PubMed Health⌕ Search

Biomedical subjects

Lei Gu

Publications and source records attributed to Lei Gu.

7 recordsLinked to original sources

[Effects of alendronate on bone mineral density, cytokines and indices of bone metabolism in postmenopausal osteoporotic patients].

OBJECTIVE: To observe the effects of alendronate on bone mineral density (BMD), cytokines and indices of bone metabolism in postmenopausal osteoporotic (PMO) patients. METHODS: 185 PMO patients, aged from 55 to 60 years, were randomized into three groups. All of them received a kind of calcium preparation, 1.0 g/d. Group A, 69 patients, received alendronate, 10 mg/d; group B, 66 patients, received tibolone 1.25 mg/d. The remaining patients, group C, received calcium preparation only. 20 women of 55 - 60 (57.4 +/- 3.5) years old were taken as normal controls. Dual-energy X-ray absorptiometry and measurement of a series of biochemical indices were carried out before and after medication at 24th and 48th week. RESULTS: After medication, BMD increased in alendronate and tibolone group. The increment in spine BMD was 2.53% and 3.65% (P < 0.05) and that in nondominant proximal femur BMD was 7.17% and 3.01% (P < 0.001). In the tibolone group, the levels of estradiol (E(2)) increased rapidly (P < 0.01), but those of IL-6, TNFalpha and type I collagen cross-linked N-telopeptides (NTX) decreased (P < 0.01). In the alendronate group, no change of levels of E(2) happened, while levels of alkaline phosphatase (ALP) and osteocalcin (BGP) increased (P < 0.05) and levels of NTX decreased (P < 0.05). There was no change of the levels of other parameters. In the calcium preparation group and control group, the levels of BMD, E(2), ALP, BGP and insulin-like growth factor I decreased (P < 0.05), while those of IL-6, TNFalpha and NTX increased (P < 0.05). CONCLUSION: Alendronate can significantly improve BMD as tibolone do. Thus it plays an important role in the treatment of osteoporosis. However calcium tablet can not prevent the loss of bone.

Alendronate↗

Novel male trait prolongs survival in suicidal mating.

Male redback spiders (Latrodectus hasselti) maximize paternity if they copulate twice with their cannibalistic mate. Facilitating cannibalistic attack during their first copulation yields paternity benefits. However, females have paired sperm-storage organs inseminated during two separate copulations, so males that succumb to partial cannibalism during the first copulation lose at least 50% of their paternity to rivals. In this paper, we describe a novel male trait--an abdominal constriction that appears during courtship--that allows males to survive and mate with females for a second time, despite the substantial cannibalistic damage inflicted during the first copulation. Constricted males that were wounded to simulate early cannibalism had higher endurance, greater survivorship, longer subsequent courtship and higher mating success than wounded males that were not constricted. Constriction was not found in a non-sacrificial congener that rarely survived simulated cannibalism, and the protective effect of constriction in redbacks was specific to the type of damage inflicted by females during the first copulation. Thus, the abdominal constriction allows males to overcome the potential fitness limit imposed by their own suicidal strategy-paradoxically, by prolonging survival across two cannibalistic copulations.

Animals↗

Modulation of the interleukin-6 receptor subunit glycoprotein 130 complex and its signaling by LMO4 interaction.

The interleukin (IL)-6-type cytokines play major roles in a variety of biological processes by signaling through a common receptor subunit, glycoprotein (gp) 130. We performed yeast two-hybrid screening to identify new binding partners of the activated gp130 and the associated Janus kinases. LMO4, a LIM domain-containing protein that belongs to a family of oncogenes, was identified in this assay. Further studies show that LMO4 associates with gp130 and Janus kinase1 in several mammalian cell types. It also interacts with protein-tyrosine phosphatase 2 (SHP2) and suppressor of cytokine signaling 3 (SOCS3). The binding domains involved in these interactions were mapped, and the interactions were shown to be in a direct manner by in vitro binding assays. It is likely that LMO4 exists in the gp130 complex. The cellular localization of LMO4 was detected primarily in the nucleus with a substantial amount also detected in the cytoplasm in several cell types. The effect of LMO4 in IL-6 signaling was subsequently examined. Overexpression of LMO4 enhanced the transcriptional activity and target gene expression of Stat 3 (signal transducers and activators of transcription 3). Consistent with this, silencing LMO4 expression in stable cell lines expressing the small interfering RNA of LMO4 decreased Stat3 activity. Furthermore, the half-life of gp130 was shortened, and the production of acute phase proteins induced by IL-6 was reduced. Together, our data reveal a positive regulatory role of LMO4 in IL-6 signaling, possibly by acting as a scaffold for stabilization of the gp130 complex. These studies may open up a link between the oncogenic effect of LMO proteins and their regulatory role in cytokine signaling in general.

Adaptor Proteins, Signal Transducing↗

Protein kinase C delta associates with the interleukin-6 receptor subunit glycoprotein (gp) 130 via Stat3 and enhances Stat3-gp130 interaction.

The transcriptional regulation of Stat proteins is controlled through their C-terminal domains, which harbor both a tyrosine phosphorylation site, required for dimerization and subsequent nuclear translocation, and a serine phosphorylation site, required for maximum transcriptional activity. Previously, we reported that protein kinase Cdelta (PKCdelta) phosphorylates and interacts with Stat3 in an interleukin (IL)-6-dependent manner. In this study, we further characterized this interaction, and investigated the potential role of such an interaction. We show here that the catalytic domain of PKCdelta interacts with the Src homology 2 domain and part of the adjacent C-terminal transactivation domain of Stat3. This interaction, which does not seem to involve a classical phosphotyrosine SH2-mediated binding, however, significantly enhances the interaction of Stat3 and the IL-6 receptor subunit glycoprotein (gp) 130, which is the initial step for Stat3 activation by IL-6. Expression of a dominant negative PKCdelta or depletion of the endogenous PKCdelta by phorbol 12-myristate 3-acetate treatment abrogates the association of Stat3 with gp130. At the same time, PKCdelta is recruited to gp130 via association with Stat3, which may facilitate its phosphorylation on the gp130 receptor. Finally, we identified Thr-890, a putative PKC phosphorylation site on gp130, to be critical for the effect of PKCdelta. Our data indicate that PKCdelta plays important regulatory roles in IL-6 signaling.

Animals↗

Evaluation of computational models for hemolysis estimation.

The potential for mechanical erythrocyte damage, or hemolysis, in heart valves and blood pumps has been estimated using computational fluid dynamics (CFD) analysis, combined with mathematical models of red cell damage mechanisms. To date, these prediction approaches have not been compared with each other in common benchmark cases, nor have they been evaluated in radically different flow geometries. In this study, four test devices, including a hemoresistometer, a spinning disk, a capillary tube, and a concentric cylinder viscometer were hemolysis tested and computationally simulated. A number of existing models were used to predict blood damage and these models were compared with each other and with actual measurement of hemolysis. The study indicates that the effectiveness of blood damage prediction from the existing models is similar and can potentially be improved with the consideration of a proposed repeated flow passage effect. It also indicates that the improved models can be used to more effectively predict blood damage in widely different situations.

Animals↗

Mechanical fragility calibration of red blood cells.

Mechanical fragility of red blood cells (RBCs) is a critical variable for the hemolysis testing of many important clinical devices, such as pumps, valves, and cannulae, and gas exchange devices. Unfortunately, no standardized test for RBC mechanical fragility is currently well accepted. Although many test devices have been proposed for the study of mechanical fragility of RBCs, no one has ever shown that their results have any relevance to a blood pump. Therefore, the fundamental objective of this study was to determine if one or more test devices could be validated as calibrators to document the fragility of the test blood used for any particular test blood. We compared five mechanical fragility test systems to each other and to a Biopump, with respect to hemolysis. All five devices seem to measure the same parameter; the hemoresistometer most closely matched the pump test results, but the stainless steel bead test may be the most practical for routine calibration purposes.

Animals↗

The PediPump: development status of a new pediatric ventricular assist device: update II.

The PediPump is a new ventricular assist device with a hydraulic output range designed for children from newborn infants to adolescents. The design is based on a mixed-flow rotary pump; the rotating assembly consists of a front impeller, front and rear radial magnetic bearings, and a central motor magnet. Two different implantable pumps were designed initially: an intravascular pump measuring 7 x 75 mm and an extravascular pump measuring 14 x 85 mm. Current prototypes are substantially smaller: The current intravascular version measures 4.5 x 55 mm, whereas the current extravascular version measures 11 x 70 mm. Both devices provide pressure and flows capable of supporting adults, far exceeding the initially defined physiologic requirements for children weighing 2 to 25 kg. This basic pump design may be used in acute or chronic clinical settings to provide right ventricular, left ventricular, or biventricular support. There are three objectives for the PediPump development program: 1) determination of basic engineering requirements for hardware and control logic including design analysis for system sizing, evaluation of control concepts, and bench testing of prototypes; 2) performance of preclinical anatomic fitting studies using CT-based 3D modeling; and 3) animal studies to provide characterization and reliability testing of the device.

Adolescent↗