Functional characterization of the disease-associated rs1024611G-rs13900T haplotype: The role of the RNA-binding protein HuR.

CC-chemokine ligand 2 (CCL2) is involved in the pathogenesis of several diseases associated with monocyte/macrophage recruitment, such as HIV-associated neurocognitive disorder (HAND), tuberculosis, and atherosclerosis. The rs1024611 (alleles:A>G; G is the risk allele) polymorphism in the -regulatory region is associated with increased CCL2 expression in vitro and ex vivo, leukocyte mobilization in vivo, and deleterious disease outcomes. However, the molecular basis for the rs1024611-associated differential CCL2 expression remains poorly characterized.

Precision Targets for Intercepting the Lethal Progression of Prostate Cancer: Potential Avenues for Personalized Therapy.

Organ-confined prostate cancer of low-grade histopathology is managed with radiation, surgery, active surveillance, or watchful waiting and exhibits a 5-year overall survival (OS) of 95%, while metastatic prostate cancer (PCa) is incurable, holding a 5-year OS of 30%. Treatment options for advanced PCa-metastatic and non-metastatic-include hormone therapy that inactivates androgen receptor (AR) signaling, chemotherapy and genome-targeted therapy entailing synthetic lethality of tumor cells exhibiting aberrant DNA damage response, and immune checkpoint inhibition (ICI), which suppresses tumors with genomic microsatellite instability and/or deficient mismatch repair. Cancer genome sequencing uncovered novel somatic and germline mutations, while mechanistic studies are revealing their pathological consequences.

Comparison of sufentanil-midazolam and sevoflurane for anesthesia induction in children undergoing cardiac surgery by real-time hemodynamic and cardiac efficiency monitoring: A prospective randomized study.

Background Intravenous sufentanil-midazolam and inhalational sevoflurane are widely used for anesthetic induction in children undergoing cardiac surgery. However, knowledge about their effects on hemodynamics and cardiac efficiency remains limited due largely to the lack of direct monitoring method. We used minimally invasive technique pressure recording analytical method (PRAM) to directly monitor hemodynamics and cardiac efficiency and compared the effects of the two anesthetic regimens in children undergoing ventricular septal defect repair.

Comparison of hemodynamic effects of sevoflurane and ketamine as basal anesthesia by a new and direct monitoring during induction in children with ventricular septal defect: A prospective, randomized research.

Background: Sevoflurane and ketamine are commonly used to obtain sedation and facilitate intravenous anesthetic induction in children undergoing cardiac surgery who are uncooperative. We used a new and direct systemic hemodynamic monitoring technique pressure recording analytical method and compared the hemodynamic effects of sevoflurane and ketamine to facilitate intravenous anesthetic induction.

Methods: Forty-four children with ventricular septal defect (2.

Prediction of Fluid Responsiveness Using Pulse Pressure Variation in Infants Undergoing Ventricular Septal Defect Repair with Median Sternotomy or Minimally Invasive Right Thoracotomy.

Fluid management is challenging in infants after cardiopulmonary bypass. Pulse pressure variation (PPV) derived from pressure recording analytical method (PRAM) is based on lung-heart interaction during mechanical ventilation. A prospective observational study conducted in operating room tested PPV to predict fluid responsiveness in ventricular septal defect infants.

Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge.

Background: An emerging paradigm holds that resistance to the development of allergic diseases, including allergic rhinoconjunctivitis, relates to an intact epithelial/epidermal barrier during early childhood. Conceivably, the immunologic and genomic footprint of this resistance is preserved in nonatopic, nonallergic adults and is unmasked during exposure to an aeroallergen.

Objective: The aim of this study was to obtain direct support of the epithelial/epidermal barrier model for allergic rhinoconjunctivitis.

Cockroach sensitization mitigates allergic rhinoconjunctivitis symptom severity in patients allergic to house dust mites and pollen.

Background: Modifiers of symptom severity in patients with allergic rhinoconjunctivitis (AR) are imprecisely characterized. The hygiene hypothesis implicates childhood microbial exposure as a protective factor. Cockroach sensitization (C+) might be a proxy for microbial exposure.

Increased expression of macrophage colony-stimulating factor and its receptor in patients with endometriosis.

Objective: To investigate the expression and regulation of colony-stimulating factor 1 (CSF-1) and its receptor, C-FMS, in endometriosis.

Design: In vivo and vitro study.

Setting: University-based academic medical center.

A brain-derived neurotrophic factor polymorphism Val66Met identifies fibromyalgia syndrome subgroup with higher body mass index and C-reactive protein.

A common single nucleotide polymorphism (SNP) in the gene of brain-derived neurotrophic factor (BDNF) results from a substitution at position 66 from valine (Val) to methionine (Met) and may predispose to human neuropsychiatric disorders. We proposed to determine whether these BDNF gene SNPs were associated with fibromyalgia syndrome (FMS) and/or any of its typical phenotypes. Patients with FMS (N = 95) and healthy normal controls (HNC, N = 58) were studied.

Derivation and characterization of novel nonhuman primate embryonic stem cell lines from in vitro-fertilized baboon preimplantation embryos.

The development of nonhuman primate (NHP) embryonic stem cell (ESC) models holds great promise for cell-mediated treatment of debilitating diseases and to address numerous unanswered questions regarding the therapeutic efficacy of ESCs while supplanting ethical considerations involved with human studies. Here we report successful establishment and characterization of 3 novel baboon (Papio cynocephalus) ESC lines from the inner cell mass of intracytoplasmic sperm injection-derived blastocysts. Embryos were cultured in an improved baboon embryo in vitro culture protocol.

Ovarian stimulation, in vitro fertilization, and effects of culture conditions on baboon preimplantation embryo development.

Objective: To evaluate the effects of ovarian stimulation and intracytoplasmic sperm injection (ICSI)-induced fertilization and efficacy of various culture systems on in vitro development of baboon embryos.

Design: In vitro study, animal model.

Setting: Research laboratory.

Cytotoxic activities, cellular uptake, gene regulation, and optical imaging of novel platinum(II) complexes.

A new class of platinum(II) coordination complexes and their dye tagged conjugates has been synthesized from N-substituted diaminocyclohexane ligands. The in vitro anticancer activities of the platinum compounds have been validated against the breast cancer cell-line MCF-7 and the normal cell-line MCF-10A via sulforhodamine B and colony formation assay. The platinum compounds and the corresponding metal-free ligands exhibited higher drug efficiencies than cisplatin and oxaliplatin against MCF-7 cells.

Induction of endometrial epithelial cell invasion and c-fms expression by transforming growth factor beta.

Transforming growth factor beta 1 (TGF-beta1) levels are increased in the peritoneal fluid of endometriosis patients, and endometrial cells express TGF-beta signaling components; however, little is known regarding the role of TGF-beta in endometriosis. Our objective was to examine the effects of TGF-beta1 on (i) the expression of macrophage colony-stimulating factor receptor encoded by the c-fms gene, (ii) transmesothelial invasiveness of endometrial cells, (iii) cellular proliferation and (iv) attachment to peritoneal mesothelial cells (PMCs). Effects of TGF-beta1 on c-fms mRNA expression were determined by real-time RT-PCR and c-fms cell-surface expression by flow cytometry.

Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants.

Objective: We previously demonstrated that adherence of endometrial epithelial (EECs) and stromal cells (ESCs) to peritoneal mesothelial cells (PMCs) is partly regulated by ESC/EEC CD44 interactions with PMC associated hyaluronan. CD44, a transmembrane glycoprotein and major ligand for hyaluronan, has numerous splice variants which may impact hyaluronan binding. Here, we assessed whether ESCs and EECs from women with endometriosis demonstrate increased adherence to PMCs and examined CD44 splice variants' potential role in this process.

Herceptin-platinum(II) binding complexes: novel cancer-cell-specific agents.

We report a new series of Herceptin-platinum(II) binding complexes, Her-nLPt(II) (Her denotes Herceptin; L denotes diamino ligands and L=L1-L4; n=1, 5, or 10). Solution chemistry studies have shown that these complexes are stable under physiological conditions (pH 7.4 in PBS).

Concurrent down-regulation of Egr-1 and gelsolin in the majority of human breast cancer cells.

Unlabelled: A growing body of evidence suggests that early growth response-1 (Egr-1), a transcription factor, may function as a tumor suppressor. The aim of this study was to gain more evidence to support the role of Egr-1 in the suppression of cancer cell growth and to examine the potential correlation between Egr-1 and gelsolin.

Materials And Methods: Histochemical staining coupled with breast cancer tissue arrays were used to examine the expression levels of Egr-1 and gelsolin.

Chiral salicyl diamines: potent anticancer molecules.

A set of 12 enantiomeric diamine-based small molecules was synthesized and screened for anticancer activity against five human cancer cell lines: NCI-H460, A549, MCF-7, SK-BR-3, and T-47D. The salicyl diamino compounds (1-6) were found to induce inhibition of the growth of cancer cells at submicromolar concentrations. The lead compound, N,N'-bis-salicyl-(1R,2R)-diaminocyclohexane (1) displayed single-reagent anticancer activity with an IC(50) value equal to or less than 2.

Elevated expression of the oncogene c-fms and its ligand, the macrophage colony-stimulating factor-1, in cervical cancer and the role of transforming growth factor-beta1 in inducing c-fms expression.

Cervical cancer is the third most common gynecologic cancer in the United States. The presence and possible involvement of several cytokines have been studied in cervical cancer; however, very little data, if any, are available on whether cervical tumors are responsive to stimulation by the macrophage colony-stimulating factor-1 (CSF-1). Given the involvement of c-fms and its ligand CSF-1 in gynecologic cancers, such as that of the uterus and the ovaries, we have examined the expression of c-fms and CSF-1 in cervical tumor (n = 17) and normal cervix (n = 8) samples.

Artificial zinc(II) complexes regulate cell cycle and apoptosis-related genes in tumor cell lines.

Various proteins involved in transcriptional regulation possess highly selective DNA-binding domains, known as zinc fingers. However, little is known about small-molecule zinc(II) complexes in the regulation of gene expression and programmed cell death. A new family of zinc(II) complexes is reported, which might be useful against human cancer cells.

Induction of aromatase expression in cervical carcinomas: effects of endogenous estrogen on cervical cancer cell proliferation.

Epidemiologic studies have implicated estrogenic exposure as well as human papilloma virus (HPV) infection in cervical carcinogenesis, and some studies have suggested that estrogen and HPV may play synergistic roles in cervical tumorigenesis. In this study, we report a novel finding that approximately 35% of cervical carcinomas tested (n = 19) express aromatase, the enzyme responsible for converting androgen to estrogen, the rate-limiting and final step in estrogen biosynthesis. On the other hand, no aromatase expression was detected in precancerous (n = 42) or normal cervical (n = 17) tissue samples.

Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic alterations in the aromatase transgenic mice.

Aromatase transgenic mice exhibit hyperplastic and dysplastic changes, attesting to the importance of local estrogen in breast carcinogenesis. These mice also show increased levels of the estrogen receptor alpha and beta (ERalpha, ERbeta) suggesting that this receptor may play an important role in the initiation of estrogen-mediated mammary hyperplasia observed in these mice. To address the specific role of ERalpha in the mammary development and in the induction of estrogen-mediated hyperplasia in aromatase transgenic mice, we have generated MMTV-aromatase x ERalpha knockout cross (referred as aromatase/ERKO).

Exercise might favor reverse cholesterol transport and lipoprotein clearance: potential mechanism for its anti-atherosclerotic effects.

Livers of C57 BL/6 mice exercised for 2 weeks showed a dramatic increase in scavenger receptor B1 (SR-B1), CD36 and low density lipoprotein (LDL) receptor and a decrease in acetyl LDL receptor gene expression. These effects on lipoprotein receptors are reminiscent of the effects mediated by peroxisome proliferator-activated receptor (PPARgamma) ligands.

Overexpression of the colony-stimulating factor (CSF-1) and/or its receptor c-fms in mammary glands of transgenic mice results in hyperplasia and tumor formation.

A number of recent studies have suggested that the colony-stimulating factor (CSF-1) and its receptor c-fms may be involved in the development of mammary glands during lactation and breast cancer. To study the role of CSF-1 or its receptor in initiation of mammary tumorigenesis, we have generated two independent lines of transgenic mice that overexpress either CSF-1 or c-fms under the control of the mouse mammary tumor virus promoter. Mammary glands of the virgin CSF-1 transgenic mice show increased ductal branching, hyperplasia, dysplasia, and other preneoplastic changes, which are indicative of increased cellular proliferation.

Profiling of human cytokines in healthy individuals with vitamin E supplementation by antibody array.

Previously, we demonstrated that vitamin E supplementation decreases autoantibodies to oxidized lipid-protein complexes (J. Med. Food 1 (2000) 247).