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Biomedical subjects

Lan Yu

Publications and source records attributed to Lan Yu.

At least 19 recordsLinked to original sources

A high-quality chromosome-level genome assembly of apple of Peru (Nicandra physalodes).

Nicandra physalodes, a member of the Solanaceae family, is known for its medicinal potential and strong natural insect-repellent properties, which are mainly attributed to its bioactive withanolides and alkaloids. Despite its ecological and pharmacological significance, genomic information for this species has remained limited. Here, we generated a chromosome-level reference genome for N. physalodes based on PacBio high-fidelity (HiFi) long-read sequencing and Hi-C scaffolding. The assembled genome is 933.97 Mb in size, with a contig N50 of 87.37 Mb, and 99.95% (933.54 Mb) of the sequences anchored to 10 pseudochromosomes. Repetitive elements account for 73.06% of the genome, and 27,925 protein-coding genes were predicted, 97.81% of which were functionally annotated. This genomic resource provides a valuable foundation for investigating the genetic basis of specialized metabolite biosynthesis, insect resistance, and environmental adaptation in N. physalodes, as well as for comparative studies within the Solanaceae family.

Genome, Plant↗

The diagnosis and treatment of HIV-infected children in China: challenges and opportunities.

BACKGROUND: HIV-infected children in China have not been well studied. This national survey describes the demographic characteristics and the associated diagnostic and antiretroviral treatment (ART) efforts directed toward surviving HIV-infected children. METHODS: A cross-sectional study was conducted in the 6 provinces with the highest HIV prevalence: 4 former plasma donation (FPD) provinces and 2 intravenous drug use (IDU) provinces. A survey on demographics and treatment-related issues was distributed to the parents or guardians of all living HIV-infected children identified through the national case reporting system. Descriptive and bivariate analyses were performed on completed surveys. RESULTS: Six hundred ninety-two (62.4%) of the total 1108 surveys were returned, and 650 were eligible for analysis. The average age in FPD provinces (mean +/- SD: 8.1 +/- 3.2 years) was significantly older than in IDU provinces (mean +/- SD: 5.4 +/- 2.2 years; P < 0.001). The average lag time from the probable date of transmission to a diagnosis for patients with mother-to-child transmission (MTCT) was 6.7 +/- 3.1 years in the FPD provinces and 4.7 +/- 1.9 years in the IDU provinces (P < 0.001). On the basis of the CD4 cell count or World Health Organization staging, 29.8% (144 of 484) of children from all 6 provinces who were not on ART needed it. CONCLUSIONS: This first national pediatric survey indicates that the age and time required for diagnosis were greater in HIV-infected children from FPD provinces compared with those from IDU provinces. In addition, this survey highlights the prolonged delay in the diagnosis and initiation of ART for children in China. Aggressive efforts to identify HIV-positive pregnant women, scale up prevention of MTCT activities, and expand early diagnosis and treatment are urgently needed.

Analysis of Variance↗

Synthesis of novel cholic acid functionalized branched oligo/poly(epsilon-caprolactone)s for biomedical applications.

Novel cholic acid functionalized branched oligo/poly(epsilon-caprolactone)s were synthesized through the ring-opening polymerization of epsilon-caprolactone initiated by cholic acid with hydroxyl groups. The molecular weight of the branched polymers can be adjusted by controlling the feed ratio of the initiator cholic acid to the monomer epsilon-caprolactone. Comparing with linear homopolymer poly(epsilon-caprolactone) (PCL), these branched oligo/poly(epsilon-caprolactone)s show much faster hydrolytic degradation rates, implies that our approach provides a convenient and effective strategy to accelerate degradation of the biodegradable polymers with slow degradation rates such as PCL. The cell culture experiment indicates the incorporation of cholic acid moiety to the polymer chain can improve both cell adherence and proliferation obviously.

Animals↗

Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: a randomized controlled study.

AIM: To observe the efficiency and safety of thymosin-alpha1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-alpha1, twice a week (T-alpha1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-alpha) each day for fifteen days, then three times weekly (IFN-alpha group) for six months. The results between two groups treated with and the group untreated with IFN-alpha which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P>0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters). RESULTS: At the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-alpha1 group and in 15 of 33 (45.5%) patients in the IFN-alpha group (chi2=1.36, P>0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-alpha1 group and in 9 of 33 (27.3%) patients in the IFN-alpha group (chi2=2.93, P>0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-alpha which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-alpha group at the end of therapy (1 of 30 vs 15 of 33, chi2=14.72, P<0.001) and in the T-alpha1 group at the end of follow-up (1 of 30 vs 14 of 29, chi2=15.71, P<0.001). In T-alpha1 and IFN-alpha treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow-up period, the proportions of ALT normalization and negative HBV DNA in the T-alpha1 group were significantly higher than those in the IFN-alpha and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-alpha1 group than in the IFN-alpha group. Unlike IFN-alpha, T-alpha1 was well tolerated by all patients, and no side effects appeared in T-alpha1 group. CONCLUSION: The results suggest that a 6-mo course of T-alpha1 therapy is effective and safe in patients with chronic hepatitis B. T-alpha1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-alpha1 is better tolerated than IFN-alpha and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.

Adjuvants, Immunologic↗

Role of galectin-3 in mast cell functions: galectin-3-deficient mast cells exhibit impaired mediator release and defective JNK expression.

Galectin-3 is a member of the beta-galactoside-binding animal lectin family expressed in various cell types, including mast cells. To determine the role of galectin-3 in the function of mast cells, we studied bone marrow-derived mast cells (BMMC) from wild-type (gal3(+/+)) and galectin-3-deficient (gal3(-/-)) mice. Cells from the two genotypes showed comparable expression of IgE receptor and c-Kit. However, upon activation by FcepsilonRI cross-linkage, gal3(-/-) BMMC secreted a significantly lower amount of histamine as well as the cytokine IL-4, compared with gal3(+/+) BMMC. In addition, we found significantly reduced passive cutaneous anaphylaxis reactions in gal3(-/-) mice compared with gal3(+/+) mice. These results indicate that there is a defect in the response of mast cells in gal3(-/-) mice. Unexpectedly, we found that gal3(-/-) BMMC contained a dramatically lower basal level of JNK1 protein compared with gal3(+/+) BMMC, which is probably responsible for the lower IL-4 production. The decreased JNK1 level in gal3(-/-) BMMC is accompanied by a lower JNK1 mRNA level, suggesting that galectin-3 regulates the transcription of the JNK gene or processing of its RNA. All together, these results point to an important role of galectin-3 in mast cell biology.

Anaphylaxis↗

Identification and expression of novel isoforms of human stromal cell-derived factor 1.

Stromal Cell-derived factor 1 (SDF-1) is a CXC chemokine that binds to the CXCR4 receptor. Recent publication indicates that the SDF-1/CXCR4 signaling pathway plays a pivotal role during development and in many patho-physiological conditions including hematopoiesis, blood vessel formation, cancer metastasis, angiogenesis and HIV infection. Two human SDF-1 isoforms, SDF-1alpha and SDF-1beta, have been reported to date. Here we report the identification of four additional human SDF-1 isoforms derived from alternative splicing events, SDF-1gamma, SDF-1delta, SDF-1epsilon and SDF-1phi. These SDF-1 splice variants all share the same first three exons but contain different fourth exons. The human SDF-1 gene spans over 88 kilobase-pairs on chromosome 10. Using the semi-quantitative RT-PCR method, we determined the tissue distribution of these SDF-1 isoforms. SDF-1alpha and SDF-1beta share similar expression patterns and the highest expression were detected in liver, pancreas and spleen. SDF-1gamma seems to be the human orthologue of recently isolated rat SDF-1gamma, and its expression was only detected in the heart. SDF-1delta expression can be detected in several adult tissues but the highest expression was detected in fetal liver. When transfected into HEK293 cells, all the SDF-1 isoforms can be detected as secreted proteins in the cell culture media. The conditioned media from transfected cells can stimulate cell migration in a CXCR4-dependent manner. These data suggest that the novel SDF-1 splice variants encode functional proteins.

Alternative Splicing↗

Study on the drug release property of cholesteryl end-functionalized poly(epsilon-caprolactone) microspheres.

End-functionalized poly/oligo(epsilon-caprolactone)s were synthesized through the ring-opening polymerization of epsilon-caprolactone initiated by cholesterol with a hydroxyl group. Using the end-functionalized poly/oligo(epsilon-caprolactone)s with different molecular weights, the microsphere drug delivery systems were fabricated using a convenient melting-emulsion method. The drug release properties of microspheres were investigated with the presence of an enzyme, Pseudomonas cepacia lipase, as well as in the absence of the enzyme. The release profiles can be fitted nicely by the classical empirical exponential expression. Under the hydrolytic condition, the drug release is mainly controlled by Fickian diffusion, and the high molecular weight of the matrix results in a slower drug release rate. Under the enzymatic condition, the drug release is dominated by combined degradation and diffusion mechanism, and the high molecular weight sample exhibits a faster release rate that is mainly caused by the higher degradation rate of the sample with lower cholesteryl moiety content.

Biocompatible Materials↗

Systematic screening for polymorphisms in the CYP3A4 gene in the Chinese population.

OBJECTIVES: Cytochrome P450 3A4 (CYP3A4) is a major CYP enzyme in the liver and intestine. It is involved in the metabolism of over 50% of all drugs currently in use. The present study was designed to determine the genetic basis of CYP3A4 variability. METHODS: Single nucleotide polymorphism (SNP) analysis of the CYP3A4 gene was performed on 60 healthy Chinese subjects consisting of 20 Han, 30 She and ten Dong subjects, using direct sequencing. Linkage disequilibrium, haplotype inference and Hardy-Weinberg equilibrium were also determined for these samples. RESULTS: A total of 20 SNPs were found in the CYP3A4 gene, including 11 known SNPs and nine novel SNPs. The known SNPs detected in our study were CYP3A4*1B, CYP3A4*1G, CYP3A4*10, CYP3A4*13, CYP3A4*14, CYP3A4*15, CYP3A4*17, CYP3A4*18, rs3091339, rs3091430 and rs28371761, and the novel SNPs were -658 A-->C, G27A (E10K), T48A, G14284A (G167D), A15623G (N191D), C15635A (L196I), T15656C (F203L), G14199A (intron 5) and C15566T (intron 6). The allelic frequencies found in our sample varied from 1-37%. The novel SNPs detected in the CYP3A4 gene suggest that the Chinese population has different patterns of allele frequency compared with other populations. CONCLUSION: Several SNPs were detected in the CYP3A4 gene. The study of genetic variants in CYP3A4 may have an important significance for the understanding of genotype and phenotype relationships.

Adult↗

[Ultrastructure of poly-DL-lactic acid as GTR membrane of soft tissue defects in goats palates].

OBJECTIVE: To study the ultrastructure changes of PDLLA as GTR membrane of soft tissue defects in the palates of goats. METHODS: To establish penetrating rectangle palate defects in 8 goats. PDLLA membranes were implanted into the defect areas to guide the regeneration of the soft tissue defects. In 1, 2, 4, 6 months after the operation, the membranes were observed with scanning electron microscope. RESULTS: The surface of PDLLA membrane was regular network before implantation. 1 month after the implantation, the edge of network became blunt. 2 months after the implantation, the surface of PDLLA membrane became coarse and irregular. 4 months after the implantation, PDLLA membrane network collapsed. 6 months after the implantation, PDLLA degraded into scraggly accumulation. CONCLUSION: PDLLA membrane supplies good supporting function during concrescence of the soft tissue defects. PDLLA gradually loses mechanic intensity and is absorbed.

Animals↗

Characterization of HSCD5, a novel human stearoyl-CoA desaturase unique to primates.

Stearoyl-CoA desaturase (SCD) is an integral membrane protein of the endoplasmic reticulum (ER) that catalyzes the formation of monounsaturated fatty acids from saturated fatty acids. Recent studies suggest that SCD is a key regulator of energy metabolism and has implications in dislipidemia and obesity. Four SCD isoforms (SCD1-4) have been identified in mouse. In human, only one SCD isoform has been characterized so far. Here we report that the previously reported human ACOD4 gene encodes a distinct stearoyl-CoA desaturase, hSCD5. GenBank database mining revealed orthologues of hSCD5 in the primates, but not in the rodents. In transiently transfected 293 cells, hSCD5 co-localized with calnexin on ER membrane. Microsome fractions prepared from hSCD1 and hSCD5 transfected cells displayed similar delta 9 desaturase activity. Quantitative real-time RT-PCR analysis suggested that hSCD5 was abundantly expressed in adult brain and pancreas. These data suggested that hSCD5 plays a role distinct from that of hSCD1 during development and in normal physiological conditions.

Amino Acid Sequence↗

[Expression and genetic immunization of hantaan virus G2 recombinant adenovirus].

AIM: To express hantaan virus(HTNV) envelope glycoprotein G(2) recombinant adenovirus(Adeno-G(2)) in vero E6 cells and explore its property of inducing immune response. METHODS: Vero E6 cells were infected with the HTNV Adeno-G(2) (100 MOI). The expression of Adeno-G(2) in the infected Vero E6 cells was detected by IFA. BALB/c mice were immunized with HTNV Adeno-G(2), then the immune response to Adeno-G(2) was tested by ELISA, microcell-culture neutralizing experiment and lymphocyte proliferation test (MTT colorimetry). RESULTS: IFA detection showed the expression of Adeno-G(2) in the infected Vero E6 cells. The titer of specific antibody was 1:40; The low-titer neutralization antibody was also detected. But the lymphocyte proliferation reaction was not notable. CONCLUSION: The HTNV Adeno-G(2) can stimulate BALB/c mice to develop specific humoral immune response instead of specific cell-mediated immunity. This study provides the experimental basis for the development of gene engineering vaccine of HFRS.

Adenoviridae↗

An association between polymorphisms of the interleukin-10 gene promoter and schizophrenia in the Chinese population.

Immunological abnormalities have been found to be associated with schizophrenia for decades. Cytokines are key proteins involved in the immune system activation. Interleukin-10 (IL-10), an important immunoregulatory cytokine, is located on chromosome 1q31-32, a region previously reported to be linked to schizophrenia in genetic studies. Thus, a study was carried out on the association between schizophrenia and three single nucleotide polymorphisms in the promoter region of IL-10 gene. Totally, 341 patients and 334 controls of Chinese descent were analyzed. Statistically significant differences were observed in both allelic and genotypic frequencies of the -592A/C polymorphism (Allele, chi(2)=4.43, df=1, P=0.032, odds ratio (OR)=1.26, 95% CI 1.02-1.56; Genotype, chi(2)=6.18, df=2, P=0.044) while the other two polymorphisms did not show such differences. The observed haplotype distributions revealed a significant association with schizophrenia (P=0.0008). These data suggest that the IL-10 gene may confer susceptibility to the development of schizophrenia in the Chinese population.

Adult↗

Galectin-12 is required for adipogenic signaling and adipocyte differentiation.

Galectin-12 is a member of the galectin family consisting of beta-galactoside-binding proteins with conserved carbohydrate recognition domains. This protein is preferentially expressed in peripheral blood leukocytes and adipocytes. We previously showed that galectin-12 is induced by cell cycle block at the G(1) phase and causes G(1) arrest when overexpressed (Yang, R.-Y., Hsu, D. K., Yu, L., Ni, J., and Liu, F.-T. (2001) J. Biol. Chem. 276, 20252-20260). Here, we show that the galectin-12 gene is expressed in mouse preadipocytes and is up-regulated when preadipocytes undergo cell cycle arrest, concomitant with acquisition of the competence to undergo differentiation in response to adipogenic hormone stimulation. Following a brief down-regulation 1 day after adipogenic treatment, its expression was once again markedly elevated when cells underwent terminal differentiation. Down-regulation of endogenous galectin-12 expression by RNA interference greatly reduced the expression of the adipogenic transcription factors CCAAT/enhancer-binding protein-beta and -alpha and peroxisome proliferator-activated receptor-gamma and severely suppressed adipocyte differentiation as a result of defective adipogenic signaling. We conclude that galectin-12 is required for signal transduction that conveys hormone stimulation to the induction of adipogenic factors essential for adipocyte differentiation. The findings suggest that galectin-12 is a major regulator of adipose tissue development.

3T3 Cells↗

Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma.

Galectin-3 is a member of a beta-galactoside-binding animal lectin family. Previous in vitro studies have demonstrated that galectin-3 is involved in a number of activities; however, the roles of this lectin in physiological and pathological processes in vivo remain to be elucidated. Herein, we show, in a murine model of ovalbumin (OVA)-induced asthma that 1) peribronchial inflammatory cells expressed large amounts of galectin-3; 2) bronchoalveolar lavage fluid from OVA-challenged mice contained significantly higher levels of galectin-3 compared to control mice; and 3) macrophages in bronchoalveolar lavage fluid were the major cell type that contained galectin-3. We investigated the role of galectin-3 in the allergic airway response by comparing galectin-3-deficient (gal3(-/-)) mice and wild-type (gal3(+/+)) mice. OVA-sensitized gal3(-/-) mice developed fewer eosinophils and lower goblet cell metaplasia, after airway OVA challenge compared to similarly treated gal3(+/+) mice. In addition, the OVA-sensitized gal3(-/-) mice developed significantly less airway hyperresponsiveness after airway OVA challenge compared to gal3(+/+) mice. Finally, gal3(-/-) mice developed a lower Th2 response, but a higher Th1 response, suggesting that galectin-3 regulates the Th1/Th2 response. We conclude that galectin-3 may play an important role in the pathogenesis of asthma and inhibitors of this lectin may prove useful for treatment of this disease.

Animals↗

Genetic structure adds power to detect schizophrenia susceptibility at SLIT3 in the Chinese Han population.

The Chinese Han population, the largest population in the world, has traditionally been geographically divided into two parts, the Southern Han and Northern Han. In practice, however, these commonly used ethnic labels are both insufficient and inaccurate as descriptors of inferred genetic clustering, and can lead to the observation of "spurious association" as well as the concealment of real association. In this study, we attempted to address this problem by using 14 microsatellite markers to reconstruct the population genetic structure in 768 Han Chinese samples, including 384 Southern Han and 384 Northern Han, and in samples from Chinese minorities including 48 Yao and 48 BouYei subjects. Furthermore, with a dense set of markers around the region 5q34-35, we built fine-scale haplotype networks for each population/subpopulation and tested for association to schizophrenia susceptibility. We found that more variants in SLIT3 tend to associate with schizophrenia susceptibility in the genetically structured samples, compared to geographically structured samples and samples without identified population substructure. Our results imply that identifying the hidden genetic substructure adds power when detecting association, and suggest that SLIT3 or a nearby gene is associated with schizophrenia.

Adult↗

[Guided reconstruction of soft tissue defects of the palate with n-HA/PA66 plates: an experimental study in goats.].

PURPOSE: To evaluate the effect of n-HA/PA66 plate as a guided implant for the regeneration of the soft tissue defects in palatal region of goats. METHODS: 12 goats were divided into experimental group and control group at random. 18.0 mm x 14.0 mm soft tissue defect and 15.0 mm x 13.0 mm hard tissue defect were formed artificially in hard palate. n-HA/PA66 plates were implanted to the defect in the experimental group. The tissue regeneration in the defects was observed and the structure of regenerating tissue was analyzed by histology. RESULTS: The mucoperiosteal tissue in the experimental group regenerated along the n-HA/PA66 plates and the mucoperiosteal defects were closed in 6 weeks. The soft and hard tissues were not closed up in control group in 6 weeks. CONCLUSION: n-HA/PA66 plates can guide the regeneration of mucoperiosteal tissue to close the palatal defects.

Animals↗