Neuro-hormonal integration of metabolism: challenges and opportunities in the postgenomic era.
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Biomedical subjects
Publications and source records attributed to Yu Wang.
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Diosgenyl saponins are the most abundant steroid saponins, and exert a large variety of biological functions. In a previous report, we showed that dioscin was able to induce cytotoxicity and apoptosis in human myeloblast leukemia HL-60 cells. This study further investigated the action mechanisms underlying this effect. The activation of caspase-9 and -3, but not caspase-8, together with the down-regulation of anti-apoptotic Bcl-2 protein, demonstrated that the apoptotic signaling triggered by dioscin was mediated through the intrinsic mitochondria-dependent pathway. We also investigated its anti-proliferative effect on human chronic myelogenous leukemia K562 cells. Flow cytometry analysis showed that dioscin treatment induced the accumulation of cells in the G(2)/M phase. Cytomorphology with DAPI and Wright-Giemsa staining demonstrated the enlargement of cell volume and multinucleation in the treated cells. Subsequent apoptosis was delineated with phosphatidylserine externalization and DNA hypodiploidy. Trillin was one of the hydrolysates of dioscin. We demonstrated that it could induce multinucleation in HL-60, K562 and human promyelocytic leukemia NB(4) cells, suggesting its extensive mitotic-arresting effects. As the diosgenyl sapogenin, diosgenin was also shown to be able to induce multinucleation and apoptosis in K562 cells in a similar manner to dioscin. These findings suggest that diosgenyl saponins have the properties to induce mitotic arrest and apoptosis, suggesting that they may be a new kind of antimitotic agent.
Two novel splice variants of CDK5RAP1, named CDK5RAP1_v3 and CDK5RAP1_v4, were isolated through the large-scale sequencing analysis of a human fetal brain cDNA library. The CDK5RAP1_v3 and CDK5RAP1_v4 cDNAs are 1923bp and 1792bp in length, respectively. Sequence analysis revealed that CDK5RAP1_v4 lacked 1 exon, which was present in CDK5RAP1_v3, with the result that these cDNAs encoded different putative proteins. The deduced proteins were 574 amino acids (designated as CDK5RAP1_v3) and 426 amino acids (CDK5RAP1_v4) in length, and shared the 420 N-terminal amino acids. RT-PCR analysis showed that human CDK5RAP1_v3 was widely expressed in human tissues. The expression level of CDK5RAP1_v3 was relatively high in placenta and lung, whereas low levels of expression were detected in heart, brain, liver, skeletal muscle, pancreas, spleen, thymus, small intestine and peripheral blood leukocytes. In contrast, human CDK5RAP1_v4 was mainly expressed in brain, placenta and testis.
Iron-deficiency or anemia in pregnancy is a major public health problem in China. This cross-sectional study was carried out to observe the association between iron status and multiple vitamin levels of Chinese pregnant women in the third trimester. We measured iron, ascorbic acid, retinol, folate and vitamin B12 in serum, and riboflavin in urine specimens of 1,163 pregnant women in four sites throughout rural and city areas in China. Based on hemoglobin concentrations (Hb), the subjects were divided into an anemia group with Hb < 110 g/L or Hb < or = 100 g/L as severe anemia group, and nonanemia group with Hb > or = 110 g/L. Results showed that 41.58% of the population with serum iron < 700 microg/L and 51.04% of the population with ferritin < 12 microg/L in the anemia group, percentages that were much higher than those in the nonanemia group. Relationships between five vitamins and hemoglobin concentrations of all subjects were observed. There was a lower level of serum ascorbic acid (291.05 microg/dL) in the Hb < or = 100 g/L group than in the Hb > or = 120 g/L group (487.79 microg/dL) (p < 0.001). Serum levels of vitamin B12 and folate were 445.67 pg/mL and 5.94 ng/mL in the Hb < or = 100 g/L group, whose levels were much lower than the levels of 502.01 pg/mL (p < 0.012) and 8.07 ng/mL (p < 0.010) respectively in the Hb > or = 120 g/L group. Further, cross-sectional analysis showed positive correlations between abnormal hematological results and prevalences of vitamin deficiencies. The subjects with iron-deficiency anemia had much higher rates of vitamin C, folate and vitamin B12 deficiencies than those in the nonanemic subjects, and especially in the deficient rates of ascorbic acid and folate in the anemia (Hb < 110 g/L) group, which reached 64.04% and 22.70% respectively. Moreover, we observed that the decreasing trends of hemoglobin concentrations were accompanied by the decreases of serum levels of vitamin A, ascorbic acid, folate and vitamin B12. In conclusion, multiple vitamin deficiencies, especially ascorbic acid, retinol and folic acid, may be associated with anemia or iron deficiency in pregnant women in the last trimester. The study suggested that anemic pregnant women in China should be supplemented with iron and multiple vitamins simultaneously.
OBJECTIVE: To investigate the correlation between impaired non-viral specific immune function of dendritic cell (DC) and viral clearance and cytotoxic T lymphocyte (CTL) response to HBV or HCV in patients with HBV and HCV coinfection. METHODS: Twenty-five patients with HBV and HCV coinfection were investigated in this study. In 1994 and 2002, biochemical and virological markers and quantitative serum HBV DNA and HCV RNA levels were detected in these patients. According to the virus clearance status, these patients were divided into 4 groups: 14 patients with both HBV and HCV clearance (Group A), 6 patients with HCV clearance only (Group B), 3 patients with HBV clearance only (Group C), and 2 patients with persistent infection of HBV and HCV (Group D). Phenotypes and immune functions of monocyte-derived DCs were compared between these groups. 51Cr release assay were used to measure CTL response to epitopes derived from HBV, HCV or influenza virus (as positive control) in HLA-A2+ patients. RESULTS: Impaired non-viral specific immune functions of DCs were observed in group B, C and D compared with group A and normal donors (Group N). These impaired functions included CD86 decreasing expression and lower capacity to stimulating allogenic T cells and uptaking antigen. The specific CTL response to HBV- and HCV-derived peptides could be induced in group A (12/12). The specific CTL response to HBV-derived peptides or to HCV-derived peptides could be induced in group C (3/3) or B (5/5), respectively. But the specific CTL response to both of two HBV-derived peptides or two HCV-derived peptides could not be induced in group C (0/3) or B (0/5), respectively. And no CTL response to HBV or HCV-derived peptides could be induced in groups D (0/1) and N (0/4). CONCLUSION: 1. The results suggest that specific CTL response to HBV or HCV play a vital role in the viral clearance. 2. The DCs with impaired non-viral specific immune functions exist in chronic patients with HBV and/or HCV infection, but do not interfere with clearance and CTL response to HBV or HCV. It is reasonable to speculate that impaired functions of DCs result from viral infection.
BACKGROUND: Molecular adsorbents recirculating system (MARS) liver support therapy is the development of albumin dialysis. This study was to assess the successful application of MARS artificial liver support therapy as a bridge to re-transplantation in two cases of long anhepatic duration. METHODS: MARS therapy was given after failure plasma-exchange (PE) treatment, which resulted in circulatory derangement and acute renal dysfunction in a 36-year-old male patient. Finally his uncontrolled anhepatic condition led to a successful re-transplantation. In another 48-year-old man who was diagnosed as having primary nonfunction (PNF) during the liver transplantation, 10-hour MARS treatment contributed to smooth bridging of his anhepatic phase. RESULTS: The two anhepatic patients were bridged for 26 and 17 hours respectively to re-transplantation with MARS therapy. CONCLUSION: Our experience proves that MARS artificial liver can be an effective support for long time bridging PNF until re-transplantation is available.
Ii protein suppression is a promising antisense drug-based therapy that dramatically enhances the immunogenicity of tumor cell major histocompatibility complex class II-presented antigenic epitopes. The strength of this approach is that the antisense only needs to be transiently effective in a fraction of the tumor cells. The systemic antitumor immune response generated subsequently eradicates both directly treated cells and distant tumor deposits. The drugs and mechanisms of this therapy are considered, in addition to practical developmental questions.
UV spectrometry measurement on the indole alkaloids (IA) contents of seven wheat varieties (KOK1679, My295, Li, Han4564 and Yanda1817, resistant to S. avenae; Shaanximazha and Lovrin10, susceptible to S. avenae) showed that during tillering and stem elongation stages, KOK1679, My295 and Li had a higher IA content (> 0.5 mg.g-1 FW); and during heading and anthesis stages, the penultimate leaves of all five resistant varieties contained higher IA (> 0.5 mg.g-1 FW). The IA content was lower in the flat leaves of both resistant and susceptible varieties, but was significantly higher in the ears of resistant varieties (up to 0.645 mg.g-1 FW in KOK1679) than in those of susceptible ones. It was showed that the IA content in wheat's ear played an important role in the resistance to S. avenae.
OBJECTIVE: To summarize and analyze the epidemic situation of hantaviruses including geographic distribution, types and prevalent intensity of epidemic areas of hantavirus for the last 30 years in China, and to discuss relative preventive measures. METHODS: Collecting and analyzing the data of hantaviruses epidemics in China. RESULTS: The annual number of cases of hantavirus disease rapidly increased from 3295 in 1970 to 115,804 in 1986 then sustained between 40,000 and 60,000 cases annually in the 1990's, and then decreased thereafter. The epidemic areas existed in all provinces except Qinhai and Xinjiang and there were the hospitalized cases of hantavirus disease reported in other provinces. In recent years, the prevalence of hantavirus infection had increased in some cities, and the seasonal distribution of the cases changed as well. CONCLUSION: Data suggested that the new epidemic characteristics of hantaviruses had emerged in China suggesting that it was necessary to strengthen surveillance programs and to take comprehensive preventive measures for the control and prevention of hantaviruses in China.
PURPOSE: To understand the present condition of statistical methods used in the Journal of Prosthetic Dentistry. METHODS: The statistical methods used in 448 treatises (from 2001 to 2003) in the journals were reviewed, classified and analysed. RESULTS: The utilization rates of statistical methods were 28.06%, 48.34% and 51.02% from 2001 to 2003,respectively. The utilization rate of statistical methods was increasing significantly with year (chi2=29.453,P<0.001). The main statistical methods were analysis of variance (ANOVA), multiple comparison, nonparametric test, t-test, linear regression and correlation and chi2 test. CONCLUSION: The utilization rates of sophisticated statistical methods and the proportion of using more than two kinds of statistical tests were all higher than that in the medical journals published in China.
OBJECTIVE: To investigate the natural history and clinical outcomes in a cohort of transfusion-related hepatitis C in northern areas of China. Methods The authors studied 283 patients (137 males, 146 females, mean age 45.79+/-9.92 age) who became infected with HCV while donating plasma 12.25 years ago. These cases were subjected to ultrasonography and liver biochemical tests and serologic anti-HCV assays. Statistical analyses were performed using the SPSS software. RESULTS: Ultrasonographic findings suggestive of liver cirrhosis were 8.3% of cases. No decompensated cirrhosis or HCC was detected. The value of ALT was higher in severe chronic hepatitis (mean 62.07+/-50.87 IU/L) and cirrhosis (mean 115.50+/-108.41 IU/L) patients than in the other groups (mean 32.30+/-29.10 IU/L). The abnormal rate of ALT was 53.3% in severe group, 100% in cirrhosis group. CONCLUSION: The natural history of transfusion-related hepatitis C in the areas seemed to be relatively mild when compared with previous data. Our cases showed relatively low rate of positive findings in ultrasonography. None of this cohort had the decompensated cirrhosis or HCC. The factor of sex but not the age at time of infection was found being related to the outcomes. In the absence of liver biopsy, ultrasonography was a suitable and sensitive method for the diagnosis of the progressive hepatitis and cirrhosis.
OBJECTIVE: To explore the possible mechanism of placental dysfunction in patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: Serum level of cholylglycine (CG) in 30 cases with ICP (ICP group) and 27 normal pregnant women (control group) was examined by radio-immunoassay before delivery. bax and bcl-2 level in placenta was detected by immunohistochemistry method. RESULTS: (1) Serum CG level in ICP group was (51.8 +/- 5.9) micro mol/L, and in control group it was (9.4 +/- 5.6) micro mol/L. The difference between the two groups was significant (P < 0.05). (2) bax expression level in syncytiotrophoblast of ICP group was: 2(-), 9(+), 11 (++), 8(+++), and bcl-2 expression level was: 12(+), 12(++), 6(+++); bax expression level in control group was: 9 (-), 13(+), 4(++), 1(+++) and bcl-2 expression level was: 3(+), 4(++), 20(+++). bax expression level in syncytiotrophoblast of ICP group was higher than that of the control (P < 0.0005), and bcl-2 expression level was lower than in the control (P < 0.0005), both significantly. A significant positive correlation between CG level and bax expression level and a negative correlation between CG and bcl-2 were found in ICP group (P < 0.005, P < 0.005). CONCLUSION: One of the possible mechanisms involved in placental dysfunction of ICP is overexpression of bax in syncytiotrophoblast caused by high concentrations of bile acid, leading to increased apoptosis.
OBJECTIVE: To review progress of clinical application of morselized bone and to investigate relative exploration on it. METHODS: The recent articles on morselized bone in the field of clinic and experimental research were extensively reviewed, and relative examination of morselized bone referring to method and mechanism were investigated carefully. RESULTS: Morselized bone worked well clinically, especially in revision of artificial total hip joint, and it was proved effective with lots of advantages. CONCLUSION: Morselized bone functions well clinically. Although its mechanism requires a further research, it still has a promising value in clinical application.
OBJECTIVE: We have shown previously that pretreatment with genistein potentiated cell killing induced by radiation in human PC-3 prostate carcinoma cell line in vitro. We tested this approach in vivo using an orthotopic prostate carcinoma model of PC-3 cells in nude mice. METHODS: Established prostate tumors were pretreated with p.o. genistein at a dose of 5 mg/d for 2 days followed by tumor irradiation with 5 Gy photons. One day after radiation, genistein was resumed and given every other day for 4 weeks. RESULTS: Genistein combined with radiation caused a significantly greater inhibition of primary tumor growth (87%) compared with genistein (30%) or radiation (73%) alone. The number of metastatic lymph nodes was also significantly decreased following genistein and radiation. Paradoxically, genistein alone increased the size of lymph nodes associated with heavy tumor infiltration. Genistein-treated prostate tumors were large with necrosis, apoptotic cells, and giant cells and have a lower proliferation index than in control tumors. Following radiation, areas of tumor destruction replaced by fibrotic tissue and inflammatory cells as well as giant cells were observed, which are typical of radiation effect. After radiation and genistein treatment, an increase in giant cells, apoptosis, inflammatory cells, and fibrosis was observed with decreased tumor cell proliferation consistent with increased tumor cell destruction. Long-term therapy with genistein after prostate tumor irradiation significantly increased survival. CONCLUSIONS: Genistein combined with prostate tumor irradiation led to a greater control of the growth of the primary tumor and metastasis to lymph nodes than genistein or radiation alone, resulting in greater survival.
The synergetic effect of dissolved oxygen (DO) in the photodegradation of propisochlor aqueous solution was investigated in the presence of UV. With the increase of dissolved oxygen concentration, from 0 to 7.5 mg/L, photodegradation of propisochlor was accelerated. After the concentration of 7.5 mg/L, the rate and efficiency of photodegradation stopped increasing and began to decrease when the concentration became higher. During the photolysis process, dissolved oxygen was consumed. It suggested that the oxygen took an active part in the photolysis. It was found by analysis that the pohtolysis products under different dissolved oxygen concentrations were almost the same, but the production of several products was different. Singlet oxygen (1O2) as the resonance intermediate in the photolysis systems was confirmed by electron spin resonance spin trapping experiments.
Cytochrome P4501A1 plays a major role in the bioactivation of a number of tobacco procarcinogens. Glutathione S-transferase( GSTM1), a member of the class of GST gene family, has been shown to be polymorphic because of gene deletion resulting in a failure to express the GSTM1 gene in 50% approximately 60% of individuals. Some CYP1 A1/GSTM1 null genotype combinations seem to predispose the lung, esophagus, and oral cavity of smokers to an even higher risk for cancer or DNA damage, requiring, however, confirmation. An easy and reliable oligonuleotide microarray approach validated through direct sequencing method is developed in order to accurately detect single nucleotide polymorphisms of CYP1 A1 gene and discriminate the presence and absence of GSTM1 gene. The m1 (Msp I) and m2 (Ile462Val) polymorphisms of CYP1 A1 gene and GSTM1 null genotype were also determined in a random population of 84 healthy, unrelated volunteers with developed microarray-based method. Of 84 cases, 47.6% were calssified as GSTM1 null, close to the published data. It's interesting that there lack three genotypes of m1 -m2 locus in the population: TT-AG, TT-GG and TC-GG. However, according to the data of the genotype frequencies independently happened at both m1 and m2 site, the combination frequencies of above three genotypes are 11.4%, 2.6%, and 3.1% respectively. Therefore we assume that the haplotypes of m1 -m2 are only T-A, C-A and C-G, but not T-G, as it were,there is no recombination happened between m1 site and m2 site. The frequencies of three haplotypes of T-A, C-A and C-G, calculated through corresponding genotypes, are 69.6%, 7.7% and 22.6% respectively.
Zinc and copper deficiency is associated with anaemia or iron deficiency and affects fetus growth and pregnant women during pregnancy. To examine iron, zinc and copper status of Chinese pregnant women with and without anaemia in the third trimester, 1185 subjects were enrolled for measurements of Hb, ferritin, transferrin, soluble transferrin receptor (sTfR), and serum iron, zinc and copper. The results showed that there were lower levels of ferritin (14.1 microg/L) and transferrin (3.33 g/L) in subjects with Hb or=101 g/L. sTfR levels in subjects with Hb or=120 g/L (38.5 nmol/L vs. 25.04 nmol/L, P<0.001). Serum iron was lower in subjects with Hb or=120 g/L (871 microg/L vs. 990 microg/L, P<0.01). Lower levels of serum iron and zinc were also found in anaemic (Hb<110 g/L) as compared with non-anaemic women (Hb>or=110 g/L). Frequencies of marginal deficiencies in serum iron and zinc were 41.58% and 51.05% respectively higher in anaemic than in non-anaemic subjects. Distribution of serum zinc and iron showed a decreasing trend as Hb decreased. Few anaemic as well as non-anaemic subjects had copper deficiency although copper and Hb levels were found inversely correlated and the ratio of copper/iron was higher in anaemic than in non-anaemic group. In conclusion, a lower level of serum zinc in anaemic pregnant women might be related to anaemia and iron deficiency during pregnancy. Therefore, combined zinc and iron supplementation should be recommended to Chinese pregnant women, especially those with anaemia.
OBJECTIVE: To investigate the expression of wild type estrogen receptor (wER) and the exon-5 deleted ER (variant ER, vER) in human hepatocellular carcinoma (HCC) samples, and thereafter analyze the possibility of HCC treatment by endocrine therapy. METHODS: The mRNA expressions of wER and vER were analysed from 28 cases of HCC by RT-PCR. The expression of ER at the protein level was detected by immunohistochemistry (IHC). RESULTS: IHC results showed that 39.3% of the HCC specimens expressed ER. The mRNA of wER was detected in 89.3% (25/28) of the HCC specimens while that of vER was detected in 96.4%(27/28). Twenty four out of 28 HCC cases (85.7 %) expressed both wER and vER. One out of 28 patients (3.5%) expressed only wER whereas 3 patients out of 28 (10.7%) expressed vER only. CONCLUSION: Ninety six percent(27/28) of the HCC patients expressed vER,which suggests that the expression of vER is an important event in the development of HCC.