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1.
Cureus ; 14(4): e23834, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35530927

RESUMO

A 23-year-old male presented to the hospital with altered mental status (AMS) and hypoglycemia requiring admission to the ICU. He had improvement in AMS after administration of dextrose 50% and naloxone and endorsed the use of alcohol, cocaine, and marijuana that morning. It was confirmed with a positive urine toxicology screen for cocaine and tetrahydrocannabinol (THC). During this hospital admission, his physical examination was notable for paraplegia with no motor abilities from the T6 dermatome and below. Sensation was intact throughout all dermatomes but he was found to have urinary retention. Workup included an abnormal MRI showing T2 signal spanning from T2-T8, raising a high suspicion of a probable acute ischemic spinal cord infarction. Several hours after admission, the patient began to exhibit the first signs of abnormal bowel function and experienced one episode of hematemesis, prolonging his ICU stay.

2.
Mol Ther Oncolytics ; 18: 419-431, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32913891

RESUMO

Cancer has proven to be an extremely difficult challenge to treat. Several fundamental issues currently underlie cancer treatment, including differentiating self from nonself, functional coupling of the recognition and therapeutic components of various therapies, and the propensity of cancerous cells to develop resistance to common treatment modalities via evolutionary pressure. Given these limitations, there is an increasing need to develop an all-encompassing therapeutic that can uniquely target malignant cells, decouple recognition from treatment, and overcome evolutionarily driven cancer resistance. We describe herein a new class of programmable self-assembling double-stranded RNA (dsRNA)-based cancer therapeutics that uniquely targets aberrant genetic sequences and in a functionally decoupled manner, undergoes oncogenic RNA-activated displacement (ORAD), initiating a therapeutic cascade that induces apoptosis and immune activation. As a proof of concept, we show that RNA strands targeting the EWS/Fli1 fusion gene in Ewing sarcoma cells that are end blocked with phosphorothioate bonds and additionally sealed with a 2'-deoxyuridine (2'-U)-modified DNA protector can be used to induce specific and potent killing of cells containing the target oncogenic sequence but not wild type.

3.
PeerJ ; 6: e4937, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29888136

RESUMO

Cell quantification assays are essential components of most biological and clinical labs. However, many currently available quantification assays, including flow cytometry and commercial cell counting systems, suffer from unique drawbacks that limit their overall efficacy. In order to address the shortcomings of traditional quantification assays, we have designed a robust, low-cost, automated microscopy-based cytometer that quantifies individual cells in a multiwell plate using tools readily available in most labs. Plating and subsequent quantification of various dilution series using the automated microscopy-based cytometer demonstrates the single-cell sensitivity, near-perfect R2 accuracy, and greater than 5-log dynamic range of our system. Further, the microscopy-based cytometer is capable of obtaining absolute counts of multiple cell types in one well as part of a co-culture setup. To demonstrate this ability, we recreated an experiment that assesses the tumoricidal properties of primed macrophages on co-cultured tumor cells as a proof-of-principle test. The results of the experiment reveal that primed macrophages display enhanced cytotoxicity toward tumor cells while simultaneously losing the ability to proliferate, an example of a dynamic interplay between two cell populations that our microscopy-based cytometer is successfully able to elucidate.

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