Biomedical subjects

Fang Sun

Publications and source records attributed to Fang Sun.

At least 19 recordsLinked to original sources

PubMed2026

Systematic Approach for Compound Angus Populations Revealing Positional Candidate Genes and Improving Prediction Accuracy in Carcass Traits.

Carcass traits, which reflect growth performance and muscle development, are economically important in beef cattle, yet their genetic determinants remain poorly characterized. Both single-population Genome-wide association studies (GWAS) methods, such as BLINK, and cross-population meta-analysis approaches are widely used to identify genetic variants, yet their comparative performance in genomic prediction for complex traits in structured populations remains underexplored. Few studies have directly compared these methods in genomic prediction. To address this gap, this study aims to (i) identify positional candidate genes associated with carcass traits and (ii) evaluate the context-dependent advantages of Covariate Adjustment (CA) and meta in genomic prediction. In this study, we analyzed carcass weight (CW), live weight (LW), and dressing percentage (DP) in 279 crossbred Angus cattle genotyped with the PHR0105_Bt140K_v1.0 SNP chip. GWAS was performed on the full population using BLINK, and results from three subpopulations were combined via meta-analysis, with significance thresholds for both approaches determined by a shuffle-based method. Candidate genes located within ±10 kb of significant SNPs were associated with different carcass traits, including STRIT1, SEL1L3, NOC4L and ANK1 for DP; SNCA and DNAH5 for CW; and GYPC, GPR158, and GUCY1A1 for LW. Prediction accuracy under MAS and MABLUP showed meta slightly outperformed BLINK in MAS, while BLINK was better with covariate adjustment; after incorporating kinship in MABLUP, meta achieved higher accuracy and population partitioning was negligible. Overall, MABLUP yielded the highest accuracy (0.52-0.79) versus MAS (0.37-0.54) in all traits. These findings provide a methodological basis for selecting appropriate GWAS strategies in structured populations and highlight candidate genes.

GS↗

PubMed2006

Sterol transfer by ABCG5 and ABCG8: in vitro assay and reconstitution.

ATP-binding cassette transporters G5 and G8 are half-transporters expressed on the apical membranes of enterocytes and hepatocytes that limit intestinal uptake and promote secretion of neutral sterols. Genetic defects that inactivate either half-transporter cause accumulation of cholesterol and plant sterols, resulting in premature coronary atherosclerosis. These observations suggest that G5 and G8 promote the translocation of sterols across membranes, but the primary transport substrate of the G5G8 complex has not been directly determined. Here we report the development of a sterol transfer assay using "inside-out" membrane vesicles from Sf9 cells expressing recombinant mouse G5 and G8. Radiolabeled cholesterol or sitosterol was transferred from donor liposomes to G5- and G8-containing membrane vesicles in an ATP-dependent and vanadate-sensitive manner; net transfer of cholesterol was associated with an increase in vesicular cholesterol mass. CTP, GTP, and UTP, as well as ATP, supported transfer but with lesser efficiency (ATP >> CTP > GTP > UTP). Transfer was specific for sterols and was stereoselective; minimal ATP-dependent and vanadate-sensitive transfer of cholesteryl oleate, phosphatidylcholine, or enantiomeric cholesterol was observed. These studies indicate that G5 and G8 are sufficient for reconstitution of sterol transfer activity in vitro and provide the first demonstration that sterols are direct transport substrates of the G5 and G8 heterodimer.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2006

Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome.

BACKGROUND: Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients. METHODS: Sixty-five unrelated cases (35 men and 30 women) who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography (CT) scan or magnetic resonance imaging (MRI). The differential diagnosis of organic acidurias and fatty acid beta-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA (T8993G, T8993C, T9176C, A8344G, A3243G) were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 (26.2%) of the patients. The diagnosis was confirmed by autopsy in 6 (9.2%) patients. RESULTS: The patients had various forms of metabolic encephalomyopathy. Fifty-nine (90.8%) of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty (30.8%) patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases (7.7%). Of these, the A8344G mutation was detected in 2 patients. The T8993G, T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) families by DNA sequencing. A G604C mutation was identified in 6 (9.2%) patients. The genotypes of 52 patients remained unknown. CONCLUSIONS: Leigh syndrome presents as a diverse array of clinical features and can result from specific mutations in nuclear or mitochondrial DNA. In this study, SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) out of 65 patients with Leigh syndrome. It indicates that SURF1 mutations might be a common cause of Leigh syndrome in China. The etiology of Leigh syndrome in Chinese patients represents a persistent challenge to clinicians.

Adolescent↗

PubMed2006

The structure of the carboxyltransferase component of acetyl-coA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme.

Acetyl-coA carboxylase (ACC) is a central metabolic enzyme that catalyzes the committed step in fatty acid biosynthesis: biotin-dependent conversion of acetyl-coA to malonyl-coA. The bacterial carboxyltransferase (CT) subunit of ACC is a target for the design of novel therapeutics that combat severe, hospital-acquired infections resistant to the established classes of frontline antimicrobials. Here, we present the structures of the bacterial CT subunits from two prevalent nosocomial pathogens, Staphylococcus aureus and Escherichia coli, at a resolution of 2.0 and 3.0 A, respectively. Both structures reveal a small, independent zinc-binding domain that lacks a complement in the primary sequence or structure of the eukaryotic homologue.

Acetyl-CoA Carboxylase↗

PubMed2006

Kainate induces rapid redistribution of the actin cytoskeleton in ameboid microglia.

Microglia are key mediators of the immune response in the central nervous system (CNS). They are closely related to macrophages and undergo dramatic morphological and functional changes after CNS trauma or excitotoxic lesions. Microglia can be directly stimulated by excitatory neurotransmitters and are known to express many neurotransmitter receptors. The role of these receptors, however, is not clear. This study describes the microglial response to the glutamate receptor agonist kainate (KA) and shows via immunochemistry that the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptor subunit GluR1 is present on cultured microglia. In the presence of 100 microM or 1 mM KA, cultured microglia underwent dramatic morphological and cytoskeletal changes as observed by time-lapse photography and quantitative confocal analysis of phalloidin labeling. KA-stimulated microglia showed condensation of cytoplasmic actin filaments, rapid de- and repolymerization, and cytoplasmic redistribution of condensed actin bundles. Rearrangement of actin filaments-thought to be involved in locomotion and phagocytosis and to indicate an increased level of activation (for reviews see Greenberg [ 1995] Trends Cell Biol. 5:93-99; Imai and Kohsaka [ 2002] Glia 40:164-174)-was significantly increased in treated vs. control cultures. Morphological plasticity and membrane ruffling were also seen. These findings suggest direct microglial excitation via glutamate receptor pathways. Thus, neurotransmitter release after brain or spinal cord injury might directly modulate the inflammatory response.

Actins↗

PubMed2006

Acute metabolic crisis induced by vaccination in seven Chinese patients.

Seven Chinese patients (5 males and 2 females) with vaccination-induced acute metabolic crisis were reported. Only one male with 21-hydroxylase deficiency had been diagnosed before vaccination. In the remaining six patients, the preexisting diagnoses were not confirmed before the vaccination. Acute metabolic crisis occurred in seven patients between 3 and 12 hours after the administration of Japanese encephalitis, diphtheria, and tetanus toxoids and acellular pertussis, hepatitis B, or measles vaccines. Patients 1 and 2 displayed acute adrenal insufficiencies at the ages of 5 years and 3 months, respectively. Patient 3 had presented with mild motor retardation previously. Patients 4 to 7 were previously healthy, but suffered from fever, seizures, coma, acidosis, and hypoglycemia after being vaccinated. Glutaric aciduria type 1 was evident in case 4. Leigh syndromes were present in Patients 5, 6, and 7. They all died from respiratory failure before 2 years of age. Symmetric foci, cystic cavitations with neuronal loss, and vascular proliferation were observed by postmortem examination. Among the seven patients, although the vaccines were not the primary cause of the acute metabolic crisis, the severe acute episodes occurred coincidentally.

Acid-Base Imbalance↗

PubMed2006

Clinical and biochemical studies on Chinese patients with methylmalonic aciduria.

Methylmalonic aciduria is a common organic aciduria disease. Recently, gas chromatography-mass spectrometry has been used to diagnose methylmalonic aciduria in China. Often, however, the diagnosis of methylmalonic aciduria is delayed because of a lack of technical expertise and the limited experience of general clinicians in China. In this study, the natural history, clinical features, and outcome of 77 Chinese patients with methylmalonic aciduria were investigated. Of the 77 patients, 31 (40.3%) had isolated methylmalonic aciduria and 46 (59.7%) had methylmalonic aciduria combined with homocystinemia. Thus, we observed a higher rate of the combined disease than studies conducted in other countries, suggesting that it might be more common in China. Total plasma homocysteine measurement might enable differential diagnoses of methylmalonic aciduria to be distinguished. The clinical spectrum of these 77 patients with methylmalonic aciduria ranged from neonatal death and severe symptoms to benign asymptomatic organic aciduria. Neonatal and infantile onset, which was a characteristic of the majority of cases, was associated with a greater severity relative to later-onset cases. Among the 17 cases who had onset after 3 years of age, only 1 patient had isolated methylmalonic aciduria and 16 had combined methylmalonic aciduria and homocystinemia. Nine of the patients with combined methylmalonic aciduria and homocystinemia completely recovered and exhibited normal intelligence, whereas seven improved, with a mild handicap.

Adolescent↗

PubMed2006

[Characteristics of erectile dysfunction in old males with lacunar infarction].

OBJECTIVE: To investigate the characteristics of erectile dysfunction (ED) in old males with lacunar infarction. METHODS: A total of 38 old patients ages from 60 to 70 years were involved. The questionnaire of international index of erectile function 5 (IIEF -5) was used to determine the status and severity of ED. According to the focus of infarction on MRI, the patients were divided into two groups, Group I with lacunar infarction and minor neurological deficits, and Group II with none. The total IIEF-5 scores were compared between the two groups and repeatedly evaluated six months after discharge. RESULTS: According to the total scores of IIEF-5, the prevalence of ED in Group II (95%) was higher, and the incidence of severe ED was significantly increased (60.0% vs. 44.4%, P < 0.05) as compared with Group II. In both the two groups, severe ED was more often seen in diabetic patients. At six months after discharge, the total scores of IIEF-5 were significantly increased (11.2 +/- 3.2 vs. 15.6 +/- 2.2, P < 0.05). CONCLUSION: ED is significantly increased in old males with lacunar infarction, and it is more severe in diabetic patients. Post-stroke rehabilitation care helps to improve ED.

Aged↗

PubMed2005

Synthetic iminosugar derivatives as new potential immunosuppressive agents.

Several iminosugar derivatives were synthesized, and their effects on the secretion of IL-4 and IFN-gamma from the mouse splenocytes were examined. The effects on membrane expression of other T cell-associated molecules (CD3, CD4, CD8) and B cell-associated molecules (CD19) were also investigated. The experimental data demonstrated that synthetic iminosugars hold potential as immunosuppressive agents.

Animals↗

PubMed2005

A non-invasive method for gastrointestinal parameter monitoring.

AIM: To propose a new, non-invasive method for monitoring 24-h pressure, temperature and pH value in gastrointestinal tract. METHODS: The authors developed a miniature, multi-functional gastrointestinal monitoring system, which comprises a set of indigestible biotelemetry capsules and a data recorder. The capsule, after ingested by patients, could measure pressure, temperature and pH value in the gastrointestinal tract and transmit the data to the data recorder outside the body through a 434 MHz radio frequency data link. After the capsule passed out from the body, the data saved in the recorder were downloaded to a workstation via a special software for further analysis and comparison. RESULTS: Clinical experiments showed that the biotelemetry capsules could be swallowed by volunteers without any difficulties. The data recorder could receive the radio frequency signals transmitted by the biotelemetry in the body. The biotelemetry capsule could pass out from the body without difficulties. No discomfort was reported by any volunteer during the experiment. In vivo pressure and temperature data were acquired. CONCLUSION: A non-invasive method for monitoring 24-h gastrointestinal parameters was proposed and tested by the authors. The feasibility and functionality of this method are verified by laboratory tests and clinical experiments.

Adult↗

PubMed2005

[Protective effect of ligusticum chuanxiong phthalides on focai cerebral ischemia in rats and its related mechanism of action].

OBJECTIVE: To study the protective effect of ligusticum chuanxiong phthalides on cerebral ischemia in rats and its related mechanism of action. METHOD: Middle cerebral artery occlusion (MCAO) model, thrombosis formation, platelet aggregation and hemorrheological parameters were measured to evaluate the protective effect of ligusticum chuanxiong phthalides. RESULT: Ligusticum chuanxiong phthalides could markedly decrease the infarct size and behavior deficits score, inhibit the thrombus formation and platelet aggregation, ameliorate hemorrheological parameters with a dose-dependent manner in rats. CONCLUSION: Ligusticum chuanxiong phthalides has protective effects on focal cerebral ischemia in rats, and its mechanism may be relevant to its inhibition of platelet-dependent thrombosis and amelioration of hemorrheological parameters.

Animals↗

PubMed2005

[Clinical and laboratory screening studies on urea cycle defects].

OBJECTIVE: To investigate the incidences of urea cycle defects (UCDs) in the patients with hyperammonemia and study their etiology, clinical and laboratory features. METHODS: In the past 7 years, 26 cases (10.2%) of UCDs were detected from 254 patients with hyperammonemia. The etiological diagnoses were made by blood amino acids analysis, urinary organic acid analysis and blood acylcarnitine profile analysis. Three patients with citrullinemia type II were further confirmed by liver pathological analysis and gene diagnosis. RESULTS: Among 26 cases with UCDs, 15 had ornithine transcarbamylase (OTC) deficiency, 5 had citrullinemia type I, 3 had citrullinemia type II and 3 patients had arginemia. The age of onset of the patients ranged from 3 days to 13 years. Three cases (11.5%) developed hyperammonemic encephalopathy during neonatal period. Thirteen (50.0%), 7 (26.9%) and 3 (11.5%) cases developed clinical symptoms at the age of 1 to 12 months, 1 to 3 years and 6 to 13 years, respectively. Positive family history was found in 11 cases (42.3%). Among 26 patients with UCDs, 9 (34.6%) were hospitalized with the complains of seizures, psychomotor retardation, vomiting and unconsciousness, 8 (30.8%) with recurrent vomiting, headache and coma, 6 due to liver dysfunction. Intrahepatic cholestatic jaundice was found in 3 patients with citrullinemia type II. Blood ammonia ranged from 58 to 259 micromol/L on their first visit to our hospital. Twenty cases (76.9%) had liver dysfunction, 4 patients (15.4%) were diagnosed postmortem. Twenty-one patients got treatment and were followed up. Among them, 7 cases died of hyperammonemic encephalopathy or upper alimentary tract bleeding. Clinical improvement was observed in 14 cases. A boy with OTC deficiency who received a partial liver transplant from his mother showed normal general condition for two years. CONCLUSIONS: UCDs are the most frequent causes of congenital hyperammonemia. In this study, 26 patients (10.2%) with UCDs were identified from 254 patients with hyperammonemia resulting in encephalopathy and liver dysfunction. Early diagnosis and treatment can contribute a lot to improve the prognosis of the patients. Blood ammonia assay and further etiological analysis should be considered in the differential diagnosis of neurological and hepatic abnormality.

Adolescent↗

PubMed2005

[The effect of maxillary and mandibular lip bumper on teeth and dental arch in late mixed dentition].

PURPOSE: To study the effect of maxillary and mandibular lip bumper on tooth and dental arch in late mixed dentition. METHODS: Twelve subjects with mild or moderate crowding were selected. They were treated with maxillary and mandibular lip bumper for eight months. Analysis of cephalometrics and model measurements were done before and after treatment and paired t test were performed respectively for their changes. RESULTS: After treatment, SNA and SNB increased by 1.02 degrees and 0.97 degrees (P<0.05). Upper and lower incisor both had controlled tipping movement. The crown of incisor moved mesially and had root apex were fixed relatively. The center of rotation was close to root apex. The upper and lower molar moved differently. Upper molar was upright distally and the center of rotation was close to the crown. However, the lower molar tipped distally and the center of rotation was close to the center of resistance.The width between the first molars and length of maxillary dental arch increased by 4.12 mm and 5.09 mm (P<0.01). The width between the first molars and length of mandibular dental arch increased by 4.07 mm and 6.86 mm (P<0.01) CONCLUSION: Clinical application of lip bumper could cause transverse and vertical changes in dental arch ,which help to decrease or remove crowding.

Dental Arch↗

PubMed2004

Protein profile of aging and its retardation by caloric restriction in neural retina.

Aging is a slow, gradual deterioration process of an organism. The only experimental intervention, which can reliably retard aging and age-related degenerative diseases, is dietary caloric restriction (CR). To gain insight into the mechanism of CR intervention, we have investigated the protein profile of aging and its retardation by CR in the neural retina of Brown Norway (BN) rats using the comprehensive proteomic approach. We found that the intensities of 18 proteins decreased significantly with age. CR intervention can completely prevent seven of them, and partially protect eight of them, from such age-related declines. The major protein targets protected by CR intervention appear to be glycolytic enzymes and molecular chaperones. These data are the first to suggest that CR may retard the age-related degeneration of retina by maintaining sufficient glucose metabolism, by ensuring proper protein folding, and/or by preventing protein denaturation in the neural retina.

Aging↗

PubMed2004

Dietary caloric restriction may delay the development of cataract by attenuating the oxidative stress in the lenses of Brown Norway rats.

Dietary caloric restriction (CR) is the only experimental intervention that can reliably retard the development of cataract in a normal animal model. Here we have studied the possible mechanisms by which CR retards the age-related degeneration of the lens of Brown Norway rats. We have found that CR slowed protein insolubilization and blunted declines of the total soluble thiols, protein thiols, reduced glutathione and ascorbic acid levels in the lenses of old BN rats. From the lens protein point of view, the development of cataract in rat lenses has 3 stages: (1) the precipitation of gamma-crystallin, (2) the insolubilization of beta-crystallin, and (3) the final precipitation of alpha-crystallin which was saturated with other denatured lens proteins. A similar sequence is also observed when the lens proteins are subjected to oxidative stress in vitro. These data are the first to suggest that CR may retard the age-related degeneration of the lens by attenuating the oxidative stress in the lens. Since oxidative stress is likely a main cause of human cataract, CR intervention may be relevant to humans as well.

Aging↗

PubMed2004

Cluster analysis of genes with significant change in expression in cells conditioned to survive TBOOH.

Immortal murine lens epithelial cells, alphaTN4-1 have been conditioned to survive H2O2, H cells, or TBOOH, T cells, at concentrations that will cause cataract in vitro. Since H cells are killed by TBOOH but T cells survive H2O2, it is of interest to examine the gene expression of these cell lines. We now report the results of cluster analysis of genes whose expression is significantly changed by TBOOH. The analysis has revealed a small group of antioxidative defense genes that contribute to the survival of T and H cells when exposed to oxidative stress.

Animals↗

PubMed2004

Characteristics of tertiary butyl hydroperoxide and hydrogen peroxide conditioned cells withdrawn from peroxide stress.

This laboratory has recently reported the preparation of immortal lens epithelial cell lines conditioned to survive in concentrations of peroxide sufficient to cause cataract with in vitro lens culture conditions. The cell conditioning process takes many months during which time the peroxide concentration is gradually increased. It was found that while the acquired resistance to H2O2 was permanent, if tertiary butyl hydroperoxide (TBOOH) was used the resistance was lost within 6-8 weeks of the withdrawal of the peroxide. We now report that resistance is lost within a few days but can be regained within 48 hr. Furthermore, cells resistant to H2O2 while vulnerable to TBOOH could also be rapidly conditioned to tolerate TBOOH in a manner similar to the reconditioning of cells that had lost their TBOOH resistance. The results suggest that a history of exposure to certain oxidative stresses produces a change in cell biology which allows the cell to rapidly respond to the same or other stresses and survive.

Animals↗

PubMed2004

Comparison of characteristics of peroxide-conditioned immortal human lens-epithelial cell lines with their murine counterparts.

Previously, this laboratory has reported the characteristics of murine immortal lens-epithelial cells (alphaTN4-1) conditioned to survive either H2O2 or tertiary butyl hydroperoxide (TBOOH) stress. This communication now describes similar observations upon human HLE-B3 cells. It was found that the human cells are more sensitive to peroxides than their murine counterpart. Similar to the murine cells, conditioning to TBOOH endows the HLE-B3 cells with resistance to H2O2 but unlike the murine cells, conditioning to H2O2 gives the human cells resistance to TBOOH. Furthermore, while withdrawal of TBOOH stress from TBOOH-conditioned alphaTN4-1 cells causes a loss of resistance to this peroxide but not H2O2, with human cells resistance to both peroxides is retained. Examination of the antioxidative defense (AOD) enzyme activities show an extraordinary increase in catalase activity and significant augmentation of most other enzymes assayed in all conditioned human cell lines. In contrast, it was previously found that only catalase and glutathione-S-transferase have considerable increases in activity in the murine lines. However, in most cases, the AOD enzyme activity in murine-control cells is about 2-fold higher than in human control cells. The gene expression of human TBOOH-conditioned (Thum) and control (Chum) lines were also examined utilizing microarray analysis. Surprisingly, no significant change in gene expression was found for any of the prominent AOD enzymes. Such results differ from the response of murine cells where many AOD enzymes have increased expression. These observations suggest while the same AOD enzymes may be utilized in both murine and human lens-epithelial cells, the levels at which they are maintained and the manner in which they are recruited in response to stress may differ.

Animals↗