keyword
https://read.qxmd.com/read/38536949/combination-nano-delivery-systems-remodel-the-immunosuppressive-tumor-microenvironment-for-metastatic-triple-negative-breast-cancer-therapy
#1
JOURNAL ARTICLE
Liya Bai, Hui Liu, Ran You, Xiaoyu Jiang, Tao Zhang, Yunan Li, Tianhe Shan, Zhanyin Qian, Yinsong Wang, Yuanyuan Liu, Chunyu Li
Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer for which effective therapies are lacking. Targeted remodeling of the immunosuppressive tumor microenvironment (TME) and activation of the body's immune system to fight tumors with well-designed nanoparticles have emerged as pivotal breakthroughs in tumor treatment. To simultaneously remodel the immunosuppressive TME and trigger immune responses, we designed two potential therapeutic nanodelivery systems to inhibit TNBC. First, the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 and the cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) were coloaded into chondroitin sulfate (CS) to obtain CS@JQ1/CXB nanoparticles (NPs)...
March 27, 2024: Molecular Pharmaceutics
https://read.qxmd.com/read/38536229/combinatorial-approach-with-mass-spectrometry-and-lectin-microarray-dissected-site-specific-glycostem-and-glycoleaf-features-of-the-virion-derived-spike-protein-of-ancestral-and-%C3%AE-variant-sars-cov-2-strains
#2
JOURNAL ARTICLE
Takahiro Hiono, Hiroaki Sakaue, Azusa Tomioka, Hiroyuki Kaji, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Atsushi Kuno
The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted public health globally. As the glycosylation of viral envelope glycoproteins is strongly associated with their immunogenicity, intensive studies have been conducted on the glycans of the glycoprotein of SARS-CoV-2, the spike (S) protein. Here, we conducted intensive glycoproteomic analyses of the SARS-CoV-2 S protein of ancestral and γ-variant strains using a combinatorial approach with two different technologies: mass spectrometry (MS) and lectin microarrays (LMA)...
March 27, 2024: Journal of Proteome Research
https://read.qxmd.com/read/38535306/plant-derived-senotherapeutics-for-the-prevention-and-treatment-of-intervertebral-disc-degeneration-and-aging
#3
REVIEW
Eleni Mavrogonatou, Dimitris Kletsas
Chronic low back pain, a major cause of disability with a great global socioeconomic impact, has been inextricably associated with intervertebral disc degeneration. On the other hand, an enhanced number of senescent cells has been identified in aged and degenerated intervertebral discs and their senescence-associated secretory phenotype (SASP) has been connected with qualitative/quantitative alterations in the extracellular matrix and ultimately with the disturbance of tissue homeostasis. Given that selective elimination of senescent cells (by the so-called senolytics) or amendment of their secretome towards a less catabolic/inflammatory phenotype (by molecules known as senomorphics) has been reported to alleviate symptoms of several age-associated diseases and to improve tissue quality during aging, here we will review the emerging role of senolytic and senomorphic agents derived from plants and natural products against intervertebral disc degeneration...
February 28, 2024: Metabolites
https://read.qxmd.com/read/38535230/hsp90-mediated-multi-drug-resistance-in-dna-polymerase-defective-strains-of-candida-albicans
#4
JOURNAL ARTICLE
Bhabasha Gyanadeep Utkalaja, Satya Ranjan Sahu, Sushree Subhashree Parida, Narottam Acharya
The incidence of infections caused by Candida species, specifically by drug-resistant isolates, is a major health concern as they can disseminate to and colonize most vital organs, enhancing morbidity and mortality. Several molecular mechanisms have been reported to be involved in drug resistance. These are mostly drug- and isolate-specific. Here, we characterized three different genetically modified strains of C. albicans that were multi-drug-resistant (MDR) and deciphered a uniform mechanism responsible for resistance...
March 19, 2024: Journal of Fungi (Basel, Switzerland)
https://read.qxmd.com/read/38534683/the-synthetic-peptide-lyetx-i-mn%C3%A2-k-derived-from-lycosa-erythrognatha-spider-toxin-is-active-against-methicillin-resistant-staphylococcus-aureus-mrsa-in-vitro-and-in-vivo
#5
JOURNAL ARTICLE
Ana Paula Gonçalves Coelho Vieira, Amanda Neves de Souza, William Gustavo Lima, Julio Cesar Moreira Brito, Daniela Carolina Simião, Lucas Vinícius Ribeiro Gonçalves, Lídia Pereira Barbosa Cordeiro, Denise de Oliveira Scoaris, Simone Odília Antunes Fernandes, Jarbas Magalhães Resende, Burkhard Bechinger, Rodrigo Moreira Verly, Maria Elena de Lima
The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA...
March 8, 2024: Antibiotics
https://read.qxmd.com/read/38534254/advancing-point-of-care-diagnosis-digitalizing-combinatorial-biomarker-signals-for-lupus-nephritis
#6
JOURNAL ARTICLE
Jiechang Guo, Aygun Teymur, Chenling Tang, Ramesh Saxena, Tianfu Wu
To improve the efficiency and patient coverage of the current healthcare system, user-friendly novel homecare devices are urgently needed. In this work, we developed a smartphone-based analyzing and reporting system (SBARS) for biomarker detection in lupus nephritis (LN). This system offers a cost-effective alternative to traditional, expensive large equipment in signal detection and quantification. This innovative approach involves using a portable and affordable microscopic reader to capture biomarker signals...
March 18, 2024: Biosensors
https://read.qxmd.com/read/38533538/cxcr4-targeted-macrophage-derived-biomimetic-hybrid-vesicle-nanoplatform-for-enhanced-cancer-therapy-through-codelivery-of-manganese-and-doxorubicin
#7
JOURNAL ARTICLE
Yeonwoo Jang, Young Seok Cho, April Kim, Xingwu Zhou, Yujin Kim, Ziye Wan, James J Moon, Hansoo Park
Immune-cell-derived membranes have garnered significant attention as innovative delivery modalities in cancer immunotherapy for their intrinsic immune-modulating functionalities and superior biocompatibilities. Integrating additional parental cell membranes or synthetic lipid vesicles into cellular vesicles can further potentiate their capacities to perform combinatorial pharmacological activities in activating antitumor immunity, thus providing insights into the potential of hybrid cellular vesicles as versatile delivery vehicles for cancer immunotherapy...
March 27, 2024: ACS Applied Materials & Interfaces
https://read.qxmd.com/read/38532137/machine-learning-guided-engineering-of-genetically-encoded-fluorescent-calcium-indicators
#8
JOURNAL ARTICLE
Sarah J Wait, Marc Expòsit, Sophia Lin, Michael Rappleye, Justin Daho Lee, Samuel A Colby, Lily Torp, Anthony Asencio, Annette Smith, Michael Regnier, Farid Moussavi-Harami, David Baker, Christina K Kim, Andre Berndt
Here we used machine learning to engineer genetically encoded fluorescent indicators, protein-based sensors critical for real-time monitoring of biological activity. We used machine learning to predict the outcomes of sensor mutagenesis by analyzing established libraries that link sensor sequences to functions. Using the GCaMP calcium indicator as a scaffold, we developed an ensemble of three regression models trained on experimentally derived GCaMP mutation libraries. The trained ensemble performed an in silico functional screen on 1,423 novel, uncharacterized GCaMP variants...
March 2024: Nature computational science
https://read.qxmd.com/read/38530327/the-spiraling-cognitive-emotional-brain-combinatorial-reciprocal-and-reentrant-macro-organization
#9
JOURNAL ARTICLE
Luiz Pessoa
This article proposes a framework for understanding the macro-scale organization of anatomical pathways in the mammalian brain. The architecture supports flexible behavioral decisions across a spectrum of spatio-temporal scales. The proposal emphasizes the combinatorial, reciprocal, and reentrant connectivity-called CRR neuroarchitecture-between cortical, BG, thalamic, amygdala, hypothalamic, and brainstem circuits. Thalamic nuclei, especially midline/intralaminar nuclei, are proposed to act as hubs routing the flow of signals between noncortical areas and pFC...
March 22, 2024: Journal of Cognitive Neuroscience
https://read.qxmd.com/read/38529797/combinatorial-transcriptomic-and-genetic-dissection-of-insulin-igf-1-signaling-regulated-longevity-in-caenorhabditis-elegans
#10
JOURNAL ARTICLE
Seokjin Ham, Sieun S Kim, Sangsoon Park, Hyunwoo C Kwon, Seokjun G Ha, Yunkyu Bae, Gee-Yoon Lee, Seung-Jae V Lee
Classical genetic analysis is invaluable for understanding the genetic interactions underlying specific phenotypes, but requires laborious and subjective experiments to characterize polygenic and quantitative traits. Contrarily, transcriptomic analysis enables the simultaneous and objective identification of multiple genes whose expression changes are associated with specific phenotypes. Here, we conducted transcriptomic analysis of genes crucial for longevity using datasets with daf-2/insulin/IGF-1 receptor mutant Caenorhabditis elegans...
March 26, 2024: Aging Cell
https://read.qxmd.com/read/38529502/geny-a-genotyping-tool-for-allelic-decomposition-of-killer-cell-immunoglobulin-like-receptor-genes
#11
Qinghui Zhou, Mazyar Ghezelji, Ananth Hari, Michael K B Ford, Connor Holley, Lisa Mirabello, Stephen Chanock, S Cenk Sahinalp, Ibrahim Numanagić
Accurate genotyping of Killer cell Immunoglobulin-like Receptor (KIR) genes plays a pivotal role in enhancing our understanding of innate immune responses, disease correlations, and the advancement of personalized medicine. However, due to the high variability of the KIR region and high level of sequence similarity among different KIR genes, the currently available genotyping methods are unable to accurately infer copy numbers, genotypes and haplotypes of individual KIR genes from next-generation sequencing data...
March 3, 2024: bioRxiv
https://read.qxmd.com/read/38528768/combinatorial-optimization-of-pathway-process-and-media-for-the-production-of-p-coumaric-acid-by-saccharomyces-cerevisiae
#12
JOURNAL ARTICLE
Sara Moreno-Paz, Rianne van der Hoek, Elif Eliana, Vitor A P Martins Dos Santos, Joep Schmitz, Maria Suarez-Diez
Microbial cell factories are instrumental in transitioning towards a sustainable bio-based economy, offering alternatives to conventional chemical processes. However, fulfilling their potential requires simultaneous screening for optimal media composition, process and genetic factors, acknowledging the complex interplay between the organism's genotype and its environment. This study employs statistical design of experiments to systematically explore these relationships and optimize the production of p-coumaric acid (pCA) in Saccharomyces cerevisiae...
March 2024: Microbial Biotechnology
https://read.qxmd.com/read/38527041/neoadjuvant-chemo-immunotherapy-is-improved-with-a-novel-pulsed-electric-field-technology-in-an-immune-cold-murine-model
#13
JOURNAL ARTICLE
Chiara Pastori, Ebtesam H O Nafie, Mukta S Wagh, Stephen J Hunt, Robert E Neal
Chemo-immunotherapy uses combined systemic therapies for resectable and unresectable tumors. This approach is gaining clinical momentum, but survival increases leave considerable room for improvement. A novel form of Pulsed Electric Field (PEF) ablation combines focal tissue destruction with immune activation in preclinical settings. The PEFs induce lethal cell damage without requiring thermal processes, leaving cellular proteins intact. This affords PEF a favorable safety profile, improved antigenicity, and significant immunostimulatory damage-associated molecular pattern release compared to other focal therapies...
2024: PloS One
https://read.qxmd.com/read/38526721/generation-of-a-na%C3%A3-ve-human-scfv-phage-display-library-and-panning-selection
#14
JOURNAL ARTICLE
Brenda Pei Chui Song, Jing Yi Lai, Theam Soon Lim
Phage display antibody libraries have been successfully used as the essential tool to produce monoclonal antibodies against a plethora of targets ranging from diseases to native biologically important proteins as well as small molecules. It is well documented that diverse antibody genes are the major genetic source for the construction of a high-quality antibody library and selection of high-affinity antibodies. Naïve antibody libraries are derived using the IgM repertoire of healthy donors obtained from B-cells isolated from human peripheral blood mononuclear cell (PBMC)...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38526664/cuminaldehyde-and-tobramycin-forestall-the-biofilm-threats-of-staphylococcus-aureus-a-combinatorial-strategy-to-evade-the-biofilm-challenges
#15
JOURNAL ARTICLE
Ritwik Roy, Payel Paul, Poulomi Chakraborty, Moumita Malik, Sharmistha Das, Sudipta Chatterjee, Alakesh Maity, Monikankana Dasgupta, Ranojit Kumar Sarker, Sarita Sarkar, Anirban Das Gupta, Prosun Tribedi
Staphylococcus aureus, an opportunistic Gram-positive pathogen, is known for causing various infections in humans, primarily by forming biofilms. The biofilm-induced antibiotic resistance has been considered a significant medical threat. Combinatorial therapy has been considered a reliable approach to combat antibiotic resistance by using multiple antimicrobial agents simultaneously, targeting bacteria through different mechanisms of action. To this end, we examined the effects of two molecules, cuminaldehyde (a natural compound) and tobramycin (an antibiotic), individually and in combination, against staphylococcal biofilm...
March 25, 2024: Applied Biochemistry and Biotechnology
https://read.qxmd.com/read/38525961/evaluation-of-the-cytosolic-uptake-of-halotag-using-a-ph-sensitive-dye
#16
JOURNAL ARTICLE
JoLynn B Giancola, Jonathan B Grimm, Joomyung V Jun, Yana D Petri, Luke D Lavis, Ronald T Raines
The efficient cytosolic delivery of proteins is critical for advancing novel therapeutic strategies. Current delivery methods are severely limited by endosomal entrapment, and detection methods lack sophistication in tracking the fate of delivered protein cargo. HaloTag, a commonly used protein in chemical biology and a challenging delivery target, is an exceptional model system for understanding and exploiting cellular delivery. Here, we employed a combinatorial strategy to direct HaloTag to the cytosol. We established the use of Virginia Orange, a pH-sensitive fluorophore, and Janelia Fluor 585, a similar but pH-agnostic fluorophore, in a fluorogenic assay to ascertain protein localization within human cells...
March 25, 2024: ACS Chemical Biology
https://read.qxmd.com/read/38525874/dual-encoded-affinity-microbead-signature-combinatorial-profiling-for-acute-myocardial-infarction-high-sensitivity-diagnosis
#17
JOURNAL ARTICLE
Luxuan He, Jiacheng Wu, Zhun Lin, Yuanqing Zhang, Peiqing Liu
The early diagnosis of acute myocardial infarction (AMI) is dependent on the combined feedback of multiple cardiac biomarkers. However, it remains challenging to precisely detect multicardiac biomarkers in complex blood early due to the lack of sensitive and specific diagnostic indicators and the low abundance and small size of associated biomarkers with high specificity (such as microRNAs). To make matters worse, spectral overlap significantly limits the multiplex analysis of cardiac biomarkers by fluorescent probes, leading to bias in the diagnosis of myocardial infarction...
March 25, 2024: ACS Sensors
https://read.qxmd.com/read/38524412/prokaryotic-dna-crossroads-holliday-junction-formation-and-resolution
#18
REVIEW
Astha Nautiyal, Manoj Thakur
Cells are continually exposed to a multitude of internal and external stressors, which give rise to various types of DNA damage. To protect the integrity of their genetic material, cells are equipped with a repertoire of repair proteins that engage in various repair mechanisms, facilitated by intricate networks of protein-protein and protein-DNA interactions. Among these networks is the homologous recombination (HR) system, a molecular repair mechanism conserved in all three domains of life. On one hand, HR ensures high-fidelity, template-dependent DNA repair, while on the other hand, it results in the generation of combinatorial genetic variations through allelic exchange...
March 19, 2024: ACS Omega
https://read.qxmd.com/read/38523522/ras-related-protein-in-brain-4a-rab4a-is-downregulated-by-mir-496-to-inhibit-the-progression-of-gastric-cancer
#19
JOURNAL ARTICLE
Rui Su, Meng Su, Yan Lu
INTRODUCTION: Ras-related protein in brain 4A (Rab4A), as a member of the Rab family, is involved in the intracellular circulation of membrane receptors or endocytic substances and regulates the progression of multiple tumors. METHOD: From our results, the knockdown of Rab4A inhibited the proliferation, migration and invasion in AGS cells. Importantly, the surface expression of epidermal growth factor receptor (EGFR) declined significantly in Rab4A knockdown cells...
October 16, 2023: Combinatorial Chemistry & High Throughput Screening
https://read.qxmd.com/read/38523316/next-gen-gwas-full-2d-epistatic-interaction-maps-retrieve-part-of-missing-heritability-and-improve-phenotypic-prediction
#20
JOURNAL ARTICLE
Clément Carré, Jean Baptiste Carluer, Christian Chaux, Chad Estoup-Streiff, Nicolas Roche, Eric Hosy, André Mas, Gabriel Krouk
The problem of missing heritability requires the consideration of genetic interactions among different loci, called epistasis. Current GWAS statistical models require years to assess the entire combinatorial epistatic space for a single phenotype. We propose Next-Gen GWAS (NGG) that evaluates over 60 billion single nucleotide polymorphism combinatorial first-order interactions within hours. We apply NGG to Arabidopsis thaliana providing two-dimensional epistatic maps at gene resolution. We demonstrate on several phenotypes that a large proportion of the missing heritability can be retrieved, that it indeed lies in epistatic interactions, and that it can be used to improve phenotype prediction...
March 25, 2024: Genome Biology
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