Hong Zhou

Peking University, Peping, Beijing, China

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Publications (25)71.4 Total impact

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    ABSTRACT: Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently we found a thienoquinolin UT inhibitor, PU-14, which exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition rate was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na(+), K(+), or Cl- levels, or non-urea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics.
    American journal of physiology. Renal physiology 10/2014; · 3.61 Impact Factor
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    ABSTRACT: Urea transporter B (UT-B) is a membrane channel protein that specifically transports urea. UT-B null mouse exhibited urea selective urine concentrating ability deficiency, which suggests the potential clinical applications of the UT-B inhibitors as novel diuretics. Primary high-throughput virtual screening (HTVS) of 50000 small-molecular drug-like compounds identified 2319 hit compounds. These 2319 compounds were screened by high-throughput screening using an erythrocyte osmotic lysis assay. Based on the pharmacological data, putative UT-B binding sites were identified by structure-based drug design and validated by ligand-based and QSAR model. Additionally, UT-B structural and functional characteristics under inhibitors treated and untreated conditions were simulated by molecular dynamics (MD). As the result, we identified four classes of compounds with UT-B inhibitory activity and predicted a human UT-B model, based on which computative binding sites were identified and validated. A novel potential mechanism of UT-B inhibitory activity was discovered by comparing UT-B from different species. Results suggest residue PHE198 in rat and mouse UT-B might block the inhibitor migration pathway. Inhibitory mechanisms of UT-B inhibitors and the functions of key residues in UT-B were proposed. The binding site analysis provides a structural basis for lead identification and optimization of UT-B inhibitors.
    Scientific Reports 07/2014; 4(5775). · 5.08 Impact Factor
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    ABSTRACT: To describe breastfeeding practices in rural China using globally recommended indicators and to compare them with practices in neighbouring countries and large emerging economies. A community-based, cross-sectional survey of 2354 children younger than 2 years in 26 poor, rural counties in 12 central and western provinces was conducted. Associations between indicators of infant and young child feeding and socioeconomic, demographic and health service variables were explored and rates were compared with the most recent data from China and other nations. Overall, 98.3% of infants had been breastfed. However, only 59.4% had initiated breastfeeding early (i.e. within 1 hour of birth); only 55.5% and 9.4% had continued breastfeeding for 1 and 2 years, respectively, and only 28.7% of infants younger than 6 months had been exclusively breastfed. Early initiation of breastfeeding was positively associated with at least five antenatal clinic visits (adjusted odds ratio, aOR: 3.48; P < 0.001) and negatively associated with delivery by Caesarean (aOR: 0.53; P < 0.001) or in a referral-level facility (aOR: 0.6; P = 0.014). Exclusive breastfeeding among children younger than 6 months was positively associated with delivery in a referral-level facility (aOR: 2.22; P < 0.05). Breastfeeding was not associated with maternal age or education, ethnicity or household wealth. Surveyed rates of exclusive and continued breastfeeding were mostly lower than in other nations. Despite efforts to promote breastfeeding in China, rates are very low. A commitment to improve infant and young child feeding is needed to reduce mortality and morbidity.
    Bulletin of the World Health Organisation 05/2013; 91(5):322-31. · 5.25 Impact Factor
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    ABSTRACT: Urea transporters (UTs) are a family of membrane channel proteins that are specifically permeable to urea and play an important role in intrarenal urea recycling and in urine concentration. Using an erythrocyte osmotic lysis assay, we screened a small-molecule library for inhibitors of UT-facilitated urea transport. A novel class of thienoquinolin UT-B inhibitors were identified, of which PU-14 had potent inhibition activity on human, rabbit, rat, and mouse UT-B. The half-maximal inhibitory concentration of PU-14 on rat UT-B-mediated urea transport was ∼0.8 μmol/l, and it did not affect urea transport in mouse erythrocytes lacking UT-B but inhibited UT-A-type urea transporters, with 36% inhibition at 4 μmol/l. PU-14 showed no significant cellular toxicity at concentrations up to its solubility limit of 80 μmol/l. Subcutaneous delivery of PU-14 (at 12.5, 50, and 100 mg/kg) to rats caused an increase of urine output and a decrease of the urine urea concentration and subsequent osmolality without electrolyte disturbances and liver or renal damages. This suggests that PU-14 has a diuretic effect by urea-selective diuresis. Thus, PU-14 or its analogs might be developed as a new diuretic to increase renal fluid clearance in diseases associated with water retention without causing electrolyte imbalance. PU-14 may establish 'chemical knockout' animal models to study the physiological functions of UTs.Kidney International advance online publication, 13 March 2013; doi:10.1038/ki.2013.62.
    Kidney International 03/2013; · 8.52 Impact Factor
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    ABSTRACT: Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) in both native and transplanted kidneys. The objective of the present study was to evaluate whether low-molecular-weight fucoidan (LMWF) could attenuate renal IRI in an animal model and in vitro cell models and study the mechanisms in which LMWF protected from IRI. Male mice were subjected to right renal ischemia for 30 min and reperfusion for 24 h, or to a sham operation with left kidney removed. Kidneys undergone IR showed characteristic morphological changes, such as tubular dilatation, and brush border loss. However, LMWF significantly corrected the renal dysfunction and the abnormal levels of MPO, MDA and SOD induced by IR. LMWF also inhibited the activation of MAPK pathways, which consequently resulted in a significant decrease in the release of cytochrome c from mitochondria, ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3, and phosphorylation of p53. LMWF alleviated hypoxia-reoxygenation or CoCl(2) induced cell viability loss and ΔΨm dissipation in HK2 renal tubular epithelial cells, which indicates LMWF may result in an inhibition of the apoptosis pathway through reducing activity of MAPK pathways in a dose-dependent manner. Our in vivo and in vitro studies show that LMWF ameliorates acute renal IRI via inhibiting MAPK signaling pathways. The data provide evidence that LMWF may serve as a potential therapeutic agent for acute renal IRI.
    PLoS ONE 01/2013; 8(2):e56224. · 3.53 Impact Factor
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    ABSTRACT: Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line. Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis. UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders.
    PLoS ONE 01/2013; 8(10):e76952. · 3.53 Impact Factor
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    ABSTRACT: Objectives  To understand the utilisation of prenatal care and hospitalised delivery among pregnant Muslim women in Ningxia, China, and to explore the effectiveness of the integrated interventions to reduce maternal mortality. Methods  Cross-sectional surveys before and after the intervention were carried out. Using multistage sampling, 1215 mothers of children <5 years old were recruited: 583 in the pre-intervention survey and 632 in the post-intervention study. Data on prenatal care and delivery were collected from face-to-face interviews. Maternal mortality ratio (MMR) data were obtained from the local Maternal and Child Mortality Report System. Results  After the intervention, the MMR significantly decreased (45.5 deaths per 100 000 live births to 32.7 deaths). Fewer children were born at home after the intervention than before the intervention (OR, 0.11; 95% CI, 0.08-0.15). The proportion of women who attended prenatal care at least once increased from 78.2% to 98.9% (OR, 24.55; 95% CI, 11.37-53.12). The proportion of women who had prenatal visit(s) in the first trimester of pregnancy increased from 35.1% to 82.6% (OR, 8.77; 95% CI, 6.58-11.69). The quality of prenatal care was greatly improved. Effects of the intervention on the utilisation of maternal care remained significant after adjusting for education level and household possessions. Conclusions  The findings suggest that integrated strategies can effectively reduce maternal mortality.
    Tropical Medicine & International Health 09/2012; · 2.94 Impact Factor
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    ABSTRACT: To investigate the inhibitory effects of heparin on PC-3M cells proliferation in vitro and B16-F10-luc-G5 cells metastasis in Balb/c nude mice and identify the protein expression patterns to elucidate the action mechanism of heparin. Human prostate cancer PC-3M cells were incubated with heparin 0.5 to 125 μg/mL for 24 h. The proliferation of PC-3M cells was assessed by MTS assay. BrdU incoporation and Ki67 expression were detected using a high content screening (HCS) assay. The cell cycle and apoptosis of PC-3M cells were tested by flow cytometry. B16-F10-luc-G5 cardinoma cells were injected into the lateral tail vein of 6-week old male Balb/c nude mice and heparin 30 mg/kg was administered iv 30 min before and 24 h after injection. The metasis of B16-F10-luc-G5 cells was detected by bioluminescence assay. Activated partial thromboplastin time (APTT) and hemorheological parameters were measured on d 14 after injection of B16-F10-luc-G5 carcinoma cells in Balb/c mice. The global protein changes in PC-3M cells and frozen lung tissues from mice burdened with B16-F10-luc-G5 cells were determined by 2-dimensional gel electrophoresis and image analysis. The protein expression of vimentin and 14-3-3 zeta/delta was measured by Western blot. The mRNA transcription of vimentin, transforming growth factor (TGF)-β, E-cadherin, and α(v)-integrin was measured by RT-PCR. Heparin 25 and 125 μg/mL significantly inhibited the proliferation, arrested the cells in G(1) phase, and suppressed BrdU incorporation and Ki67 expression in PC-3M cells compared with the model group. But it had no significant effect on apoptosis of PC-3M cells. Heparin 30 mg/kg markedly inhibits the metastasis of B16-F10-luc-G5 cells on day 8. Additionally, heparin administration maintained relatively normal red blood hematocrit but had no influence on APTT in nude mice burdened with B16-F10-luc-G5 cells. Thirty of down-regulated protein spots were identified after heparin treatment, many of which are related to tumor development, extracellular signaling, energy metabolism, and cellular proliferation. Vimentin and 14-3-3 zeta/delta were identified in common in PC-3M cells and the lungs of mice bearing B16-F10-luc-G5 carcinoma cells. Heparin 25 and 125 μg/mL decreased the protein expression of vimentin and 14-3-3 zeta/delta and the mRNA expression of α(v)-integrin. Heparin 125 μg/mL decreased vimentin and E-cadherin mRNA transcription while increased TGF-β mRNA transcription in the PC-3M cells, but the differences were not significant. Transfection of vimentin-targeted siRNA for 48 h significantly decreased the BrdU incoporation and Ki67 expression in PC-3M cells. Heparin inhibited PC-3M cell proliferation in vitro and B16-F10-luc-G5 cells metastasis in nude mice by inhibition of vimentin, 14-3-3 zeta/delta, and α(v)-integrin expression.
    Acta Pharmacologica Sinica 06/2012; 33(6):798-808. · 2.35 Impact Factor
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    ABSTRACT: Sexual and reproductive health among adolescents have become increasingly important and aroused international concerns. In this study, we investigate sexual knowledge, attitudes, sexual behaviors, the unwanted pregnancy and the abortion rate and to explore related determinants among college students in Beijing. This study is based on a cross-sectional survey of college students' knowledge, attitudes and behavior. Multistage cluster sampling was used to select subjects in Beijing. The self-questionnaire designed by our research group including general information, knowledge, attitude and behavior about sexuality was used to collect information. A total of 2003 questionnaires were collected from June to July 2010. The data showed that most of the college students lacked knowledge about reproductive health. Only 17.9% of the respondents knew the appropriate time of abortion. Data also showed that the respondents had high-risk attitude about sex, 58.7% could accept premarital sex, and 29.7% had negative attitude towards contraception. Moreover, sexual activity of the respondents was active. Data showed that 18.5% of the respondents had had sexual activities. Significantly more boys than girls had sex (χ(2) = 73.374, P < 0.001). Among the boys and girls who reported sexual history, 43.1% of the boys had impregnated girlfriend and 49.3% of the girls among those people who have sex had unwanted pregnancies. Logistic regression analysis showed that the variables the gender (OR = 3.12, 95%CI: 2.39 - 4.11), grade (OR = 1.78, 95%CI: 1.40 - 2.26), specialty (OR = 1.35, 95%CI: 1.12 - 1.74), family situation (OR = 1.66, 95%CI: 1.15 - 2.38), score of knowledge (OR = 0.74, 95%CI: 0.58 - 0.95) and attitude to sex activity (OR = 0.09, 95%CI: 0.04 - 0.22) had a significant effect on having sexual behavior. College students lack knowledge and methods to avoid risky sexual behaviors in Beijing. College students have high-risk sexual attitude and behaviors. Therefore, suitable and effective sex health measures to protect college students would be strongly recommended.
    Chinese medical journal 03/2012; 125(6):1153-7. · 0.90 Impact Factor
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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by massive enlargement of fluid-filled cysts in the kidney. However, there is no effective therapy yet for this disease. To examine whether ginkgolide B, a natural compound, inhibits cyst development, a Madin-Darby canine kidney (MDCK) cyst model, an embryonic kidney cyst model, and a PKD mouse model were used. Interestingly, ginkgolide B significantly inhibited MDCK cyst formation dose dependently, with up to 69% reduction by 2 μM ginkgolide B. Ginkgolide B also significantly inhibited cyst enlargement in the MDCK cyst model, embryonic kidney cyst model, and PKD mouse model. To determine the underlying mechanisms, the effect of ginkgolide B on MDCK cell viability, proliferation, apoptosis, chloride transporter CFTR activity, and intracellular signaling pathways were also studied. Ginkgolide B did not affect cell viability, proliferation, and expression and activity of the chloride transporter CFTR that mediates cyst fluid secretion. Ginkgolide B induced cyst cell differentiation and altered the Ras/MAPK signaling pathway. Taken together, our results demonstrate that ginkgolide B inhibits renal cyst formation and enlargement, suggesting that ginkgolide B might be developed into a novel candidate drug for ADPKD.
    AJP Renal Physiology 02/2012; 302(10):F1234-42. · 4.42 Impact Factor
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    ABSTRACT: The World Health Organization reported that inappropriate feeding in children is responsible for one-third of the cases of malnutrition. This cross-sectional study aimed to determine the prevalence of malnutrition and identify the relationship between feeding practices and malnutrition in children below 5 years, in 7 remote and poor counties of China. A sample of 2201 children and 1978 caregivers were obtained with multistage cluster random sampling. A survey about feeding practices among the caregivers was implemented using a structured questionnaire, and the health status of children was evaluated using anthropometric measurements. We found 5 problems: first, high prevalence of stunting, underweight and wasting in children below 5 years old (19.3%, 13.1% and 5.5%); second, short duration of breastfeeding for children below 36 months; third, low prevalence of exclusive breastfeeding among children below 6 months of age and continued breastfeeding to 1 year (17.5% and 32.2%). Fourth, although most of the infants (81.1%) between 6 and 8 months of age were given complementary foods, some of the 6- to 8-month-old infants did not receive any complementary foods. Last, a higher prevalence of stunting among Chinese children who had never been breastfed, who had been breastfed for less than 1 year, or had been fed with semi-solid foods of poor quality. Therefore, we suggest that more programs to increase caregivers' feeding knowledge and practices be conducted, to improve the health of children in remote and poor areas in China.
    Asia Pacific Journal of Clinical Nutrition 01/2012; 21(2):234-40. · 1.06 Impact Factor
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    ABSTRACT: To identify the immediate economic impact of maternal death on rural Chinese households. Results are reported from a study that matched 195 households who had suffered a maternal death to 384 households that experienced a childbirth without maternal death in rural areas of three provinces in China, using quantitative questionnaire to compare differences of direct and indirect costs between two groups. The direct costs of a maternal death were significantly higher than the costs of a childbirth without a maternal death (US$4,119 vs. $370, p<0.001). More than 40% of the direct costs were attributed to funeral expenses. Hospitalization and emergency care expenses were the largest proportion of non-funeral direct costs and were higher in households with maternal death than the comparison group (US$2,248 vs. $305, p<0.001). To cover most of the high direct costs, 44.1% of affected households utilized compensation from hospitals, and the rest affected households (55.9%) utilized borrowing money or taking loans as major source of money to offset direct costs. The median economic burden of the direct (and non-reimbursed) costs of a maternal death was quite high--37.0% of the household's annual income, which was approximately 4 times as high as the threshold for an expense being considered catastrophic. The immediate direct costs of maternal deaths are extremely catastrophic for the rural Chinese households in three provinces studied.
    PLoS ONE 01/2012; 7(6):e38467. · 3.53 Impact Factor
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    ABSTRACT: Urea transporters UT-A2 and UT-B are expressed in epithelia of thin descending limb of Henle's loop and in descending vasa recta, respectively. To study their role and possible interaction in the context of the urine concentration mechanism, a UT-A2 and UT-B double knockout (UT-A2/B knockout) mouse model was generated by targeted deletion of the UT-A2 promoter in embryonic stem cells with UT-B gene knockout. The UT-A2/B knockout mice lacked detectable UT-A2 and UT-B transcripts and proteins and showed normal survival and growth. Daily urine output was significantly higher in UT-A2/B knockout mice than that in wild-type mice and lower than that in UT-B knockout mice. Urine osmolality in UT-A2/B knockout mice was intermediate between that in UT-B knockout and wild-type mice. The changes in urine osmolality and flow rate, plasma and urine urea concentration, as well as non-urea solute concentration after an acute urea load or chronic changes in protein intake suggested that UT-A2 plays a role in the progressive accumulation of urea in the inner medulla. These results suggest that in wild-type mice UT-A2 facilitates urea absorption by urea efflux from the thin descending limb of short loops of Henle. Moreover, UT-A2 deletion in UT-B knockout mice partially remedies the urine concentrating defect caused by UT-B deletion, by reducing urea loss from the descending limbs to the peripheral circulation; instead, urea is returned to the inner medulla through the loops of Henle and the collecting ducts.
    AJP Renal Physiology 08/2011; 301(6):F1251-9. · 4.42 Impact Factor
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    ABSTRACT: Urea transporter B is one of urea transporters that selectively transport urea driven by urea gradient across membrane and expressed abundantly in brain. To determine the physiological role of UT-B in brain, UT-B localization, urea concentration, tissue morphology of brain, and behavioral phenotypes were studied in UT-B heterozygous mice via UT-B null mice. UT-B mRNA was expressed in olfactory bulb, cortex, caudate nucleus, hippocampus and hypothalamus of UT-B heterozygous mice. UT-B null mice exhibited depression-like behavior, with urea accumulation, nitric oxide reduction, and selective neuronal nitric oxide synthase level increase in hippocampus. After acute urea loading, the urea level increased, NO production decreased in hippocampus from both types of mice. Moreover, urea level was higher, and NO concentration was lower consistently in UT-B null hippocampus than that in heterozygous hippocampus. In vitro, 25 mM urea inhibited NO production too. Furthermore, UT-B knockout induced a long-lasting notable decrease in regional cerebral blood flow and altered morphology, such as loss of neurons in CA3 region, swelling, and membranous myelin-like structure formation within myelinated and unmyelinated fibers in hippocampus. These results suggest that urea accumulation in the hippocampus induced by UT-B deletion can cause depression-like behavior, which possibly attribute to disturbance in NOS/NO system.
    Journal of Molecular Neuroscience 07/2011; 46(2):362-72. · 2.89 Impact Factor
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    Ying Sun, Hong Zhou, Bao-xue Yang
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    ABSTRACT: In polycystic kidney disease (PKD), a most common human genetic diseases, fluid-filled cysts displace normal renal tubules and cause end-stage renal failure. PKD is a serious and costly disorder. There is no available therapy that prevents or slows down the cystogenesis and cyst expansion in PKD. Numerous efforts have been made to find drug targets and the candidate drugs to treat PKD. Recent studies have defined the mechanisms underlying PKD and new therapies directed toward them. In this review article, we summarize the pathogenesis of PKD, possible drug targets, available PKD models for screening and evaluating new drugs as well as candidate drugs that are being developed.
    Acta Pharmacologica Sinica 06/2011; 32(6):805-16. · 2.35 Impact Factor
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    ABSTRACT: Autosomal dominant polycystic kidney disease, a common inherited disease affecting about 1/1000 and 1/400 live births, is characterized by massive enlargement of fluid-filled cysts and eventually causes renal failure. The purpose of this study is to identify the inhibitory effect of curcumin on renal cyst development and to investigate the inhibitory mechanism. Madin-Darby canine kidney (MDCK) cyst model and murine embryonic kidney cyst model were used to evaluate inhibitory activity. Cell viability, proliferation, apoptosis, CFTR function and expression, and signaling pathways in MDCK cells were determined to explore the mechanism of cyst inhibition. Curcumin was found to significantly inhibit MDCK cyst development. At maximum dose curcumin caused 62% inhibition of the cyst formation (IC(50) was 0.12 μM). Curcumin slowed cyst enlargement in both MDCK cyst model and embryonic kidney cyst model with dose-response relationship. Curcumin neither induced cytotoxicity nor apoptosis in MDCK cells at <100 μM. Curcumin failed to affect the chloride transporter CFTR expression and function. Interestingly, curcumin inhibited forskolin-promoted cell proliferation and promoted the tubule formation in MDCK cells, which indicates curcumin promotes MDCK cell differentiation. Furthermore, curcumin reduced the intracellular signaling proteins Ras, B-raf, p-MEK, p-ERK, c-fos, Egr-1, but increased Raf-1 and NAB2 in MDCK cells exposed to forskolin. These results define that curcumin inhibits renal cyst formation and enlargement and suggest that curcumin might be developed as a candidate drug for polycystic kidney disease.
    European journal of pharmacology 03/2011; 654(1):92-9. · 2.59 Impact Factor
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    ABSTRACT: Female ICR mice were administered with bovine colostrum and were treated with cyclophosphamide to establish immunosuppressed status. The cytokine levels in sera and splenocyte culture supernatants and splenic T cell subpopulations were determined. Bovine colostrum substantially restored the percentage of the total T cell population (CD3+) and effector CD4+ T lymphocyte, as well as influencing the CD4:CD8 ratio in the spleen. It was effective in increasing the concentrations of interleukin (IL)-2, interferon-γ, granulocyte-macrophage colony-stimulating factor and decreasing the levels of IL-6 in vivo and in vitro. The levels of IL-10 in splenocyte culture supernatants were increased, whereas the levels of IL-4 in splenocyte culture supernatants were dramatically decreased. Moreover, bovine colostrum was efficacious in enhancing the production of IL-1α in vitro. Thus, bovine colostrum could exhibit immunoregulatory effects via modulating splenic T lymphocytes subpopulations. Bovine colostrum may have pleiotropic effects on the production of cytokines in vivo and in vitro.
    International Dairy Journal. 01/2010;
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    ABSTRACT: Milk contains considerable quantities of estrogens and progesterone and as such may be one of the risk factors for hormone-related cancers. To determine the hormonal effects of commercial and traditional types of milk, we performed uterotrophic tests. Forty-five rats were ovariectomized and divided into three groups of 15 animals each. The animals were kept for 7 days on powdered chow and one of three different liquids: commercial milk (C), traditional milk (T), or water. At autopsy, wet and dry uterine weights were determined. The cell heights of the uterine epithelium and endometrium were determined. The uterine 5-bromo-2-deoxyuridine (BrdU) labeling index of the epithelium and endometrium gland epithelium was also assessed. The weights of wet and dry uterus were 142 ± 13 and 112 ± 10 mg in the C group, 114 ± 30 and 91 ± 24 mg in the T group, and 87 ± 6 and 69 ± 5 mg in the W group. Significant differences in wet and dry uterus weights were found between all pairs of groups. The ratio of the wet uterine weight to body weight was significantly higher in the C and T groups than in the W group. The heights of the uterine epithelium and endometrium were higher and BrdU labeling index was greater in the C group than in the T and W groups. Commercially available milk and traditional milk have uterotrophic effects on young ovariectomized rats. Our findings indicate that these uterotrophic effects in the milk groups were partly due to the estrogen and progesterone in the milk.
    Environmental Health and Preventive Medicine 12/2009; 15(3):162-8.
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    ABSTRACT: To detect the content of estrogen and progesterone in commercial milk in China and to compare the differences between commercial cows and traditional cows in the content of estrogen and progesterone of the milk, the breeding of cows and the process of milk production. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the estrone, estradiol and progesterone in commercial and traditional milk, and literature review and field investigation was used to compare the differences of breeding and milk production. The mean concentration of estrone, estradiol and progesterone in Mongolian traditional cow milk was (98.5 +/- 12.4) pg/ml, (24.6 +/- 3.0) pg/ml and (0.2 +/- 0.3) ng/ml, respectively. The concentrations of estrone were (150.2 +/- 8.4), (131.3 +/- 16.3) and (128.9 +/- 13.0) pg/ml; The concentrations of estradiol were (35.4 +/- 2.2), (30.3 +/- 3.1) and (30.0 +/- 2.0) pg/ml; The concentrations of progesterone were (20.2 +/- 1.5), (18.1 +/- 2.2) and (16.5 +/- 2.4) ng/ ml, respectively. The content of estrogen and progesterone in commercial milks were higher than that in traditional milks (estrone comparison: t = 5.43, 19.23, 5.89; estradiol comparison: t = 4.14, 4.93, 14.03; progesterone comparison: t = 28.47, 32.73, 22.82; P < 0.05). Mongolian traditional cows did not lactate during the latter half of pregnancy. However, modern commercial cows might lactate almost in an entire period of pregnancy. Moreover, the lactating period was longer and milk production was higher in modern commercial cows than that in traditional cows. The content of estrogen and progesterone in commercial milk in Chinese market detected might be higher than that in traditional milk.
    Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 06/2009; 43(6):509-12.
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    Hong Zhou, Xuejun Li, Min Gao
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    ABSTRACT: Antiglucocorticoid therapy in depressed patients is effective, which indicates that glucocorticoids play a key role in the occurrence of depression. Our previous work demonstrated the efficacy of curcumin in treating depression in rat and mouse models. We characterized the protective effects of curcumin against corticosterone-induced cytotoxicity in PC12 cells and explored the mechanisms of these protective effects in association with the phosphorylation and expression of ERK1/2 in PC12 cells. MTT assay showed that curcumin significantly protected PC12 cells from corticosterone-induced cytotoxicity. Curcumin at concentrations from 10(-8) to 10(-6) M rescued PC12 cells from corticosterone-induced cytotoxicity. Cell viability was increased more than 20% with curcumin treatment. Western blot analysis showed that corticosterone increased ERK1/2 phosphorylation in PC12 cells and curcumin 10(-9) M to 10(-6) M significantly inhibited corticosterone-induced ERK1/2 phosphorylation in PC12 cells in a dose-dependent manner. These results suggest that curcumin is able to protect PC12 cells which may be associated with inhibition of ERK phosphorylation.
    Basic & Clinical Pharmacology & Toxicology 02/2009; 104(3):236-40. · 2.18 Impact Factor