PubMed Health⌕ Search

Biomedical subjects

Li Hua

Publications and source records attributed to Li Hua.

13 recordsLinked to original sources
PubMed2025

Altered mitochondrial DNA methylation in blood in individuals with mild cognitive impairment.

BACKGROUND: Previous studies reported that altered mitochondrial methylation in Alzheimer's disease (AD), however, whether epigenetic modifications in mitochondrial genomes contribute to preclinical AD remains unclear. This study aimed to investigate mitochondrial methylation changes in individuals with cognitive decline. RESEARCH DESIGN AND METHODS: We examined whole mitochondrial genome methylation in 50 individuals with mild cognitive impairment (MCI) and 50 individuals without MCI, using bisulfite amplicon sequencing, assessing methylation at 366 Cytosine-guanine oligodeoxynucleotide (CpG) sites. RESULTS: We found the overall methylation level of mitochondrial DNA (mtDNA) in each subject was relatively low, ranging from 0% to 15%. Global methylation was significantly higher in individuals with cognitive decline compared to controls (3.86% vs. 3.46%, p = 0.037), with 34 differentially methylated CpG sites identified. Methylation differences (MD) between cognitive decline individuals and controls were 22.93 ± 5.60% at chrM6465 (Q = 0.013), 12.55 ± 3.02% at chrM9612 (Q = 0.013), 11.45 ± 3.88% at chrM11762 (Q = 0.159) and 11.03 ± 3.88% at chrM11766 (Q = 0.172), respectively, while the level of MD at chrM15812 was -13.11 ± 4.31% (Q = 0.159) after Benjamini-Hochberg FDR adjusted. Furthermore, Methylation at specific sites were significantly correlated with Mini-Mental State Examination scores, distinguishing individuals with cognitive decline from controls. CONCLUSIONS: Our study provides an mtDNA methylation map and suggests a role for these sites in preclinical AD pathogenesis.

Humans↗
PubMed2006

Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane.

Sensitization of the pain-transducing ion channel TRPV1 underlies thermal hyperalgesia by proalgesic agents such as nerve growth factor (NGF). The currently accepted model is that the NGF-mediated increase in TRPV1 function during hyperalgesia utilizes activation of phospholipase C (PLC) to cleave PIP2, proposed to tonically inhibit TRPV1. In this study, we tested the PLC model and found two lines of evidence that directly challenge its validity: (1) polylysine, a cationic phosphoinositide sequestering agent, inhibited TRPV1 instead of potentiating it, and (2) direct application of PIP2 to inside-out excised patches dramatically potentiated TRPV1. Furthermore, we show four types of experiments indicating that PI3K is physically and functionally coupled to TRPV1: (1) the p85beta subunit of PI3K interacted with the N-terminal region of TRPV1 in yeast 2-hybrid experiments, (2) PI3K-p85beta coimmunoprecipitated with TRPV1 from both HEK293 cells and dorsal root ganglia (DRG) neurons, (3) TRPV1 interacted with recombinant PI3K-p85 in vitro, and (4) wortmannin, a specific inhibitor of PI3K, completely abolished NGF-mediated sensitization in acutely dissociated DRG neurons. Finally, simultaneous electrophysiological and total internal reflection fluorescence (TIRF) microscopy recordings demonstrate that NGF increased the number of channels in the plasma membrane. We propose a new model for NGF-mediated hyperalgesia in which physical coupling of TRPV1 and PI3K in a signal transduction complex facilitates trafficking of TRPV1 to the plasma membrane.

Androstadienes↗
PubMed2006

[Effects of Jianpi Yiqi Huoxue Decoction on bronchial asthma with recurrent respiratory infection in children].

OBJECTIVE: To investigate the clinical efficacy of Jianpi Yiqi Huoxue Decoction (JYHD) on children bronchial asthma complicated with recurrent respiratory infection (RRI) that could not be effectively controlled by regular inhalation of corticosteroid (ICS). METHODS: Fifty-eight patients were divided into 2 groups: both were treated with anti-infective and symptomatic therapy, but JYHD was given additionally to patients in the treated group. Changes in clinical symptoms of RRI and asthma as well as the serum contents of IgA, IgG and IgM were observed. RESULTS: Compared with the control group, the frequency of respiratory infection occurred, duration of fever, cough and asthma sustained and time of antibiotics used were all lower significantly in the treated group (P < 0.05). The serum contents of IgA and IgG increased in the treated group after treatment, as compared with those before treatment and in the control group, all showed significant difference (P < 0.05). CONCLUSION: For children suffered from intractable bronchial asthma complicated RRI, application of JYHD in addition with the conventional treatment could prevent RRI effectively, so as th reduce the frequency of asthma attack and alleviate the severity of the disease.

Anti-Bacterial Agents↗
PubMed2005

Antioxidant-like protein 1 is altered in non-pyramidal cells and expressed in astrocytes in the gerbil hippocampal CA1 region after transient forebrain ischemia.

In the present study, we observed chronological changes of antioxidant-like protein 1 (AOP-1) in the gerbil hippocampal CA1 region after 5 min of transient forebrain ischemia using immunohistochemistry and western blot. AOP-1 was significantly altered in the CA1 region after transient ischemia. In the sham-operated group, AOP-1 immunoreactivity was detected in pyramidal and non-pyramidal cells of the CA1 region. At 30 min after ischemic insult, AOP-1 immunoreactivity and protein level was decreased in the CA1 region. At 12 h after ischemic insult, AOP-1 immunoreactivity and protein level was highest in this region. At this time, after ischemia, AOP-1 immunoreactivity in non-pyramidal cells was high compared to the sham-operated group. Based on double immunofluorescence study, AOP-1-immunoreactive neurons were identified as GABAergic, which were stained with GAD or parvalbumin. Thereafter, AOP-1 immunoreactivity and protein levels were decreased time-dependently. From 4 days after ischemic insult, AOP 1 immunoreactivity was generally expressed in astrocytes. Five days after ischemic insult, AOP-1 immunoreactivity and protein level was increased again to 1.4 folds compared to that of the sham-operated group. In brief, AOP-1 immunoreactivity was increased in GABAergic non-pyramidal cells in the hippocampal CA1 region at early time after ischemic insult and was expressed in astrocytes at late time after ischemia. This result suggests that AOP-1 may be important role in homeostasis of GABAergic neurons because these neurons are resistant to ischemic damage.

Animals↗
PubMed2005

Cells with pathogenic biallelic mutations in the human MUTYH gene are defective in DNA damage binding and repair.

Inherited biallelic mutations in the human MUTYH gene are responsible for the recessive syndrome--adenomatous colorectal polyposis (MUTYH associated polyposis, MAP)--which significantly increases the risk of colorectal cancer (CRC). Defective MUTYH activity causes G:C to T:A transversions in tumour APC and other genes thereby altering genomic integrity. We report that of the four established cell lines, derived from patients with the MAP phenotype and containing biallelic MUTYH mutations, three contain altered expressions of MUTYH protein (MUTYH Y165C(-/-), MUTYH 1103delC/G382D and MUTYH Y165C/G382D but not MUTYH G382D(-/-)), but that all four cell lines have wild type levels of MUTYH mRNA. Mutant MUTYH proteins in these four cell lines possess significantly lowered binding and cleavage activities with heteroduplex oligonucleotides containing A.8-oxoG and 8-oxoA.G mispairs. Transfection of mitochondrial or nuclear MUTYH cDNAs partially correct altered MUTYH expression and activity in these defective cell lines. Finally, we surprisingly find that defective MUTYH may not alter cell survival after hydrogen peroxide and menadione treatments. The Y165C and 1103delC mutations significantly reduce MUTYH protein stability and thus repair activity, whereas the G382D mutation produces dysfunctional protein only suggesting different functional molecular mechanisms by which the MAP phenotype may contribute to the development of CRC.

Adenomatous Polyposis Coli↗
PubMed2005

Factors affecting the sporulation capacity during long-term storage of the aphid-pathogenic fungus Pandora neoaphidis grown on broomcorn millet.

Aphid-pathogenic fungus, Pandora neoaphidis, grown on broomcorn millet possesses greater sporulation capacity (C(s)) than aphid cadavers. The most sporulating cultures (32.0x10(4) spores millet(-1) grain) with water content (C(w)) of 48.7% were prepared by incubation at 20 degrees C for 15 days and used to study the effect of temperature and humidity on C(s) during long-term storage. Cultures were sealed with paper to retain ambient humidity, with parafilm for saturated humidity, or kept in 85% and 98% RH chambers. The C(w) and C(s) were monitored during 200-day storage at 5-20 degrees C. The paper-sealed cultures at 5 degrees C, associated with 21-25% of C(w), were best preserved and their 120-day C(s) was similar to that of the fresh cadavers. Consistently or variably high RH at 5 degrees C resulted in significantly higher C(w) and lower C(s) despite longer viability. The regimes at 10 degrees C preserved the cultures for 40 days. The observations fit well to the logistic model C(s)=35.28/{1+exp[-2.36+(-0.003C(w)+0.001C(w)T)t]} (r(2)=0.95) for all regimes of temperature (T) or C(s)=35.55/[1+exp(-2.33+0.001C(w)t)] (r(2)=0.93) at 5 degrees C only. The rate of decline of C(s) of -0.003C(w)+0.001C(w)T or 0.001 C(w) over days (t) highlights the primary effect of C(w). The daily C(s)-decline rates obtained for the best-stored cultures and air-dried cadavers stored at 5 degrees C were surprisingly identical. The results suggest a possible cheap method for preparing and storing large quantities of P. neoaphiodis inocula.

Entomophthorales↗
PubMed2005

Broomcorn millet grain cultures of the entomophthoralean fungus Zoophthora radicans: sporulation capacity and infectivity to Plutella xylostella.

The shelled grains of glutinous broomcorn millet, Panicum miliaceum, were used as solid substrate to prepare granular cultures of Zoophthora radicans, an entomophthoralean biocontrol agent against numerous insect pests. Steamed millet grains were inoculated by mixing 15 g millet grains (D.W.) with mashed pieces of half a 60-mm-dish colony in 3 ml modified Sabouraud dextrose broth and incubated at 15 degrees C and L:D 12:12 for up to 24 d. 20 grains were sampled at 3 d intervals from day six onwards and individually assessed for their sporulation capacity using a self-designed device for spore collection. The millet cultures after > or = 12 d incubation produced 12.0 - 14.9 x 10(4) spores grain(-1) during a 7 d period. The maximal sporulation capacity associated with the 21 d-old culture was about half of that of Z. radicans-killed Plutella xylostella larvae (28.7 x 10(4) spores cadaver(-1)), which individually were at least three times larger than the millet grains. Based on the time-concentration-mortality responses of second-instar P. xylostella larvae to Z. radicans in three independent bioassays, the spores ejected from the cultured millet grains, from the mycelial mats from liquid culture, and from larval cadavers displayed insignificant variations in infectivity to the host species, and yielded similar LC50 and LT50 estimates. Conclusively, the millet-based technology for production of granular cultures of Z. radicans was easy, inexpensive and highly efficient, and it could be superior to previous methods used in mass production of mycelium-based preparations of Entomophthorales since this new approach requires no special additives, drying, freezing and milling. This technology may suit to mass production of culturable but nutritionally fastidious entomopathogens from the Entomophthorales.

Animals↗
PubMed2005

Functional interactions between A' helices in the C-linker of open CNG channels.

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels that are activated by the direct binding of the cyclic nucleotides cAMP and cGMP. The region linking the last membrane-spanning region (S6) to the cyclic nucleotide binding domain in the COOH terminus, termed the C-linker, has been shown to play an important role in coupling cyclic nucleotide binding to opening of the pore. In this study, we explored the intersubunit proximity between the A' helices of the C-linker regions of CNGA1 in functional channels using site-specific cysteine substitution. We found that intersubunit disulfide bonds can be formed between the A' helices in open channels, and that inducing disulfide bonds in most of the studied constructs resulted in potentiation of channel activation. This suggests that the A' helices of the C-linker regions are in close proximity when the channel is in the open state. Our finding is not compatible with a homology model of the CNGA1 C-linker made from the recently published X-ray crystallographic structure of the hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channel COOH terminus, and leads us to suggest that the C-linker region depicted in the crystal structure may represent the structure of the closed state. The opening conformational change would then involve a movement of the A' helices from a position parallel to the axis of the membrane to one perpendicular to the axis of the membrane.

Amino Acid Sequence↗
PubMed2005

[Role of interleukin-1 receptor antagonist in protecting kidney from injury induced by asphyxia in neonatal rats].

OBJECTIVE: To observe the role of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) in protecting kidney from injury induced by asphyxia in neonatal rats. METHODS: Neonatal rats were used as experimental animals. The changes in intrarenal inflammatory response and renal injury were examined in the control group (n=13), and 2, 24 and 48 hours after asphyxia followed by normal saline treatment in those treated with rhIL-1ra. RESULTS: In normal saline group, the white blood cell count, the blood interleukin-1 (IL-1), IL-8, IL-6, nitric oxide (NO), endothelin (ET-1) levels, and the renal coefficient (LRC), the scores of injured tubules of the left kidney were significantly increased at 2 hours (n=10), 24 hours (n=11), and 48 hours (n=10, P<0.05 or P<0.01). Compared with the normal saline group, the levels of the above parameters, except IL-6, were significantly decreased in rhIL-1ra treatment group at the same time points (P<0.05 or P<0.01). Serum IL-6 at 24 hours and 48 hours was also decreased in rhIL-1ra treatment group significantly (P<0.05 or P<0.01). CONCLUSION: The results suggest that rhIL-1ra may protect renal injury after asphyxia via inhibiting intrarenal inflammatory response.

Animals↗
PubMed2004

LigAmp for sensitive detection of single-nucleotide differences.

We developed the LigAmp assay for sensitive detection and accurate quantification of viruses and cells with single-base mutations. In LigAmp, two oligonucleotides are hybridized adjacently to a DNA template. One oligonucleotide matches the target sequence and contains a probe sequence. If the target sequence is present, the oligonucleotides are ligated together and detected using real-time PCR. LigAmp detected KRAS2 mutant DNA at 0.01% in mixtures of different cell lines. KRAS2 mutations were also detected in pancreatic duct juice from patients with pancreatic cancer. LigAmp detected the K103N HIV-1 drug resistance mutation at 0.01% in plasmid mixtures and at approximately 0.1% in DNA amplified from plasma HIV-1. Detection in both systems is linear over a broad dynamic range. Preliminary evidence indicates that reactions can be multiplexed. This assay may find applications in the diagnosis of genetic disorders and the management of patients with cancer and infectious diseases.

Biomarkers, Tumor↗
PubMed2003

New use of broomcorn millets for production of granular cultures of aphid-pathogenic fungus Pandora neoaphidis for high sporulation potential and infectivity to Myzus persicae.

Glutinous broomcorn millets from the crop Panicum miliaceum were first used as substrate to produce granular cultures of Pandora neoaphidis, an obligate fungal pathogen specific to aphids. Carrying a water content of 36.5% after being steamed in a regular autoclaving procedure, millet grains of each 15 g (dry weight) in a 100-ml flask were mixed with 3 ml modified Sabouraud dextrose broth containing half a mashed colony of P. neoaphidis grown on egg yolk milk agar and then incubated at 20 degrees C and a light/dark cycle of 12 h/12 h for 21 days. Based on individually monitoring conidial production potential of 20 millet grains sampled from an arbitrarily taken flask at 3-day intervals, the millet cultures incubated for 6-15 days were capable of producing 16.8-23.4 x 10(4) conidia per millet grain with conidial ejection lasting for up to 6 days. The cultured millet grains individually produced significantly more conidia than apterous adults of Myzus persicae killed by P. neoaphidis (8.4 x 10(4) conidia per cadaver) and sporulated twice longer. The modeling of time-dose-mortality data from bioassays on M. persicae apterae exposed to conidial showers from the cultured millet grains and the mycelial mats produced in liquid culture resulted in similar estimates of LC(50) (millets: 21.4, 7.3, and 4.9 conidia mm(-2) on days 5-7 after exposure; mycelial mats: 22.1, 10.6, and 7.7 conidia mm(-2)) although the LT(50) estimated at a given conidial concentration was slightly smaller for the millet cultures than for the mycelial mats. This indicates that the millet grains cultured with P. neoaphidis produced conidia as infective as or slightly more infective to M. persicae than those from the mycelial mats. Based on the sporulation potential, infectivity, and ease and cost of the millet cultures, the method developed in this study highly improved in vitro cultures of P. neoaphidis and may adapt to culturing other entomophthoralean fungi for microbial control of insect pests.

Animals↗
PubMed2002

8-Hydroxyguanosine repair is defective in some microsatellite stable colorectal cancer cells.

Mutator phenotypes are involved in the carcinogenesis of some cancers, e.g., defects in mismatch repair produce a mutator phenotype that drives carcinogenesis and causes microsatellite instability in hereditary nonpolyposis colon cancers and some sporadic colorectal cancers (CRC). Less understood, however, is the potential role of mutator phenotypes in microsatellite stable (MSS) CRC carcinogenesis. A novel transversion mutator phenotype was reported recently in an MSS CRC cell line. We hypothesized that 8-hydroxyguanosine could be involved and found elevations in 5 of 15 (33%) MSS CRC cell lines analyzed. Repair of an adenine*8-hydroxyguanosine mispair was functionally defective in the same five cell lines. The human MutY homologue transcript and MutY homologue protein levels were also decreased. These findings may reflect a MSS mutator phenotype contributing to the development of CRC.

Adaptor Proteins, Signal Transducing↗