Cystathionine Gamma-Lyase Regulates TNF-α-Mediated Injury Response in Human Colonic Epithelial Cells and Colonoids.

Cystathionine gamma-lyase (CSE) and TNF-α are now recognized as key regulators of intestinal homeostasis, inflammation, and wound healing. In colonic epithelial cells, both molecules have been shown to influence a variety of biological processes, but the specific interactions between intracellular signaling pathways regulated by CSE and TNF-α are poorly understood. In the present study, we investigated these interactions in normal colonocytes and an organoid model of the healthy human colon using CSE-specific pharmacological inhibitors and siRNA-mediated transient gene silencing in analytical and functional assays in vitro.

Hydrogen Sulfide Ameliorates SARS-CoV-2-Associated Lung Endothelial Barrier Disruption.

Recent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of HS in several pathological processes and provided a rationale for considering the therapeutic implications of HS in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing HS donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in vitro, after challenging the cells with plasma samples from COVID-19 patients or inactivated SARS-CoV-2 virus.

3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics.

Background And Purpose: During angiogenesis, quiescent endothelial cells (ECs) are activated by various stimuli to form new blood vessels from pre-existing ones in physiological and pathological conditions. Many research groups have shown that hydrogen sulfide (H S), the newest member of the gasotransmitter family, acts as a proangiogenic factor. To date, very little is known about the regulatory role of 3-mercaptopyruvate sulfurtransferase (3-MST), an important H S-producing enzyme in ECs.

Differences in the viral genome between HPV-positive cervical and oropharyngeal cancer.

Human papillomavirus (HPV)-driven oropharyngeal cancer incidence in the United States has steadily increased in the past decades and has now become the most frequently diagnosed HPV-associated cancer type, surpassing cervical cancer. Variations in the HPV genome correlate with tumorigenic risk, and the distribution of genetic variants is extensively studied in cervical cancer, but very little is known about new mutations or the distribution of HPV types and variants in oropharyngeal cancer. Here we present an archival tissue cohort study that compares genomic characteristics of HPV associated with cervical versus oropharyngeal tumors using DNA sequence analysis.

PDGF-AA mediates mesenchymal stromal cell chemotaxis to the head and neck squamous cell carcinoma tumor microenvironment.

Background: The robust desmoplasia associated with head and neck squamous cell carcinoma (HNSCC) suggests that the tumor microenvironment may be an important component in the pathophysiology of this cancer. Moreover, the high recurrence rate and poor clinical response to chemotherapy and radiation treatment further underscores that the non-cancerous cells of the microenvironment, such as mesenchymal stromal cells (MSCs), cancer associated fibroblasts (CAFs), and pericytes, may be important in the pathophysiology of HNSCC.

Methods: Confocal microscopy and immunohistomchemistry approaches were used to identify MSCs tumor microenvironment from patients with oral cavity and oral pharyngeal squamous cell carcinoma (SCC).

8-Oxoguanine DNA glycosylase1-driven DNA repair-A paradoxical role in lung aging.

Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies.

Temporal characterization of lymphatic metastasis in an orthotopic mouse model of oral cancer.

Background: The overall mortality rate in cases of head and neck squamous cell carcinoma (HNSCC) has not improved over the past 30 years, mostly because of the high treatment failure rate among patients with regionally metastatic disease. To better understand the pathobiologic processes leading to lymphatic metastasis development, there is an urgent need for relevant animal models.

Methods: HNSCC cell lines were implanted into the tongues of athymic nude mice.

Activation of cellular signaling by 8-oxoguanine DNA glycosylase-1-initiated DNA base excision repair.

Accumulation of 8-oxo-7,8-dihydroguanine (8-oxoG) in the DNA results in genetic instability and mutagenesis, and is believed to contribute to carcinogenesis, aging processes and various aging-related diseases. 8-OxoG is removed from the DNA via DNA base excision repair (BER), initiated by 8-oxoguanine DNA glycosylase-1 (OGG1). Our recent studies have shown that OGG1 binds its repair product 8-oxoG base with high affinity at a site independent from its DNA lesion-recognizing catalytic site and the OGG1•8-oxoG complex physically interacts with canonical Ras family members.

Carcinoma matrix controls resistance to cisplatin through talin regulation of NF-kB.

Extracellular matrix factors within the tumor microenvironment that control resistance to chemotherapeutics are poorly understood. This study focused on understanding matrix adhesion pathways that control the oral carcinoma response to cisplatin. Our studies revealed that adhesion of HN12 and JHU012 oral carcinomas to carcinoma matrix supported tumor cell proliferation in response to treatment with cisplatin.

Effects of Colostrinin on gene expression-transcriptomal network analysis.

Colostrinin (CLN) is a uniform mixture of low-molecular weight proline-rich polypeptides isolated from the mother's first milk, colostrum. Exposure of cells to CLN decreases intracellular levels of reactive oxygen species by regulating glutathione metabolism and modulating activities of antioxidant enzymes and mitochondrial function. It also inhibits beta amyloid-induced apoptosis and induces neurite outgrowth of pheochromocytoma cells.

Scanning cytometry with a LEAP: laser-enabled analysis and processing of live cells in situ.

Background: Scanning cytometry now has many of the features (and power) of multiparameter flow cytometry while keeping its own advantages as an imaging technology. Modern instruments combine capabilities of scanning cytometry with the ability to manipulate cells. A new technology, called LEAP (laser-enabled analysis and processing), offers a unique combination of capabilities in cell purification and selective macromolecule delivery (optoinjection).