A Novel Therapeutic Method in Gastro-esophageal Reflux Disease.

Background: Gastro-esophageal reflux disease (GERD/GORD) is a chronic condition in which gastric acid flows backwards up into the esophagus, causing heart burn and a higher disposition to esophageal cancer. The reflux is caused by impairment of the lower esophageal sphincter (LES). Over the past century gastro-esophageal reflux has become the principal gastrointestinal condition of our time.

A Novel Isobaric (Gas-Less) Laparoscopic Surgery Device.

Background: Laparoscopic Surgery is performed using carbon dioxide gas insufflated into the abdominal cavity to create a space for endoscopic visualization. During a laparoscopic surgical dissection plume is formed from electrocautery dissection. This plume contains viruses and sometimes COVID-19 viruses.

Jagged-1 is induced by mTOR inhibitors in renal cancer cells through an Akt/ALK5/Smad4-dependent mechanism.

The mammalian target of rapamycin (mTOR) plays an important role in the aggressiveness and therapeutic resistance of many cancers. Targeting mTOR continues to be under clinical investigation for cancer therapy. Despite the notable clinical success of mTOR inhibitors in extending the overall survival of patients with certain malignancies including metastatic renal cell carcinomas (RCCs), the overall impact of mTOR inhibitors on cancers has been generally disappointing and attributed to various compensatory responses.

-Induced Bronchoalveolar Lavage Gene Expression Signature in Latent Tuberculosis Infection Is Dominated by Pleiotropic Effects of CD4 T Cell-Dependent IFN-γ Production despite the Presence of Polyfunctional T Cells within the Airways.

Tuberculosis (TB) remains a worldwide public health threat. Development of a more effective vaccination strategy to prevent pulmonary TB, the most common and contagious form of the disease, is a research priority for international TB control. A key to reaching this goal is improved understanding of the mechanisms of local immunity to , the causative organism of TB.

A nonrandomized trial of vitamin D supplementation for Barrett's esophagus.

Background: Vitamin D deficiency may increase esophageal cancer risk. Vitamin D affects genes regulating proliferation, apoptosis, and differentiation and induces the tumor suppressor 15-hydroxyprostaglandin dehydrogenase (PGDH) in other cancers. This nonrandomized interventional study assessed effects of vitamin D supplementation in Barrett's esophagus (BE).

Transcriptomic-metabolomic reprogramming in EGFR-mutant NSCLC early adaptive drug escape linking TGFβ2-bioenergetics-mitochondrial priming.

The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent.

Identification of early transcriptome signatures in placenta exposed to insulin and obesity.

Objective: The purpose of this study was to investigate the effects of insulin on human placental transcriptome and biological processes in first-trimester pregnancy.

Study Design: Maternal plasma and placenta villous tissue were obtained at the time of voluntary termination of pregnancy (7-12 weeks) from 17 lean (body mass index, 20.9±1.

Kinetic analysis of anterior cervical discectomy and fusion supplemented with transarticular facet screws.

OBJECT The clinical success rates of anterior cervical discectomy and fusion (ACDF) procedures are substantially reduced as more cervical levels are included in the fusion procedure. One method that has been proposed as an adjunctive technique for multilevel ACDF is the placement of screws across the facet joints ("transfacet screws"). However, the biomechanical stability imparted by transfacet screw placement (either unilaterally or bilaterally) has not been reported.

Prx1 and 3.2kb Col1a1 promoters target distinct bone cell populations in transgenic mice.

Bones consist of a number of cell types including osteoblasts and their precursor cells at various stages of differentiation. To analyze cellular organization within the bone, we generated Col1a1CreER-DsRed transgenic mice that express, in osteoblasts, CreER and DsRed under the control of a mouse 3.2kb Col1a1 promoter.

Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A.

Many solid cancers display cellular hierarchies with self-renewing, tumorigenic stemlike cells, or cancer-initiating cells (CICs) at the apex. Whereas CICs often exhibit relative resistance to conventional cancer therapies, they also receive critical maintenance cues from supportive stromal elements that also respond to cytotoxic therapies. To interrogate the interplay between chemotherapy and CICs, we investigated cellular heterogeneity in human colorectal cancers.

Aptamer identification of brain tumor-initiating cells.

Glioblastomas display cellular hierarchies with self-renewing tumor-initiating cells (TIC), also known as cancer stem cells, at the apex. Although the TIC hypothesis remains controversial and the functional assays to define the TIC phenotype are evolving, we and others have shown that TICs may contribute to therapeutic resistance, tumor spread, and angiogenesis. The identification of TICs has been informed by the use of markers characterized in normal stem cells, but this approach has an inherent limitation to selectively identify TICs.

The microRNAs, MiR-31 and MiR-375, as candidate markers in Barrett's esophageal carcinogenesis.

There is a critical need to identify molecular markers that can reliably aid in stratifying esophageal adenocarcinoma (EAC) risk in patients with Barrett's esophagus. MicroRNAs (miRNA/miR) are one such class of biomolecules. In the present cross-sectional study, we characterized miRNA alterations in progressive stages of neoplastic development, i.

Molecular phenotype of monocytes at the maternal-fetal interface.

Objective: The purpose of this study was to gain insight into the pathways that are associated with inflammation at the maternal-fetal interface. This study examined the molecular characteristics of monocytes that were derived from the maternal circulation and the placenta of obese women.

Study Design: Mononuclear cells were isolated from placenta, venous maternal, and umbilical cord blood at term delivery; activated monocytes were separated with CD14 immunoselection.

MicroRNA-375 and MicroRNA-221: Potential Noncoding RNAs Associated with Antiproliferative Activity of Benzyl Isothiocyanate in Pancreatic Cancer.

The deregulated presence or absence of microRNAs (miRNAs) might play an important role in molecular pathways leading to neoplastic transformation. At present, it is also thought that the approaches to interfere miRNA functions should be helpful for developing novel therapeutic opportunities for human cancer. In this study, we provide evidence that the anticancer agent benzyl isothiocyanate (BITC) has the ability to modulate the level of miRNAs such as miR-221 and miR-375, known to be abnormally expressed in pancreatic cancer patients.

The myeloid transcription factor KLF2 regulates the host response to polymicrobial infection and endotoxic shock.

Precise control of myeloid cell activation is required for optimal host defense. However, this activation process must be under exquisite control to prevent uncontrolled inflammation. Herein, we identify the Kruppel-like transcription factor 2 (KLF2) as a potent regulator of myeloid cell activation in vivo.

Distinct transcriptomes define rostral and caudal serotonin neurons.

The molecular architecture of developing serotonin (5HT) neurons is poorly understood, yet its determination is likely to be essential for elucidating functional heterogeneity of these cells and the contribution of serotonergic dysfunction to disease pathogenesis. Here, we describe the purification of postmitotic embryonic 5HT neurons by flow cytometry for whole-genome microarray expression profiling of this unitary monoaminergic neuron type. Our studies identified significantly enriched expression of hundreds of unique genes in 5HT neurons, thus providing an abundance of new serotonergic markers.

Perimysial fibroblasts of extraocular muscle, as unique as the muscle fibers.

Purpose: Extraocular muscle (EOM) has a distinct skeletal muscle phenotype. The hypothesis for the study was that fibroblasts support the unique EOM phenotype and that perimysial fibroblasts derived from EOM have properties that distinguish them from fibroblasts derived from other skeletal muscle.

Methods: Perimysial fibroblasts from leg muscle (LM-Fibro) and EOM (EOM-Fibro) of mice were derived and maintained in culture.

Elevated AF1q expression is a poor prognostic marker for adult acute myeloid leukemia patients with normal cytogenetics.

Nearly half of the patients with newly diagnosed acute myeloid leukemia have normal cytogenetics (NC-AML) and are classified as intermediate risk, but their 5-year overall survival (OS) ranges from 24 to 42%. Therefore, molecular biomarkers to identify poor-risk patients are needed. Elevated AF1q expression in the absence of specific poor cytogenetics is associated with poor outcomes in pediatric patients with AML and adult patients with myelodysplastic syndrome.

microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells.

The reduced expression of nuclear factor of activated T cells-1 (NFAT1) protein in umbilical cord blood (UCB)-derived CD4+ T cells and the corresponding reduction in inflammatory cytokine secretion after stimulation in part underlies their phenotypic differences from adult blood (AB) CD4+ T cells. This muted response may contribute to the lower incidence and severity of high-grade acute graft-versus-host disease (aGVHD) exhibited by UCB grafts. Here we provide evidence that a specific microRNA, miR-184, inhibits NFAT1 protein expression elicited by UCB CD4+ T cells.

Effects of long-term administration of 9-cis-retinyl acetate on visual function in mice.

Purpose: Long-term effects of treatment with 9-cis-retinyl acetate (9-cis-R-Ac), an artificial retinoid prodrug, were tested on changes in rod and cone visual functions in mice.

Methods: The acetyl ester of the functional geometric chromophore 9-cis-retinal was delivered by oral gavage to C57BL/6 female mice. In initial experiments, 10-month-old mice were used for the single treatment with 9-cis-R-Ac or the control vehicle.

Gene array analysis of a rat model of pulmonary arteriovenous malformations after superior cavopulmonary anastomosis.

Objective: Pulmonary arteriovenous malformations commonly develop in children who have undergone a cavopulmonary anastomosis as part of the palliative sequence for single-ventricle physiology.

Methods: We developed a rat model of cavopulmonary anastomosis that results in pulmonary arteriovenous malformations that are angiographically and histologically similar to the human condition. We used this model to analyze the gene expression profile associated with pulmonary arteriovenous malformations developing after cavopulmonary anastomosis.

Phenotypic differences between healthy effector CTL and leukemic LGL cells support the notion of antigen-triggered clonal transformation in T-LGL leukemia.

T cell large granular lymphocyte leukemia (T-LGL) is a chronic clonal lymphoproliferation of CTL. In many ways, T-LGL clones resemble terminal effector CTL, including down-modulation of CD28 and overexpression of perforin, granzymes, and CD57. We studied the transcriptome of T-LGL clones and compared it with healthy CD8+CD57+ effector cells as well as CD8+CD57- populations.

Molecular changes associated with the endolymphatic hydrops model.

Hypothesis: Hearing loss and cochlear degeneration in the guinea pig model of endolymphatic hydrops (ELH) results, in part, from toxic levels of excitatory amino acids (EAAs) such as glutamate, which in turn leads to changes in the expression of genes linked to intracellular glutamate homeostasis and apoptosis, leading to neuronal cell death.

Background: EAAs have been shown to play a role in normal auditory signal transmission in mammalian cochlea, but have also been implicated in neurotoxicity when levels are elevated. Changes in the expression of specific genes involved in the glutamatergic and apoptotic pathway would serve as evidence for excitotoxicity linked to elevated levels of glutamate.

Gene expression microarrays and respiratory muscles.

The routine measurement of the expression of tens of thousands of gene transcripts, simultaneously, is a defining advance of the last decade which has been made possible by microarray technology. Using this very powerful approach, a pattern has emerged from a number of studies that suggest a molecular niche for the diaphragm which is quite different from that occupied by limb muscle. All indications are that this is true not only in regard to differential gene transcription patterns in healthy muscles but also in the changes in transcription occurring in association with different diseases.

Effects of potent inhibitors of the retinoid cycle on visual function and photoreceptor protection from light damage in mice.

Regeneration of the chromophore 11-cis-retinal is essential for the generation of light-sensitive visual pigments in the vertebrate retina. A deficiency in 11-cis-retinal production leads to congenital blindness in humans; however, a buildup of the photoisomerized chromophore can also be detrimental. Such is the case when the photoisomerized all-trans-retinal is produced but cannot be efficiently cleared from the internal membrane of the outer segment discs.