Biomedical subjects

Jiang Xia

Publications and source records attributed to Jiang Xia.

15 recordsLinked to original sources

PubMed2007

Application of artificial neural network coupling particle swarm optimization algorithm to biocatalytic production of GABA.

The biotransformation of L-sodium glutamate (L-MSG) to gamma-aminobutyric acid (GABA) catalyzed by the cells of Lactobacillus brevis with higher glutamate decarboxylase activity was investigated. The results showed that pH, temperature, and FeSO(4) x 7H(2)O concentration had significantly positive effect on GABA yield. The individual and interactive effects of pH, temperature, and FeSO(4) x 7H(2)O concentration were further optimized in terms of GABA yield. In the present work, an artificial neural network (ANN) and response surface methodology (RSM) models were developed, which incorporated pH, temperature, and FeSO(4) x 7H(2)O concentration as input variables, and GABA yield as output variable. The optimized ANN topology included four neurons in the hidden layer and the best network architecture was 3-4-1. The trained ANN gave total root-mean square error (sigma) equal to 1.84 for GABA yield while the RSM gave sigma equal to 2.63. The results demonstrated a slightly higher prediction accuracy of ANN compared to RSM. The modeled maximum GABA yield was identified by applying particle swarm optimization algorithm to the ANN model developed. The modeled maximum GABA yield reached 91 mM under the following optimal conditions: 25 mL Na(2)HPO(4)-citric acid buffer (100 mM, pH 4.23), 120 mM L-MSG, 0.83 g/L FeSO(4) x 7H(2)O, 10 microM PLP, the resting cells obtained from a 60-h culture broth, 2.68 g dry cell weight (DCW)/L, and without agitation at 40 degrees C for 5 h. The previous high value of GABA yield that was observed was 81.8 mM. The optimized conditions allowed GABA yield to be increased from 81.8 to 90.57 mM after verification experiments test.

Algorithms↗

PubMed2006

A randomized intervention of smoking for adolescents in urban Wuhan, China.

BACKGROUND: Tobacco use is a significant public health problem in China. Culturally specific smoking prevention programs are needed for Chinese adolescents. This study evaluated a school-based smoking prevention curriculum with a social normative approach developed in the United States for adolescents in urban Wuhan, China. METHODS: As a randomized trial, the intervention was implemented in 1998 with 7th grade students in seven schools with seven matched control schools. Multilevel logistic regression models were used to compare ever and recent (past-month) smoking behaviors for the control and program conditions. RESULTS: At the 1-year follow-up, smoking had increased more rapidly in the control schools than in the program schools. The odds of baseline nonsmokers initiating smoking did not differ between the program and control groups (OR=1.08 with 95% CI=0.71, 1.64). The program prevented progression to recent smoking among boys who were baseline ever smokers. Among boys who were recent smokers at baseline, the prevention program significantly reduced risk of remaining recent smokers at follow-up (OR=0.45 with 95% CI=0.23, 0.88). CONCLUSIONS: This social normative smoking prevention curriculum did not demonstrate a significant primary prevention effect but showed potential for secondary prevention. Culturally specific smoking prevention programs are needed for Chinese adolescents.

Adolescent↗

PubMed2006

Inhibition of HLA-DQ2-mediated antigen presentation by analogues of a high affinity 33-residue peptide from alpha2-gliadin.

Human leukocyte antigen DQ2 is a class II major histocompatibility complex protein that plays a critical role in the pathogenesis of Celiac Sprue by binding to epitopes derived from dietary gluten and triggering the inflammatory response of disease-specific T cells. Inhibition of DQ2-mediated antigen presentation in the small intestinal mucosa of Celiac Sprue patients therefore represents a potentially attractive mode of therapy for this widespread but unmet medical need. Starting from a pro-inflammatory, proteolytically resistant, 33-residue peptide, LQLQPFPQPELPYPQPELPYPQPELPYPQPQPF, we embarked upon a systematic effort to dissect the relationships between peptide structure and DQ2 affinity and to translate these insights into prototypical DQ2 blocking agents. Three structural determinants within the first 20 residues of this 33-mer peptide, including a PQPELPYPQ epitope, its N-terminal flanking sequence, and a downstream Glu residue, were found to be important for DQ2 binding. Guided by the X-ray crystal structure of DQ2, the L11 and L18 residues in the truncated 20-mer analogue were replaced with sterically bulky groups so as to retain high DQ2 affinity but abrogate T cell recognition. A dimeric ligand, synthesized by regiospecific coupling of the 20-mer peptide with a bifunctional linker, was identified as an especially potent DQ2 binding agent. Two such ligands were able to attenuate the proliferation of disease-specific T cell lines in response to gluten antigens and, therefore, represent prototypical examples of pharmacologically suitable DQ2 blocking agents for the potential treatment of Celiac Sprue.

Amino Acid Sequence↗

PubMed2006

Rational design of combination enzyme therapy for celiac sprue.

Celiac sprue (also known as celiac disease) is an inheritable, gluten-induced enteropathy of the upper small intestine with an estimated prevalence of 0.5%-1% in most parts of the world. The ubiquitous nature of food gluten, coupled with inadequate labeling regulations in most countries, constantly poses a threat of disease exacerbation and relapse for patients. Here, we demonstrate that a two-enzyme cocktail comprised of a glutamine-specific cysteine protease (EP-B2) that functions under gastric conditions and a PEP, which acts in concert with pancreatic proteases under duodenal conditions, is a particularly potent candidate for celiac sprue therapy. At a gluten:EP-B2:PEP weight ratio of 75:3:1, grocery store gluten is fully detoxified within 10 min of simulated duodenal conditions, as judged by chromatographic analysis, biopsy-derived T cell proliferation assays, and a commercial antigluten antibody test.

Amino Acid Sequence↗

PubMed2005

Main chain hydrogen bond interactions in the binding of proline-rich gluten peptides to the celiac disease-associated HLA-DQ2 molecule.

Binding of peptide epitopes to major histocompatibility complex proteins involves multiple hydrogen bond interactions between the peptide main chain and major histocompatibility complex residues. The crystal structure of HLA-DQ2 complexed with the alphaI-gliadin epitope (LQPFPQPELPY) revealed four hydrogen bonds between DQ2 and peptide main chain amides. This is remarkable, given that four of the nine core residues in this peptide are proline residues that cannot engage in amide hydrogen bonding. Preserving main chain hydrogen bond interactions despite the presence of multiple proline residues in gluten peptides is a key element for the HLA-DQ2 association of celiac disease. We have investigated the relative contribution of each main chain hydrogen bond interaction by preparing a series of N-methylated alphaI epitope analogues and measuring their binding affinity and off-rate constants to DQ2. Additionally, we measured the binding of alphaI-gliadin peptide analogues in which norvaline, which contains a backbone amide hydrogen bond donor, was substituted for each proline. Our results demonstrate that hydrogen bonds at P4 and P2 positions are most important for binding, whereas the hydrogen bonds at P9 and P6 make smaller contributions to the overall binding affinity. There is no evidence for a hydrogen bond between DQ2 and the P1 amide nitrogen in peptides without proline at this position. This is a unique feature of DQ2 and is likely a key parameter for preferential binding of proline-rich gluten peptides and development of celiac disease.

Amino Acid Sequence↗

PubMed2005

Equilibrium and kinetic analysis of the unusual binding behavior of a highly immunogenic gluten peptide to HLA-DQ2.

HLA-DQ2 predisposes an individual to celiac sprue by presenting peptides from dietary gluten to intestinal CD4(+) T cells. A selectively deamidated multivalent peptide from gluten (LQLQPFPQPELPYPQPELPYPQPELPYPQPQPF; underlined residues correspond to posttranslational Q --> E alterations) is a potent trigger of DQ2 restricted T cell proliferation. Here we report equilibrium and kinetic measurements of interactions between DQ2 and (i) this highly immunogenic multivalent peptide, (ii) its individual constituent epitopes, (iii) its nondeamidated precursor, and (iv) a reference high-affinity ligand of HLA-DQ2 that is not recognized by gluten-responsive T cells from celiac sprue patients. The deamidated 33-mer peptide efficiently exchanges with a preloaded peptide in the DQ2 ligand-binding groove at pH 5.5 as well as pH 7.3, suggesting that the peptide can be presented to T cells comparably well through the endocytic pathway or via direct loading onto extracellular HLA-DQ2. In contrast, the monovalent peptides, and the nondeamidated precursor, as well as the tight-binding reference peptide show a much poorer ability to exchange with a preloaded peptide in the DQ2 binding pocket, especially at pH 7.3, suggesting that endocytosis of these peptides is a prerequisite for T cell presentation. At pH 5.5 and 7.3, dissociation of the deamidated 33-mer peptide from DQ2 is much slower than dissociation of its constituent monovalent epitopes or the nondeamidated precursor but faster than dissociation of the reference high-affinity peptide. Oligomeric states involving multiple copies of the DQ2 heterodimer bound to a single copy of the multivalent 33-mer peptide are not observed. Together, these results suggest that the remarkable antigenicity of the 33-mer gluten peptide is primarily due to its unusually efficient ability to displace existing ligands in the HLA-DQ2 binding pocket, rather than an extremely low rate of dissociation.

Amides↗

PubMed2004

Respiratory symptoms in relation to residential coal burning and environmental tobacco smoke among early adolescents in Wuhan, China: a cross-sectional study.

BACKGROUND: Cigarette smoking and coal burning are the primary sources of indoor air pollution in Chinese households. However, effects of these exposures on Chinese children's respiratory health are not well characterized. METHODS: Seventh grade students (N = 5051) from 22 randomly selected schools in the greater metropolitan area of Wuhan, China, completed an in-class self-administered questionnaire on their respiratory health and home environment. RESULTS: Coal burning for cooking and/or heating increased odds of wheezing with colds [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.07-2.29] and without colds (OR = 1.44, 95% CI: 1.05-1.97). For smoking in the home, the strongest associations were seen for cough (OR = 1.74, 95% CI: 1.17-2.60) and phlegm production (OR = 2.25, 95% CI: 1.36-3.72) without colds among children who lived with two or more smokers. CONCLUSIONS: Chinese children living with smokers or in coal-burning homes are at increased risk for respiratory impairment. While economic development in China may decrease coal burning by providing cleaner fuels for household energy use, the increasing prevalence of cigarette smoking is a growing public health concern due to its effects on children. Adverse effects of tobacco smoke exposure were seen despite the low rates of maternal smoking (3.6%) in this population.

Adolescent↗

PubMed2004

Antigen presentation to celiac lesion-derived T cells of a 33-mer gliadin peptide naturally formed by gastrointestinal digestion.

Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T cell responses to ingested wheat gluten proteins. A peptide fragment of 33 residues (alpha(2)-gliadin 56-88) produced by normal gastrointestinal proteolysis contains six partly overlapping copies of three T cell epitopes and is a remarkably potent T cell stimulator after deamidation by tissue transglutaminase (TG2). This 33-mer is rich in proline residues and adopts the type II polyproline helical conformation in solution. In this study we report that after deamidation, the 33-mer bound with higher affinity to DQ2 compared with other monovalent peptides harboring gliadin epitopes. We found that the TG2-treated 33-mer was presented equally effectively by live and glutaraldehyde-fixed, EBV-transformed B cells. The TG2-treated 33-mer was also effectively presented by glutaraldehyde-fixed dendritic cells, albeit live dendritic cells were the most effective APCs. A strikingly increased T cell stimulatory potency of the 33-mer compared with a 12-mer peptide was also seen with fixed APCs. The 33-mer showed binding maximum to DQ2 at pH 6.3, higher than maxima found for other high affinity DQ2 binders. The 33-mer is thus a potent T cell stimulator that does not require further processing within APC for T cell presentation and that binds to DQ2 with a pH profile that promotes extracellular binding.

Amino Acid Sequence↗

PubMed2004

Project EX--a teen smoking cessation initial study in Wuhan, China.

The increasing smoking prevalence in China indicates a need for effective smoking cessation programs, yet, to our knowledge, no studies have evaluated the effects of smoking cessation programs among Chinese adolescents. A group of 46 10th-grade-level cigarette smokers from two schools in Wuhan, China, were provided with Project EX, an eight-session school-based clinic smoking cessation program developed in the United States. Efforts of translation of the Project EX curriculum, verification of translation, curriculum modification, and cultural adaptation were made to adapt the curriculum to the local culture. The 46 smokers represented 71% of all the self-reported 30-day smokers among 622 10th graders at these two schools. Only one student dropped out from the clinic program. Four-month follow-up data indicated a 10.5% 30-day quit rate and a 14.3% 7-day quit rate. The students who did not quit smoking reported a 16% reduction in daily cigarette consumption at posttest and a 33% reduction at 4-month follow-up. Use of a 2 1/2-week prebaseline-to-baseline clinic assessment indicated a clinic cohort nonassisted quit rate of 3%. These data provided evidence that Project EX can be adapted in another country, such as China; can be very well received; and can lead to promising results on cessation.

Adolescent↗

PubMed2004

Indoor allergens, asthma, and asthma-related symptoms among adolescents in Wuhan, China.

PURPOSE: Information on indoor allergen exposures among non-Western populations, which have lower prevalence of atopic illness, is scant. We examined whether exposures to common indoor allergens were associated with doctor-diagnosed asthma and asthma-related symptoms among Chinese adolescents. METHODS: A cross-sectional study of 4,185 ninth grade students was conducted at 22 randomly selected schools in Wuhan, China. Information on respiratory health and exposures to indoor allergens was obtained by a self-administered questionnaire completed in class. RESULTS: Having animals currently was associated with persistent cough [prevalence odds ratio (POR)=1.54, 95% confidence interval (CI ): 1.21-2.11] and wheeze (POR=1.41, 95% CI: 1.03-1.94). Early-life exposure to animals was also associated with doctor-diagnosed asthma (POR=1.95, 95% CI: 1.35-2.82). Associations with respiratory symptoms strengthened with higher levels of exposure and for exposure in both early childhood and in adolescence. Exposure to cockroaches and having mold/water damage in the home contributed especially to wheezing (POR=2.03, 95% CI: 1.41-2.90 for cockroaches; POR=2.49, 95% CI: 1.82-3.40 for mold/water damage). CONCLUSIONS: Indoor allergen exposures were positively associated with asthma diagnosis and persistent respiratory symptoms among Chinese adolescents. Neither early-life nor current exposure to animals was protective for asthma or asthma-related symptoms.

Adolescent↗

PubMed2003

Deprotonation of zinc(II)-water and zinc(II)-alcohol and nucleophilicity of the resultant zinc(II) hydroxide and zinc(II) alkoxide in double-functionalized complexes: theoretical studies on models for hydrolytic zinc enzymes.

The factors governing the deprotonation ability of zinc(II)-water and zinc(II)-alcohol and nucleophilicity of the resultant zinc(II) hydroxide and zinc(II) alkoxide as complex models for zinc enzymes have been investigated through Hartree-Fock and density-functional theory methods with the 6-311++G(d,p) basis set. Our calculations showed that in these double-functionalized complexes (i.e., zinc complexes having both a zinc(II)-alcohol motif and a zinc(II)-water motif) zinc(II)-alcohol is preferred in deprotonation over zinc(II)-water (i.e., zinc(II)-alcohol has a much lower pK(a) than zinc-coordinated water in the same molecule). Natural bond orbital analysis revealed that zinc(II) alkoxides are more nucleophilic than their respective counterparts zinc(II) hydroxides. The analysis of the transition state in the transformation reaction from zinc(II) hydroxide species to zinc(II) alkoxide species indicates that zinc(II) alkoxides are the preferred deprotonated species not only thermodynamically but also kinetically. Further examination of the proposed mechanisms of the zinc(II) alkoxide-promoted transesterification path and the zinc(II) hydroxide-promoted hydrolysis path revealed the structures of the intermediates and energy diagrams in the reactions. These results, entitled double-functionalized complexes, for the first time, put a firm theoretical foundation of why the zinc(II)-alcoholic OH is a better model for hydrolytic zinc enzymes (having both stronger acidity and better nucleophilicity).

Alcohols↗

PubMed2003

The relations between neurite development and the subcellular structures of hippocampal neuron somata.

The relations between neurite development and the subcellular structures of the hippocampal neuron somata have been studied with atomic force microscopy (AFM). The conformation of the neuron was achieved by the synapse-like structures found by AFM scanning along a neurite of the cell. Hippocampal neuron somata were divided into two or three subcellular parts by one or two horizontal grooves. The upper parts increased while the middle and the lower parts decreased with the number and the length of the neurites and the formation of the neurosynapse-like structures. When neurites sufficiently developed, the middle parts were lost and the lower parts became very small. Mitosis inhibitors could prevent the formation of such subcellular structures of hippocampal neuron somata, which was accompanied by the loss of ability to form synapse-like structures. These results suggest that the upper parts are responsible for neuritogenesis while the middle and the lower parts only have indirect effect on it.

Animals↗

PubMed2003

Weight perception and psychological factors in Chinese adolescents.

PURPOSE: To investigate the pattern of weight perception and its relationship with psychological distress among Chinese adolescents. METHODS: A sub-cohort of 2179 healthy Chinese adolescents randomly selected from schools in Wuhan, China, including 1156 boys and 1023 girls 11 to 15 years of age was included in the current study. Weight, height, self-perceptions of weight status, depressive psychological symptoms including anxiety, depression, perceived peer isolation, and other constructs were measured by a structured questionnaire. A General Linear Model was used to compare psychological differences between actual and perceived weight groups. RESULTS: Perceived underweight was more likely to occur in boys, whereas perceived overweight was more likely to occur in girls. Compared with objective body weight status defined by the International Obesity Task Force (IOTF) and the World Health Organization (WHO) age- and gender-specific body mass index (BMI) cutoffs, girls were more likely to misperceive themselves as overweight, whereas relatively more boys misclassified their weight status as underweight. After adjusting for age, parents' educational attainment, and urban residence, perceived overweight boys and girls were more likely to experience anxiety and depression than perceived normal and underweight subjects (p <.05). Perceived overweight girls and perceived underweight boys experienced higher peer isolation than other groups (p <.05). Significant differences were not found in social support, school connectedness, trouble with teachers, and family disharmony among different weight-perception groups. CONCLUSIONS: Our results suggested distortion of weight perception was prevalent, and may have detrimental psychological influences in Chinese adolescents.

Adolescent↗

PubMed2002

Carboxyester hydrolysis catalyzed by a novel dicopper(II) complex with an alcohol-pendant macrocycle.

A novel hexaaza macrocycle bearing two hydroxyethyl pendants (L), 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22,2,2,2(11,14)]triaconta-1,11,13,24,27,29-hexaene, was synthesized as a potential binucleating ligand. The corresponding Cu(II) complex [Cu(2)LCl(2)]Cl(2) small middle dot5.5H(2)O was isolated as a blue crystal, triclinic, space group P with a= 9.4920(19) A, b = 4.783(3) A, c = 16.553(3) A, alpha = 63.87(3) degrees, beta = 86.10(3) degrees, gamma = 83.8(3) degrees, V = 2072.8(7) A(-3), Z = 2, R1 = 0.0658, and wR2 = 0.1839. Both Cu ions adopt the geometry of a distorted trigonal bipyramid in a pentacoordinated environment. A complexation study on the novel title complex has revealed that the alcoholic OH groups of the complex Cu(2)L exhibit an obvious acidity with rather low pK(a) values at 25 degrees C. The Cu(II)-bound alkoxides, which act as reactive nucleophiles toward the hydrolysis of 4-nitrophenyl acetate in 10% (v/v) CH(3)CN at 25 degrees C, with I = 0.10 (NaNO(3)) and pH 9.3, have shown a second-order rate constant, 0.41 +/- 0.02 M(-1) s(-1), a value that is approximately 10 times greater than the corresponding value for the mononuclear Cu(II) complex formed by a relatively simple tripodal ligand (L1). The pH-rate profile gave a sigmoidal curve. The possible catalytic mechanism has been proposed, and the reason for the high catalytic activity of the title complex has been discussed.

Journal Article↗

PubMed2002

Use of the fagerstrom tolerance questionnaire for measuring nicotine dependence among adolescent smokers in China: a pilot test.

The validity of the Prokhorov adolescent version of the Fagerstrom Tolerance Questionnaire (FTQ) has not been demonstrated in assessing nicotine dependence among Chinese adolescents in China. Data for 48 tenth-grader 30-day smokers in Wuhan, China (ages 16-17 years), were analyzed. Two different item scoring protocols were used, and self-reports of smoking were validated with saliva cotinine. When items were scored using Protocol A, Cronbach's alphas were .42 and .63 for the 7-item and the 4-item scales, respectively; while using Protocol B, the alphas were .67 and .79 for the 7-item and 4-item scales, respectively. The total FTQ scores were significantly associated with self-reported smoking and saliva cotinine levels. These results support the reliability and validity of the Prokhorov FTQ.

Adolescent↗