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Biomedical subjects

Jing He

Publications and source records attributed to Jing He.

At least 73 records · Page 4Linked to original sources

Exercise training increases intramyocellular lipid and oxidative capacity in older adults.

Intramyocellular lipid (IMCL) has been associated with insulin resistance. However, an association between IMCL and insulin resistance might be modulated by oxidative capacity in skeletal muscle. We examined the hypothesis that 12 wk of exercise training would increase both IMCL and the oxidative capacity of skeletal muscle in older (67.3 +/- 0.7 yr), previously sedentary subjects (n = 13; 5 men and 8 women). Maximal aerobic capacity (Vo(2 max)) increased from 1.65 +/- 0.20 to 1.85 +/- 0.14 l/min (P < 0.05), and systemic fat oxidation induced by 1 h of cycle exercise at 45% of Vo(2 max) increased (P < 0.05) from 15.03 +/- 40 to 19.29 +/- 0.80 (micromol.min(-1).kg fat-free mass(-1)). IMCL, determined by quantitative histological staining in vastus lateralis biopsies, increased (P < 0.05) from 22.9 +/- 1.9 to 25.9 +/- 2.6 arbitrary units (AU). The oxidative capacity of muscle, determined by succinate dehydrogenase staining intensity, significantly increased (P < 0.05) from 75.2 +/- 5.2 to 83.9 +/- 3.6 AU. The percentage of type I fibers significantly increased (P < 0.05) from 35.4 +/- 2.1 to 40.1 +/- 2.3%. In conclusion, exercise training increases IMCL in older persons in parallel with an enhanced capacity for fat oxidation.

Aged↗

Biosynthetic origin of the rare nitroaryl moiety of the polyketide antibiotic aureothin: involvement of an unprecedented N-oxygenase.

The antibiotic aureothin is a rare natural nitroaromatic compound produced by Streptomyces thioluteus. By labeling experiments, we demonstrate for the first time that p-nitrobenzoate (PNBA) serves as a polyketide synthase starter unit. Cloning, heterologous expression, and inactivation experiments reveal that this unusual primer is synthesized from p-aminobenzoate (PABA) by means of AurF, a novel N-oxygenase.

Anti-Bacterial Agents↗

Postnatal glucocorticoid exposure alters the adult phenotype.

We examined the effect of six doses of dexamethasone (Dex) administered daily (2-7 days of age) to postnatal rats on body weight gain, food and water intake, peripheral hormonal/metabolic milieu, and hypothalamic neuropeptides that regulate food intake. We observed a Dex-induced acute (3 days of age) suppression of endogenous corticosterone and an increase in circulating leptin concentrations that were associated with a decrease in body weight in males and females. Followup during the suckling, postsuckling, and adult stages (7-120 days of age) revealed hypoleptinemia in males and females, and hypoinsulinemia, a relative increase in the glucose-to-insulin ratio, and a larger increase in skeletal muscle glucose transporter (GLUT 4) concentrations predominantly in the males, reflective of a catabolic state associated with a persistent decrease in body weight gain. The increase in the glucose-to-insulin ratio and hyperglycemia was associated with an increase in water intake. In addition, the changes in the hormonal/metabolic milieu were associated with an increase in hypothalamic neuropeptide Y content in males and females during the suckling phase, which persisted only in the 120-day-old female with a transient postnatal decline in alpha-melanocyte-stimulating hormone and corticotropin-releasing factor. This increase in neuropeptide Y (NPY) during the suckling phase in males and females was associated with a subsequent increase in adult food intake that outweighed the demands of body weight gain. In contrast to the adult hypothalamic findings, cerebral ventricular dilatation was more prominent in adult males. We conclude that postnatal Dex treatment causes permanent sex-specific changes in the adult phenotype, setting the stage for future development of diabetes (increased glucose:insulin ratio), obesity (increased NPY and food intake), and neurological impairment (loss of cerebral volume).

Animals↗

Global search for chromosomal abnormalities in infiltrating ductal carcinoma of the breast using array-comparative genomic hybridization.

Array-comparative genomic hybridization (a-CGH) is a molecular cytogenetic technique for detection of multiple chromosomal abnormalities in genomic DNA samples. Using an a-CGH with 287 probes, we examined 14 cases of breast infiltrating ductal carcinoma (IDCA) that had previously been classified by fluorescent in situ hybridization (FISH) as either human epidermal growth factor receptor-2 positive (HER2+) or HER2- and analyzed the data by hierarchical, K-means, and principal component analyses. The aim of the study was to identify the genetic abnormalities that are present in breast IDCAs and determine if the global status of 287 cytogenetic locations could be used as a more objective method for breast IDCA classification. Concordance between FISH and a-CGH at the HER2 locus was 78.6% (11/14). In general, a-CGH detected more abnormalities in HER2+ cases. In HER 2+ cases, chromosomes 1, 2, 3, 7, 9, 17, and 20 had more regions that showed statistically significant (P < or = 0.01) changes in DNA copy number. Among all the aberrant cytogenetic locations detected, 20q13, 7p12.3 approximately p12.1, and 17q23.2 approximately q25.3, which contain among others, genes for TNFRSF6B, EGFR, and TK1 showed statistically significant gains (P < or = 0.01) in 83, 66.7, and 50% of the HER2+ IDCA cases, respectively. Chromosome location 8q24.12 approximately q24.13 was the only region that showed consistent amplification in approximately 50% of the HER2- cases. Unsupervised hierarchical and K-means cluster analyses and principal component analysis using the DNA copy number status of 287 cytogenetic locations or the 177 cytogenetic locations that showed statistically significant differences revealed a cluster consisting of mainly HER2- IDCA cases. Even though this study demonstrates the usefulness of a-CGH in the rapid identification of aberrant DNA regions in tumor samples, we conclude that an array-CGH with more than 287 probes will be needed for a more precise mapping of DNA aberrations at the global level.

Breast Neoplasms↗

Effects of weight loss and physical activity on muscle lipid content and droplet size.

OBJECTIVES: To address the potential effects of weight loss and physical activity (WL + Ex) on intramyocellular lipid (IMCL) and lipid droplet size in overweight and obese previously sedentary individuals. RESEARCH METHODS AND PROCEDURES: IMCL and lipid droplet size was determined in vastus lateralis, obtained by percutaneous biopsy, from 21 obese volunteers (9 men/12 women), using Oil Red O staining, along with succinate dehydrogenase histochemistry and mitochondrial immunohistochemistry as measures of skeletal muscle oxidative capacity. Insulin sensitivity (IS) was determined by glucose clamp. RESULTS: A 4-month WL + Ex intervention resulted in approximately 10% WL and approximately 15% increase in maximal oxygen uptake, leading to a 46% increase in IS (all p < 0.01). IMCL did not significantly change (p = 0.36). However, the size of lipid droplets decreased after WL + Ex (p < 0.01), and this decrease in lipid droplet size correlated with increased IS (p < 0.01) and the amount of physical activity (p < 0.05). Succinate dehydrogenase activity and mitochondrial labeling increased significantly (p < 0.01), without a significant shift in fiber type distribution. DISCUSSION: In summary, IMCL does not decrease in response to WL + Ex in obese, previously sedentary individuals, yet the lipid within muscle is dispersed into smaller droplets. This change in the size of lipid droplets, likely coupled with a concomitant increase in oxidative enzyme capacity, is correlated to improved IS.

Adult↗

Increased serum levels of neopterin and soluble interleukin-2 receptor in intrahepatic cholestasis of pregnancy.

OBJECTIVES: The etiology of intrahepatic cholestasis of pregnancy (ICP), a pregnancy-specific complication, remains not completely understood. Some alterations of immunity in ICP were reported, but the profile of immune alteration was far from clarified. The aim of this investigation was to characterize the changes of serum levels of neopterin, a marker for the activation of macrophage, and soluble interleukin-2 receptor (sIL-2R), a marker for the activation of lymphocyte, in ICP. METHODS: Serum levels of neopterin and sIL-2R were assayed with enzyme linked immunosorbent assay (ELISA) in 30 patients with ICP and 30 normal pregnant women. Student's t-test was used for statistic analysis, and p < 0.05 was considered significant. RESULTS: Compared with control, serum levels of neopterin (p < 0.005) and sIL-2R (p < 0.05) were increased significantly in women with ICP. CONCLUSIONS: Activation of monocyte-macrophage and lymphocyte was demonstrated in ICP, and the participation of the activation of macrophage and lymphocyte in pathogenesis of the disease could be assumed.

Adult↗

T-cell receptor transgenic response to an endogenous polymorphic autoantigen determines susceptibility to diabetes.

We have produced a T-cell receptor (TCR) transgenic NOD mouse, 6.9TCR/NOD, in which the expression of both diabetogenic T-cells and naturally occurring autoantigen were simultaneously controlled. The parent T-cell clone, BDC-6.9, and T-cells from 6.9TCR/NOD mice recognize a currently unidentified antigen present in NOD but not in BALB/c islet cells. A gene that codes for the antigen, or a protein that regulates the antigen, was previously mapped to a locus on chromosome 6. We have developed transgenic mice bearing the TCR alpha- and beta-chains from the BDC-6.9 T-cell clone on a NOD congenic background in which the antigen locus on chromosome 6 of the NOD mouse is replaced by a segment from BALB/c. These NOD.C6 congenic mice lack the NOD islet cell antigen to which the BDC-6.9 T-cell clone responds. Diabetes in both male and female 6.9TCR/NOD mice is dramatically accelerated, but in 6.9TCR/NOD.C6 mice lacking the NOD islet cell autoantigen, we have not observed diabetes for up to 1 year of age. Thus, the generation of 6.9TCR transgenic mice provides a model of autoimmune diabetes whereby controlled expression of an endogenous polymorphic autoantigen effectively determines disease development.

Animals↗

[Effect of forest litter on microenvironment conditions of forestland].

Litter is a very important component in forest ecosystem. This paper made a systematic review on the previous studies about the effects of litter on forestland microsites. Litter significantly reduced the light on the soil surface of forestlands, and the light transmittance was varied with the type, water content and weight of litter. The spectral composition of the light was dramatically shifted to longer wavelengths after transmitted through forest capony, especially through moist litter leaves, intact forest litter, and even the thinner soil layer, which greatly reduced the R/FR ratio and PPFD (photosynthetic photo flux density) beneath litter and surface soil (2 mm depth), and resulted in a stronginhibitory effect on the germination of photoblastic seeds, and on the growth of seedling and sapling. It was the reason why the appearance of massive numbers of pioneer plants and their successful establishment required relatively large gaps of the forest canopy. Many references concerned the effects of litter on soil nutrient cycling and water and soil conservation. The previous studies indicated that litter could create a moist micro-site above soil, and make soil more moist and fertile. Furthermore, litter could also increase the numbers of arthropods such as Carabidae adults and larvae, crickets, millipedes, spiders, ants and others. An increase in the activity of herbivorous arthropods might produce the negative effects on the establishment of individual seedlings. Although the mechanical barrier of litter was neglected in the paper, litter might act as a mechanical impediment to the emergence of the seedlings of pioneer species with small seeds. The effects of litter on micro-sites were of complexity because it varied greatly with the density, age, structure and species composition of the canopy, sunfleck frequency, presence of gaps, as well as litter thickness, moisture, and species composition, and also with climate and topography factors. The effects of litter were comprehensive, including positive and negative effects on seed germination and seedling growth. Each effect of litter on regeneration was dependent on species physiology, litter physical properties and environmental conditions. Therefore, it should be encouraged to integrate the physical properties (such as changing light, temperature and moisture) of litter with the physiological ecology (including seed, germination and growth natures) of species, and with environment (vegeneration, climate and topography propersities) on the basis of combination of regeneration patterns of litter, understory and gap scales.

Animals↗

[Effect of curcumin on STAT5 signaling molecule in K562 cells].

OBJECTIVE: To investigate the effect of curcumin on STAT 5 signaling molecule in K562 cells and its molecular mechanism of antileukemia. METHODS: Cell proliferation was studied by tetrazolium dye assay. The expressions of STAT5 mRNA and protein were assayed by in situ hybridization, and Western blotting respectively. RESULTS: Curcumin could inhibit K562 cell proliferation in a time- and dose-dependent manner. The percentage of STAT5-positive cells was 19% in curcunin group, significantly less than 31% of that in K562 cell group (P < 0.01). The A value of the expression level of STAT5 protein in curcumin group was 15 266 +/- 769, significantly less than 25 781 +/- 1240 of that in K562 cell group (P < 0.01). CONCLUSION: The expressions of STAT5 mRNA and protein in K562 cells were inhibited by curcumin and curcumin could inhibit K562 cell proliferation.

Cell Proliferation↗

[The effect of electroacupuncture on the weakening of CPP of morphine dependence rats and the mechanism therein involved].

OBJECTIVE: To address the research questions whether electroacupuncture can weaken the CPP of morphine dependence rats and whether the neurobiological mechanism for control of anxiety is related to the transcription of DBI mRNA. METHODS: Twenty-four SD rats were randomly divided into the control group, electroacupuncture group and morphine group. After the CPP model was constructed. The time of CPP was examined on the 5th and 10th day as the interventional electroacupuncture was instituted. The total RNA was extracted from the brain of sacrificed rat and was defected by use of RT-PCR. RESULTS: The CPP time of the electroacupuncture group was significantly decreased on the 5th and 10th day after abstinence (P<0.05). The transcription of the DBI mRNA of the electroacupuncture group was obviously lower than that of the morphine group (P<0.05), and there was no difference between the electroacupuncture group and control group. CONCLUSION: Electroacupuncture can weaken the CPP of the morphine dependence rats, and the neurobiological mechanism may be related to the electroacupuncture-induced transcription of DBI mRNA.

Animals↗

[Epidemiologic features, clinical diagnosis and therapy of first cluster of patients with severe acute respiratory syndrome in Beijing area].

OBJECTIVE: Investigate the features of outbreak epidemic, clinical disease progression of the first SARS cases in Beijing and evaluate the efficacy of therapeutic regimen. METHODS: Twenty-nine patients (11 men and 18 women, 20 - 74 years old age range) were diagnosed with infectious SARS and admitted in our hospital from the March 5th to April 14th, 2003 in this study. The data of clinical presentation and disease progression of all the patients including index subject as the infectious SARS resource patient, her family infected members and 21 health care workers were abstracted. RESULTS: The first SARA outbreak in Beijing was characterized with the cluster feature of resource patient family members and health care providers. The incubation period ranged from 2 to 14 days. All the patients had a fever (temperature > 38 degrees C for over 24 hours) and other manifestations as reported before. Serial chest radiographs showed progressive pathologic air-space disease. Twenty patients showed the severe syndrome with various time ranged from 1 day to 14 days. Two patients died of progressive acute respiratory distress disease. The histologic analysis of one death patient showed diffuse alveolar damage in the two lungs. Twenty-six patients receiving the combined therapy including use of corticosteroid, antiviral ribavirin agents after the onset of symptoms and showed they had an acute self-limited disease course. The oldest patient (74 year old, male) received the healthy convalescent plasma infusion (50 ml) from recovered SARS subject and completely recovered within 21 days, having a shorter disease course. CONCLUSION: SARS is a kind of new self-limited and acute infectious disease. Early diagnosis, early isolation, early antiviral therapy for patients and efficient prevention for health care providers are urgently recommended. In particular, a combinational therapy of use of antiviral agents, preventive antibacterial antibiotics and pulsed dosage of corticosteroid can efficiently raise the clinical recovery rate and decrease mortality of SARS patients.

Adult↗

Postnatal intracerebroventricular exposure to neuropeptide Y causes weight loss in female adult rats.

We investigated the effect of repetitive postnatal (2-7 days) intracerebroventricular administration of neuropeptide Y (NPY) on food intake and body weight gain in the 3- to 120-day-old Sprague-Dawley rats. NPY caused a 32% transient increase in body weight gain with elevated circulating insulin concentrations within 24 h. This early intervention led to the persistence of hyperinsulinemia and relative hyperleptinemia with euglycemia in the 120-day-old female alone. This perturbation was associated with 50% suppression in adult female hypothalamic NPY concentrations and a 50-85% decline in NPY immunoreactivity in the paraventricular and arcuate nuclei. This change was paralleled by a approximately 20% decline in food intake and body weight gain at 60 and 120 days. However, when exogenous NPY was stereotaxically reinjected into the paraventricular nucleus of the approximately 120-day-old adult females who were pretreated with NPY postnatally, an increase in food intake and body weight gain was noted, attesting to no disruption in the NPY end-organ responsivity. We conclude that postnatal intracerebroventricular NPY has long-lasting effects that predetermine the resultant adult phenotype in a sex-specific manner.

Aging↗

Insulin-induced translocation of facilitative glucose transporters in fetal/neonatal rat skeletal muscle.

We examined the effect of insulin on fetal/neonatal rat skeletal muscle GLUT-1 and GLUT-4 concentrations and subcellular distribution by employing immunohistochemical analysis and subcellular fractionation followed by Western blot analysis. We observed that insulin did not alter total GLUT-1 or GLUT-4 concentrations or the GLUT-1 subcellular distribution in fetal/neonatal or adult skeletal muscle in 60 min. The basal and insulin-induced changes in subcellular distribution of GLUT-4 were different between the fetal/neonatal and adult skeletal muscle. Under basal conditions, sarcolemma-associated GLUT-4 was higher in the newborn compared with the adult, translating into a higher glucose transport. In contrast, insulin-induced translocation of GLUT-4 to the sarcolemma- and insulin-induced glucose transport was lower in the newborn compared with the adult. This age-related change results in enhanced basal glucose transport to fuel myocytic proliferation and differentiation while relatively curbing the insulin-dependent glucose transport in the newborn.

Aging↗

The effect of curcumin on mismatch repair (MMR) proteins hMSH2 and hMLH1 after ultraviolet (UV) irradiation on HL-60 cells.

To understand the expression and effect of mismatch repair genes, hMSH2 and hMLH1, and to investigate anti-leukemic cell proliferation mechanism of curcumin, the levels of both genes were detected by multiple comparative RT-PCR. The protein of hMSH2 was determined by flow cytometry (FCM) and the gene mutation of hMSH2 and hMLH1 were detected by PCR-SSCP and microsatellite instability assay. After UV irradiation, the gene expression of hMSH2 and hMLH1 was not increased and showed no response. This phenomenon was not ascribed to gene mutation, because PCP-SSCP and microsatellite instability assay revealed no abnormal gel-shift band in both genes. After irradiation and addition of curcumin, the expression of hMSH2 mRNA increased and the cellular apoptotic rate also increased at the same time. The difference was statistically significant as compared with groups without addition of curcumin and control groups (P < 0.05). Our results suggested that when MMR system was inhibited by the same agents, curcumin can remove this suppression and switch to cellular apoptosis.

Antineoplastic Agents, Phytogenic↗

Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex.

The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans 137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a modular PKS and 15 additional genes. The extensive similarity to the partially characterized candicidin gene cluster in Streptomyces griseus IMRU3570, especially for genes involved in mycosamine biosynthesis, prompted us to compare the compounds produced by Streptomyces sp. FR-008 and Streptomyces griseus IMRU3570, and we found that FR-008 and candicidin complex are identical. A model for biosynthesis of a set of four structurally related FR-008/candicidin compounds was proposed. Deletion of the putative regulatory genes abolished antibiotic production, while disruption of putative glycosyltransferase and GDP-ketosugar aminotransferase functionalities led to the productions of a set of nonmycosaminated aglycones and a novel polyene complex with attachment of altered sugar moiety, respectively.

Amino Acid Sequence↗

Iteration as programmed event during polyketide assembly; molecular analysis of the aureothin biosynthesis gene cluster.

Analysis of the type I modular polyketide synthase (PKS) involved in the biosynthesis of the rare nitroaryl polyketide metabolite aureothin (aur) from Streptomyces thioluteus HKI-227 has revealed only four modules to catalyze the five polyketide chain extensions required. By heterologous expression of the aur PKS cluster, direct evidence was obtained that these modules were sufficient to support aureothin biosynthesis. It appears that one module catalyzes two successive cycles of chain extension, one of the first examples of a PKS in which such iteration or "stuttering" is required to produce the normal polyketide product. In addition, lack of a specified loading domain implicates a novel PKS priming mechanism involving the unique p-nitrobenzoate starter unit. The 27 kb aur gene cluster also encodes a novel N-oxidase, which may represent the first member of a new family of such enzymes.

Binding Sites↗