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PubMed1997

Dietary xylitol retards the ovariectomy-induced increase of bone turnover in rats.

The effects of 10% dietary xylitol supplementation in ovariectomized rats were studied on the degradation of bone organic and inorganic structures. The osseal concentrations of hydroxyproline, pyridinoline, and deoxypyridinoline were analyzed by high-performance liquid chromatography. Bone resorption was measured in [3H]tetracycline-prelabeled rats by urinary excretion of 3H, and by the amount of 3H preserved in bone. Bone trabeculation was measured by a computer image analyzer from sections stained by the method of von Kossa. The amount of collagen in bone organic fraction was lower in ovariectomized rats as compared with the sham-operated controls. This most likely is partly a consequence of an increased resorption, and partly a consequence of a higher proportion of immature periosteal bone in the ovariectomized animals, leading to a higher ratio of noncollagenous protein to collagen. The number of pyridinium crosslinks was lower in proportion, indicating no selective changes in the structure of collagen. Dietary xylitol significantly retarded the ovariectomy-associated decrease in the relative amount of collagen and the number of its mature crosslinks. Ovariectomy doubled the excretion of 3H and caused a significant decrease in the amount of 3H preserved in bone; both these changes were significantly retarded by the 10% dietary xylitol supplementation. Ovariectomy significantly decreased the volume of bone trabeculae, but this effect was also significantly inhibited by the xylitol supplementation in the diet. In conclusion, these findings suggest a dietary xylitol-induced normalizing effect on the rate of bone turnover in ovariectomized rats.

Animals↗
PubMed1997

Biochemical markers of bone turnover in Camurati-Engelmann disease: a report on four cases in one family.

Moderate increases in "classical" biochemical markers of bone turnover have been described only in some patients with Camurati-Engelmann disease. However, the determination of the following "new" markers has not been previously performed: serum osteocalcin (BGP), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), aminoterminal propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxyterminal of type I collagen (ICTP), urinary pyridinoline (PYR), crosslinked N-telopeptides of type I collagen (NTX), and Crosslaps (CL). Such a determination may improve the evaluation of the disease activity. To evaluate the usefulness of biochemical markers of bone turnover reflecting Camurati-Engelmann disease activity we measured the levels of all these markers in four affected patients. The results were compared with bone scintigraphic indices of disease activity. Except for PICP and TRAP, bone formation and resorption markers were abnormal in all patients and were related to bone scan indices of disease activity. Among the markers of bone formation PINP, BAP, and BGP showed the highest values, whereas NTX and CL were the most sensitive markers of bone resorption. These results suggest that the determination of NTX or CL, and PINP or either BAP and BGP, associated with bone scan evaluation, provides the best assessment of Camurati-Engelmann disease activity.

Acid Phosphatase↗
PubMed2006

Spatial and temporal patterns of expression of melanocortin type 2 and 5 receptors in the fetal mouse tissues and organs.

In the present study to analyze the role of ACTH in fetal tissues and organs, we observed the expression of melanocortin type 2 (MC2) and 5 (MC5) receptors in ICR mouse embryos from E11.5 to E18.5 by immunohistochemistry. In the adrenal gland and testis, both receptors were expressed from E13.5 to E18.5. In the genital ridge and the ovary, melanocortin type 2 receptors (MC2R) was detected from E11.5 to E12.5 and from E13.5 to E18.5, respectively, while melanocortin type 5 receptors (MC5R) was not detected. In the mesonephros, MC2R and MC5R were expressed from E11.5 to E12.5, and in the metanephros, MC2R and MC5R were expressed from E12.5 to E18.5 and from E14.5 to E18.5, respectively. In the lung, MC2R was expressed from E11.5 to E14.5, but MC5R was not expressed at all. In blood cells, MC5R was detected at all stages examined, while MC2R was detected at none. MC2R was observed in the brain and spinal cord from E11.5 to E13.5, while MC5R was detected only in the telencephalon and only from E16.5 to E18.5. At different temporal patterns, MC2R, but not MC5R, was detected in the choroid plexus, while MC5R, but not MC2R, was expressed in the liver and in the nasal epithelium, and both MC2R and MC5R were expressed in the dorsal root ganglion and the trigeminal ganglion. These findings show the spatio-temporal specific expression patterns of MC2R and MC5R in the mouse embryo and suggest that ACTH may be related to histogenesis and/or prenatal function of various tissues and organs via MC2R and/or MC5R.

Adrenocorticotropic Hormone↗
PubMed2000

Responses of immunocompetent cells in the dental pulp to replantation during the regeneration process in rat molars.

Responses of immunocompetent cells to tooth replantation during the regeneration process of the dental pulp in rat molars were investigated by immunocytochemistry using antibodies to class II major histocompatibility complex (MHC) molecules (OX6 antibody), monocyte/macrophage lineage cells (ED1 antibody) and protein gene product 9.5 (PGP 9.5), as well as by histochemical reaction for periodic acid-Schiff (PAS). Tooth replantation caused an increase in both the number of OX6- and ED1-positive cells and their immunointensity in the replanted pulp, but almost all PGP 9.5-immunoreactive nerves diminished in the initial stages. By postoperative day 3, many OX6- and ED -immunopositive cells had accumulated along the pulp-dentin border to extend their cytoplasmic processes into the dentinal tubules in successful cases. Once reparative dentin formation had begun after postoperative day 7, OX6- and ED1-immmunopositive cells became scattered in the odontoblast layer, while reinnervation was found in the coronal pulp. The temporal appearance of these immunocompetent cells at the pulp-dentin border suggests their participation in odontoblast differentiation as well as in initial defense reactions during the pulpal regeneration process. On postoperative day 14, the replanted pulp showed three regeneration patterns: (1) reparative dentin, (2) bone-like tissue formation, and (3) an intermediate form between these. In all cases, PAS-reactive cells such as polymorphonuclear leukocytes (PML) and mesenchymal cells occurred in the pulp space. However, the prolonged stagnation of inflammatory cells was also discernible in the latter two cases. Thus, the findings on PAS reaction suggest that the migration of the dental follicle-derived cells into the pulp space and the subsequent total death of the proper pulpal cells are decisive factors for eliciting bone-like tissue formation in the replanted pulp.

Animals↗
PubMed1999

Exposure of macrophage-like cells to titanium particles does not affect bone resorption, but inhibits bone formation.

We examined the capacity of culture supernatants of macrophage-like cells exposed to titanium particles to influence bone formation and bone resorption, our aim being to elucidate the mechanism of implant loosening. A mouse macrophage-like cell line, J774, was exposed to titanium particles and the concentrations of prostaglandin E2, tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-6 in the supernatants were measured. Titanium particles stimulated the J774 cells to release tumor necrosis factor-alpha, whereas prostaglandin E2, interleukin-1alpha and interleukin-6 concentrations remained low. The bone resorptive activity of the supernatants was measured by determining 45Ca release from cultured pre-labeled newborn mouse calvariae. The culture supernatants of J774 cells exposed to titanium particles showed no significant difference in bone resorptive activity in mouse calvariae from that of culture supernatants of J774 cells not exposed to titanium particles. The bone-forming activity of the supernatant was evaluated by determining bone nodule formation and alkaline phosphatase activity in cultured mouse calvaria cells. The bone-forming activity of the supernatants exposed to titanium particles was significantly decreased compared with the supernatants of unexposed J774 cells. This inhibition was reversed by the addition of anti-tumor necrosis factor-alpha neutralizing antibody. We conclude that tumor necrosis factor-alpha released from J774 cells exposed to titanium particles played an important role in the inhibition of bone formation rather than in the stimulation of bone resorption.

Alkaline Phosphatase↗
PubMed2006

Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy--a review.

Infection of infants in their first year of life, children and elderly people with the respiratory syncytial virus (RSV) endangers the life of the patient. An attempt to develop a formalin-inactivated RSV (FI-RSV) vaccine during the 1960s resulted in an aggravated infection in immunized children, leading to hospitalization, while infection of non-immunized children produced much milder symptoms. The reason for this remained an enigma, one which was gradually solved over the last decade by many researchers who studied the molecular biology of RSV infection of respiratory ciliary cells. Clinical studies of RSV-infected patients indicated increased levels of Th2 cytokines and IgE in the patients' sera, suggesting that an allergy-like condition developed during infection. The biomarkers of allergy caused by endogenous or environmental allergens include a marked increase of the Th2 cytokine IL-4 and IgE non-neutralizing antibodies to the allergen. The way allergens trigger allergy was deciphered recently, and will be discussed later. Studies of RSV infection led to the suggestion that RSV patients suffer from allergy prior to RSV infection, a concept that was later abandoned. Studies on HIV-1 [Y. Becker, Virus Genes 28, 319-331 (2005)] research led me to the hypothesis that since HIV-1 infection induces a marked increase of IL-4 and IgE in serum, an allergy-like condition, the AIDS stage is the result of an allergen motif that is embedded in the shed viral gp120 molecules. It is hypothesized that the viral-soluble G glycoprotein (sG) contains a T cell superantigen (Tsag) that is capable of binding to the V(H)3 domain of IgE/FcepsilonRI(+) hematopoietic cells, basophils, mast cells and monocytes, similar to the case of allergens, and that this aggregation causes these innate system cells to degranulate and release large amounts of Th2 cytokines (IL-4, IL-5, IL-10, IL-13) into the blood. The way these Th2 cytokines skew the Th1/Th2 balance toward Th2 > Th1 will be discussed. The aim of the present review is to base RSV pathogenicity on the numerous very good analyses of the virus genes and to suggest a therapeutic approach to treatment that is directed at preventing the inhibitory effects of Th2 cytokines on the adaptive immune system of the patients, instead of inhibiting RSV replication by antivirals. The review of the molecular research on the role of the viral fusion (F) and attachment (G) glycoproteins of RSV provided information on their role in the virus infection: early in infection the F glycoprotein induces Th1 cells to release the Th1 cytokines IL-2, IL-12 and IFN-gamma to activate precursors CTLs (pCTLs) to become anti-RSV CTLs. The G and sG glycoproteins attach to FKNR1(+) ciliary respiratory epithelial cells as well as directly to eosinophils to the lungs. The sG T cell antigen can also induce the release of large amounts of Th2 cytokines from CD4(+) T cells and from FCepsilonRI(+) mast cells, basophils and monocytes. By comparison to HIV-1 gp120 it is possible to show that in the G and sG proteins the T cell antigen resembles the CD4(+) T cell superantigen (=allergen) domain of HIV-1 gp120 which aggregates with IgE/FCepsilonRI(+) hematopoietic cells. The increased IL-4 level in the serum inhibits the adaptive immune response: IL-4Ralpha(+) Th1 cells stop Th1 cytokine synthesis and IL-4Ralpha(+) B cells stop the synthesis of antiviral IgG and IgA and switch to IgE synthesis. In addition, the hematopoietic cells release histamine and prostaglandin which induce wheezing. The gradual increase of sG molecules creates a gradient of fractalkine (FKN) which directs IL-5-activated eosinophils to the lungs of the patient.

Animals↗
PubMed1994

Detection of sulfur mustard-induced DNA modifications.

Sulfur mustard is acutely toxic to the skin, eyes, and respiratory tract, and is considered carcinogenic to humans by the IARC. Since all of these toxicities are thought to be initiated by DNA alkylation, the level of DNA damage should serve as a biomarker for exposure. To develop methods of detecting this damage, DNA was modified by [14C]-labeled sulfur mustard and DNA adducts were released by mild acid hydrolysis. Radioactivity co-eluted on HPLC analysis with marker 7-(2-hydroxyethylthioethyl) guanine and 3-(2-hydroxyethylthio-ethyl) adenine synthesized from 2-chloroethyl 2-hydroxy-ethyl sulfide. Unambiguous identification of the major adduct, 7-(2-hydroxy-ethylthioethyl) guanine, was provided by gas chromatography combined with mass spectrometric detection. The most abundant adduct, 7-(2-hydroxyethyl-thioethyl) guanine, accounted for 61% of the total alkylation and could be detected as a fluorescent HPLC peak with a detection limit of 10 pmol. To demonstrate the applicability of this method to biological samples, DNA was extracted from the white blood cells of human blood exposed to 131 microM sulfur mustard in vitro and shown to contain 470 pmol of 7-(2-hydroxyethylthio-ethyl) guanine per mg of DNA.

Animals↗
PubMed1991

Serum osteocalcin (bone Gla-protein), an index of bone growth in lambs. Comparison with age-related histomorphometric changes.

In 96 normal male sheep, we studied the variations with age of serum osteocalcin (bone Gla-protein), measured with an assay specific for ovine osteocalcin. We compared serum osteocalcin with the main histomorphometric parameters of bone growth measured on the metacarpus of 20 normal lambs from birth to 90 days of age. Serum osteocalcin significantly decreased with age (r = -0.70, p less than 0.001), particularly during the first 90 days of life (r = -0.85, p less than 0.001). During this growth period, serum osteocalcin was significantly correlated with the appositional rate (r = +0.73, p less than 0.001), the rate of longitudinal bone growth (r = +0.68, p less than 0.002), the rate of production of chondrocytes in the growth plate (r = +0.60, p less than 0.007), and the thickness of the growth plate (r = +0.79, p less than 0.001). In low birth weight male lambs (growth-retarded animals), serum osteocalcin was significantly lower at birth when compared to normal lambs (271 +/- 156 vs. 535 +/- 169 micrograms/l, p less than 0.001), and was also significantly correlated with histomorphometric parameters. We conclude that serum osteocalcin, which is already known as a sensitive and specific marker of bone formation, is also a sensitive biochemical marker of skeletal growth in normal and growth-retarded lambs. In addition, sheep appears as a valid animal for experimental studies on bone growth.

Age Factors↗
PubMed2026

Transcriptomic insights into the molecular mechanism of antifouling agent-induced settlement inhibition in the Pacific oyster Crassostrea gigas.

Marine biofouling remains a persistent challenge to maritime industries and marine ecosystems worldwide. In this study, we systematically evaluated the acute toxicity, settlement inhibitory efficacy, and underlying molecular mechanisms of an N-oleyl-1,3-propanediamine-based antifouling agent using pediveliger larvae of the Pacific oyster Crassostrea gigas. The 96 h-LC50 of the agent was determined to be 0.81 mg/L, and exposure to 1.68 mg/L achieved complete larval settlement inhibition without inducing significant acute toxicity. Transcriptomic analysis identified 791 differentially expressed genes, dominated by downregulated genes associated with ribosomal function, translation, cell adhesion, and cytoskeletal organization. The agent exerts its inhibitory effect primarily through the global suppression of protein synthesis, disruption of cell-substrate adhesion and cytoskeletal integrity, and induction of proteotoxic stress responses. These findings reveal a multi-pathway molecular mechanism underlying antifouling agent-induced settlement inhibition in oyster larvae and provide key molecular biomarkers to support the development of eco-friendly antifouling technologies.

Animals↗
PubMed2026

Sea urchin co-culture boosts abalone growth by reducing environmental stress and remodeling gut microbiota.

Biofouling and microenvironmental deterioration are major bottlenecks restricting the intensive aquaculture of Pacific abalone (Haliotis discus hannai). While co-culturing offers an eco-friendly mitigation strategy, the underlying mechanisms promoting abalone growth remain poorly understood. This study evaluated the growth performance of H. d. hannai co-cultured with varying densities of the sea urchin (Strongylocentrotus intermedius). By employing transcriptome and 16S rRNA sequencing of the abalone gut, we investigated the synergistic responses of host gene expression and gut microbiota. Compared with the monoculture group, the co-culture groups showed significantly less biofouling and greater growth of abalone, with the co-culture (n = 15) exhibiting the best outcomes. Transcriptomic analysis revealed 1444, 760, and 508 DEGs in G5, G10, and G15, respectively, compared with G0. These DEGs were significantly enriched in metabolic pathways, including glycolysis and sterol metabolism, indicating a shift in intestinal energy metabolism from stress defense toward growth under co-culture conditions. Gut microbiota profiling identified Proteobacteria and Firmicutes as the dominant phyla, with specific functional taxa (e.g., Psychrilyobacter and Akkermansia) enriched in a density-dependent manner. Furthermore, correlation analysis demonstrated that growth traits positively correlated with growth-promoting taxa (e.g., the unclassified AB1 lineage), but negatively correlated with potentially opportunistic taxa (e.g., Tabrizicola). These findings provide insights into a potential synergistic mechanism of "environmental stress alleviation-metabolic reprogramming-microecological remodeling" driving abalone growth, providing a theoretical foundation for optimizing co-culture systems and developing growth-associated biomarkers.

Animals↗
PubMed2006

Analysis of human serum by liquid chromatography-mass spectrometry: improved sample preparation and data analysis.

Discovery of biomarkers is a fast developing field in proteomics research. Liquid chromatography coupled on line to mass spectrometry (LC-MS) has become a powerful method for the sensitive detection, quantification and identification of proteins and peptides in biological fluids like serum. However, the presence of highly abundant proteins often masks those of lower abundance and thus generally prevents their detection and identification in proteomics studies. To perform future comparative analyses of samples from a serum bank of cervical cancer patients in a longitudinal and cross-sectional manner, methodology based on the depletion of high-abundance proteins followed by tryptic digestion and LC-MS has been developed. Two sample preparation methods were tested in terms of their efficiency to deplete high-abundance serum proteins and how they affect the repeatability of the LC-MS data sets. The first method comprised depletion of human serum albumin (HSA) on a dye ligand chromatographic and immunoglobulin G (IgG) on an immobilized Protein A support followed by tryptic digestion, fractionation by cation-exchange chromatography, trapping on a C18 column and reversed-phase LC-MS. The second method included depletion of the six most abundant serum proteins based on multiple immunoaffinity chromatography followed by tryptic digestion, trapping on a C18 column and reversed-phase LC-MS. Repeatability of the overall procedures was evaluated in terms of retention time and peak area for a selected number of endogenous peptides showing that the second method, besides being less time consuming, gave more repeatable results (retention time: <0.1% RSD; peak area: <30% RSD). Application of an LC-MS component detection algorithm followed by principal component analysis (PCA) enabled discrimination of serum samples that were spiked with horse heart cytochrome C from non-spiked serum and the detection of a concentration trend, which correlated to the amount of spiked horse heart cytochrome C to a level of 5 pmol cytochrome C in 2 microl original serum.

Animals↗
PubMed2006

Pediatric reference intervals for bone markers.

Bone markers are specific bone-derived molecules that reflect bone remodeling activity and can be classified into two categories: bone formation and bone resorption markers. Children have significantly elevated bone marker levels due to high skeletal growth velocity and rapid bone turnover during childhood growth. Many physiological and pathological processes may influence bone metabolism and bone marker concentrations during childhood growth. Measurements of bone markers may be useful in investigating skeletal diseases in children and monitoring the response to treatment. This review documents recent advances in analytical methods, preanalytical considerations related to each marker and particularly highlights the most valuable bone formation markers, bone alkaline phosphatase and osteocalcin, and bone resorption markers, pyridinium cross-links and cross-linked telopeptides. Age- and sex-specific pediatric reference intervals and their limitations in clinical application are also discussed.

Biomarkers↗
PubMed2025

Heme oxygenase 1 (HO-1) is a drug target for reversing cisplatin resistance in non-small cell lung cancer.

INTRODUCTION: Platinum-based drugs, the most widely used chemotherapeutic drugs in clinical oncology, have long faced the problem of drug resistance, which is urgently in need of resolution. Identifying biomarkers of drug resistance may help reduce platinum resistance and improve therapeutic efficacy. OBJECTIVES: This study aims to identify potential biomarkers associated with the development of cisplatin resistance in non-small cell lung cancer (NSCLC) and explore mechanisms to overcome chemoresistance. METHODS: NSCLC cisplatin resistance cell lines were constructed, and transcriptome sequencing was performed. Results were validated using Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Molecular docking, proteomics sequencing, and in vitro and in vivo experiments were conducted to evaluate the role of Heme Oxygenase 1 (HO-1) in cisplatin resistance. RESULTS: NSCLC cisplatin resistance cell lines, GEO and TCGA data identified HMOX1, downstream of Nrf2, as a key drug resistance gene induced by cisplatin. Activation of the Nrf2/HO-1 pathway was found to induce ferroptosis resistance, a critical mechanism of cisplatin resistance. Candidate compounds SB 202190 and Nordihydroguaiaretic acid (NDGA) effectively reactivated ferroptosis by inhibiting HO-1, thereby increasing cisplatin sensitivity. CONCLUSION: The Nrf2/HO-1 pathway is a significant contributor to cisplatin resistance in NSCLC. Targeting HO-1 with SB 202190 and NDGA presents a promising strategy to overcome resistance and improve chemotherapy outcomes.

Cisplatin↗
PubMed2006

Longitudinal changes in bone health as assessed by the speed of sound in very low birth weight preterm infants.

OBJECTIVE: To assess longitudinal changes in speed of sound (SOS) in very low birth weight (VLBW) infants and investigate the relationship with markers of osteopathy of prematurity (OP) and clinical illness. STUDY DESIGN: Twenty-five infants were recruited. Eighteen infants, median gestation 27 weeks (range 24-32), median birth weight 957 g (range 625-1500 g), had serial scans. SOS was measured at both tibiae weekly until 35 to 37 weeks corrected gestational age (CGA). RESULTS: Initial median SOS standard deviation score (SDS) (Z) score was -0.07 (range-1.3-1.3). SOS correlated with gestation (r, 0.8, P<.005), and birth weight (r, 0.67, P<.005.) SOS fell from a median of 2923 m/s (2672-3107) at birth to 2802 m/s (2502-2991) at 35 to 37 weeks CGA (P<.05). This fall was greater in the 24- to 27-week gestation cohort with a median reduction of 2.2 SDS (1.6, 4.0) compared with 1.3 SDS (0.8-2.2) in those>28 weeks (P<.05). There was a negative correlation between SOS, at the end of the study, peak serum alkaline phosphatase (ALP) (r, 0.6, P<.05), CRIB (Clinical Risk Index for Babies)/CRIB II scores (both r, 0.6, P<.05), and duration of total parenteral nutrition (TPN) (r, 0.58, P<.05.) CONCLUSIONS: Although tibial SOS was within the expected range at birth, there was a subsequent failure to gain SOS, and this was most marked in infants of a lower gestation.

Alkaline Phosphatase↗
PubMed2005

Effects of phosphorus intake on phosphorus flow in growing pigs: application and comparison of two models.

A comparison of the models of Vitti et al. (2000, J. Anim. Sci. 78, 2706-2712) and Fernández (1995c, Livest. Prod. Sci. 41, 255-261) was carried out using two data sets on growing pigs as input. The two models compared were based on similar basic principles, although their aims and calculations differed. The Vitti model employs the rate:state formalism and describes phosphorus (P) flow between four pools representing P content in gut, blood, bone and soft tissue in growing goats. The Fernández model describes flow and fractional recirculation between P pools in gut, blood and bone in growing pigs. The results from both models showed similar trends for P absorption from gut to blood and net retention in bone with increasing P intake, with the exception of the 65 kg results from Date Set 2 calculated using the Fernández model. Endogenous loss from blood back to gut increased faster with increasing P intake in the Fernández than in the Vitti model for Data Set 1. However, for Data Set 2, endogenous loss increased with increasing P intake using the Vitti model, but decreased when calculated using the Fernández model. Incorporation of P into bone was not influenced by intake in the Fernández model, while in the Vitti model there was an increasing trend. The Fernández model produced a pattern of decreasing resorption in bone with increasing P intake, with one of the data sets, which was not observed when using the Vitti model. The pigs maintained their P homeostasis in blood by regulation of P excretion in urine.

Animal Feed↗