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PER1 modulates SGLT1 transcription in vitro independent of E-box status.

BACKGROUND AND AIMS: The intestine demonstrates profound circadian rhythmicity in glucose absorption in rodents, mediated entirely by rhythmicity in the transcription, translation, and function of the sodium glucose co-transporter SGLT1 (Slc5a1). Clock genes are rhythmic in the intestine and have been implicated in the regulation of rhythmicity of other intestinal genes; however, their role in the regulation of SGLT1 is unknown. We investigated the effects of one clock gene, PER1, on SGLT1 transcription in vitro. METHODS: Caco-2 cells were stably transfected with knockdown vectors for PER1 an

Metal ion modulation of cystinyl aminopeptidase.

Cystinyl aminopeptidase has one Zn2+-binding motif and is a member of the M1 aminopeptidase family. Ion modulation of its catalytic activity was studied in membranes of CHO-K1 cells (Chinese-hamster ovary K1 cells) using L-leucine-p-nitroanilide as substrate. The planar bidentate chelators 1,10-phenanthroline and 2,2'-bipyridine inhibited the activity in a concentration-dependent manner with Hill slopes of 3.32+/-1.78 and 2.10+/-0.26 respectively. The acetic acid-containing chelators EDTA, EGTA and DTPA (diethylenetriamine-N,N,N',N'',N''-penta-acetic acid) weakly affected the activity, but the

S1PR4-dependent Воздействие этрасимод на первичную активацию миэлоидных иммунных клеток человека.

ИСТОРИЯ ВОПРОСА: Sphingosine-1-phosphate (S1P) и его five Рецепторы S1PR1-5 играть важную роль в миграции, дифференциации и активации различных иммунных клеток. Недавно было утверждено несколько модуляторов S1PR с особой избирательностью для лечения различных подстрекательских заболеваний. Среди них Озанимод, S1PR1/5 Модулятор, утвержденный для лечения язвительного колита и множественных склерозов, и Etrasimod, S1PR1/4/5 Модулятор, утвержденный для лечения язвительного колита. Хронические самовоспалительные заболевания, такие, как вспыльчивые болезни кишечника (ББК) и язвительный колит, характ

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… Global S1PR4 expression was clearly increased in the CHO_S1PR4 cells compared to wt CHO cells ( Figure 8A ). Importantly, short-time treatment (30 min) with S1PR modulators did not affect global S1PR4 expression ( Figure 8B ). … Briefly, a CHO cell line expressing SNAP-tagged S1PR1 or S1PR4, respectively, was treated with S1P, Etrasimod or Ozanimod. …

Novel Alzheimer risk factor IQ motif containing protein K is abundantly expressed in the brain and is markedly increased in patients with Alzheimer's disease.

Alzheimer's disease (AD) is complex and highly heterogeneous. Less than 10% of AD cases are early-onset (EOAD) caused by autosomal dominantl … cytoplasm of SH-SY5Y neuroblastoma cells as well as HeLa cells but not in either HMC3 microglial or CHO cells. By immunohistochemistry (IHC), we also show that IQCK is expressed in both mouse and human neurons, including neuronal processes in vivo in the mouse brain. IHC data also show that the IQCK protein is widely expressed throughout the mouse brain, al …

Biological and toxicological evaluation of Rhus trilobata Nutt. (Anacardiaceae) used traditionally in mexico against cancer.

BACKGROUND: Rhus trilobata Nutt. (Anacardiaceae) (RHTR) is a plant of Mexico that is traditionally used as an alternative treatment for several types of cancer. However, the phytochemical composition and potential toxicity of this plant have not been evaluated to support its therapeutic use. Therefore, this study aimed to evaluate the biological activity of RHTR against colorectal adenocarcinoma cells, determine its possible acute toxicity, and analyze its phytochemical composition. METHODS: The traditional preparation was performed by decoction of stems in distilled water (aqueous extract, A

Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease.

Fabry disease (FD) is a progressive multisystemic disease characterized by lysosomal enzyme deficiency. Enzyme replacement therapy (ERT) is one of the most significant advancements and breakthroughs in treating FD. However, limited resources and the high cost of ERT might prevent patients from receiving prompt and effective therapy, thereby resulting in severe complications. Future progress in ERT can uncover promising treatment options. In this study, we developed and validated a recombinant enzyme (Lanzyme) based on a CHO-S cell system to provide a new potential option for FD therapy. Our re

Near-infrared photoimmunotherapy targeting GPR87: Development of a humanised anti-GPR87 mAb and therapeutic efficacy on a lung cancer mouse model.

BACKGROUND: GPR87 is a G-protein receptor that is specifically expressed in tumour cells, such as lung cancer, and rarely expressed in normal cells. GPR87 is a promising target for cancer therapy, but its ligand is controversial. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy in which a photosensitiser, IRDye700DX (IR700), binds to antibodies and specifically destroys target cells by irradiating them with near-infrared-light. Here, we aimed to develop a NIR-PIT targeting GPR87. METHODS: We evaluated the expression of GPR87 in resected specimens of lung cancer and maligna

Ethenzamide Exerts Analgesic Effect at the Spinal Cord via Multiple Mechanisms of Action Including the 5HT2B Receptor Blockade in the Rat Formalin Test.

Ethenzamide (ETZ), an antipyretic analgesic categorized as a non-steroidal anti-inflammatory drug (NSAID), is widely used as an OTC drug in combination with other NSAIDs. However, its site of action and mechanism underlying its analgesic action have not yet been fully elucidated. In this study, we performed in vitro pharmacological assays to identify the mechanism underlying the analgesic action of ETZ, and also conducted the rat formalin test to investigate its analgesic effect and site of action. Of the 85 receptors, ion channels, transporters and enzymes tested, we found that ETZ binds to t

Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction.

Cardiomyocyte proliferation stops at birth when the heart is no longer exposed to maternal blood and, likewise, to regulatory T cells (Tregs) that are expanded to promote maternal tolerance towards the fetus. Here, we report a role of Tregs in promoting cardiomyocyte proliferation. Treg-conditioned medium promotes cardiomyocyte proliferation, similar to the serum from pregnant animals. Proliferative cardiomyocytes are detected in the heart of pregnant mothers, and Treg depletion during pregnancy decreases both maternal and fetal cardiomyocyte proliferation. Treg depletion after myocardial infa

Rational design of triazololipopeptides analogs of kisspeptin inducing a long-lasting increase of gonadotropins.

New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-resistant amide mimic and a serum albumin-binding motif, respectively. These triazololipopeptides are highly potent full agonists of KISS1R and are >100 selective over the closely related NPFF1R. When injected in ewes with a quiescent reproductive system, the best compound of our s

Amino acid substitutions in the heptad repeat A and C regions of the F protein responsible for neurovirulence of measles virus Osaka-1 strain from a patient with subacute sclerosing panencephalitis.

Measles virus (MV) is the causative agent of subacute sclerosing panencephalitis (SSPE). We previously reported that the F gene of the SSPE Osaka-2 strain is the major determinant of MV neurovirulence. Because the sites and extents of mutations differ among SSPE strains, it is necessary to determine the mutations responsible for the SSPE-specific phenotypes of individual viral strain. In this study, recombinant viruses containing the envelope-associated genes from the SSPE Osaka-1 strain were generated in the IC323 wild-type MV background. Hamsters inoculated with MV containing the H gene of t

Entry of Bacillus anthracis spores into epithelial cells is mediated by the spore surface protein BclA, integrin α2β1 and complement component C1q.

Inhalational anthrax is initiated by pulmonary exposure to Bacillus anthracis spores. Spore entry into lung epithelial cells is observed both in vitro and in vivo and evidence suggests it is important for bacterial dissemination and virulence. However the specific host receptor and spore factor that mediate the entry process were unknown. Here, we report that integrin α2β1 is a major receptor for spore entry. This is supported by results from blocking antibodies, siRNA knock-down, colocalization, and comparison of spore entry into cells that do or do not express α2. BclA, a major spore surface

Roles for the galactose-/N-acetylgalactosamine-binding lectin of Entamoeba in parasite virulence and differentiation.

Entamoeba histolytica, an intestinal protozoan parasite, is a major cause of morbidity and mortality in developing countries. The pathology of the disease is caused by the colonization of the large intestine by the amoebic trophozoites and the invasion of the intestinal epithelium. Some of the trophozoites will eventually differentiate into the infectious cyst form, allowing them to be transmitted out of the bowel and into water supplies to be passed from person to person. Both the virulence of the organism and the differentiation process relies on a galactose-/N-acetylgalactosamine (GalNAc)-b

Manifestations and mechanisms of radiation-induced genomic instability in V-79 Chinese hamster cells.

PURPOSE: The relationship between different forms of persistent radiation damage in irradiated cells was investigated in order to identify a common underlying mechanism. MATERIAL AND METHODS: V-79 Chinese hamster cells were irradiated with different doses of X-rays, neutrons and alpha-particles. In the progeny of surviving cells, up to 4 weeks after irradiation, delayed reproductive death, delayed micronuclei, delayed appearance of dicentric chromosomes and delayed apoptosis were investigated in parallel. RESULTS: A similar dose-response relationship was found for all endpoints, with a steep

Comparison of Helicobacter mustelae and Helicobacter pylori adhesion to eukaryotic cells in vitro.

BACKGROUND & AIMS: Bacterial adhesion to mucosal surfaces is an important pathogenic mechanism for Helicobacter-induced gastritis. The aims of this study were to compare binding of selected Helicobacter mustelae and Helicobacter pylori strains to lipids extracted from HEp-2, Chinese hamster ovary, human embryonic lung cells, and ferret gastrointestinal tissues as well as to intact tissue culture cells and to analyze the fatty acids of the receptor. METHODS: Thin-layer chromatography overlay binding and a receptor-based immunoassay detected adhesion of bacteria to commercial lipids and to indi

In vivo and in vitro growth-stimulatory effects of pigeon milk.

Pigeon milk (PM) was tested for its effect on growth in vivo and in vitro. Eleven-day-old mice sucklings given a supplementary feeding of 125 mg PM per day for 3 days showed a significant increase in the weight of stomach and distal intestine, and the length of small intestine; there was, however, a significant decrease in heart size. In PM-fed animals the protein content of stomach, and RNA content of stomach, caecum and distal intestine increased whereas protein content of testes and distal intestine and DNA content of stomach decreased. Crude homogenates of PM stimulated 3H-thymidine incorp

Improved proteostasis in the secretory pathway rescues Alzheimer's disease in the mouse.

The aberrant accumulation of toxic protein aggregates is a key feature of many neurodegenerative diseases, including Huntington's disease, amyotrophic lateral sclerosis and Alzheimer's disease. As such, improving normal proteostatic mechanisms is an active target for biomedical research. Although they share common pathological features, protein aggregates form in different subcellular locations. Nε-lysine acetylation in the lumen of the endoplasmic reticulum has recently emerged as a new mechanism to regulate the induction of autophagy. The endoplasmic reticulum acetylation machinery includes

Dissecting PUGNAc-mediated inhibition of the pro-survival action of insulin.

Previous studies utilizing PUGNAc, the most widely used β-N-acetylglucosaminidase (OGA) inhibitor to increase global O-N-acetylglucosamine (GlcNAc) levels, have reported a variety of effects including insulin resistance as a direct result of elevated O-GlcNAc levels. The notion of OGA inhibition causing insulin resistance was not replicated in studies in which elevated global O-GlcNAc levels were achieved using two other OGA inhibitors. Related to insulin action, work by others has suggested that O-GlcNAc elevation may inhibit the anti-apoptotic action of insulin. Thus, we examined the pro-sur

Re-engineering an alphoid(tetO)-HAC-based vector to enable high-throughput analyses of gene function.

Human artificial chromosome (HAC)-based vectors represent an alternative technology for gene delivery and expression with a potential to overcome the problems caused by the use of viral-based vectors. The recently developed alphoid(tetO)-HAC has an advantage over other HAC vectors because it can be easily eliminated from cells by inactivation of the HAC kinetochore via binding of tTS chromatin modifiers to its centromeric tetO sequences. This provides unique control for phenotypes induced by genes loaded into the alphoid(tetO)-HAC. However, inactivation of the HAC kinetochore requires transfec

Schistosoma haematobium: identification of new estrogenic molecules with estradiol antagonistic activity and ability to inactivate estrogen receptor in mammalian cells.

We have previously identified the expression of an estradiol (E2)-related molecule by Schistosoma haematobium total antigen (Sh). We now show that this molecule has an antagonistic effect of estradiol in vitro. Our results are consistent with the existence of an estrogenic molecule that antagonizes the activity of estradiol. We found evidence for this molecule as we identified and characterized by mass spectrometry new estrogenic molecules previously unknown, present in schistosome worm extracts and sera of Schistosoma-infected individuals. We also show that Sh is able to interact in vitro wit