cicek, Mehmet Gonen, Ceyda Acilan
Unlike normal cells, cancer cells frequently exhibit supernumerary centrosomes, leading to formation of multipolar spindles that can trigger cell death. Nevertheless, cancer cells with supernumerary centrosomes escape the deadly consequences of unequal segregation of genomic material by coalescing their centrosomes into two poles. This unique trait of cancer cells presents a promising target for cancer therapy, focusing on selectively attacking cells with supernumerary centrosomes. Nek2A is a kinase involved in mitotic regulation, including the centrosome cycle, where it phosphorylates linker proteins to separate centrosomes...
March 16, 2024: Cell Death & Disease
https://read.qxmd.com/read/38493114/high-throughput-sequencing-reveals-differences-in-microbial-community-structure-and-diversity-in-the-conjunctival-tissue-of-healthy-and-type-2-diabetic-mice
#11
JOURNAL ARTICLE
Fengjiao Li, Shuo Yang, Ji Ma, Xiaowen Zhao, Meng Chen, Ye Wang
BACKGROUND: To investigate the differences in bacterial and fungal community structure and diversity in conjunctival tissue of healthy and diabetic mice. METHODS: RNA-seq assays and high-throughput sequencing of bacterial 16 S rDNA and fungal internal transcribed spacer (ITS) gene sequences were used to identify differentially expressed host genes and fungal composition profiles in conjunctival tissues of diabetic BKS-db/db mice and BKS (control) mice. Functional enrichment analysis of differentially expressed genes and the correlation between the relative abundance of bacterial and fungal taxa in the intestinal mucosa were also performed...
March 16, 2024: BMC Microbiology
https://read.qxmd.com/read/38493069/ptip-safeguards-the-epigenetic-control-of-skeletal-stem-cell-quiescence-and-potency-in-skeletogenesis
#12
JOURNAL ARTICLE
Jianfei Liang, Jing Wang, Bingdong Sui, Yibo Tong, Jihua Chai, Qin Zhou, Chenxi Zheng, Hao Wang, Liang Kong, Haojian Zhang, Yi Bai
Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells (SSCs) in skeletogenesis governed by a key regulator, Ptip (also known as Paxip1, Pax interaction with transcription-activation domain protein-1). Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen (Col2)+ progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia...
February 29, 2024: Science Bulletin
https://read.qxmd.com/read/38493014/targeting-fks1-proteins-for-novel-antifungal-drug-discovery
#13
REVIEW
Vinit Kumar, Juan Huang, Yawen Dong, Ge-Fei Hao
Fungal infections are a major threat to human health. The limited availability of antifungal drugs, the emergence of drug resistance, and a growing susceptible population highlight the critical need for novel antifungal agents. The enzymes involved in fungal cell wall synthesis offer potential targets for antifungal drug development. Recent studies have enhanced our focus on the enzyme Fks1, which synthesizes β-1,3-glucan, a critical component of the cell wall. These studies provide a deeper understanding of Fks1's function in cell wall biosynthesis, pathogenicity, structural biology, evolutionary conservation across fungi, and interaction with current antifungal drugs...
March 15, 2024: Trends in Pharmacological Sciences
https://read.qxmd.com/read/38493006/targeting-hematologic-malignancies-by-inhibiting-e-selectin-a-sweet-spot-for-aml-therapy
#14
REVIEW
Geoffrey L Uy, Daniel J DeAngelo, Jay N Lozier, Dennis M Fisher, Brian A Jonas, John L Magnani, Pamela S Becker, Hillard M Lazarus, Ingrid G Winkler
E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewisx ) on acute myeloid leukemia (AML) cells leads to chemotherapy resistance in vivo. Uproleselan (GMI-1271) is a carbohydrate analog of sialyl Lewisx that blocks E-selectin binding...
February 28, 2024: Blood Reviews
https://read.qxmd.com/read/38492956/magnetic-nano-tweezer-for-interrogating-mechanosensitive-signaling-proteins-in-space-and-time
#15
JOURNAL ARTICLE
Minsuk Kwak
Spatiotemporal interrogation of signal transduction at the single-cell level is necessary to understand how extracellular cues are converted into biochemical signals and differentially regulate cellular responses. Using single-cell perturbation tools such as optogenetics, specific biochemical cues can be delivered to selective molecules or cells at any desired location and time. By measuring cellular responses to provided perturbations, investigators have decoded and deconstructed the working mechanisms of a variety of neuroelectric and biochemical signaling processes...
2024: Methods in Enzymology
https://read.qxmd.com/read/38492918/the-tale-of-sox2-focusing-on-lncrna-regulation-in-cancer-progression-and-therapy
#16
REVIEW
Peng Huang, Feng Wen, YiShan Li, Qiu Li
Long non-coding RNAs (lncRNAs) have emerged as influential contributors to diverse cellular processes, which regulate gene function and expression via multiple mechanistic pathways. Therefore, it is essential to exploit the structures and interactions of lncRNAs to comprehend their mechanistic functions within cells. A growing body of evidence has revealed that deregulated lncRNAs are involved in multiple regulations of malignant events including cell proliferation, growth, invasion, and metabolism. SRY-related high mobility group box (SOX)2, a well-recognized member of the SOX family, is commonly overexpressed in various types of cancer, contributing to tumor progression and maintenance of stemness...
March 14, 2024: Life Sciences
https://read.qxmd.com/read/38492906/structural-cell-heterogeneity-underlies-the-differential-contribution-of-il-17a-il-17f-and-il-23-to-joint-versus-skin-chronic-inflammation
#17
REVIEW
Marie Robert, Pierre Miossec
The current therapeutic strategy used in immune-mediated inflammatory diseases (IMIDs) primarily targets immune cells or associated-pathways. However, recent evidence suggests that the microenvironment modulates immune cell development and responses. During inflammation, structural cells acquire a pathogenetic phenotype and the interactions with immune cells are often greatly modified. Understanding the importance of these tissue-specific interactions may allow to explain why some biologics are effective in some IMIDs but not in others...
March 14, 2024: Autoimmunity Reviews
https://read.qxmd.com/read/38492895/olfactory-ensheathing-cells-as-candidate-cells-for-chronic-pain-treatment
#18
REVIEW
Mei-Chen Liu, Qing-Fa Guo, Wei-Wei Zhang, Hong-Liang Luo, Wen-Jun Zhang, Hai-Jun Hu
Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients' quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain...
March 14, 2024: Journal of Chemical Neuroanatomy
https://read.qxmd.com/read/38492876/jak2-stat3-as-a-new-potential-target-to-manage-neurodegenerative-diseases-an-interactive-review
#19
REVIEW
Siva Prasad Panda, Adarsh Kesharwani, Samaresh Datta, D S N B K Prasanth, Sunil Kumar Panda, Ajay Guru
Neurodegenerative diseases (NDDs) are a collection of incapacitating disorders in which neuroinflammation and neuronal apoptosis are major pathological consequences due to oxidative stress. Neuroinflammation manifests in the impacted cerebral areas as a result of pro-inflammatory cytokines stimulating the Janus Kinase2 (JAK2)/Signal Transducers and Activators of Transcription3 (STAT3) pathway via neuronal cells. The pro-inflammatory cytokines bind to their respective receptor in the neuronal cells and allow activation of JAK2...
March 14, 2024: European Journal of Pharmacology
https://read.qxmd.com/read/38492846/monitoring-the-interaction-between-solid-lipid-nanoparticles-and-alveolar-macrophages-via-the-label-free-technique
#20
JOURNAL ARTICLE
Pijush Kumar Paul, Wei Wu, Teerapol Srichana
Macrophages are employed as targets for delivering genes, drugs, or lipid nanoparticles into tumors or other specific sites. Studying the interaction between solid lipid nanoparticles (SLNs) and macrophages is essential for assessing nanotoxicity and advancing the development of nanomedicines. However, limited data are currently available on the membrane microstructure and biochemical changes that occur when macrophages interact with SLNs. We conducted a label-free morphological and biochemical investigation of NR8383 macrophages using optical diffraction tomography (ODT), which validated the efficiency of the SLNs as a drug delivery system...
March 14, 2024: Journal of Pharmaceutical Sciences
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