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Biomedical subjects

Bin Yu

Publications and source records attributed to Bin Yu.

At least 19 recordsLinked to original sources
PubMed2026

Chinese herbal medicine Xiangsu Hewei Granules in treating non-erosive gastroesophageal reflux disease with liver stomach stagnation heat syndrome: A multicentre, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiangsu Hewei Granules are an herbal preparation that has shown potential for controlling symptoms of nonerosive gastroesophageal reflux disease (NERD) in preliminary studies. However, high-quality randomized controlled evidence for its use in NERD remains lacking. AIM: To verify the efficacy and safety of Xiangsu Hewei Granules in treating NERD with liver stomach stagnation heat syndrome. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, multicentre phase III trial included 480 patients (aged 18-65 years) with confirmed NERD (GerdQ&#x2265;8; negative H. pylori) and traditional Chinese medicine (TCM) liver stomach stagnation heat syndrome. Patients were randomized 3:1 to receive either Xiangsu Hewei Granules or placebo, thrice daily for 8 weeks. The primary outcomes were the effective rate of the response based on visual analog scale (VAS) scores for heartburn and acid regurgitation at week 8. The secondary outcomes included reductions in the TCM syndrome score, etc. RESULTS: 479 participants (mean age 48.5 years, SD10.2; 54.3% female) entered the full analysis set and safety set (360 tests group; 119 control group, 1 participant in the control group withdrawing before medication). At week 8, compared with the control group, the test group demonstrated significantly better effective rate of VAS score response for heartburn(76.39% vs 21.01%, 95% CI 55.38 (45.98, 62.94) %, p&#x202f;<&#x202f;0.01),acid regurgitation (79.72% vs 23.53%, 95% CI56.39 (46.90, 64.12) %, p&#x202f;<&#x202f;0.01), and TCM syndrome score (69.23% vs 30.13%, p&#x202f;<&#x202f;0.01) at week 8. CONCLUSION: In this selected population of NERD patients with liver-stomach stagnation heat syndrome (e.g., negative H. pylori, no pH-impedance phenotype, and low anxiety/depression scores), Xiangsu Hewei Granules demonstrated efficacy and safety in improving heartburn, acid regurgitation, and TCM syndrome scores. However, generalizability to the broader NERD population and its comparative effectiveness against standard proton pump inhibitor therapy require further investigation.

Humans↗
PubMed2026

Evidence supporting the role of GIGYF2 in synapse development and autism.

Autism spectrum disorder (ASD) is a heterogeneous condition in which genetically defined subtypes offered insights into underlying biological mechanisms and potential targeted treatments. Here, we investigate the clinical and pathogenic significance of GIGYF2 variants in ASD through an integrated approach combining clinical genetics, conditional knockout (cKO) mouse models, neurobiology, and molecular studies. Through targeted sequencing, large-scale genomic data analysis of neurodevelopmental disorder cohorts, and international collaborations, we identified ten affected individuals from eight families harboring de novo or dominantly inherited likely gene-disruptive (LGD) variants and 13 affected individuals from 13 families with de novo missense variants in GIGYF2. Clinical characterization of 16 probands with GIGYF2 variants revealed common features, including ASD, language problems, intellectual disability, and anxiety. In a Gigyf2 cKO mouse model, we observed pronounced autistic-like behaviors, cognitive deficits, and anxiety-like behaviors, mirroring phenotypes observed in affected individuals. Mechanistically, Gigyf2 deficiency disrupted synaptic homeostasis, as evidenced by altered spine density and miniature excitatory postsynaptic currents, and impaired IGF-1R/mTOR signaling, along with dysregulation of synapse-related genes such as Nrp2. Pharmacological inhibition of mTOR with rapamycin or Torin1, as well as Nrp2 knockdown rescued synaptic defects in Gigyf2 KO neurons. These findings define a novel ASD subtype associated with GIGYF2 variants and establish GIGYF2 as a key regulator of synaptic development and function, implicating GIGYF2 dysfunction in ASD pathogenesis and highlighting the IGF-1R/mTOR pathway as a potential therapeutic target for GIGYF2-related ASD subtype.

Journal Article↗
PubMed2006

Maternal dietary exposure to fiber during pregnancy and mammary tumorigenesis among rat offspring.

Maternal diet during pregnancy has been proposed to modify female offspring's later susceptibility to develop breast cancer; however, most of the dietary factors identified thus far have led to increased risk. To identify dietary factors that might reduce offspring's breast cancer risk, pregnant rat dams were fed diets containing 6% fiber originating either from cellulose (control), or oat, whole wheat or defatted flax flour. At birth, dams were switched to the AIN93 semi-purified diet. Mammary tumor incidence and multiplicity, induced by administering the offspring 5 mg 7,12-dimethylbenz[a]anthracene (DMBA) at the age of 50 days, was reduced in the whole wheat flour-exposed offspring and increased in the defatted flax-exposed offspring. To identify the mechanisms mediating the effects of in utero dietary exposures, changes in mammary gland morphology and gene expression were assessed before puberty onset (3 weeks of age) and at the time rats are most susceptible to malignant transformation (8 weeks of age). The number of terminal end buds (TEBs), i.e., the targets of malignant transformation, was reduced in the mammary glands of whole wheat- and oat flour-exposed offspring, as compared to the controls. Further, the number of apoptotic epithelial cells (based on ISOL assay) was elevated in the whole wheat flour offspring, but no changes in cell proliferation (PCNA), estrogen receptor alpha (ER-alpha) or cyclin D1 mRNA or protein levels were seen. The mRNA and/or protein levels of BRCA1 and p53 were significantly increased in the mammary glands of whole wheat flour offspring. Further, the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA damage, were significantly reduced in these rats, suggesting that maternal dietary exposure to whole wheat during pregnancy may reduce offspring's breast cancer risk by improving DNA damage repair mechanisms.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Molecular basis for the aromatization reaction and exemestane-mediated irreversible inhibition of human aromatase.

Aromatase converts androgens to aromatic estrogens. Aromatase inhibitors have been used as first-line drugs in the treatment of hormone-dependent breast cancer. Structural basis of the aromatization reaction and drug recognition by aromatase has remained elusive because of its unknown three-dimensional structure. In this study, recombinant human aromatase was expressed and purified from Escherichia coli. Using this purified and active preparation, the three-dimensional folding of aromatase was revealed by proteomic analysis. Combined with site-directed mutagenesis, several critical residues involved in enzyme catalysis and suicide inhibition by exemestane were evaluated. Based on our results, a new clamping mechanism of substrate/exemestane binding to the active site is proposed. These structure-function studies of aromatase would provide useful information to design more effective aromatase inhibitors for the prevention and the treatment of hormone-dependent breast cancer.

Amino Acid Motifs↗
PubMed2006

Interstitial cells of Cajal could regenerate and restore their normal distribution after disrupted by intestinal transection and anastomosis in the adult guinea pigs.

Surgical manipulations of the gastrointestinal (GI) tract usually lead to loss of interstitial cells of Cajal (ICCs). The present study prepared to investigate whether ICCs can regenerate and restore their normal distribution up to 5 months after semitransection and end-to-end anastomosis of small intestines of adult guinea pigs. The segments of anastomosis were studied by immunohistochemistry with anti-KIT, 5-bromo-2'-deoxyuridine (BrdU), stem cell factor (SCF), and neurofilament 200 antibodies and also by transmission electron microscopy (TEM). At early stage, intestinal surgery led to intestinal wall impairment and ICCs loss, and ICCs near the site of anastomosis gradually increased in numbers. About 150 days postoperation, the distribution of ICCs and the microstructure of intestinal wall appeared to be similar with those of the control. By double immunostaining with BrdU and KIT antibodies, a number of proliferated ICCs were seen near the site of transection/anastomosis. Furthermore, KIT ligand, SCF, was mainly observed in the smooth muscle cells (SMCs), which are located close to ICCs. TEM observation revealed a number of immature and mature ICCs in this region. Our results indicated that ICCs could regenerate and restore their normal distribution after intestinal surgery and SMCs might be involved in the regenerated events of ICCs in the adult guinea pig GI tract.

Anastomosis, Surgical↗
PubMed2006

Phosphatidylglycerol biosynthesis in chloroplasts of Arabidopsis mutants deficient in acyl-ACP glycerol-3- phosphate acyltransferase.

The biosynthesis of phosphatidylglycerol represents a central pathway in lipid metabolism in all organisms. The enzyme catalyzing the first reaction of the pathway in the plastid, glycerol-3-phosphate acyl-acyl carrier protein acyltransferase, is thought to be encoded in Arabidopsis by the ATS1 locus. A number of genetic mutants deficient in this activity have been described. However, the corresponding mutant alleles have not yet been analyzed at the molecular level and a causal relationship between the mutant phenotypes and a deficiency at the ATS1 locus has not been established. The presence in all known ats1 mutants of near wild-type amounts of phosphatidylglycerol raised the question of whether an alternative pathway of phosphatidylglycerol assembly in the plastid exists. However, detailed analysis of several independent ats1 mutant alleles revealed that all are leaky. Reduction by RNAi of ats1-1 RNA levels in the ats1-1 mutant background led to a more severe growth phenotype (small green plants and reduced seed set), but did not decrease the relative amount of phosphatidylglycerol. In contrast, when the amount of ATS2 mRNA encoding the plastidic lysophosphatidic acid acyltransferase catalyzing the second reaction of the pathway was reduced by RNAi in the ats1-1 mutant background, phosphatidylglycerol amounts decreased, leading to a growth phenotype (small pale-yellow plants) that is reminiscent of the pgp1-1 mutant deficient in a late step of plastidic phosphatidylglycerol biosynthesis. These observations indicate coordinated regulation of plastid lipid metabolism and plant development.

Alleles↗
PubMed2006

Transgenically expressed viral RNA silencing suppressors interfere with microRNA methylation in Arabidopsis.

HEN1-dependent methylation of the 3'-terminal nucleotide is a crucial step in plant microRNA (miRNA) biogenesis. Here we report that several viral RNA silencing suppressors (P1/HC-Pro, p21 and p19) inhibit miRNA methylation. These suppressors have distinct effects on different miRNAs. We also show that miRNA* is methylated in vivo in a suppressor-sensitive manner, suggesting that the viral proteins interfere with miRNA/miRNA* duplexes. p19 and p21 bind both methylated and unmethylated miRNA/miRNA* duplexes in vivo. These findings suggest miRNA/miRNA* as the in vivo substrates for the HEN1 miRNA methyltransferase and raise intriguing possibilities regarding the cellular location of miRNA methylation.

Arabidopsis↗
PubMed2006

Known-plaintext attack on optical encryption based on double random phase keys.

We demonstrate a new approach to known-plaintext attack on an optical encryption scheme based on double random phase keys. With this attack an opponent can access both random phase keys with the help of the phase retrieval technique. This demonstration shows that an optical encryption scheme based on double random encoding is vulnerable to known-plaintext attack.

Journal Article↗
PubMed2006

Confinement-induced novel morphologies of block copolymers.

Self-assembly of block copolymers confined in cylindrical nanopores is studied systematically using a simulated annealing technique. For diblock copolymers which form two-dimensional hexagonally packed cylinders with period L0 in the bulk, novel structures such as helices and stacked toroids spontaneously form inside the cylindrical pores. These confinement-induced morphologies have no counterpart in the bulk system and they depend on the pore diameter (D) and the surface-polymer interactions, reflecting the importance of structural frustration and interfacial interactions. On tightening the degree of confinement, transitions from helices to toroids to spheres are observed. Mechanisms of the morphological transitions can be understood based on the degree of structural frustration parametrized by the ratio D/L0.

Journal Article↗
PubMed2006

Testing the conformational hypothesis of passive membrane permeability using synthetic cyclic peptide diastereomers.

Little is known about the effect of conformation on passive membrane diffusion rates in small molecules. Evidence suggests that intramolecular hydrogen bonding may play a role by reducing the energetic cost of desolvating hydrogen bond donors, especially amide N-H groups. We set out to test this hypothesis by investigating the passive membrane diffusion characteristics of a series of cyclic peptide diastereomers based on the sequence cyclo[Leu-Leu-Leu-Leu-Pro-Tyr]. We identified two cyclic hexapeptide diastereomers based on this sequence, whose membrane diffusion rates differed by nearly two log units. Results of solution NMR studies and hydrogen/deuterium (H/D) exchange experiments showed that membrane diffusion rates correlated with the degree of intramolecular hydrogen bonding and H/D exchange rates. The most permeable diastereomer, cyclo[d-Leu-d-Leu-Leu-d-Leu-Pro-Tyr] (1), exhibited a passive membrane diffusion rate comparable to that of the orally available drug cyclosporine A.

Cell Membrane Permeability↗
PubMed2006

HEN1 recognizes 21-24 nt small RNA duplexes and deposits a methyl group onto the 2' OH of the 3' terminal nucleotide.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) in plants bear a methyl group on the ribose of the 3' terminal nucleotide. We showed previously that the methylation of miRNAs and siRNAs requires the protein HEN1 in vivo and that purified HEN1 protein methylates miRNA/miRNA* duplexes in vitro. In this study, we show that HEN1 methylates both miRNA/miRNA* and siRNA/siRNA* duplexes in vitro with a preference for 21-24 nt RNA duplexes with 2 nt overhangs. We also demonstrate that HEN1 deposits the methyl group on to the 2' OH of the 3' terminal nucleotide. Among various modifications that can occur on the ribose of the terminal nucleotide, such as 2'-deoxy, 3'-deoxy, 2'-O-methyl and 3'-O-methyl, only 2'-O-methyl on a small RNA inhibits the activity of yeast poly(A) polymerase (PAP). These findings indicate that HEN1 specifically methylates miRNAs and siRNAs and implicate the importance of the 2'-O-methyl group in the biology of RNA silencing.

Escherichia coli Proteins↗
PubMed2006

Outcome of posterolateral fusion versus circumferential fusion with cage for lumbar stenosis and low degree lumbar spondylolisthesis.

OBJECTIVE: To evaluate the outcome of two methods for stabilization and fusion: posterolateral fusion and circumferential fusion involving posterior lumbar interbody fusion for lumbar stenosis with Grades 1 and 2 lumbar spondylolisthesis. METHODS: From April 1998 to April 2003, 45 patients suffering from lumbar stenosis with low degree lumbar spondylolisthesis treated in our hospital were retrospectively reviewed and assigned to two groups. Among them, 24 patients (group A) were treated with instrumented posterolateral fusion and 21 patients (group B) with instrumented circumferential fusion. The two groups were compared for clinical and radiological outcomes. RESULTS: All patients were followed up for 12 to 72 months. In group A, results showed preoperative clinical symptoms disappeared completely in 12 of 24 patients, and pain relief was seen in 91.7% (22/24). Two cases suffered from residual symptoms. Twenty-two cases obtained complete reduction of olisthy vertebral bodies, and anatomical reduction rate was 91.7%. No infection or neurological complication occurred in this group. In group B, results showed preoperative clinical symptoms disappeared completely in 13 of 21 patients, and pain relief was seen in 90.5% (19/21). One case suffered from residual symptoms. Twenty cases obtained complete reduction of the olisthy vertebral bodies, and anatomical reduction rate was 95.2%. Four cases of infection or neurological complication occurred in this group. Both groups indicated no significant difference in clinical outcomes and anatomical reduction rate during follow-up. But group A had better intraoperative circumstances and postoperative outcome than group B, while group B had better postoperative parameters in X-ray of Angle of Slipping and Disc Index than group A. CONCLUSIONS: The first choice of surgical method for lumbar stenosis with low degree lumbar spondylolisthesis is instrumented posterolateral fusion. Only when patients suffer from severe preoperative disc degeneration and low back pain or intervertebral instability should we consider indications for additional use of CAGE.

Adult↗
PubMed2006

Corrective surgery of congenital scoliosis with type II split spinal cord malformation.

OBJECTIVE: To investigate the corrective results of congenital scoliosis with type II split spinal cord malformation. METHODS: By reviewing the medical records and roentgenograms of congenital scoliosis patients with type II split spinal cord malformation that underwent corrective surgery, septum location and length, curve type, coronal and sagittal Cobb's angles, apical vertebral rotation and translation, and trunk shift were measured and analyzed. RESULTS: A total of 23 congenital scoliosis patients with type II split spinal cord malformation were studied, 6 cases were due to failure of segmentation, 8 cases due to failure of formation, and the remaining 9 cases due to mixed defects. The fibrous septums were located in the thoracic spine in 8 patients, lumbar spine in 4 patients, thoracic and lumbar spine in 10 patients, and from cervical to lumbar spine in 1 patient The septum extended an average of 4.9 segments. Corrective surgeries included anterior correction with instrumentation in 2 patients, posterior correction with instrumentation in 11 patients, anterior release and posterior correction with instrumentation in 6 patients, anterior and posterior resection of the hemivertebra and posterior correction with instrumentation in 4 patients. The pre- and postoperative coronal Cobb's angles, apical vertebral translations, apical vertebral rotations, trunk shifts were 61.9 degrees and 32.5 degrees (P < 0.001), 48.9 mm and 31.5 mm (P < 0.001), 1.2 and 1.1, 12.7 mm and 8.2 mm, respectively. The average correction rate of coronal Cobb's angle was 47.5%. The sagittal balance was also well improved. The fibrous septums were all left in situ. There was no neurological complication. CONCLUSION: For congenital scoliosis with type II split spinal cord malformation, positive correction results with no neurological complication may be obtained without resection of the fibrous septum.

Adolescent↗
PubMed2006

[Exercises at different intensities and sequential changes of rat skeletal muscle cell apoptosis].

OBJECTIVE: To study the effect of exercises of different intensities on rat skeletal muscle cell apoptosis. METHODS: Rat models of exhaustive exercise-induced skeletal muscle injury was established using tread mill exercises at different speeds, and the skeletal muscle cell apoptosis was detected using propidium iodide (PI) staining and flow cytometry. RESULT: No obvious gastrocnemius cell apoptosis was observed in rats with normal exercise (P>0.05), but the cell apoptosis index was statistically significant in moderate and exhaustive exercise groups (P<0.05), reaching the highest level in exhaustive exercise group after exercising. The gastrocnemius cell apoptosis index increased obviously on days 1 and 3 of exercise, and stabilized in moderate and exhaustive exercise groups. CONCLUSION: Exercises can evoke cell apoptosis and accelerate apoptotic cell clearance, and the imbalance between the two events during exercises may contribute to skeletal muscle injury.

Animals↗
PubMed2005

Cylinder-gyroid-lamella transitions in diblock copolymer solutions: a simulated annealing study.

The morphological transition of an asymmetric diblock copolymer [A3-b-B9] in A-selective solvents is investigated using a simulated annealing technique. The study was carried out at high copolymer concentrations. Phase-transitions among hexagonally packed cylinders (C), gyroid (G), and lamellae (L) are observed. The phase transition sequence, C-->G-->L, was obtained with decreasing copolymer concentration and/or increasing B-solvent interaction. The predicted phase-transition sequence is consistent with experiments of diblock copolymers with similar volume fractions in selective solvents of different selectivity. The morphological transitions were further analyzed in terms of the average contact numbers for A or B monomers with other molecules and the total surface area of the core or matrix in each structure. It is found that these quantities correlate with the structures, providing an understanding of the phase-transition mechanisms.

Journal Article↗
PubMed2005

Nucleolar localization of cirhin, the protein mutated in North American Indian childhood cirrhosis.

Cirhin (NP_116219), the product of the CIRH1A gene is mutated in North American Indian childhood cirrhosis (NAIC/CIRH1A, OMIM 604901), a severe autosomal recessive intrahepatic cholestasis. It is a 686-amino-acid WD40-repeat containing protein of unknown function that is predicted to contain multiple targeting signals, including an N-terminal mitochondrial targeting signal, a C-terminal monopartite nuclear localization signal (NLS) and a bipartite nuclear localization signal (BNLS). We performed the direct determination of subcellular localization of cirhin as a crucial first step in unraveling its biological function. Using EGFP and His-tagged cirhin fusion proteins expressed in HeLa and HepG2, cells we show that cirhin is a nucleolar protein and that the R565W mutation, for which all NAIC patients are homozygous, has no effect on subcellular localization. Cirhin has an active C-terminal monopartite nuclear localization signal (NLS) and a unique nucleolar localization signal (NrLS) between residues 315 and 432. The nucleolus is not known to be important specifically for intrahepatic cholestasis. These observations provide a new dimension in the study of hereditary cholestasis.

Adolescent↗
PubMed2005

Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in Arabidopsis.

Small RNAs of 21-25 nucleotides (nt), including small interfering RNAs (siRNAs) and microRNAs (miRNAs), act as guide RNAs to silence target-gene expression in a sequence-specific manner. In addition to a Dicer homolog, DCL1, the biogenesis of miRNAs in Arabidopsis requires another protein, HEN1. miRNAs are reduced in abundance and increased in size in hen1 mutants. We found that HEN1 is a miRNA methyltransferase that adds a methyl group to the 3'-most nucleotide of miRNAs, but the role of miRNA methylation was unknown. Here, we show that siRNAs from sense transgenes, hairpin transgenes, and transposons or repeat sequences, as well as a new class of siRNAs known as trans-acting siRNAs, are also methylated in vivo by HEN1. In addition, we show that the size increase of small RNAs in the hen1-1 mutant is due to the addition of one to five U residues to the 3' ends of the small RNAs. Therefore, a novel uridylation activity targets the 3' ends of unmethylated miRNAs and siRNAs in hen1 mutants. We conclude that 3'-end methylation is a common step in miRNA and siRNA metabolism and likely protects the 3' ends of the small RNAs from the uridylation activity.

Amino Acid Sequence↗