Molecular biomedicine

Inflammatory changes caused by viruses, bacteria, exposure to toxins, commonly used drugs and even surgical intervention have the potential of causing abnormal epithelial permeability, which is manifest as infiltrative processes on computed tomography (CT), including the widespread infiltrates seen in COVID-19 pneumonia and acute respiratory distress syndrome (ARDS). We utilized a previously published mouse model of ARDS, intranasal delivery of LPS, to induce the alveolar-capillary barrier permeability seen in lung disease. We intravenously injected mice with Cy7 or 68-Gallium (68Ga) labeled mouse albumin and imaged using optical imaging (OI)/CT and PET. We observed significantly increased lung levels of Cy7-albumin on 3D OI/CT, which matched the abnormal appearance on microCT. This uptake correlated with fluorescence seen on sectioned lungs. To examine the translational potential of these findings, we radiolabeled albumin with 68Ga. We found that in mice with LPS-induced lung injur...

A limited subset of human leukemia cells has a self-renewal capacity and can propagate leukemia upon their transplantation into animals, and therefore, are named as leukemia stem cells, in the early 1990’s. Subsequently, cell subpopulations with similar characteristics were detected in various kinds of solid cancers and were denoted as cancer stem cells. Cancer stem cells are presently presumed to be crucially involved in malignant progression of solid cancer: chemoresitance, radioresistance, immune evasion, and metastasis. On the contrary, less attention has been paid to cancer non-stem cell population, which comprise most cancer cells in cancer tissues, due to the lack of suitable markers to discriminate cancer non-stem cells from cancer stem cells. Chronic myeloid leukemia stem cells generate a larger number of morphologically distinct non-stem cells. Moreover, accumulating evidence indicates that poor prognosis is associated with the increases in these non-stem cells including b...

NeuroAIDS (Neuro Acquired Immunodeficiency Syndrome) or HIV (Human Immunodeficiency Virus) associated neuronal abnormality is continuing to be a significant health issue among AIDS patients even under the treatment of combined antiretroviral therapy (cART). Injury and damage to neurons of the brain are the prime causes of neuroAIDS, which happens due to the ingress of HIV by direct permeation across the blood-brain barrier (BBB) or else via peripherally infected macrophage into the central nervous system (CNS). The BBB performs as a stringent barricade for the delivery of therapeutics drugs. The intranasal route of drug administration exhibits as a non-invasive technique to bypass the BBB for the delivery of antiretroviral drugs and other active pharmaceutical ingredients inside the brain and CNS. This method is fruitful for the drugs that are unable to invade the BBB to show its action in the CNS and thus erase the demand of systemic delivery and thereby shrink systemic side effect...

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Hypergammaglobulinemia and the presence of autoantibodies in sarcoidosis suggest active humoral immunity to unknown antigen(s). We developed a complex cDNA library derived from tissues of sarcoidosis patients. Using a high throughput method, we constructed a microarray platform from this cDNA library containing large numbers of sarcoidosis clones. After selective biopanning, 1070 sarcoidosis-specifc clones were arrayed and immunoscreend with 152 sera from patients with sarcoidosis and other pulmonary diseases. To identify the sarcoidosis classifiers two statistical approaches were conducted: First, we identified significant biomarkers between sarcoidosis and healthy controls, and second identified markers comparing sarcoidosis to all other groups. At the threshold of an False Discovery Rate (FDR) 

Prostate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA ...