Progress in the research of negative feedback effect of thyroglobulin / 南方医科大学学报

Thyroglobulin is the most important and abundant protein in thyroid follicles and has been widely studied as a tumor marker of thyroid cancer recurrence and persistence. Tg is considered the material basis of thyroid hormone synthesis and does not participate in the regulation of thyroid hormone synthesis and secretion. This review summarizes the recent progress in the research of thyroid hormone synthesis and secretion regulation via a negative feedback regulation mechanism by the thyroid-hypothalamus-pituitary axis. Thyroglobulin can negatively regulate the synthesis of thyroid hormone by thyroid follicular cells and antagonize the positive regulation of thyrotropin TSH. The function of thyroid follicular cells is presumably a result of Tg and TSH interaction, and a follicular cycle model is proposed to explain the causes of follicular heterogeneity in glands. We also discuss the prospects and clinical significance of studies into the negative feedback regulation mechanism of the thyroid-hypothalamus-pituitary axis and compare two theories for this mechanism.

Dynamics Modeling and Anti-Drug Resistance Strategy Analysis Based on Let7-LIN28 Bistable Phenomena / 医用生物力学

Objective To find the key factors that have great influences on the bistable properties between let7 and LIN28 by exploring the effects of different parameters on the negative feedback bistable system, and provide insights for regulating the drug resistance generated during treatment. Methods The bistability of two-dimensional system was studied by dynamics modeling, and the influence of the parameters on stability behavior of the system was investigated from the portrait of nullclines. Results The parameters showed heterogeneous effects on bistability behavior of the system. A shift in parameter values could regulate the characteristics of bistability and might even make a switch back and forth between bistability and monostability. Conclusions Targeted regulation of sensitive parameters can potentially achieve the goal of controlling drug resistance.

Research progress of JAK/STAT signal transduction pathway and traditional Chinese medicine intervention in the treatment of ischemic stroke / 中国药理学通报

Ischemic stroke, gravely affecting human health with its increasing incidence rate , is a common disease of old age . JAK/STAT way , a recently discovered signaling pathway , is not only widely involved in processes of cell growth ,differentiation, and apoptosis ,but also closely related to the pathophysiology of stroke.However,the pathway function and mechanism in ische-mic cerebral stroke has not yet been fully elucidated .We will review the role and mechanism of JAK/STAT signal transduction pathway in ischemic stroke ,and scientifically draw network chart between various related signal molecules in the process of ische-mic stroke neuropathy combining both domestic and foreign re-search reported in this paper , in order to better understand the pathological mechanism process of brain stroke , find new drugs for the treatment of cerebral ischemic diseases ,then provide more systematic scientific literature support .

Negative feedback effection of DNA methylation on expression of DNMT1 in patients with systemic lupus erythematosus / 中国免疫学杂志

Objective:To analyse the whole DNA methylation status , expression of DNMT1 and DNA methylation status of DNMT1 promoter from patients with systemic lupus erythematosus ( SLE) .To assess the negative feedback effection of DNA methylation on the expression of DNMT1 in the patients with SLE.Methods:The whole DNA methylation status in T cells from 34 SLE patients and 23 healthy controls was assessed by the specific monoclonal antibodies to 5-methylcytosine (5-mc) and the DNA methylation status of DNMT1 promoter was assessed by the Bisulfite Conversion Kit and sequencing.Real time RT-PCR was applied to analyse DNMT 1 mRNA levels in T cells from the patients and controls.Results: SLE patients had siginificantly whole DNA hypomethylation than controls(P<0.05),and the whole DNA methylation was negative correlated with the SLE-DAI.There was no difference in levels of DNA methylation of DNMT1 promoter between patients and controls ,also no correlation between the levels of DNA methylation of DNMT 1 promoter and DNMT1 mRNA.Conclusion:There was no negative feedback effection of DNA methylation on the expression of DNMT 1 in the patients with SLE.The mechanism of lower expression of DNMT 1 in patients with SLE should be studied further.

Induction of Resistance to BRAF Inhibitor Is Associated with the Inability of Spry2 to Inhibit BRAF-V600E Activity in BRAF Mutant Cells

The clinical benefits of oncogenic BRAF inhibitor therapies are limited by the emergence of drug resistance. In this study, we investigated the role of a negative regulator of the MAPK pathway, Spry2, in acquired resistance using BRAF inhibitor-resistant derivatives of the BRAF-V600E melanoma (A375P/Mdr). Real-time RT-PCR analysis indicated that the expression of Spry2 was higher in A375P cells harboring the BRAF V600E mutation compared with wild-type BRAF-bearing cells (SK-MEL-2) that are resistant to BRAF inhibitors. This result suggests the ability of BRAF V600E to evade feedback suppression in cell lines with BRAF V600E mutations despite high Spry2 expression. Most interestingly, Spry2 exhibited strongly reduced expression in A375P/Mdr cells with acquired resistance to BRAF inhibitors. Furthermore, the overexpression of Spry2 partially restored sensitivity to the BRAF inhibitor PLX4720 in two BRAF inhibitor-resistant cells, indicating a positive role for Spry2 in the growth inhibition induced by BRAF inhibitors. On the other hand, long-term treatment with PLX4720 induced pERK reactivation following BRAF inhibition in A375P cells, indicating that negative feedback including Spry2 may be bypassed in BRAF mutant melanoma cells. In addition, the siRNA-mediated knockdown of Raf-1 attenuated the rebound activation of ERK stimulated by PLX4720 in A375P cells, strongly suggesting the positive role of Raf-1 kinase in ERK activation in response to BRAF inhibition. Taken together, these data suggest that RAF signaling may be released from negative feedback inhibition through interacting with Spry2, leading to ERK rebound and, consequently, the induction of acquired resistance to BRAF inhibitors.

Angiogenic growth factor responses to long-term treadmill exercise in mice.

We sought to determine whether VEGF and other angiogenic growth factors and their receptors might be subject to negative feedback regulation during two weeks of treadmill-exercise conditioning in inbred strains of mice. C57BL/6 mice exhibited greater VEGF mRNA and protein responses in gastrocnemius muscle to a single bout of treadmill exercise compared to BALB/c mice. The patterns of VEGF, VEGFR1, VEGFR2, Ang2 and Tie2 mRNA expression in gastrocnemius muscles of C57BL/6 mice during long-term exercise support the hypothesis that they may be subject to negative feedback regulation. The combination of expression patterns for growth factors and their receptors suggests that multiple layers of control mechanisms may exist to prevent angiogenesis following a single bout of exercise and to promote angiogenesis following long-term exercise.

Expression of pituitary glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase 1 in obese diabetic rats / 中华内分泌代谢杂志

Diabetic rat model was induced by high fat diet combined with streptozotocin (STZ). After the model was established, blood samples were taken from jugular veins to examine plasma adrenocorticotropic hormone (ACTH) and corticosterone, and hypothalamus and pituitary were removed for real-time PCR. There were no significant differences in basal plasma ACTH and corticosterone level among control, obese, and obese diabetic rats (P=0.07). The corticosterone rhythm in obese and obese diabetic rats was impaired. Hypothalamus glucocorticoid receptors (GR) mRNA expressions yielded similar results in the groups, but 11β-HSD1 mRNA expression in obese diabetic rats was up-regulated ( vs control rats, P<0.05 ). The expressions of GR and 11β-HSD1 in pituitary of obese diabetic and obese rats were significantly down-regulated (both P<0.05). In the obese diabetic rats, the impaired glucocorticoid negative feedback was partly due to down-regulation of 11 β-HSD1 and GR expressions in pituitary.

Effect of instrument compliance on the polymerization shrinkage stress measurements of dental resin composites / 대한치과보존학회지

The purpose of this study was to evaluate the effect of instrument compliance on the polymerization shrinkage stress measurements of dental composites. The contraction strain and stress of composites during light curing were measured by a custom made stress-strain analyzer, which consisted of a displacement sensor, a cantilever load cell and a negative feedback mechanism. The instrument can measure the polymerization stress by two modes: with compliance mode in which the instrument compliance is allowed, or without compliance mode in which the instrument compliance is not allowed. A flowable (Filtek Flow: FF) and two universal hybrid (Z100: Z1 and Z250: Z2) composites were studied. A silane treated metal rod with a diameter of 3.0 mm was fixed at free end of the load cell, and other metal rod was fixed on the base plate. Composite of 1.0 mm thickness was placed between the two rods and light cured. The axial shrinkage strain and stress of the composite were recorded for 10 minutes during polymerization, and the tensile modulus of the materials was also determined with the instrument. The statistical analysis was conducted by ANOVA, paired t-test and Tukey's test (alpha<0.05). There were significant differences between the two measurement modes and among materials. With compliance mode, the contraction stress of FF was the highest: 3.11 (0.13), followed by Z1: 2.91 (0.10) and Z2: 1.94 (0.09) MPa. When the instrument compliance is not allowed, the contraction stress of Z1 was the highest: 17.08 (0.89), followed by FF: 10.11 (0.29) and Z2: 9.46 (1.63) MPa. The tensile modulus for Z1, Z2 and FF was 2.31 (0.18), 2.05 (0.20), 1.41 (0.11) GPa, respectively. With compliance mode, the measured stress correlated with the axial shrinkage strain of composite; while without compliance the elastic modulus of materials played a significant role in the stress measurement.

The Difference in Biological Properties between Parental and v-Ha-ras Transformed NIH3T3 Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We performed experiments to investigate the change in cellular signaling that occurs during the transformation of a normal cell to a cell capable of cancerous growth, and we did so by using the NIH 3T3 cells that were transformed by transfection with the v-Ha-ras oncogene. MATERIALS AND METHODS: Parental and v-Ha-ras transfected NIH 3T3 cells were chosen as test systems. The siRNA transfections were performed using Lipofectamine 2000. The cell proliferation reagent WST-1 was used for the quantitative determination of cellular proliferation. Immunoblot analysis was performed using the ECL-Plus chemiluminescent system and a KODAK Image Station 4000R. RESULTS: The v-Ha-ras-transformed cells were found to be significantly more resistant to PP2 treatment, which is a potent inhibitor of the Src family tyrosine kinases, than were the parental cells at earlier times after treatment. However, PP2 induced growth arrest and the senescence-like phenotypes in both cell lines after longer treatment. Furthermore, the Raf-1 kinase of the v-Ha-ras-transformed cells was not affected by the expressed level of Sprouty proteins, which are negative regulators of the MAPK pathway, as evidenced by the failure of siRNA-mediated knockdown of Spry4 to activate Raf-1 kinase. Dephostatin (a tyrosine phosphatase inhibitor) effectively inhibited the proliferation of the v-Ha-ras transformed cells, whereas dephostatin had only a small effect on the parental cells' proliferation. This implied an inhibitory role for tyrosine phosphatase that is specific to the signaling pathway in the v-Ha-ras transformed cells. CONCLUSION: Taken together, our results show that the sustained activation of the oncogenic pathways through their resistance to negative feedback regulation might contribute to the transformation of NIH 3T3 cells.

Negative feedback system theory in pathophysiology teaching application / 中华医学教育探索杂志

According to Wiener's cybernetics,the author deduces the fundamental principle of negative feedback teaching and builds its model.On the basis of the model,author raises the approach of negative feedback in pathophysiology teaching.

Role of suppressor of cytokine signaling in the regulation of negative feedback in the JAK/STAT signaling pathway / 医学研究生学报

Suppressors of cytokine signaling (SOCS) associates with receptor-mediated signal transduction pathway,which can regulate cell proliferation,growth,differentiation and inflammation et al. The aim of this review is to identify SOCS and cytokines on the combination of different sites and pathway,and then to explore the pathogenesis of the role of negative feedback regulation of JAK/STAT signaling pathway.

Apical Turn Vibratory Response Changes Following Cisplatin Application in the Living Guinea Pig Cochlea / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cisplatin (cis-diamminodichloroplatinum) exercises its ototoxic effect by damaging hair cells of the inner ear. The effect of cisplatin on the vibratory response of the inner ear was investigated in the apical turn of the cochlea in 11 living guinea pigs. MATERIALS AND METHODS: The exposed turn was sealed and fluid coupled to the objective lens of a slit confocal microscope. Individual cells were identified with the microscope and the vibration was measured with a confocal heterodyne interferometer. The vibration was made in response to tones applied to the ear canalat at selected locations such as the reticular lamina (Hensen cells and outer hair cells), and the basilar membrane adjacent to the outer Hensen cell edge. Vibration measurements were made before and after intravenous injections of cisplatin (16 mg/kg). RESULTS: The drug effect took place approximately 35 minutes after administering cisplatin. The vibration amplitude changes produced by cisplatin were not reversible with time. At the level of the reticular lamina, cisplatin reduced the vibration amplitude at almost all frequencies. However, these effects were small. In contrast to the reticular lamina response, at the basilar membrane, the vibration amplitude increased following cisplatin application. CONCLUSION: These experiments show that damage to the hair cells in the apical turn of the cochlea leads to an increase in the basilar membrane vibration. These observations support the concept of negative Feedback in the apical turn of the cochlea.

THE NEGATIVE FEEDBACK REGULATION OF PITUITARY N-POMC SECRETION BY GLUCO CORTICOIDS WAS BLUNTED IN CUSHING'S DISEASE / 中华内分泌代谢杂志

The effect of hydrocortisone (135 nag i.v. as a bolus) on the levels of serum N-POMC was studied in the patients with Cushing's disease [including three groups: untreated (CD, n=8), post-adrenolectomy without Nelson's syndrome (CDA, n=5), and Nelson's syndrome (NS, n=4)]; Addison's disease (AD, n = 13) and congenital adrenal hyperplasia (CAH, n=4). The results showed that the levels of serum N-POMC were decreased after the administration of hydrocortisone in all three groups of Cushing's disease, however the suppression rate of N-POMC was much lower in these groups than that in AD and CAH (P

Modulatory effect of histamine H_3 receptor on cardiovascular system / 中国药理学通报

The intracellular signal transduction pathway of histamine H 3 receptor was reviewed. The modulatory effect to some neurotransmitters on cardiovascular system and the therapeutic potential of histamine H 3 receptor agonist was summarized.