Innovative Bioluminometric Quantification of Cancer Cell Load in Target Organs: Implications for Studying Anticancer Drugs, Including ROS Enhancers.

Animal models are essential for developing effective drugs for treating human cancer. Examination of the formation of lung surface foci of B16-F10 melanoma cells is a widely used animal model for studying cancer metastasis and drug intervention. This model, however, suffers from several drawbacks, including its non-quantitative nature and inability to yield information on cancer cell load inside the target organ.

Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice.

We sought to determine if a selective HDAC6 inhibitor (ACY-738) decreases disease in NZB/W mice. From 22 to 38weeks-of-age, mice were injected intraperitoneally with 5 or 20mg/kg of ACY-738, or vehicle control. Body weight and proteinuria were measured every 2weeks, while sera anti-dsDNA, Ig isotypes, and cytokine levels were measured every 4weeks.

HDAC expression and activity is upregulated in diseased lupus-prone mice.

Prior studies have shown that pan-HDAC inhibition can decrease disease in lupus mice; however, the mechanisms(s) remain to be elucidated. MRL/MpJ-Fas(lpr) (MRL/lpr) mice develop a lupus-like disease characterized by anti-dsDNA production, lymphoproliferation, and immune complex-mediated glomerulonephritis. Early- and late-disease (12 and 20weeks-of-age respectively) female MRL/lpr mice were compared to age-matched, healthy C57BL/6 mice for HDAC expression and activity in bone marrow (BM) B cells, splenic B and T cells, and glomerular cells.

Cutting Edge: Plasmacytoid Dendritic Cells in Late-Stage Lupus Mice Defective in Producing IFN-α.

Plasmacytoid dendritic cells (pDCs) are professional type I IFN producers believed to promote lupus. However, questions exist about whether they function at the same level throughout the course of lupus disease. We analyzed high-purity pDCs sorted from lupus mice.

Identification of novel allosteric modulator binding sites in NMDA receptors: A molecular modeling study.

The dysfunction of N-methyl-d-Aspartate receptors (NMDARs), a subtype of glutamate receptors, is correlated with schizophrenia, stroke, and many other neuropathological disorders. However, not all NMDAR subtypes equally contribute towards these disorders. Since NMDARs composed of different GluN2 subunits (GluN2A-D) confer varied physiological properties and have different distributions in the brain, pharmacological agents that target NMDARs with specific GluN2 subunits have significant potential for therapeutic applications.

Prevalence and characterization of methicillin-resistant Staphylococcus aureus isolates from healthy university student athletes.

Background: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has been increasing in the general population, and there is concern that close or physical contact, such as in professional and collegiate sports, may increase spread of MRSA. We sought to determine the prevalence of MRSA colonization of male and female athletes from 9 different sports at a major, Division I University during a 12-week period, and determine the USA and SCCmec type from select isolates.

Methods: Swabs for culture of MRSA were obtained from nasal, axillary, and inguinal sites from healthy, asymptomatic student athletes and support staff each week for 12 weeks.

Substance P is associated with hypothalamic paraventricular nucleus activation that coincides with increased urotensin 2 mRNA in chicks.

Exogenous administration of substance P (SP) exerts anorexigenic effects in both chicks and rats, but the central mechanism mediating this response is poorly understood. Therefore, this study was designed to elucidate mechanisms of SP-induced anorexia using chicks as models. Chicks that received intracerebroventricular (ICV) injections of SP dose-dependably reduced their food intake with no effect on water intake.

Paraoxonases function as unique protectors against cardiovascular diseases and diabetes: Updated experimental and clinical data.

Paraoxonase (PON) refers to a family of three enzymes, namely PON1, PON2, and PON3. PON1 and PON3 are found in circulation bound to high-density lipoprotein, whereas PON2 is an intracellular protein. PON1 was first discovered as an enzyme to hydrolyze the organophosphate pesticide paraoxon, an activity that both PON2 and PON3 lack.

MicroRNA-let-7a promotes E2F-mediated cell proliferation and NFκB activation in vitro.

Epigenetic factors, including altered microRNA (miRNA) expression, may contribute to aberrant immune cell function in systemic lupus erythematosus (SLE). MiRNA-let-7a (let-7a) has been shown to directly alter cell cycle progression and proinflammatory cytokine production. Due to the crucial role of let-7a in cell division and inflammation, we investigated let-7a-mediated proliferation and NFκB translocation in J774A.

Oxidative stress and redox signaling mechanisms of alcoholic liver disease: updated experimental and clinical evidence.

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality in the United States and Europe. The spectrum of ALD ranges from fatty liver to alcoholic hepatitis and cirrhosis, which may eventually lead to hepatocellular carcinoma. In developed countries as well as developing nations, ALD is a major cause of end-stage liver disease that requires liver transplantation.

Histone deacetylase 9 deficiency protects against effector T cell-mediated systemic autoimmunity.

Co-repressor histone deacetylase 9 (HDAC9) plays a key role in the development and differentiation of many types of cells, including regulatory T cells. However, the biological function of HDAC9 in T effector cells is unknown. Systemic autoimmune diseases like lupus, diabetes, and rheumatoid arthritis have dysfunctional effector T cells.

Telesonography: foundations and future directions.

The practice of telesonography has yielded promising results in several domestic and international projects aimed at providing basic sonography services. Common themes that recur within telesonography-based research include the quality of transmitted images, clinical applications, and technical and nontechnical barriers to implementation. The research base continues to grow in concert with expanding telecommunications capabilities and refinement of small portable sonographic devices.

Treatment of neurodegenerative disorders with radical nanomedicine.

In engineering and materials science, nanotechnology has provided many advances that effectively reduce oxidative damage generated by free radical production. Despite such advances, there has been little application to biomedical problems. Increased oxidative stress and free radical production are associated with neurodegenerative conditions, including aging, trauma, Alzheimer's and Parkinson's diseases, and many others.

Radical nanomedicine.

Nanotechnology has made significant advances in the reduction of free radical damage in the field of materials science. Cross-disciplinary interactions and the application of this technology to biological systems has led to the elucidation of novel nanoparticle antioxidants, which are the subject of this review. Recent reports suggest that cerium oxide and other nanoparticles are potent, and probably regenerative, free radical scavengers in vitro and in vivo.

Hypothyroidism alters striatal dopamine release mediated by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy).

Microdialysis cannulas were surgically implanted into the striatum of thyroparathyroidectomized (TX) and sham rats in order to determine differences in dopamine release and core body temperature following MDMA administration. Rats were subsequently treated with MDMA (10 mg/kg, s.c.

N-methyl-D-aspartate receptor in human prostate cancer.

Expression of the N-methyl-D-aspartate receptor (NMDAr) and its involvement in cellular proliferation is well-known in tumors of neuronal tissue, such as glioma and neuroblastoma. We have investigated NMDAr expression in the normal, hyperplastic and neoplastic human prostate by immunohistochemistry. Low stromal NMDAr immunostaining was observed in 2 of 12 (17%) normal prostate specimens, but epithelial NMDAr staining was not seen.

Nanoparticles and cell longevity.

The field of engineering has made substantial strides in nanotechnology, in the realm of materials science and construction of nanoscale devices. Nanomedicine encompasses application of cutting edge engineered nanostructures to biological systems and development of novel strategies for disease intervention. In the current review, we discuss the pharmacological application of nanoparticles as free radical scavengers and the capacity of nanoparticles to promote cell and organismal longevity.

Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid.

Epigenetic regulation of gene expression is involved in the development of many diseases. Histone acetylation is a posttranslational modification of the nucleosomal histone tails that is regulated by the balance of histone deacetylases and histone acetyltransferases. Alterations in the balance of histone acetylation have been shown to cause aberrant expression of genes that are a hallmark of many diseases, including systemic lupus erythematosus.

Potentiation of the antiproliferative activity of MKT-077 by loperamide, diltiazem and tamoxifen.

MKT-077, a delocalized lipophilic cation, selectively targets cancer cells. MKT-077 has been reported to inhibit the growth of several tumor types and has undergone phase I clinical testing. We have examined the effect of MKT-077, alone and in combination with the antidiarrheal drug loperamide.

Activity of potassium channel-blockers in breast cancer.

Background: Potassium ion (K+) channels are known to play a key role in breast cancer proliferation.

Materials And Methods: We investigated the expression of Kv1.3 voltage-gated K+ channels in 60 human breast cancer specimens by immunohistochemistry.

Sacroiliac joint dysfunction in athletes.

The sacroiliac (SI) joint is a common source of low back pain in the general population. Because it is the link between the lower extremities and the spine, it sustains even higher loads during athletic activity, predisposing athletes to a greater probability of joint dysfunction and pain. The diagnosis and treatment of SI joint dysfunction remains controversial, due to complex anatomy and biomechanics, and a lack of universally accepted nomenclature and terminology, consistently reliable clinical tests and imaging studies, and consistently effective treatments.