Effects of metabolic abnormalities, hyperandrogenemia and clomiphene on liver function parameters among Chinese women with polycystic ovary syndrome: results from a randomized controlled trial.

PURPOSE: To investigate the effects of metabolic abnormalities, hyperandrogenemia and ovulation induction by clomiphene/acupuncture on liver function parameters among women with polycystic ovary syndrome (PCOS). METHODS: This is a secondary analysis of a randomized controlled trial. All 1000 subjects were diagnosed as PCOS by modified Rotterdam criteria. Liver function parameters, metabolic panel and hormone profile were measured at baseline and after treatment. The relationship between liver parameters with metabolic, hormonal parameters and ovulation induction was examined. RESULTS: PCOS women with metabolic syndrome had higher liver enzyme levels but lower bilirubin and bile acid levels than without. PCOS women with hyperandrogenemia had higher liver enzyme, bilirubin levels than without. Correlation analyses showed that worsening of metabolic parameters was associated with higher liver enzyme levels but lower bilirubin and bile acid levels, while increased androgen levels were associated with higher liver enzyme, bilirubin and bile acid levels. Ovulation induction with clomiphene citrate could decrease bilirubin and bile acid levels, while acupuncture had no obvious effect on liver function. CONCLUSIONS: Among PCOS women, metabolic abnormalities and hyperandrogenemia impaired different liver function parameters. Clomiphene could decrease the bilirubin and bile acid levels while acupuncture had no obvious effect on liver function.

Resveratrol induces apoptosis of pancreatic cancers cells by inhibiting miR-21 regulation of BCL-2 expression

OBJECTIVE: Resveratrol is an edible polyphenolic phytoalexin present in different plant species and plays important role in inhibiting proliferation and inducing apoptosis of pancreatic cancer cells. In this paper, the mechanism of resveratrol on PANC-1, CFPAC-1 and MIA Paca-2 cells apoptosis was examined. METHODS: We first evaluated the effect of resveratrol on viability of PANC-1, CFPAC-1 and MIA Paca-2 cells using MTT assay. Next, we performed real-time PCR to assess the effect of resveratrol on miR-21 expression. We also used Western blot to measure BCL-2 protein levels after down-regulation of miR-21 expression. Finally, we evaluated the effect of miR-21 on resveratrol-induced anti-tumor activity using miR-21 mimic. RESULTS: Resveratrol induced a significant inhibition of PANC-1, CFPAC-1 and MIA Paca-2 cells viability in a dose-dependent manner. Resveratrol also decreased the expression of miR-21. Besides, down-regulation of miR-21 expression can inhibit BCL-2 expression in PANC-1, CFPAC-1 and MIA Paca-2 cells. Over-expression of miR-21 expression can reverse down-regulation of BCL-2 expression and apoptosis induced by resveratrol.CONCLUSIONS: In this study, we demonstrated that the effect of resveratrol on apoptosis is due to inhibiting miR-21 regulation of BCL-2 expression (AU)

Effective control of blood glucose status and toxicity in streptozotocin-induced diabetic rats by orally administration of vanadate in an herbal decoction.

Vanadium compounds have been well recognized for hypoglycemic effects, but questions remain on gastrointestinal disturbance and possible tissue vanadium accumulation thus slowing the acceptance of vanadium compounds as diabetic therapeutic agents. Our intestinal permeability and toxicity studies of vanadium compounds have suggested that the co-administration of vanadate with Salvia miltiorrhiza Bunge decoction could benefit the therapeutic use of hypoglycemic vanadium compounds. In the present paper, we tested the hypoglycemic effects of vanadate ingested in an aqueous extract of S. Bunge using a streptozocin (STZ)-induced diabetic rat model. Oral administration of vanadate in S. Bunge herbal decoction produced a stable (free of hypoglycemic shock) and long-lasting ( approximately 70day) control of blood glucose status. Effective protection of animal organs from hyperglycemic damage was also observed. As expected, the herbal extract significantly alleviated vanadium toxicity, i.e. GI stress and metal accumulation. In addition, the result suggesting that vanadium-induced amelioration of the diabetic state appears to be secondary to the preservation of a functional portion of the pancreatic beta-cells which initially survived STZ-toxicity. These studies provide new insight into the therapeutic treatment of diabetics with vanadium compounds.

Dorsal column is not involved in the mechanism of the hypotensive effect by simulating acupuncture on rat hindlimb.

The present study investigated the role of the dorsal column (DC) in the mechanism of the hypotensive effect induced by simulating acupuncture on rat hindlimb. The femoral arterial pressure and electrocardiogram (ECG) of rats were recorded when the hypothalamic paraventricular nucleus (PVN) was electrically stimulated with or without DC lesion. Stimulation of the deep peroneal nerve (DPN) decreased the pressor response elicited by electrical stimulation of the PVN. Thirty minutes after micro-dissection of the right DC, the inhibitory effect of stimulating the right or left DPN on the pressor response induced by stimulation of the contralateral PVN was not altered. Of 6 rats tested, the inhibitory effect of stimulating the right or left DPN could still be observed five days after the right DC was destroyed. The pain responses of both hindlimbs of the rats with the right DC destroyed showed no obvious difference when compared with the sham control rats. These data suggest that the DC is not involved in the inhibitory effect of stimulating the DPN on the pressor response induced by the PVN activation.

Chemical analysis of Radix Astragali (Huangqi) in China: a comparison with its adulterants and seasonal variations.

Radix Astragali (root of Astragalus; Huangqi) is a popular traditional Chinese medicine, and Astragalus membranaceus and A. membranaceus var. mongolicus are two commonly used species; however, there are many Astragalus species that could act as adulterants of Radix Astragali. To find the chemical composition of Radix Astragali, the main constituents including flavonoids, saponins, polysaccharides, amino acids, and trace elements were determined in two Radices Astragali, A. membranaceus and A. membranaceus var. mongolicus, and its eight adulterants, Astragalus propinquus, Astragalus lepsensis, Astragalus aksuensis, Astragalus hoantchy, Astragalus hoantchy subsp. dshimensis, Astragalus lehmannianus, Astragalus sieversianus, and Astragalus austrosibiricus. The results showed that the amounts of main constituents such as isoflavonoids and astragalosides varied in different species. In distinction, A. membranaceus and A. membranaceus var. mongolicus contained a higher amount of astragaloside I and IV. In addition, the main constituents of A. membranaceus var.mongholicus changed according to seasonal variation and age of the plant. The chemical composition of different species of Astragalus would provide useful information for the quality control of Radix Astragali.

Identification of three annexin IX isoforms generated by alternative splicing of the carboxyl-terminal exon in silkworm, Bombyx mori.

Annexins (ANXs) are a family of structurally related proteins with Ca(2+)-dependent phospholipid-binding properties. Here we report the cloning of three cDNAs each encoding annexin IX (ANX IX) isoforms from unfertilized eggs of the silkworm, Bombyx mori. The analysis of exon/intron structures showed that the three mRNAs, named ANX IX-A (2300bp), ANX IX-B (1884bp) and ANX IX-C (1409bp), respectively, were generated from a single gene by alternative usage of a 3'-splice site of the last exon. Thus the three isoforms have an identical sequence from amino acid residues 1 to 307 and this region shows approximately 77% identity to Drosophila melanogaster ANX IX. Only amino acid residues 308-324 (A) or 308-323 (B and C), which correspond to the C-terminal tail, are different in the three proteins. A RT-PCR analysis indicated that the three isoforms of silkworm ANX IX were specifically expressed in various larval tissues and development stages. Interestingly, the C-terminal tail in ANXs I, II and V were previously confirmed as a binding region for protein kinase C. Thus generation of the three ANX IX isoforms in the silkworm, that are different from other ANXs, may have a functional significance other than binding to Ca(2+).

Isolation, characterization, and mapping of a novel human KRAB zinc finger protein encoding gene ZNF463.

A novel human KRAB (Krüppel associated box) type zinc finger protein encoding gene, ZNF463, was obtained by mRNA differential display and RACE. It consists of 1904 nucleotides and encodes a protein of 463 amino acids with an amino-terminal KRAB domain and 12 carboxy-terminal C2H2 zinc finger units. The gene is mapped to chromosome 19q13.3 approximately 4 by FISH. As from Northern blot analysis ZNF463 is only expressed in testis, RT-PCR indicates that ZNF463 is expressed more highly in normal fertile adults than in fetus and azoospermic patients suggesting that it may play a role in human spermatogenesis.

[Experimental study of ta chengchi tang decoction for relieving lung injury during acute necrotizing pancreatitis].

The objectives of the study were to investigate the changes of leukocyte adhesiveness and tumor necrosis factor (TNF) in the early stage of acute necrotizing pancreatitis (ANP), to go further into the relation of those changes to lung injury of ANP, and to evaluate the prohibitive effect of ta chengchi tang Decoction on leukocyte adhesion and TNF secretion. 14 canines were randomly divided into 3 groups. The treatment group (n = 5): experimental ANP model treated with ta chengchi tang Decoction; the saline control group (n = 5): experimental ANP model treated with normal saline; and the sham operative group (n = 4). The adhesion of leukocytes to vascular endothelial cells and TNF activities in serum and in bronchi-alveolar lavage fluid (BALF) were observed and measured, and the degrees of lung injury were assessed. The results showed that the adhesiveness of leukocytes was markedly increased and the activities of TNF were elevated in peripheral blood and BALF during ANP; that the leukocyte adhesiveness in the treatment group was weaker than that in the saline group (P < 0.05) and the serum and BALF TNF activities were also significantly lower than those in the saline group (P < 0.01); and that the degrees of lung injury in the treatment group were significantly milder than those in the saline group. These indicate that the increased leukocyte adhesiveness and hypersecretion of TNF take part in the pathogenesis of lung injury in ANP, and ta chengchi tang Decoction is demonstrated an efficacious medicine for alleviating the degree of lung injury mediated by both the leukocyte adhesion and TNF in ANP.

[Ethnopharmacology of Phyllanthus emblica L].

This paper deals with the ethnopharmacology of P. emblica, a traditional herbal medicine used by many peoples in the world. The paper introduces the biological characters, geographical distribution-patterns, chemical constitution and pharmacology of the plant. By cross-cultural comparative study, this paper indicates that there are 17 countries and nations of the world using various parts of P. emblica in their medical treatment. The medicinal plant is good for anti-hepatitis, anti-cancer, anti-tumor and regulation of stomachal function. The plant is also regarded as a traditional immunomodulator and a natural adaptogen. The result of the study reveals that P. emblica is an important traditional medicine with broad prospects.

Comparative effects of interferon-consensus 1, interferon-alpha 2a, and interferon-beta 1b on HLA expression and lymphoproliferation: a preclinical model for treatment of multiple sclerosis.

Interferon-consensus 1 (IFN-Con 1) is a novel synthetic protein generated from codons for the most frequent amino acids in different type 1 IFNs. Compared with natural IFNs, IFN-Con 1 has been shown to have higher specific activity and antiproliferative activity and a higher ability to induce natural killer cells. In this study, the effects of IFN-Con 1 were compared with those of IFN-beta 1b and IFN-alpha 2a on HLA expression and lymphoproliferation. Human umbilical vein endothelial cells (HUVEC) express HLA class I but not class II molecules; however, both class I and class II molecules can be upregulated by IFN-gamma. IFN-Con-1 shared with IFN-beta 1b and IFN-alpha 2a the capacity to enhance HLA class I expression on HUVEC, alone and in combination with IFN-gamma. Although IFN-Con 1 had no effect on the basal expression of HLA class II molecules, it inhibited the IFN-gamma-induced class II expression on the HUVEC in a dose-dependent fashion. When this effect was compared among the three IFNs on mass basis, IFN-Con 1 activity was intermediate between that of IFN-beta 1b and IFN-alpha 2a. IFN-Con 1 also demonstrated an inhibitory effect on mitogen-driven lymphoproliferation similar to that of IFN-alpha 2a and exceeded that of IFN-beta 1b. The results indicate that IFN-Con 1 has immunomodulatory effects similar to those of IFN-beta 1b and IFN-alpha 2a, which could be relevant to the treatment of autoimmune and virus-mediated diseases.

Regional chemotherapy using continuous intravesical infusion doxorubicin for the treatment of muscle invasive transitional cell bladder carcinoma in a rat model.

Previously established animal models of invasive transitional cell bladder carcinoma and continuous infusion intravesical drug delivery were combined to evaluate the urothelial toxicity and antineoplastic efficacy of continuous intravesical infusion doxorubicin (DOX). Dose-response toxicity experiments studied histologic changes in the rat urinary bladder following urothelial exposure to three different urinary levels of DOX, as a function of the duration of drug infusion. Systemic and local drug absorption, as measured by DOX levels in serum, bladder, retroperitoneal lymph nodes, and liver, was measured at intervals during drug administration. In vitro chemosensitivity assays were used to determine tumor sensitivity to DOX. Treatment studies evaluated the impact of 14-day continuous infusion DOX beginning seven days following tumor implantation. No histologically discernable changes in the normal urothelium were noted in bladders of animals receiving continuous intravesicle DOX at mean urinary concentrations of 0.05 micrograms./ml. (n = 5), 0.56 micrograms./ml. (n = 10), and 5.69 micrograms./ml. (n = 10) for periods of up to 14 days. Serum drug concentrations demonstrated a non-significant upward trend following the start of therapy. Significant increases in tissue DOX levels were noted in the bladder and retroperitoneal lymph nodes on chemotherapy days 7 and 14. Mean tissue DOX concentrations in both the bladder and lymph nodes were greater than the IC50 observed in the in vitro sensitivity assay. DOX-treated tumor-bearing animals (n = 17) had a mean tumor volume (+/- standard deviation) of 0.65 gm. +/- 0.52 gm. compared to an average tumor volume of 1.20 gm. +/- 0.66 gm. in the control group (n = 18) (p = 0.0112). Continuous infusion intraluminal chemotherapy demonstrated a clear cytoreductive effect with minimal local toxicity in this model. Drug tissue levels were observed in regional lymphatic drainage fields as well as the bladder wall. Further study to evaluate this approach as a bladder-sparing alternative to muscle invasive disease is warranted.