Biomedical subjects

Hua Wei

Publications and source records attributed to Hua Wei.

At least 19 recordsLinked to original sources

PubMed2025

Global burden of peripheral arterial disease (1990-2021), global burden trends and the impact of blood lead on peripheral arterial disease: a multidimensional analysis based on NHANES, GBD, and Mendelian randomization.

OBJECTIVE: Peripheral arterial disease (PAD) is a common cardiovascular disease that it is an important reason for the decline of patients' quality of life and the increase of family economic burden. To systematically evaluate the association between environmental lead exposure and peripheral arterial disease (PAD) and to characterize the global distribution of PAD disease burden, while exploring differences among regions with varying socioeconomic development. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES), the Global Burden of Disease (GBD) database, and genome-wide association studies (GWAS), we employed multivariable logistic regression to examine the link between lead exposure and PAD. Mendelian randomization (MR) was used to infer causality, and we analyzed PAD disease burden trends across countries of differing income levels. RESULTS: The burden on PAD patients worldwide shows a downward trend. In high SDI and high middle SDI countries, the burden of PAD gradually decreases, while in low middle SDI and low SDI countries, the burden of PAD gradually decreases. After adjusting for potential confounders, a significant dose-response relationship was observed between blood lead levels and PAD risk (OR = 1.04, 95% CI: 1.00-1.09). This association was more pronounced among males (OR = 1.07, 95% CI: 1.05-1.09), individuals with higher education (OR = 1.24, 95% CI: 1.16-1.32), and patients with hypertension (OR = 1.07, 95% CI: 1.05-1.09). MR analysis supported a causal link between lead exposure and PAD. Global trend analysis indicated that PAD burden is declining in high-income countries but rising in low-income regions, highlighting significant health inequities. CONCLUSION: Environmental lead exposure is significantly associated with increased PAD risk, with notable differences in population susceptibility. These findings underscore the necessity of environmental exposure control and tailored prevention strategies to enhance cardiovascular health worldwide.

Humans↗

PubMed2007

Synergistic effects of Lactobacillus rhamnosus ZDY114 and bovine colostrums on the immunological function of mouse in vivo and in vitro.

The synergistic effects of Lactobacillus rhamnosus and bovine colostrums on the immunity of mice in vivo and in vitro were investigated. Eight- to ten-week-old mice were used for two series experiments; one part of mice were immunocompromised by intraperitoneal injections of cyclophosphamide. In series I, immunocompromised mice were continuously fed with diet A (L. rhamnosus ZDY114 5 x 10(7) CFU/kg), B (bovine colostrums 0.5 g/kg), C (combination of diet A and B), and D (sterile saline) for 4 weeks and killed. Thereof, phagocytosis ratio and index of macrophage to chicken red blood cells in abdominal cavity and lymphocyte transformation rate were determined. In series II, both normal and immunocompromised mice were used to investigate the in vitro stimulation of lymphocyte proliferation by substances from the overnight culture of L. rhamnosus ZDY114 by the MTT colorimetric method. Compared with diet D, in the diet A, B, and C groups, the phagocytosis ratio of macrophages increased by 1.63, 1.54, and 2.3-fold, respectively, and the lymphocyte transformation ratio by 1.78, 2.08, and 2.35-fold, respectively. In vitro test with MTT showed that 3, 10, 50 kD substances from the overnight culture of L. rhamnosus ZDY114 significantly increased the growth of lymphocyte by 1.63, 1.53, and 1.34-fold, respectively. In conclusion, L. rhamnosus and bovine colostrums can enhance the functions of immune system supported by lymphocytes and peritoneal macrophages either in vivo or in vitro.

Animals↗

PubMed2007

Fabrication and characterization of a novel composite PNIPAAm hydrogel for controlled drug release.

Novel composite poly(N-isopropylacrylamide) (PNIPAAm) hydrogels, containing poly(N-isopropylacrylamide)-block-poly(methyl methacrylate) (PNIPAAm-b-PMMA) micelles for sustained drug delivery were prepared and characterized. Various amounts of thermal sensitive PNIPAAm-b-PMMA micelles were incorporated physically into thermosensitive PNIPAAm bulk hydrogel to form composite PNIPAAm hydrogels. The resultant composite hydrogels were characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) for morphological and thermal properties, respectively. The temperature dependence of swelling ratio and response kinetics upon heating or cooling were also investigated to understand the smart properties, that is, temperature-sensitive properties of the composite PNIPAAm hydrogels. These composite PNIPAAm hydrogels exhibited a faster shrinking kinetics than the one of pure PNIPAAm hydrogels. In addition, prednisone acetate, used as model drug, was loaded into the micelles incorporated to the composite PNIPAAm hydrogels. The controlled release behavior of the novel composite PNIPAAm hydrogels at different temperatures (22 and 37 degrees C) was examined.

Acrylic Resins↗

PubMed2006

A ventricular pressure-clamping system for the study of mechano-electrical feedback.

It is necessary to control the mechanical stimuli precisely in the studies of cardiac mechano-electrical feedback (MEF). In the present study a ventricular pressure-clamping system has been developed, which can be applied to isolated-perfused rabbit hearts. Controlled by a computer, this system not only can make the left ventricle follow a command defining the same pressure wave as that during a beating cycle under physiological condition, but also deliver mechanical stimuli with a proper waveform to the ventricle at a particular time phase. This system integrates multiple functions, including perfusing, pacing, recording of electrocardiogram and monophasic action potentials, and clamping and measuring of ventricular pressures in isolated-perfused hearts. Thus, it is a distinct system for investigating the phenomena and mechanisms of cardiac MEF at organ level.

Action Potentials↗

PubMed2006

Structural shifts of mucosa-associated lactobacilli and Clostridium leptum subgroup in patients with ulcerative colitis.

To understand the role of mucosa-associated microbiota in the pathogenicity of ulcerative colitis (UC), paired biopsies were obtained during colonoscopy from the ulcerated and nonulcerated gut mucosa of 24 patients with UC. Denaturing gradient gel electrophoresis analysis was employed to profile the composition of the dominant bacteria (16S rRNA gene V3 region) and three important groups: lactobacilli, the Clostridium leptum subgroup, and Bacteroides spp. The Pearson coefficient was used to estimate similarities between the bacterial communities of the paired biopsies for each patient. The average similarity values of bacterial composition between the paired samples were 94.8 +/- 3.8% for dominant bacteria, 59.9 +/- 26.1% for lactobacilli, 79.2 +/- 22.6% for the Clostridium leptum subgroup, and 88.7 +/- 16.4% for Bacteroides spp. The data revealed that lactobacilli and the Clostridium leptum subgroup were significantly different between the ulcerated and the nonulcerated regions. It also was noted that for lactobacilli, the composition varied significantly between biopsy sites irrespective of the location of UC in the gut but that the composition of the Clostridium leptum subgroup showed significant differences between paired samples from UC in the rectum and not in the left colon. Localized dysbiosis of the mucosa-associated intestinal microflora, especially for lactobacilli and the Clostridium leptum subgroup, may be closely related to UC.

Bacteroides↗

PubMed2006

Direct evidence that two cysteines in the dopamine transporter form a disulfide bond.

We have generated a fully functional dopamine transporter (DAT) mutant (dmDATx7) with all cysteines removed except the two cysteines in extracellular loop 2 (EL2). Random mutagenesis at either or both EL2 cysteines did not produce any functional transporter mutants, suggesting that the two cysteines cannot be replaced by any other amino acids. The cysteine-specific reagent MTSEA-biotin labeled dmDATx7 only after a DTT treatment which reduces disulfide bond. Since there are no other cysteines in dmDATx7, the MTSEA-biotin labeling must be on the EL2 cysteines made available by the DTT treatment. This result provides the first direct evidence that the EL2 cysteines form a disulfide bond. Interestingly, the DTT treatment had little effect on transport activity suggesting that the disulfide bond is not necessary for the uptake function of DAT. Our results and previous results are consistent with the notion that the disulfide bond between EL2 cysteines is required for DAT biosynthesis and/or its delivery to the cell surface.

Amino Acid Sequence↗

PubMed2006

Self-assembled, thermosensitive micelles of a star block copolymer based on PMMA and PNIPAAm for controlled drug delivery.

A four-arm star block copolymer, comprised of a hydrophobic PMMA arm and an average of three hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) arms were designed and synthesized from the molecular level. The amphiphilic star block copolymer is capable of self-assembling into micelles in water, which was confirmed by FT-IR, (1)H NMR and fluorescence spectroscopy. Transmission electron microscopy images showed that these nanoparticles were regularly spherical in shape. The micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PNIPAAm at around 34 degrees C, observed by optical absorbance measurements. Resulted polymeric micelles loaded with prednisone acetate showed a much improved drug release behavior due to the special micellar structure.

Acrylic Resins↗

PubMed2006

Self-assembled thermo- and pH responsive micelles of poly(10-undecenoic acid-b-N-isopropylacrylamide) for drug delivery.

An amphiphilic AB block copolymer composed of poly(N-isopropylacrylamide) as a hydrophilic segment and poly(10-undecenoic acid) as a hydrophobic segment was synthesized. Cytotoxicity study of this copolymer exhibited no significant cytotoxicity. The lower critical solution temperature (LCST) of the copolymer was 30.8 degrees C, as determined by the turbidity method. The block copolymer forms micelles in an aqueous medium at the temperature lower than the LCST. Transmission electron microscopy images showed that these micelles were regularly spherical in shape. The micelle size determined by size analysis was around 160 nm. The anti-inflammation drug prednisone acetate was incorporated into the micelles and the release profiles of prednisone acetate showed a dramatic thermoresponsive switching behavior and a unique pH responsive behavior. Moreover, the pH responsive behavior was in relation to the thermoresponsive behavior. That is, the micelles were not pH sensitive at the temperature below the LCST, but the aggregates were pH sensitive at the temperature above the LCST. Based on these results, the thermo- and pH responsive micelles have great potential to be a novel carrier for drug delivery.

Acrylic Resins↗

PubMed2006

Optimizing imaging polarimeters constructed with imperfect optics.

Imaging polarimeters are often designed and optimized by assuming that the polarization properties of the optics are nearly ideal. For example, we often assume that the linear polarizers have infinite extinction ratios. It is also usually assumed that the retarding elements have retardances that do not vary either spatially or with the angle of incidence. We consider the case where the polarization optics used to develop an imaging polarimeter are imperfect. Specifically, we examine the expected performance of a system as the extinction ratio of the diattenuators degrades, as the retardance varies spatially, and as the retardance varies with incidence angle. It is found that the penalty in the signal-to-noise ratio for using diattenuators with low extinction ratios is not severe, as an extinction ratio of 5 causes only a 2.0 dB increase in the noise in the reconstructed Stokes parameter images compared with an ideal diattenuator. Likewise, we find that a system can be optimized in the presence of spatially varying retardance, but that angular positioning error is far more important in rotating retarder imaging polarimeters.

Journal Article↗

PubMed2006

Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter.

There are three known high-affinity targets for cocaine: the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). Decades of studies support the dopamine (DA) hypothesis that the blockade of DAT and the subsequent increase in extracellular DA primarily mediate cocaine reward and reinforcement. Contrary to expectations, DAT knockout (DAT-KO) mice and SERT or NET knockout mice still self-administer cocaine and/or display conditioned place preference (CPP) to cocaine, which led to the reevaluation of the DA hypothesis and the proposal of redundant reward pathways. To study the role of DAT in cocaine reward, we have generated a knockin mouse line carrying a functional DAT that is insensitive to cocaine. In these mice, cocaine suppressed locomotor activity, did not elevate extracellular DA in the nucleus accumbens, and did not produce reward as measured by CPP. This result suggests that blockade of DAT is necessary for cocaine reward in mice with a functional DAT. This mouse model is unique in that it is specifically designed to differentiate the role of DAT from the roles of NET and SERT in cocaine-induced biochemical and behavioral effects.

Animals↗

PubMed2006

Topical ketanserin attenuates hyperalgesia and inflammation in arthritis in rats.

We investigated effects of topical application of ketanserin, a 5-HT2A receptor antagonist, on hyperalgesia and edema in the arthritic rat, a chronic pain model with inflammation. Unilateral, but not bilateral, arthritis was induced with intra-articular injection of a mixture of kaolin and carrageenan in one side, as indicated by the shortened paw withdrawal latency and an increase in the circumference of the knee joint. Topical application of ketanserin onto skin over the arthritic joint delivered in a mixture of gelatin, glycerol and kaolin produced dose-dependent attenuation of nociceptive and inflammatory effects resulting from intra-articularly injected kaolin/carrageenan. One and 3% ketanserin produced significant or even complete anti-hyperalgesia, as well as a remarkable anti-inflammatory effect (50-70% reduction of edema) while 0.3% ketanserin and placebo failed to produce any effect. Moreover, the effects of ketanserin were maintained for 13 days without decline. In contrast, 3% ketanserin applied to skin of the knee joint on the non-inflamed side for 2 weeks did not alter nociceptive thresholds of the paw and the size of the knee joint in both the inflamed and non-inflamed limbs. These results indicate that 5-HT2A receptors in the periphery play a significant role in the maintenance and/or development of inflammatory pain. The present study suggests that topical ketanserin is a promising direction for potential clinical exploration to relieve established hyperalgesia and inflammation in arthritis without adverse effects and tolerance.

Administration, Topical↗

PubMed2006

Molecular profiling of the Clostridium leptum subgroup in human fecal microflora by PCR-denaturing gradient gel electrophoresis and clone library analysis.

A group-specific PCR-based denaturing gradient gel electrophoresis (DGGE) method was developed and combined with group-specific clone library analysis to investigate the diversity of the Clostridium leptum subgroup in human feces. PCR products (length, 239 bp) were amplified using C. leptum cluster-specific primers and were well separated by DGGE. The DGGE patterns of fecal amplicons from 11 human individuals revealed host-specific profiles; the patterns for fecal samples collected from a child for 3 years demonstrated the structural succession of the population in the first 2 years and its stability in the third year. A clone library was constructed with 100 clones consisting of 1,143-bp inserts of 16S rRNA gene fragments that were amplified from one adult fecal DNA with one forward universal bacterial primer and one reverse group-specific primer. Eighty-six of the clones produced the 239-bp C. leptum cluster-specific amplicons, and the remaining 14 clones did not produce these amplicons but still phylogenetically belong to the subgroup. Sixty-four percent of the clones were related to Faecalibacterium prausnitzii (similarity, 97 to 99%), 6% were related to Subdoligranulum variabile (similarity, approximately 99%), 2% were related to butyrate-producing bacterium A2-207 (similarity, 99%), and 28% were not identified at the species level. The identities of most bands in the DGGE profiles for the same adult were determined by comigration analysis with the 86 clones that harbored the 239-bp group-specific fragments. Our results suggest that DGGE combined with clone library analysis is an effective technique for monitoring and analyzing the composition of this important population in the human gut flora.

Adult↗

PubMed2006

Intrapulmonary channel for one-stage correction of aortic arch obstruction.

There are several methods of surgical repair of aortic coarctation or interruption; the optimal technique is still controversial. The purpose of this study was to assess a new surgical method: intrapulmonary channel for one-stage repair of aortic coarctation or interruption associated with intracardiac anomalies. Between 1993 and 1995, 4 patients with aortic coarctation or interruption and intracardiac anomalies received one-stage surgical correction. Their ages ranged from 5 to 26 years (mean, 16 years). The aortic arch lesions were preductal coarctation in 2, and type B interruption in 2. Coexisting anomalies consisted of patent ductus arteriosus in 4, ventricular septal defect in 3, and aortopulmonary window in 1. An intrapulmonary channel was constructed in all patients, and co-existing anomalies were corrected simultaneously. There was no hospital death or late mortality. A cerebral complication occurred in one patient because of air embolism. Mean follow-up was 9.5 years (range, 8.5-11.5 years). There was no evidence of recoarctation or late aneurysm formation. For selected patients with aortic coarctation or interruption and intracardiac anomalies, an intrapulmonary channel might be an option for one-stage correction.

Adolescent↗

PubMed2005

Molecular cloning and functional characterization of the dopamine transporter from Eloria noyesi, a caterpillar pest of cocaine-rich coca plants.

Cocaine is produced by coca plants as a chemical defense to deter feeding by insects. It has been shown that cocaine sprayed on tomato leaves reduces insect feeding, causes abnormal behaviors at low doses and kills feeding insects at doses equivalent to that in coca leaves [Nathanson, J.A., Hunnicutt, E.J., Kantham, L., Scavone, C., 1993. Cocaine as a naturally occurring insecticide. Proc. Natl. Acad. Sci. U. S. A. 90, 9645-9648.]. Most insects avoid coca leaves except the larvae of Eloria noyesi, a caterpillar pest of coca plants, which feeds preferentially on coca leaves. In the current study, we cloned and characterized the dopamine transporters (DATs) from caterpillars of E. noyesi (enDAT) and the silkworm, Bombyx mori (B. mori, bmDAT). The two insect DATs shared 88% amino acid sequence homology and functional similarity. Although enDAT and bmDAT showed the highest affinity for dopamine among endogenous amines, they were more sensitive to mammalian NET-selective inhibitors than to mammalian DAT-selective inhibitors. Despite a high cocaine content in the food source for E. noyesi, cocaine sensitivity of enDAT was similar to that of bmDAT, suggesting that mechanisms other than DAT insensitivity to cocaine, such as cocaine sequestration, might be responsible for cocaine resistance in this species. Given the significant differences in pharmacological profile from mammalian DATs, invertebrate DATs provide excellent tools for identifying regions and residues in the transporters that contribute to high-affinity binding of psychostimulants and antidepressants.

Amino Acid Sequence↗

PubMed2005

Self-assembled thermoresponsive micelles of poly(N-isopropylacrylamide-b-methyl methacrylate).

To achieve a combination of spatial specificity in a passive manner with a stimuli-response targeting mechanism, a temperature-responsive polymeric micelle was prepared using block copolymers of poly(N-isopropylacrylamide-b-methyl methacrylate) (PNIPAAm-b-PMMA). The critical micelle concentration of amphiphilic block copolymers in aqueous solution was determined by fluorescence spectroscopy using pyrene as a fluorescence probe. Transmission electron microscopy images showed that these nanoparticles were regularly spherical in shape. Micelle size determined by size analysis was around 190 nm. The micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PNIPAAm at around 33 degrees C, observed by optical absorbance measurements and dynamic light scattering (DLS). The anti-inflammation drug prednisone acetate was loaded as the model drug in the polymeric nanoparticles. In vitro release behavior of prednisone acetate was investigated, which showed a dramatic thermoresponsive fast/slow switching behavior according to the temperature-responsive structural changes of a micellar shell structure. The reversible and sensitive thermoresponse of this micelle might provide opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia.

Acrylamides↗

PubMed2005

A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada.

The transcriptional activity of many sequence-specific DNA binding proteins is directly regulated by posttranslational covalent modification. Although this form of regulation was first described nearly two decades ago, it remains poorly understood at a mechanistic level. The prototype for a transcription factor controlled by posttranslational modification is E. coli Ada protein, a chemosensor that both repairs methylation damage in DNA and coordinates the resistance response to genotoxic methylating agents. Ada repairs methyl phosphotriester lesions in DNA by transferring the aberrant methyl group to one of its own cysteine residues; this site-specific methylation enhances tremendously the DNA binding activity of the protein, thereby enabling it to activate a methylation-resistance regulon. Here, we report solution and X-ray structures of the Cys-methylated chemosensor domain of Ada bound to DNA. The structures reveal that both phosphotriester repair and methylation-dependent transcriptional activation function through a zinc- and methylation-dependent electrostatic switch.

Crystallography, X-Ray↗

PubMed2005

Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase.

Type IIA DNA topoisomerases play multiple essential roles in the management of higher-order DNA structure, including modulation of topological state, chromosome segregation, and chromatin condensation. These diverse physiologic functions are all accomplished through a common molecular mechanism, wherein the protein catalyzes transient cleavage of a DNA duplex (the G-segment) to yield a double-stranded gap through which another duplex (the T-segment) is passed. The overall process is orchestrated by the opening and closing of molecular "gates" in the topoisomerase structure, which is regulated by ATP binding, hydrolysis, and release of ADP and inorganic phosphate. Here we present two crystal structures of the ATPase domain of human DNA topoisomerase IIalpha in different nucleotide-bound states. Comparison of these structures revealed rigid-body movement of the structural modules within the ATPase domain, suggestive of the motions of a molecular gate.

Adenosine Diphosphate↗

PubMed2005

Driver's views and behaviors about safety in China--what do they NOT know about driving?

Driving safety has become an extremely severe problem in China due to rapid motorization. Unless more effective measures are taken, the fatality risk and the total fatalities due to road traffic accidents are expected to continue to increase. Therefore, focus group discussions were conducted to explore driver attitudes and safe driver characteristics. The results were then compared with a similar study conducted with US drivers. Although similarities were found, differences were of more importance. The Chinese drivers concentrate more on driving skills and capabilities, whereas the US drivers concentrate more on practical safe driving guidelines. Then direct field observations were conducted for the Chinese drivers to empirically investigate the issues discovered. The use of safety belts, running lights, headlights, and turn signals were observed to investigate the drivers' behaviors. Results show that the safety belt use ratio is about 64%, running light use is nearly zero during rainy and snowy weather, headlights use after sunset is substantially delayed, and only about 40% of drivers use turn signals to indicate their intention to change lanes. These findings indicate that the authorities need to take appropriate countermeasures to change the views of the Chinese drivers regarding driving safety and their unsafe driving behaviors. Improvement of training content and methods as well as police enforcement would be recommended.

Accidents, Traffic↗