ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. METHODS: The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro. RESULTS: The patients were well-controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL-5, IL-13 and IL-9 in response to IL-25, IL-33 plus IL-2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL-5, IL-13 and IL-9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment. CONCLUSION: The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK-STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.

[Research advances on inflammatory responses involved in keloid development].

Keloid is a hyperplastic pathological scar of body caused by infection, trauma, and surgery or formed spontaneously for unknown reasons. It is an excessive tissue response of body to dermal injury. The paper introduces the research advances on inflammatory responses involved in keloid development and keloid treatment by inhibiting inflammatory responses from the aspects of inflammation inducing factors, inflammatory cells, inflammatory mediators, inflammatory effectors, and influencing factors of inflammatory responses. The research results suggest that inflammatory responses are not only essential process to normal wound healing, but also key factors on keloid formation and development.

Increased Angiogenesis and Decreased Programmed Cell Death Increases the Risk of Uterine Cervical Cancer.

INTRODUCTION: Cervical cancer is one of the most common female malignancies and leading cause for high mortality rate. In the present study we made an attempt to determine the extent of angiogenesis, apoptosis, accumulation of mutant p53 protein, cell proliferation rate in the uterine cervical cancer tissues. MATERIALS AND METHODS: Cervical cancer samples were obtained from patients and they were subjected to PCR analysis and immunocytochemistry. RESULTS: A total of 30 cervical cancer tissue samples were analyzed, by PCR, we found 25 collected cervical cancer samples showed HPV-16 and E6 positive. Further, we observed the increased CD34 expression was associated with HPV-16 and E6 positive cancer tissues when compared to the corresponding control tissues. This elevated level of CD34 confirms the increased extent of angiogenesis in cervical cancer tissues. Further by immunocytochemistry we have demonstrated that the rate of apoptosis is reduced, over expression of bcl-2, Ki 67 and thus increases rate of cell proliferation. DISCUSSION: Therefore, our data suggest that development of new anticancer or antiviral drugs could efficiently compromise the HPV-16 mediated angiogenesis and reduced apoptosis in cervical cancer and thus will improve the survival rate of patients.

Advances in biopharmaceutical analysis in the People's Republic of China: 1993-1995.

Progress in biopharmaceutical analysis of drugs and their metabolites by liquid and gas chromatography between April 1993 and March 1995 has been reviewed. The evaluation and validation of these methods, as well as their applications in pharmacokinetics and metabolic studies, are also discussed.

[RP-HPLC determination of 1-(p-methylphenyl-2-(2-piperidinoacetyl- 1,2,3,4-tetrahydroisoquinoline hydrochloride in rabbit plasma and its pharmacokinetic parameters].

A reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for the determination of rabbit plasma levels of 1-(p-methylphenyl-2-(2-piperidinoacetyl)-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride (70026), a new antiarrhythmic agent with promising prospects. Its pharmacokinetic parameters were obtained from the rabbit plasma level-time curve measured. 70026 plasma sample was determined by extracting with ether and 0.2 mol/L sulfuric acid, chromatographing on LiChrosorb RP-C18 column, and detecting at 230 nm. The mobile phase selected was methanol-water-triethylamine-phosphoric acid (63:37:1:0.8 v/v). The average recovery of the entire procedure from plasma was 99.94 +/- 3.10 (SD) %; the average CV of within-day and between-day were 4.12% and 3.95% respectively; the minimum detection limit was 3 ng; 70026 plasma concentration ranging from 25-2000 ng/ml yielded a good linear relationship with the peak area ratios, Y = 0. 002865X-0.01346, r = 0. 9999. No endogeneous interference was found in chromatograms of plasma sample. The purity of chromatographic peak of 70026 was identified and proved by mass spectrometry. In urine sample, the hydrolysate of 70026 was found as the original and bound forms. The rabbit plasma level of 70026 after intravenous administration versus time curve was found to be in correspondence with two-compartment model, T1/2 = 4.80 + 1.522 (h).

Ca2+ signaling in fowl aortic smooth muscle increases during maturation but is impaired in neointimal plaques.

Many bird species show the spontaneous development of high arterial pressure and vascular lesions in the aorta and other large arteries. In chickens, arterial pressure tends to increase with age/maturation (particularly in males), and subendothelial hyperplasia (neointima) in the abdominal aorta is often seen prior to sexual maturation. The mechanisms involved, however, are not known. Our aim, therefore, was to determine (1) whether cytosolic Ca2+ signaling (CCS) responses to vasoactive substances in fowl aortic smooth muscle differ among chickens at different maturation stages and (2) whether CCS responses to Ca2+ channel agonists in neointimal plaques differ from those in normal aortic smooth muscle. K+ increased CCS in a dose-dependent manner in isolated and superfused abdominal aortic smooth muscle tissue from chicks (5-9 weeks old), pullets (11-18 weeks old) and adult hens (20 weeks and older); CCS responses increased as chickens matured. The addition of Bay K 8644 (10(-6)mol l-1) to Ringer's solution containing 50 mmol l-1 K+ further increased CCS, and this response was reduced to half by nifedipine (10(-6)mol l-1). Norepinephrine did not alter CCS in chicks, whereas marked dose-dependent increases in CCS were noted in pullets. In contrast to the CCS responses to K+, the norepinephrine-induced CCS responses became smaller in adult hens. Isolated neointimal plaques showed only slight increases in CCS in response to 50 mmol l-1 K+ plus Bay K 8644, whereas clear responses were noted in aortic smooth muscle tissue underlying the plaques. These results suggest (1) that CCS responses to Ca2+ channel agonists increased with sexual maturation in fowl, but (2) that CCS responses to norepinephrine were low in mature hens and to K+ plus Bay K 8644 were low in spontaneously developed neointima, suggesting that phenotypic modulation of Ca2+ channel/norepinephrine receptors may have occurred during maturation/aging and in neointima.

Vascular angiotensin II receptor and calcium signaling in toadfish.

The renin-angiotensin system evolved during the early evolution of vertebrates and regulates blood pressure/blood volume homeostasis in nonmammalian and mammalian vertebrates. Properties of vascular angiotensin (ANG) receptors and signal pathways in primitive animals are, however, not well understood. We aimed to determine whether vascular ANG II receptors in the toadfish, Opsanus tau, an aglomerular teleost, pharmacologically resemble either the ANG subtype 1 receptor (AT1) or the subtype 2 receptor (AT2) by examining (i) the effects of selective ANG receptor antagonists on ANG II-induced vasopressor action and binding and (ii) ANG II's effect on cytosolic Ca2+ signaling. [Asn1, Val5]ANG II (native teleost ANG II) dose-dependently increased the mean arterial pressure of conscious toadfish. ANG II-induced pressor responses (100-500 ng/kg) were inhibited substantially (79-83%) by [Sar1, Ile8]ANG II (5 microg x kg-1 + 5 microg x kg-1 x min-1) and moderately (34-53%) by losartan (AT1 antagonist, 10 mg/kg + 20 mg x kg-1 x h-1) and by PD 123319 (AT2 antagonist, 10 mg/kg + 20 mg x kg-1 x h-1) (36-60%). Likewise, the [Asp1, Val5, His9]ANG I-induced pressor effect was completely eliminated by an ANG I-converting enzyme inhibitor, SQ 14,225. Specific 125I-ANG II binding to vascular smooth muscle (VSM) membrane fractions was displaced completely by [Asn1, Val5]ANG II and [Sar1, Ile8]ANG II. Losartan, but not PD 123319, partly displaced ANG II binding at 10(-10)-10(-6) M. Furthermore, ANG II (10(-7) or 10(-8) M) caused a rapid, transient increase in the cytosolic Ca2+ signal (fluorescence ratio (FR) of 340/380 nm) of isolated VSM tissues measured by fura-2 and a dual wavelength fluorospectrometer, whereas extracellular K+ induced sustained, dose-dependent (P < 0.01) increases in FR. The results indicate that toadfish VSM tissues possess a rather nonselective ANG receptor; partial inhibition of ANG II binding by losartan and stimulation of cytosolic Ca2+ signaling by ANG II suggest that the receptor has some resemblance to AT1 homologous receptors.

[Trace elements and extracellular matrix].

OBJECTIVE: To investigate the effects of trace elements on the metabolism of extracellular matrix and explore the physiological and pathological mechanism of trauma. METHODS: Based on the experimental and clinical data, it was studied that the action of trace elements in the metabolism of extracellular matrix in trauma repairing. RESULTS: During wound healing, the trace elements were the components of many kinds of enzymes, carriers and proteins. They took part in the synthesis of hormones and vitamins as well as the transmission of information system. They activated many different kinds of enzymes and regulate the levels of free radicals. The trace elements had the complicated effects on the synthesis, decompose, deposition and reconstruction of collagen and other extracellular matrix. CONCLUSION: The trace elements play an important role in regulating the metabolism of extracellular matrix.