Shi-pi-xiao-ji formula suppresses hepatocellular carcinoma by reducing cellular stiffness through upregulation of acetyl-coA acetyltransferase 1

World Journal of Gastrointestinal Oncology, Journal Year: 2024, Volume and Issue: 16(6), P. 2727 - 2741

Published: June 14, 2024

Previous studies have shown that the Shi-pi-xiao-ji (SPXJ) herbal decoction formula is effective in suppressing hepatocellular carcinoma (HCC), but underlying mechanisms are not known. Therefore, this study investigated whether antitumor effects of SPXJ treating HCC were mediated by acetyl-coA acetyltransferase 1 (ACAT1)-regulated cellular stiffness. Through a series experiments, we concluded inhibits progression upregulating expression level ACAT1, lowering cholesterol cell membrane, and altering stiffness, which provides new idea for research traditional Chinese medicine against HCC.

Language: Английский

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Glyoxal-methyl-ethylene sulfonic acid fixative enhances the fixation of cytoskeletal structures for Förster resonance energy transfer measurements

Histochemistry and Cell Biology, Journal Year: 2024, Volume and Issue: 162(4), P. 337 - 347

Published: June 17, 2024

Language: Английский

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Cellular Traction Force Holds the Potential as a Drug Testing Readout for In Vitro Cancer Metastasis

Cellular and Molecular Bioengineering, Journal Year: 2024, Volume and Issue: 17(3), P. 203 - 217

Published: June 1, 2024

Abstract Introduction Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents primary tumor to halt cancer growth but not in metastasis. Unlike tumors, requires cells exert sufficient cellular traction force through actomyosin machinery migrate away from site. Therefore, we seek explore as a novel readout screening that target Methods In vitro invasive and non-invasive breast were first established using MDA-MB-231 MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like spherical cells. The baseline quantified Traction Microscopy technique. Cisplatin, paradigm antimetastatic drug, 5-Fluorouracil (5FU), non-antimetastatic selected evaluate drug testing Results exhibited significantly higher compared Treatment with an demonstrated distinct These findings correlate observed two models. Conclusion emerges promising metric evaluating efficacy inhibiting This approach could enhance development anti-metastatic therapies, addressing critical gap current research.

Language: Английский

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Computational analysis of non-synonymous SNPs in the human LCN2 gene

Egyptian Journal of Medical Human Genetics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Aug. 20, 2024

Abstract Background Lipocalin-2 (LCN2), a neutrophil gelatinase-associated protein, plays an important role in iron homeostasis, infection, and inflammation. Polymorphism the LCN2 gene is linked to various diseases such as cardiovascular disease, renal damage, colorectal pancreatic cancer. Identifying deleterious functional non-synonymous SNPs crucial understanding how these genetic variations affect its structure function. Methods Several silico tools SIFT, Polyphen-2, PROVEAN, PREDICT SNP, MAPP, SNAP2 followed by I-MUTANT 2.0, MUpro, ConSurf, NetsurfP-2.0, secondary of protein SOPMA PSIPRED, while interaction with other genes proteins was analyzed using GeneMANIA STRING, respectively, AlphaFold for protein's 3D prediction. Results The study identified 6 potentially harmful nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) their function were prediction tools. 2.0 predicted increase stability shows decrease which validated MUpro. ConSurf high-risk be conserved regions protein. result showed that rs11556770, rs368926734 found highly variant amino acids. According NetsurfP-2.0 server, rs11556770 (Q39H), rs139418967 (L6P), (Y135H) exposed rs142623708 (M71I), rs200107414 (Y52C), (Y135) buried. PSIPRED server analysis indicated predominant strand, lesser occurrences coil helix. Conclusion Overall, detrimental computational could used large population-based investigations diagnosis.

Language: Английский

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Altered Mechanobiology of PDAC Cells with Acquired Chemoresistance to Gemcitabine and Paclitaxel

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 13, 2024

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) acquired resistance to chemotherapy poses a major limitation patient survival. Despite understanding of some biological mechanisms chemoresistance, much those remain be uncovered. Mechanobiology, which studies physical properties cells, holds promise as potential target for addressing challenges chemoresistance in PDAC. Therefore, we here an initial step, assessed the altered mechanobiology PDAC cells with gemcitabine and paclitaxel. Methods Five cell lines six stably-resistant subclones were force generation on elastic micropillar arrays. Those measurements mechanical phenotype complemented by single-cell motility invasion collagen matrix investigated using 2D models 3D extracellular matrix-mimetic, respectively. Further nuclear translocation Yes-associted protein (YAP), measure active status, was compared, biomarkers epithelial-to-mesenchymal transition (EMT) evaluated RT-PCR. Results exert higher traction forces than their parental/wild-type (WT) cells. In 2D, all chemoresistant cell-type specific pattern. 3D, spheroids able invade matrix, remodel more WT clones. However, YAP EMT not significantly relation changes other parameters. Conclusion This is first study investigate report mechanobiological features that have chemoresistance. A better could help identifying future targets overcome

Language: Английский

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