Publications by authors named "Saleh Khawaled"

Article Synopsis
  • Fasting has been shown to enhance health, lifespan, and tissue repair across various organisms, including humans, but the impact of post-fast refeeding on adult stem cells and cancer development is not well understood.
  • Research indicates that refeeding after fasting boosts intestinal stem cell growth and increases the risk of tumors, especially when the tumor suppressor gene Apc is absent in the stem cells.
  • The study's findings highlight the activation of mTORC1 in post-fast-refed stem cells, which promotes protein synthesis and regeneration, suggesting that diet strategies should carefully manage refeeding to avoid raising cancer risks.
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Background & Aims: Single-cell RNA sequencing (scRNA) has empowered many insights into gastrointestinal microenvironments. However, profiling human biopsies using droplet-based scRNA (D-scRNA) is challenging since it requires immediate processing to minimize epithelial cell damage. In contrast, picowell-based (P-scRNA) platforms permit short-term frozen storage before sequencing.

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For more than a century, fasting regimens have improved health, lifespan, and tissue regeneration in diverse organisms, including humans. However, how fasting and post-fast refeeding impact adult stem cells and tumour formation has yet to be explored in depth. Here, we demonstrate that post-fast refeeding increases intestinal stem cell (ISC) proliferation and tumour formation: Post-fast refeeding augments the regenerative capacity of 5 intestinal stem cells (ISCs), and loss of the tumour suppressor in ISCs under post-fast refeeding leads to a higher tumour incidence in the small intestine and colon than in the fasted or (AL) fed states.

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Tumor progression and metastasis are the major causes of death among cancer associated mortality. Metastatic cells acquire features of migration and invasion and usually undergo epithelia-mesenchymal transition (EMT). Acquirement of these various hallmarks rely on different cellular pathways, including TGF-β and Wnt signaling.

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Efficient delivery of nucleic acids into cells still remains a great challenge. Peptide nucleic acids (PNAs) are DNA analogues with a neutral backbone and are synthesized by solid phase peptide chemistry. This allows a straightforward synthetic route to introduce a linear short peptide (a.

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Osteosarcoma (OS) is an aggressive malignancy affecting mostly children and adolescents. MicroRNAs (miRNAs) play important roles in OS development and progression. Here we found that miR-16-1-3p and miR-16-2-3p "passenger" strands, as well as the "lead" miR-16-5p strand, are frequently downregulated and possess strong tumor suppressive functions in human OS.

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Triple-negative breast cancer (TNBC) is a heterogeneous, highly aggressive, and difficult to treat tumor type. The tumor suppressor spans FRA16D, a common fragile site that is commonly altered in breast cancer. Despite recent progress, the role of WWOX in TNBC metastasis is unknown.

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We have recently shown that neutrophil antitumor cytotoxicity is Ca dependent and is mediated by TRPM2, an HO-dependent Ca channel. However, neutrophil antitumor activity is dependent on context and is manifested in the premetastatic niche, but not at the primary site. We therefore hypothesized that expression of TRPM2 and the consequent susceptibility to neutrophil cytotoxicity may be associated with the epithelial/mesenchymal cellular state.

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Neutrophils play a critical role in cancer, with both protumor and antitumor neutrophil subpopulations reported. The antitumor neutrophil subpopulation has the capacity to kill tumor cells and limit metastatic spread, yet not all tumor cells are equally susceptible to neutrophil cytotoxicity. Because cells that evade neutrophils have greater chances of forming metastases, we explored the mechanism neutrophils use to kill tumor cells.

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Article Synopsis
  • Inhibition of gene function is commonly studied using RNA interference, but this method may lead to off-target effects, complicating results.
  • Genetic mutation techniques like CRISPR/cas9 show differences from RNA interference, sometimes due to compensatory mechanisms rather than just off-target effects.
  • A combined approach using both RNA inhibition and CRISPR/cas9 reveals the critical role of Sema4B in glioma biology, highlighting off-target effects and the importance of specific splice variants for glioma cell growth.
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Preexisting diabetes is a risk factor for the development of multiple types of cancer. Additionally, diabetic patients face a poorer prognosis when diagnosed with cancer. To gain insight into the effects of hyperglycemia, a hallmark of diabetes, on tumor growth and metastatic progression, we combined mouse models of cancer and hyperglycemia.

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Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents and young adults. The essential mechanisms underlying osteosarcomagenesis and progression continue to be obscure. MicroRNAs (miRNAs) have far-reaching effects on the cellular biology of development and cancer.

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MicroRNAs are key players in most biological processes. Some microRNAs are involved in the genesis of tumors and are therefore termed oncomiRs, while others, termed metastamiRs, play a significant role in the formation of cancer metastases. Previously, we identified ten different cellular microRNAs that downregulate the expression of MICB, a ligand of the activating NK receptor NKG2D.

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The WW domain-containing oxidoreductase (WWOX) is commonly inactivated in multiple human cancers, including breast cancer. Wwox null mice die prematurely precluding adult tumor analysis. Nevertheless, aging Wwox-heterozygous mice at C3H genetic background develop higher incidence of mammary tumors.

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