Association of RANTES gene polymorphisms with susceptibility to childhood asthma: A meta-analysis.

BACKGROUND: Previous investigations have illustrated that regulated upon activation, normal T-cell expressed and secreted (RANTES) polymorphisms are linked to susceptibility to childhood asthma; nevertheless, the findings continue to be controversial. Accordingly, we conducted the present meta-analysis to clarify the impact of RANTES genetic polymorphisms (-403G/A and -28C/G) on childhood asthma vulnerability. METHODS: A search for published literature was performed using the PubMed, EMBASE, Chinese National Infrastructure, Cochrane Library, Scopus, Web of Science, and WanFang databases and selected in the form of PICOS (participants, interventions, comparisons, outcomes, and study design) to identify all eligible research works. The link between RANTES genetic polymorphisms and childhood asthma susceptibility was evaluated by a pooled odds ratio with a 95% confidence interval. RESULTS: In total, 14 case-control studies were included in the analysis. No significant association existed between risk of childhood asthma and the -403G/A polymorphism subjected to any genetic framework in the overall population. In the stratified analysis, according to ethnicity, the -403G/A polymorphism was linked to augmented vulnerability to childhood asthma in Caucasians (allelic model: odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.04-2.57, P = .034; codominant model: OR = 2.20, 95% CI = 1.28-3.78, P = .004; dominant model: OR = 1.78, 95% CI = 1.01-3.13, P = .047; and recessive model: OR = 1.92, 95% CI = 1.11-3.30, P = .019). For the stratified analysis by atopic status, the -403G/A polymorphism was linked to augmented childhood asthma in the codominant (OR = 1.39, 95% CI = 1.02-1.91, P = .037) and dominant models (OR = 1.43, 95% CI = 1.02-2.01, P = .037) in atopic asthma. For the -28C/G polymorphism, there was a significant association between childhood asthma and the -28C/G variant (allelic model: OR = 1.33, 95% CI = 1.08-1.65, P = .009; codominant framework: OR = 2.14, 95% CI = 1.47-3.10, P < .001; dominant model: OR = 1.44, 95% CI = 1.07-1.93, P = .017; and recessive model: OR = 2.08, 95% CI = 1.44-3.02, P < .001). Stratified analysis based on ethnicity and the -28C/G polymorphism was linked to augmented vulnerability to childhood asthma in Asian and Caucasian populations. For the subgroup analysis by atopic status, no association was found in atopic and non-atopic asthma. CONCLUSION: The present meta-analysis indicated that the RANTES -403G/A and -28C/G polymorphisms contributed to the development of childhood asthma.

[Two-dimensional synchronous correlation spectroscopy for probing fluorescence energy transfer].

In the present paper, the authors developed a new approach by constructing two-dimensional (2D) UV-Vis/fluorescence heterogeneous synchronous spectrum based on the orthogonal sample design scheme (OSD) developed in our previous works to characterize energy transfer among different lanthanide ions during the luminescence process. The authors use the EuCl3-NdCl3 system as an example. The preliminary experimental results on the 2D synchronous spectra of EuCl3-NdCl3 mixture solutions have demonstrated that cross peaks can be observed among the UV-Vis absorption bands from Nd3+ and fluorescence emission bands from Eu3+. The cross peaks in the 2D synchronous spectra of EuCl3-NdCl3 mixture solutions manifested the interaction between the fluorescence emission from Eu3+ and UV-Vis absorbance from Nd3+, and therefore gives out experimental evidences for the occurrence of energy transfer between Eu3+ and Nd3+ ions. The cross peaks are not from the interaction between the solvent, water, and the solute, Eu3+ or Nd3+ ions. Mathematical analysis performed on 2D synchronous spectra using variable concentration as an external perturbation shows that the orthogonal sample design scheme is indispensable in removing the interfering cross peaks in 2D synchronous spectra. In fact, if the authors detect, respectively, the fluorescence emission spectra of pure Eu3+ solutions and the UV-Vis absorbance spectra of pure Nd3+ solutions, then use these spectra data to construct a series of synthesized spectra of an assumed mixture solution in which Eu3+ and Nd3+ are not mixed together, because Eu3+ and Nd3+ ions are spatially separated, there are no intermolecular interactions that should have occurred. Therefore, there are no cross-peaks that can be observed in the comparative 2D synchronous spectra. The cross peaks in 2D synchronous correlation spectra gives out a new approach to characterizing energy transfer among different lanthanide ions during the luminescence process.

[Fluorescence spectra and protonation of ofloxacin in strong acidic solutions].

Fluorescence and UV-Vis spectra of ofloxacin (OFL) in sulfuric acid were studied. In the present paper, a new protonation state of OFL was observed. In hydrochloric acid, OFL produced bright green fluorescence upon excitation by UV radiation. The maximal emission wavelength of OFL is about 505 nm. However, OFL produces violet fluorescence when dissolved in concentrated sulfuric acid. The maximal emission wavelength changes into 400 nm. Further analysis demonstrated that the above changes arise from the variation of protonation states of OFL molecule. In dilute sulfuric acid, OFL accepted one proton, resulting in a protonation state that is similar to the OFL molecule dissolved HCl solution. The corresponding fluorescence band occurs at 505 nm. In concentrated sulfuric acid solution, OFL might accept additional protons. As a result, the size of the conjugated system is reduced and the fluorescence band exhibits a blue shift. In sulfuric acid of moderate concentrations, two bands at 505 and 400 nm respectively were found in the fluorescence emission spectra, indicating that OFL in two different protonation states coexists in the solution. In addition, both excitation band in excitation spectra and absorption bands in UV-Vis spectra exhibit red-shifted with the decrease in the concentration of sulfuric acid. Based on the above result, OFL can be used as a spectral probe to reflect the variation of H+ in strong acid environment.

[Study on malignant and normal rectum tissues using IR and 1H and 31P NMR spectroscopy].

In the present paper, NMR spectroscopy, an effective tool to detect the variation in, molecular structure and changes in chemical composition of metabolites in tissues, was used to study the differences between malignant and normal tissues from rectum. 1H and 31P spectra of seven malignant rectum tissue samples and five normal control tissues were investigated by using a 300 M NMR spectrometers and compared with the results of the infrared spectra of normal and malignant rectum organ tissues. The results indicate that the 1H and 31P spectra of rectum cancer tissues are significantly different from those of the normal controls and most differences present in the form of variation in relative intensities of the characteristic peaks of various metabolites. Systematic differences in the NMR spectra between malignant tissues and normal controls are as follows: in the 1H NMR spectra, differences lie in fatty acids with the concentration of fatty acid decreasing significantly in malignant tissues. In the 31P NMR spectra, differences lie in phospholipid, with the chemical shift of phospholipid decreasing significantly in malignant tissues. This phenomenon may reflect the fact that the activity of protein synthesis is enhanced in cancerous tissues. The difference in the chemical shift of phospholipid between normal rectal tissue and malignant tissue may be considered as a detection criterion. Therefore, the above spectral variations in 31P NMR spectra may be utilized as a potential tool to diagnose rectum cancer.

[Study of malignant and normal tissues of the rectum using NMR spectroscopy].

In the present paper, NMR spectroscopy, an effective tool to detect the variation in molecular structure and changes in chemical composition of metabolites in tissues, was used to study the differences between malignant and normal tissues from rectum. 1H spectra of four malignant rectum tissue samples and two normal control tissues were investigated by using a 500M NMR high-resolution magic angle spinning magnetic resonance spectrometers (HR-MAS NMR). The results indicate that the 1H HR-MAS spectra of rectum cancer tissues are significantly different from those of the normal controls and most differences are presents in the form of variation in the relative intensities of the characteristic peak of various metabolites. In order to characterize the variation in the relative intensities in a quantitative manner, the intensity of the methyl peak of fatty acid at 0.88 was utilized as inner standard. Systematic differences between NMR spectra of malignant tissue and normal controls are as follows: (1) The concentration of amino acid increases significantly in malignant tissues, since the relative intensities of characteristic peaks of amino acid including valine, isoleucine, leucine, lysine, glutamate, glutamine, and aspartate are stronger in the NMR spectra of the malignant tissues. This phenomenon may reflect the fact that the activity of protein synthesis is enhanced in cancerous tissues. (2) The intensities of the characteristic peaks of lactic acid in malignant tissues are higher than those from normal controls. This may be related to the nature of anaerobic metabolism activity in malignant tissues. (3) The level of choline and its derivatives, taurine and creatine, increases significantly in malignant tissues, suggesting that the metabolic activity of malignant tissues changes. (4) In the spectral region between 4.5 and 10, observable changes occur on the peaks for unsaturated fatty acid and nuclear acids. Therefore, the above spectral variations in high resolution magic angle spinning NMR spectroscopy may be utilized as a potential tool to diagnose rectum cancer.

[Progress in nuclear magnetic resonance spectroscopy for early cancer diagnosis].

Based on more than 100 references, the present paper reviews the progress in the application of nuclear magnetic resonance (NMR) spectroscopy, an effective method to study the variation in chemical composition and molecular structure in biological samples for early diagnosis of cancer at molecular level. In the past several decades, numerous works have demonstrated that NMR spectroscopy may be developed into a sensitive diagnosis method to detect cancer in early stage. Because of the rapid development of NMR spectroscopic techniques, it becomes possible to record NMR spectra of biological samples in both in-vitro and in-vivo manner. Systematic spectral differences between biological samples from cancer patients and normal controls can be observed from both liquid-state and solid-state 1H, 31P NMR spectra and used to reflect the changes in metabolic behavior of malignant tissues. This paper has summarized NMR spectroscopic investigation on biological fluid, cultured cancerous cells, resected tissues, as well as in-vivo malignant tissues by using various advanced NMR techniques including recently developedhigh-resolution magic angle spinning (HR-MAS)and magnetic resonance spectroscopy and imaging (MRSI) methods. First, characteristic peaks, which are related to choline, phosphocholine (PC) and glycerophosphocholine, can be observed in both 1H and 31P NMR spectra of biological fluid samples from cancer patients. These results indicate that alternation in the metabolic pattern occurs with the progression of cancer. The research on cultured cells by using NMR spectroscopy showed that the signal of various phospholipids and their metabolites such as PME increased significantly in cultured cancer cells. For resected tissues, two methods can be utilized. The first one is to investigate the tissues directly by using HR-MAS spectroscopy. The second method is to extract various metabolites with various solvents such as CHCl3/methonal mixtures, HClO4 solutions, etc. and then analysis of the extracted solutions is performed using conventional liquid NMR spectroscopy. Significant differences on the content of various amino acids, metabolites of phospholipids, can be observed between malignant tissues and normal controls in NMR spectra. Recently, MRSI that can acquire 1H-NMR spectra of suspected tissues during the process of MRI diagnosis is available. The approach makes it possible for the surgeons to judge whether the suspected tissues are malignant or not before surgical operation. The above results demonstrate that NMR spectroscopy possesses bright perspective in diagnosing cancers and differentiating different types of cancers based on the metabolic behavior of cancerous tissues.

[A study on the NMR spectrum of methyl-ofloxacin].

Ofloxacin ((+/-)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2, 3-dihydro-7H-pyrido[1,2,3-de]-1, 4-benzoxazine-6-carboxylic acid) is a totally synthetic fluoroquinolone antimicrobial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and atypical pathogens such as Mycoplasma, Chlamydia and Legionella. Even though it is widely used for the treatment of gastrointestinal, pulmonary, urinary, and other infections, the comprehensive mechanism of action at molecular level has not been known so far. It is very important to understand the structural characteristics of the drug and the effects that are caused by the environments. With the purpose of deeply investigating the structure of Ofloxacin, an analog of Ofloxacin, Methyl-Ofloxacin (Me-OFL), was synthesized by methylation of 4'N in piperazine ring from Ofloxacin with CH3I. Then appropriate Me-OFL was dissolved in DC1/D2O and NaOH/D2O to prepare corresponding acidic and alkaline solutions. Systematic NMR spectroscopic investigation on Me-OFL in both acidic and alkaline solution was conducted using quantitative 1H and 13C spectra, DEPT, HSQC together with HMBC techniques. The spectra were recorded with Bruker AM-300 spectrometer and DRX500 spectrometer. Chemical shifts have been given in values referred to dioxane (deltaJ = 3.7, deltac = 67.8). Complete assignments on 1H and 13C signals of Me-OFL were obtained in different pH environments where the coupling constant between 13 C and 19F was found to be very helpful for the assignment of aromatic 13C signals. A comprehensive comparison between the 1H, 13C chemical shifts, together with the structural transformation in acidic and alkaline solutions was made and discussed in details. Due to the formation of hydrogen bond between COOH and C==O, the COOH and aromatic ring are in the same plane. As a result, a weak O...H--C hydrogen bond forms between C==O from the carboxyl group and 5-H from aromatic ring. In alkaline solution, the deprivation of H+ from COOH destroys not only the hydrogen bond between COOH and carbonyl group but also the weak hydrogen between the C==O from COOH and 5H. As a result, the 5H exhibited remarkable shift toward high field (1.02). Meanwhile, the chemical shift of 6C, 13C, 7C, 15C also exhibited remarkable shift to low field at 12. 04, 7.46, 4.33, 2.88 respectively. Such variations were related to the changes of p electrons from carboxyl group caused by the transformation between the carboxyl group and the carboxylate group in different pH environments. Comparison of deltaH, deltac data between Me-OFL and OFL in acidic solution and OFL in alkaline was made. In Me-OFL acidic solution, the chemical shift of 3'C, 5'C, 7'C, 8'C also exhibited remarkable shift to low field at 6.66-7.32 respectively, the chemical shift of 2'C and 6'C also exhibited remarkable shift to high field 6.04. In OFL acidic solution, the chemical shift of 2'C, 3'C, 5'C, 6'C, 7'C, 8'C also exhibited remarkable shift to high field within 2.39, Comparison between the protonation and the methylation on the 4'N atom from the piperazine ring was also made. The distribution of positive charge also showed difference. When protonation occurred on the piperazine ring, the positive charge was on the proton connected with 4'N. However, if methylation occurred, the positive charge is on the 4'-N atom.

[Studies on coordination and hydrogen bond intermolecular interaction using 1D & 2D FTIR spectroscopy].

Two-dimensional (2D) correlation spectroscopy is a powerful method to study the intermolecular interactions between different molecules/functional groups. In the present paper, variable concentrations were selected to construct 2D synchronous spectrum for studying the weak intermolecular interactions in solutions. Mathematical analysis performed on 2D synchronous spectra using variable concentration as an external perturbation shows that the "Orthogonal Sample Design Scheme" is necessary for eliminating the interfering cross peaks in 2D synchronous spectra. The authors prepared four mixed-solutes-solutions whose concentration series satisfy the "Orthogonal Sample Design Scheme" for each chemical system and the consequent 2D synchronous spectrum was calculated from the corresponding four 1D spectra. Thus, by 1D & 2D FTIR spectra together with solid grinding reaction, the intermolecular interactions in two chemical systems (Sodium 2-Aminobenzoate/NdCl3 in aqueous solution, and 2-ethylhexyl phosphonic acid mono 2-ethylhexyl ester (PC88A)/Naphthenic Acid (NA) in heptane solution) were studied, where the intermolecular interactions only induce subtle spectral variations in conventional 1D spectra. First, the cross peaks between f-f transition bands of Nd3+ ion at 521, 574, 741, 795 and 865 nm and pi-pi transition band of Sodium 2-Aminobenzoate at 308 nm in 2D synchronous spectrum confirm the coordination interaction between Sodium 2-Aminobenzoate and Nd3+. Solid grinding reaction between Sodium 2-Aminobenzoate and NdCl3 and FTIR spectra of the product indicate that the vibration bands of amino, carboxyl groups from sodium 2-aminobenzoate show considerable changes. Based on the spectral result above, a conclusion is drawn that Nd3+ can coordinate with Sodium 2-Aminobenzoate by amino and carboxyl groups. Second, the cross peaks between POH stretching band of PC88A at 983 cm(-1) and COOH stretching band of NA at 1 710 cm(-1) in 2D spectra confirm the interaction between PC88A and NA. Subtraction spectrum demonstrates that when PC88A is mixed with NA in heptane solution, and P=O stretching band of PC88A shifts from 1 199 to 1161 cm(-1), and POH stretching band shifts from 983 to 965 cm(-1). Based on the spectral result above, a conclusion was made that PC88A and NA can interact with each other by forming new assemblies with POH and COOH groups.

[Study on the malignant and normal rectum tissues using 1H NMR spectroscopy].

Cancer is one of the most serious diseases, a threat to human body's health and a causes of death. The early diagnosis of cancer and timely therapy is significant for improving the survival. Owing to the complexity and limit of conventional medical diagnosis, misdiagnosis of ten occurs in many cases. NMR spectroscopy is an effective technique for characterizing molecular structure and component changes. The component and structural information of nucleic acid, protein, lipid and glucide in the biologic tissues can also be distinguished from NMR data. In the present paper, a new method was developed for the diagnosis of tumor using the advanced physical chemistry (NMR) and biomedicine technique. Nine rectum tissue samples and their corresponding normal tissues of rectum were measured using NMR spectroscopy. Each tissue sample obtained from the operation was quickly separated into two parts averagely: one was dipped into 10% formalin solution and prepared for conventional pathological examination; the other was preserved in liquid nitrogen for further NMR detection. Before NMR detection, the corresponding sample was thawed at room temperature and was dipped into 0.5 mL D2O. Dioxane was used as external reference. The obtained NMR spectra were analyzed and compared by OMNIC5.0 and SPSS 11.0 Software. The differences of metabolite in the tissues samples were studied and a method for the diagnosis of cancer using NMR data was initially explored. The result indicates that the 1H NMR spectra of rectum cancer tissues are significantly different from those of their corresponding normal rectum tissues. This is shown by the differences in the integral area ratio at characteristic peak region. A0.9/A3.0, A1.3/A3.0, A2.0/ A3.0, A1.3/A0.9 and A4.1/A3.0 of the normal rectum tissues are higher than those of their corresponding cancer tissues, but A3.2/A3.0 is lower than that of the rectum cancer tissues. From the above result it is concluded that the concentration of fatty acid, inositol and lactate is lower in the rectum cancer tissues than in the normal tissues, while that of choline bases compounds is higher. The NMR judgments were also consistent with the pathological examination results. So the NMR spectra may be developed into a method of early diagnosing rectum cancer through these differences.

[Effect of artemisinin on ischemia/reperfusion injury of isolated rat myocardium].

OBJECTIVE: To observe the effect of artemisinin on the ischemia/reperfusion injury of the iisolated rat myocardium and to preliminarily study the possible mechanism. METHOD: Fifty Wistar rats were randomly divided into 5 groups: a control group, an ischemia/reperfusion (I/R) group, and 3 artemisinin (AS) groups (10, 100, 1000 micromol x L(-1)), 10 rats in each group. Ischemia/reperfusion injury of the isolated rat myocardium was induced by a Langendorff system. The electrocardiogram, the cardiac functional parameters, coronary flow, and the activities of LDH (lactate dehydrogenase), CPK (creatine phosphokinase), SOD (superoxide dis-mutase) and the level of malondiadehyde (MDA) in myocardial tissue, and the myocardial ultrastructures were investigated. RESULT: AS (10,100 micromol x L(-1)) could significantly improve the index of the myocardial function (+/- dp/dt(max), LVSP) after the ischemia/reperfusion, increase the coronary flow, decrease the leakage of LDH and CPK, and increase the SOD activity and decrease the MDA level in cardiac tissues, and alleviate the myocardial ultrastructure injury. But, AS (1000 micromo x L(-1)) did not have the above effects. CONCLUSION: AS (10, 100 micromol x L(-1)) alleviate the myocardial ischemia/reperfusion injury in rats. The mechanism may be related to its functions of antioxidation and scavenging free radicals.

[Protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism in mice].

This study is to investigate the protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism. The cardiotoxicity was induced by intraperitoneal injection of adriamycin (ADR) at a single dose of 20 mg x kg(-1). Mice were randomly divided into 5 groups (n=20): normal control group, ADR 20 mg x kg(-1) group, quercetin (50, 100, and 200 mg x kg(-1) groups, intragastric administration, once a day, for 7 days before ADR administration). The health conditions, electrocardiogram, activity of iNOS, SOD and LDH, levels of NO and MDA in serum or tissue homogenate, the ultrastructure and the expression of p53 protein in cardiac tissue of mice were observed. Compared with the normal control group, ADR decreased the amplitude of ECG's R wave (P < 0.001), increased the incidence of arrhythmia (to 60%), injured myocardial ultrastructure, increased the activity of LDH and iNOS, and levels of NO and MDA, decreased the activity of SOD, and increased the expression of p53 (P < 0.001). Compared with ADR 20 mg x kg(-1) group, the quercetin decreased the levels of LDH, iNOS, NO and MDA, increased the activity of SOD, restored the amplitude of R wave, decreased the incidence of arrhythmia and p53 expression (P < 0.001 , P < 0.01 or P < 0.05), and markedly reduced the myocardial ultrastructure injury. Quercetin had protective effect against adriamycin-induced cardiotoxicity. The mechanism may be related to its enhancing myocardial SOD activity, decreasing iNOS activity and inhibiting myocardial apoptosis.