Anti-Tn Monoclonal Antibody Ameliorates Hyperoxia-Induced Kidney Injury by Suppressing Oxidative Stress and Inflammation in Neonatal Mice.

The Tn antigen, an N-acetylgalactosamine structure linked to serine or threonine, has been shown to induce high-specificity, high-affinity anti-Tn antibodies in mice. Maternal immunization with the Tn vaccine increases serum anti-Tn antibody titers and attenuates hyperoxia-induced kidney injury in neonatal rats. However, immunizing mothers to treat neonatal kidney disease is clinically impractical.

Beat-to-beat and spectral analyses of the noninvasive radial pulse and laser-Doppler signals in patients with hypertension.

This study performed beat-to-beat and spectral analyses of 20-minute skin-surface laser-Doppler-flowmetry (LDF) and radial blood-pressure-waveform (BPW) signals in order to compare the blood-flow perfusion condition and regulatory mechanisms between essential-hypertension (EHT) patients and aged-matched control subjects. Beat-to-beat LDF analyses yielded the pulse width (PW), AC-to-DC ratio (AD), and their corresponding variability indices (coefficients of variation [CVs]). The relative energy contributions (RECs) of five characteristic frequency peaks (defined as FR1-FR5) were also calculated.

Anti-Tn Monoclonal Antibody Attenuates Hyperoxia-Induced Lung Injury by Inhibiting Oxidative Stress and Inflammation in Neonatal Mice.

Maternal immunization with Tn vaccine increases serum anti-Tn antibody titers and attenuates hyperoxia-induced lung injury in neonatal rats. This study determined whether anti-Tn monoclonal antibody can protect against hyperoxia-induced lung injury in neonatal mice. Newborn BALB/c mice were exposed to room air (RA) or normobaric hyperoxia (85% O) for 1 week, creating four study groups as follows: RA + phosphate-buffered saline (PBS), RA + anti-Tn monoclonal antibody, O + PBS, and O + anti-Tn monoclonal antibody.

Immunization with anti-Tn immunogen in maternal rats protects against hyperoxia-induced kidney injury in newborn offspring.

Background: Neonatal hyperoxia increases oxidative stress and adversely disturbs glomerular and tubular maturity. Maternal Tn immunization induces anti-Tn antibody titer and attenuates hyperoxia-induced lung injury in neonatal rats.

Methods: We intraperitoneally immunized female Sprague-Dawley rats (6 weeks old) with Tn immunogen (50 μg/dose) or carrier protein five times at biweekly intervals on 8, 6, 4, 2, and 0 weeks before the delivery day.

Maternal Tn Immunization Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats Through Suppression of Oxidative Stress and Inflammation.

Hyperoxia therapy is often required to treat newborns with respiratory disorders. Prolonged hyperoxia exposure increases oxidative stress and arrests alveolar development in newborn rats. Tn antigen is N-acetylgalactosamine residue that is one of the most remarkable tumor-associated carbohydrate antigens.

Tn (N-acetyl-d-galactosamine-O-serine/threonine) immunization protects against hyperoxia-induced lung injury in adult mice through inhibition of the nuclear factor kappa B activity.

Prolonged hyperoxia exposure leads to inflammation and acute lung injury. Since hyperoxia activates nuclear factor kappa B (NF-κB) and proinflammatory mediators in lung fibroblasts and murine lungs, and proinflammatory cytokines upregulate Tn (N-acetyl-d-galactosamine-O-serine/threonine) expression in human gingival fibroblasts. We hypothesized connections exist between Tn expression and inflammation regulation.

Sclerostin vaccination mitigates estrogen deficiency induction of bone mass loss and microstructure deterioration.

Sclerostin (SOST) is a Wnt signaling inhibitor detrimental to osteogenic differentiation and bone mineral acquisition. While control of SOST action delays the pathogenesis of skeletal disorders, the effects of SOST vaccination on the estrogen deficiency-induced bone deterioration remain elusive. In this study, we generated a SOST-Fc fusion protein which was composed of a SOST peptide Pro-Asn-Ala-Ile-Gly along with an IgG Fc fragment.

The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn.

Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. There are also reports that Tn is elevated in inflammatory tissues. However, the molecular mechanism for its elevated levels in cancer and inflammation is unclear.

Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer.

DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success.

Cancer risk in HBV patients with statin and metformin use: a population-based cohort study.

Chronic infection with hepatitis B virus (HBV) often causes chronic inflammation of the liver with an increased incidence of hepatocellular carcinoma (HCC). HBV-infected individuals may also have an increased incidence of nonliver cancers. Taking statin or metformin may decrease inflammation and infiltration, which may, as a result, reduce the risk of liver cancer or other major cancers in patients with HBV infection.

A vaccine targeted at CETP alleviates high fat and high cholesterol diet-induced atherosclerosis and non-alcoholic steatohepatitis in rabbit.

Low HDL-C levels are associated with atherosclerosis and non-alcoholic steatohepatitis, and increased levels may reduce the risk of these diseases. Inhibition of cholesteryl ester transfer protein (CETP) activity is considered a promising strategy for increasing HDL-C levels. Since CETP is a self-antigen with low immunogenicity, we developed a novel CETP vaccine (Fc-CETP6) to overcome the low immunogenicity of CETP and for long-term inhibition of CETP activity.

CFS-1686 causes cell cycle arrest at intra-S phase by interference of interaction of topoisomerase 1 with DNA.

CFS-1686 (chemical name (E)-N-(2-(diethylamino)ethyl)-4-(2-(2-(5-nitrofuran-2-yl)vinyl)quinolin-4-ylamino)benzamide) inhibits cell proliferation and triggers late apoptosis in prostate cancer cell lines. Comparing the effect of CFS-1686 on cell cycle progression with the topoisomerase 1 inhibitor camptothecin revealed that CFS-1686 and camptothecin reduced DNA synthesis in S-phase, resulting in cell cycle arrest at the intra-S phase and G1-S boundary, respectively. The DNA damage in CFS-1686 and camptothecin treated cells was evaluated by the level of ATM phosphorylation, γH2AX, and γH2AX foci, showing that camptothecin was more effective than CFS-1686.

Production of a neutralizing antibody against envelope protein of dengue virus type 2 using the linear array epitope technique.

Dengue virus (DENV; genus Flavivirus) contains a positive-stranded RNA genome. Binding of DENV to host cells is mediated through domain III of the viral envelope protein. Many therapeutic mAbs against domain III have been generated and characterized because of its high antigenicity.

Tight regulation of a timed nuclear import wave of EKLF by PKCθ and FOE during Pro-E to Baso-E transition.

Erythropoiesis is a highly regulated process during which BFU-E are differentiated into RBCs through CFU-E, Pro-E, PolyCh-E, OrthoCh-E, and reticulocyte stages. Uniquely, most erythroid-specific genes are activated during the Pro-E to Baso-E transition. We show that a wave of nuclear import of the erythroid-specific transcription factor EKLF occurs during the Pro-E to Baso-E transition.

Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis.

Long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Our previous studies reveal significant associations between promoter single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 and T2DM, as well as between SNPs in genes encoding IL-4/IL-4 receptor and high density lipoproteins. Our animal study reveals that IL-4 regulates glucose/lipid metabolism by promoting glucose tolerance and inhibiting lipid deposits.

Reciprocal relationship of Tn/NF-κB and sTn as an indicator of the prognosis of oral squamous cell carcinoma.

Aims: In order to determine whether the expression of tumour-associated carbohydrate antigens (Tn/sTn) and a representative inflammation marker, nuclear factor-κB (NF-κB), is associated with the invasiveness of oral squamous cell carcinoma (OSCC), this study has attempted to investigate the correlation of the aforementioned markers with the well-established invasive pattern grading score (IPGS) and clinicopathological parameters.

Methods And Results: Specimens from 143 OSCC patients with classified clinicopathological parameters and IPGS were stained immunohistochemically using anti-Tn, sTn and NF-κB antibodies. Our results showed that the expression of both Tn and NF-κB was correlated positively with staging (P = 0.

Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone.

Thyroid hormone induces tumor cell and blood vessel cell proliferation via a cell surface receptor on heterodimeric integrin αvβ3. We investigated the role of thyroid hormone-induced internalization of nuclear integrin αv monomer. Physiological concentration of thyroxine (free T4, 10(-10) M), but not 3,5,3'-triiodo-l-thyronine (T3), induced cellular internalization and nuclear translocation of integrin αv monomer in human non-small-cell lung cancer (H522) and ovarian carcinoma (OVCAR-3) cells.

Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol.

Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer OVCAR-3 cells, concomitant with an increase in the expression of COX-2 and p53 phosphorylation.

A novel synthetic bipartite carrier protein for developing glycotope-based vaccines.

Development of successful vaccines against glycotopes remains a major challenge. In the current studies, we have successfully developed a novel carrier protein for glycotopes based on the concept of antigen clustering and specific stimulation of T helper cells to mount strong antibody response to glycotopes. The bipartite carrier protein consists of a tandem repeat of a cysteine-rich peptide for docking of clustered glycotopes to effectively activate B cells and an Fc domain for antigen delivery to antigen presenting cells (APCs).

Phosphorylation-dependent SUMOylation of the transcription factor NF-E2.

Nuclear factor erythroid-derived 2 (NF-E2), a heterodimer composed of p45 and p18, is a transcriptional activator in hematopoietic progenitors. The transcriptional activity of NF-E2 is not only upregulated by SUMOylation but also stimulated by the cAMP-dependent protein kinase A (PKA). However, the relationship between SUMOylation and phosphorylation in the activation of NF-E2 is unclear.

Phosphorylation of Ubc9 by Cdk1 enhances SUMOylation activity.

Increasing evidence has pointed to an important role of SUMOylation in cell cycle regulation, especially for M phase. In the current studies, we have obtained evidence through in vitro studies that the master M phase regulator CDK1/cyclin B kinase phosphorylates the SUMOylation machinery component Ubc9, leading to its enhanced SUMOylation activity. First, we show that CDK1/cyclin B, but not many other cell cycle kinases such as CDK2/cyclin E, ERK1, ERK2, PKA and JNK2/SAPK1, specifically enhances SUMOylation activity.

UBC9 autosumoylation negatively regulates sumoylation of septins in Saccharomyces cerevisiae.

Sumoylation regulates a wide range of cellular processes. However, little is known about the regulation of the SUMO machinery. In this study, we demonstrate that two lysine residues (Lys-153 and Lys-157) in the C-terminal region of the yeast E2-conjugating enzyme Ubc9 are the major and minor autosumoylation sites, respectively.

One-pot synthesis of luotonin A and its analogues.

Starting with inexpensive reagents, a self-directed chemical process with the aid of a single metal triflate was readily achieved to concomitantly construct quinazoline and pyrroloquinoline cores to afford the synthesis of luotonin A and its analogues. Among all compounds prepared, 2c, 2d, and 3b exhibit more potent inhibitory activity than luotonin A against human topoisomerase I.

Glial cell adhesive molecule unzipped mediates axon guidance in Drosophila.

Axon guidance needs help from the glial cell system during embryogenesis. In the Drosophila embryonic central nervous system (CNS), longitudinal glia (LG) have been implicated in axon guidance but the mechanism remains unclear. We identified the protein encoded by the Drosophila gene unzipped (uzip) as a novel cell adhesion molecule (CAM).

Immobilizing topoisomerase I on a surface plasmon resonance biosensor chip to screen for inhibitors.

Background: The topoisomerase I (TopI) reaction intermediate consists of an enzyme covalently linked to a nicked DNA molecule, known as a TopI-DNA complex, that can be trapped by inhibitors and results in failure of re-ligation. Attempts at new derivative designs for TopI inhibition are enthusiastically being pursued, and TopI inhibitors were developed for a variety of applications. Surface plasmon resonance (SPR) was recently used in TopI-inhibition studies.