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Biomedical subjects

Biao Chen

Publications and source records attributed to Biao Chen.

At least 19 recordsLinked to original sources

Multi-omics insights into the physiological mechanisms of bile acid accumulation in the gallbladder in brumation-like snakes.

Hibernation/brumation represents an important physiological adaptation for animals to cope with seasonal environmental changes. Field observations suggested increased gallbladder weight in the Five-pacer viper (Deinagkistrodon acutus) during brumation, and our quantitative measurements confirmed this increase together with bile acid accumulation. By integrating a multi-omic approach, this study elucidates the regulatory mechanisms of bile acid accumulation in the gallbladder during brumation. Results showed that taurocholic acid (TCA) and taurodeoxycholic acid (TDCA) were the major components in the gallbladder of the brumation-like group, with significantly elevated concentrations of bile acids, whereas bile acid concentrations in serum and intestinal contents were markedly reduced, indicating suppression of the enterohepatic circulation and consequent accumulation of bile acids in the gallbladder. Hepatic transcriptomic analysis revealed significant downregulation of bile acid synthesis and regulatory genes in brumation-like snakes. In contrast, the alternative synthesis pathway gene sterol 27-hydroxylase (CYP27A1) and some transporter genes were slightly upregulated. Further, some modification genes and regulatory genes showed no significant differences between active and brumation-like states. Gut microbiota analysis demonstrated Akkermansia muciniphila, Bacteroides fragilis, and Citrobacter freundii were more enriched in the active group, which were common microbes related to bile acid metabolism, and the correlation analysis confirmed this relationship. Taken together, these findings indicate that the "physiological bile acid accumulation" observed in snakes during brumation-like state is jointly driven by suppressed hepatic synthesis, reduced enterohepatic circulation, and remodeled microbial community structure. The study provides novel comparative physiological insights into extreme metabolic homeostasis in animals.

Animals↗

Cigarette smoke impairs NK cell-dependent tumor immune surveillance.

In this study, we investigated the impact of cigarette smoke on tumor immune surveillance and its consequences to lung tumor burden in a murine lung metastasis model. Cigarette smoke exposure significantly increased the numbers of lung metastases following B16-MO5 melanoma challenge. This effect was reversible; we observed significantly fewer tumor nodules following smoking cessation. Using RAG2(-/-) and RAG2(-/-)gamma(c)(-/-) mice, we provide strong evidence that increased tumor incidence was NK cell dependent. Furthermore, we show that cigarette smoke suppressed NK activation and attenuated NK CTL activity, without apparent effect on activating or inhibitory receptor expression. Finally, activation of NK cells through bone marrow-derived dendritic cells conferred protection against lung metastases in smoke-exposed mice; however, protection was not as efficacious as in sham-exposed mice. To our knowledge, this is the first experimental evidence showing that cigarette smoke impairs NK cell-dependent tumor immune surveillance and that altered immunity is associated with increased tumor burden. Our findings suggest that altered innate immunity may contribute to the increased risk of cancer in smokers.

Animals↗

Characterization of ZNF23, a KRAB-containing protein that is downregulated in human cancers and inhibits cell cycle progression.

The Krupple-associated box-containing zinc-finger proteins (KRAB-ZFPs) make up one of the largest family of transcription factors. Several members of the KRAB-ZFPs modulate cell growth, survival and are implicated in malignant disorders. However, most members are not well characterized and their functions are largely unknown. Here we report that ZNF23, a member of KRAB-ZFPs, inhibits cell cycle progression. ZNF23 protein localized to the nucleus and was ubiquitously expressed in all tested normal tissues. However, the expression levels of ZNF23 protein were lost or greatly reduced in human cancer. Ectopic expression of ZNF23 led to enhancement of p27(kip-1) expression, growth inhibition and cell cycle arrest in G(1) phase. Downregulation of p27(kip-1) by siRNA against p27(kip-1) reversed growth inhibition induced by ZNF23. Furthermore, the growth-inhibitory effect of ZNF23 was p53-independent. Deletion analysis revealed that the effect of ZNF23 did not rely on its KRAB domain, but on the C-terminal zinc fingers. Thus, we have identified a new member of KRAB-ZNF superfamily with growth-inhibitory ability and its downregulation may contribute to carcinogenesis.

Cell Cycle↗

[Diffusion tensor imaging of the normal-appearing brain tissue in relapsing-remitting multiple sclerosis].

OBJECTIVE: To investigate whether normal-appearing brain tissue (NABT) on conventional MRI has occult damage in patients with relapsing-remitting multiple sclerosis (RRMS) by using diffusion tensor imaging (DTI) histogram analysis, and to determine the correlations between DTI histogram-derived measures of the NABT and expanded disability status scale (EDSS) scores, disease durations, T2WI lesion volumes and brain tissue volumes in RRMS patients. METHODS: Conventional MRI and DTI scans were performed in 24 patients with RRMS and 24 sex- and age-matched healthy controls. After segmentation of the NABT, the mean diffusivity (MD) and fractional anisotropy (FA) histograms of the NABT were created and analyzed. RESULTS: In patients with RRMS, the average MD (1.014 x 10(-3) mm2 x s(-1)) of the NABT was higher than that (0.910 x 10(-3) mm2 x s(-1)) of control subjects (t = 7.238, P < 0.001); the MD histogram peak height (8.858 per thousand) of the NABT was lower than that (0.767 per thousand) of control subjects (t = 6.161, P < 0.001); the MD histogram peak location (0.809 x 10(-3) mm2 x s(-1)) of the NABT was higher than that (0.767 x 10(-3) mm2 x s(-1)) of control subjects (t = 5.324, P < 0.001); the average FA (0.231) of the NABT was lower than that (0.254) of control subjects (t = 6.217, P < 0.001); the FA histogram peak height (4.502 per thousand) of the NABT was higher than that (4.107 per thousand) of control subjects (t = 4.198, P < 0.001); no significant difference was found in the FA histogram peak location of the NABT between these two groups (t = 1.223, P = 0.227); none of the DTI histogram-derived measures correlated with EDSS scores or disease durations (P > 0.05); the average MD and all the FA histogram-derived measures correlated with T2WI lesion volumes (P < 0.05); and the average MD, the MD histogram peak height and all the FA histogram-derived measures correlated with brain tissue volumes (P < 0.05). In healthy controls, however, only the average FA of the NABT correlated with brain tissue volumes. CONCLUSION: Patients with RRMS had occult damage in the NABT and the extent of NABT damage was related to the lesion load of brain and to the extent of brain tissue atrophy.

Adolescent↗

Rectification of excitation with bathochromic shift induced by intense absorption of organic ligands during emission measurement of Eu(III) complex.

Bathochromic shift in excitation spectrum was observed during emission measurement of Eu(DBM)(3)Phen containing dilute solution in methyl methacrylate (MMA). Detailed analysis shows that the reason of bathochromic shift is not the formation of molecule aggregation. It is caused by the intense absorption of ligands in the complex. Based on this model, a new method has been established to rectify excitation spectra before emission measurement of systems with different concentration. There exists a critical value of the absorption strength, which is 0.87 from calculation. Higher absorption than this value will cause the bathochromic shift of excitation peak. The wavelength whose absorbance is 0.87 will be the position of the strongest excitation peak. With 200 ppm and 500 ppm Eu(DBM)(3)Phen as the standard sample, relations between relative concentration and wavelength of excitation peak in Eu(DBM)(3)Phen system were deduced and plotted. Theoretical curves are in good agreement with experiment data except extra-dilute concentration, for partial decomplexation of the beta-diketonate and phenanthroline ligands.

Absorption↗

No mutation was detected in the LMNA gene among sporadic Charcot-Marie-Tooth patients.

OBJECTIVE: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. METHODS: Twelve exons of the LMNA gene were amplified from genetic DNA. PCR products of each exon were analyzed by single strand conformational polymorphism (SSCP). RESULTS: No abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected. CONCLUSION: The CMT diseases resulted from the mutations of LMNA gene were rare.

Charcot-Marie-Tooth Disease↗

Biological properties of neural progenitor cells isolated from the hippocampus of adult cynomolgus monkeys.

BACKGROUND: The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells (NPCs) from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro. METHODS: NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis. RESULTS: During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-beta III-tubulin (Tuj1) and 84% expressed astrocyte specific marker-fibrillary acidic protein (GFAP). In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. CONCLUSIONS: NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.

Animals↗

Mutation frequency for Charcot-Marie-Tooth disease type 1 in the Chinese population is similar to that in the global ethnic patients.

PURPOSE: To investigate the genetic loci/mutations among the Chinese Charcot-Marie-Tooth disease type 1 (CMT1), which accounts for approximately 70% of Charcot-Marie-Tooth; and to study the genetic heterogeneity and mutation frequency. METHODS: CMT1A duplication and mutations at loci of MPZ, Cx32/GJB1, EGR2, and LITAF/SIMPLE were analyzed among 32 clinically diagnosed CMT1 patients of Chinese ancestry. RESULTS: The CMT1A duplication was detected in 62.5% (20/32) CMT1 patients. This duplication accounts for the major mutation for Chinese CMT1. Among 12 cases that have no CMT1A duplication detected, three point mutations including one (3.1%) in MPZ and two (6.3%) in Cx32 were identified. No mutation was detected in genes PMP22, EGR2 and LITAF among the remaining nine (28.1%) CMT1 patients. CONCLUSION: The mutation frequency for the Chinese CMT1 is similar to that seen in the global ethnic population. Molecular testing of the CMT1A duplication, along with the loci of MPZ and Cx32, may detect the majority of Chinese CMT1 patients.

Amino Acid Substitution↗

[Polymorphisms of neural nicotinic cholinergic receptor alpha 4 gene of Chinese].

OBJECTIVE: To screen for polymorphisms in alpha 4 subunit (principal subunit of nAChR) gene (CHRNA4). METHODS: DNA was extracted from leukocytes of all subjects including 100 healthy senior people and 100 patients with Parkinson's disease (PD). The exons and adjacent intron regions of CHRNA4 were amplified with PCR. SNPs were screened by denatured high performance liquid chromatography (DHPLC) techniques and restriction fragment length polymorphisms. Potential mutations were confirmed by sequencing. RESULTS: Total 10 polymorphisms were detected and identified in coding and adjacent intron regions of nAChR alpha 4 gene, that are 420C/T (0.873/0.127), 870C/T (0.828/0.172), 1440A/C (0.858/0.142), 1860C/T (0.738/0.262), 1890C/T (0.605/0.395), intron 5 +14T/C (0.553/0.447), intron 2 +22G/A (0.873/0.127), intron 3 +182 Del22bp (0.813/0.187), 1758C/T and 1809C/T (reference for coding sequence is GenBank SNPs 000744), of which the last three are novel mutations. PD patients appeared higher frequency of deletion in intron 3+182(0.235) than normal controls (0.140)(P=0.015). CONCLUSION: nAChR alpha 4 gene is polymorphic. PD patients take higher frequency of intron3+182 Del 22 bp.

Aged↗

[Possible association between polymorphisms of human leukocyte antigen-DQ genes and susceptibility to trichloroethylene-induced severe generalized dermatitis].

OBJECTIVE: To investigate the association between genetic polymorphisms of human leukocyte antigen-DQ (HLA-DQ) and susceptibility to trichloroethylene (TCE)-induced severe generalized dermatitis. METHODS: A case-control study was conducted which included 112 patients with TCE-induced severe generalized dermatitis and 142 healthy controls exposed to TCE in the same workshop. The DNA sequences in exon2 of HLA-DQA1 and HLA-DQB1 were performed by direct sequencing of polymerase chain reaction (PCR) products. The frequencies distribution of allelic genotypes and codon polymorphisms were compared. RESULTS: The frequencies of DQA1*0201 and 060101/0602 in cases [7.6% (17/224) and 16.1% (36/224)] were significantly higher than those of the exposed controls [3.5% (10/284) and 7.0% (20/284)], while frequencies of DQA1*0103 and 050101/0503/0505 in cases [5.8% (13/224) and 8.9% (20/224)] were significantly lower than those of exposed controls [10.9% (31/284) and 17.3% (49/284)]. In terms of codon polymorphisms, there were 5 codons of DQA1 (25, 41, 52, 54 and 69) showing significant differences between cases and controls. There were no significant differences in the frequencies of allelic genotypes of HLA-DQB1 between cases and exposed controls. CONCLUSION: The genetic polymorphisms of HLA-DQA1 might be one of the factors influencing the individual susceptibility to TCE-induced severe generalized dermatitis.

Adolescent↗

A QSPR treatment for the thermal stabilities of second-order NLO chromophore molecules.

Quantitative structure-property relationships were studied between descriptors representing the molecular structures and thermal decomposition temperatures (T(d)) for a diverse set of 90 second-order nonlinear optical (NLO) chromophores. A seven-parameter model was developed for the prediction of molar thermal decomposition function Y(d) (T(d) M, where M represents the molar weight) with R2 = 0.9642 and SEE = 14.01 by multilinear regression analysis. The mean relative error for the prediction of T(d) was 4.46%. The stability of the proposed model was validated using leave-one-out cross-validation. All descriptors involved in the model were derived solely from the chemical structures of the NLO chromophores.

Molecular Structure↗

Prediction of glass transition temperatures of OLED materials using topological indices.

The QSPR study was performed between topological indices and glass transition temperatures (T(g)s) of organic light-emitting diode materials based on a diverse set of 80 compounds. A five-parameter correlation with the squared correlation coefficient R2 = 0.9304 and an average absolute error of 7.7 K was obtained through step-wise multi-linear regression analysis with leave-one-out cross-validation. The new model proposed is predictive and requires only topological indices in the calculations and has the advantage of the relative ease in calculating the descriptors, which makes it easier to apply. The predicted results of the new model are comparable to those of the existing equation by using the Comprehensives Descriptors for Structural and Statistical Analysis approach.

Glass↗

[The characteristics of gene mutations in Chinese patients with Charcot-Marie-Tooth disease].

OBJECTIVE: To study the characteristics of gene mutations in Chinese patients with Charcot-Marie-Tooth disease (CMT). METHODS: Real-time quantitative PCR, PCR-SSCP, and/or direct sequencing were used to analyze the mutation of the pathogenic genes PMP22, MPZ, CX32, EGR2, GDAP1, NEFL, HSP22 and HSP27 in 113 probands of CMT families, 45 of which had family history, from different provinces in China. The whole family members of the subjects with abnormal electrophoretic bands and 50 normal controls underwent the same examination. RESULTS: Thirty-six cases of PMP22 duplication, 7 cases of CX32 mutation, 1 case of HSP22 mutation, 1 case of HSP27 mutation, 1 case of MPZ mutation, and 1 case of GDAP1 mutation were found in the 113 CMT probands. No point mutation was found in PMP22, EGR2 and NEFL genes. CONCLUSION: Among the Chinese CMT patients 31.9% are caused by PMP22 duplication, 6.2% by CX32, and 0.9% by HSP22, HSP27, MPZ and GDAP1. Point mutations of PMP22, EGR2 and NEFL are rare.

Adolescent↗

Characterization of spectroscopic of Pr(DBM)3(TPPO)2 containing poly(methyl methacrylate).

The absorption and fluorescence spectra of Pr(DBM)3(TPPO)2 (DBM: dibenzoylmethane, TPPO: triphenylphosphine oxide) containing poly(methyl methacrylate) (PMMA) were measured. The energy levels are assigned and analyzed in terms of the free-ion Hamiltonian model. From the data available in the absorption spectrum, various spectroscopic parameters such as the spherically symmetric part of the free-ion Hamiltonian (E(AVG)), Slater-Condon (F2, F4, F6), spin-orbit interaction (zeta), Judd-Ofelt (omega2, omega4, omega6) parameters and the reduced matrix elements are derived. The radiative properties of Pr(DBM)3(TPPO)2 containing PMMA were also predicted according to the Judd-Ofelt theory. The values of the fluorescence branching ratio and the emission cross section of 3P0 --> 3F2 fluorescence transition revealed that Pr(DBM)3(TPPO)2 containing PMMA is an efficient luminescent material.

Models, Chemical↗

Identification of a novel Wee1 isoform.

We have identified a novel isoform of Wee1 kinase (Wee1i), which uses Met215 of Wee1 as its initiation codon. RT-PCR, Western blot, and in situ hybridization verified wee1i expression in mammalian cells, rat brain, and rat thymus. Recombinant and partially purified Wee1i from rat thymus displayed kinase activity comparable to or higher than Wee1. The N-terminal 214 residues of Wee1 facilitate its ubiquitin-dependent degradation to trigger mitotic entry. Since Wee1i, lack of these 214 residues, it may evade this degradation and thus provide constitutive Wee1-like kinase activity to inhibit mitotic cell proliferation. Thus, Wee1i may play an important role in differentiation and in tumor suppression.

Animals↗

Mutation analysis of the small heat shock protein 27 gene in chinese patients with Charcot-Marie-Tooth disease.

BACKGROUND: Charcot-Marie-Tooth (CMT) disease, the most common hereditary peripheral neuropathy, is highly clinically and genetically heterogeneous, and mutations in at least 18 genes have been identified. Recently, mutations in small heat shock protein 27 (Hsp27) were reported to cause CMT disease type 2F and distal hereditary motor neuropathy. OBJECTIVE: To investigate the frequency and phenotypic features of an Hsp27 mutation in Chinese patients with CMT disease. DESIGN: DNA samples from 114 unrelated patients with CMT disease were screened for mutations in Hsp27 by polymerase chain reaction and direct sequencing. A cosegregated study was performed using the MbiI restriction endonuclease, and 50 healthy control subjects were analyzed. Haplotype analysis was performed using 5 short tandem repeat markers to analyze whether the families with the same mutation probably had a common ancestor. RESULTS: One missense mutation, C379T, was detected in 4 autosomal dominant families with CMT disease type 2, and haplotype analysis indicated that the 4 families probably had a common founder. The frequency of the Hsp27 mutation is 0.9% (1/111) in Chinese patients with CMT disease in our study, and the phenotypes were characterized by later onset (age, 35-60 years) and mild sensory impairments. Electrophysiological findings showed moderately to severely slowed nerve conduction velocities in lower limb nerves but normal or mildly reduced velocities in upper limb nerves. CONCLUSIONS: To our knowledge, this is the first report of an Hsp27 mutation in the People's Republic of China. The C379T mutation in Hsp27 also causes CMT disease type 2, except for distal hereditary motor neuropathy, and the phenotypes are distinct from the family with CMT disease type 2F described previously. A mutation of Hsp27 may be uncommon in Chinese patients with CMT disease.

Adult↗

[NQ01 gene polymorphism C609T associated with an increased risk for cognitive dysfunction and sporadic Alzheimer's disease in Chinese].

OBJECTIVE: To investigate the association between the C609T polymorphism of NADP (H): quinoneoxidoreductase 1 (NQ01) gene and decreased cognitive function and sporadic Alzheimer's disease (AD) in a community cohort. METHODS: Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC) and sequencing were used to determine the genotype of NQ01 in 110 subjects without cognitive dysfunction, 21 with cognitive dysfunction, and 65 AD patients from a community cohort. RESULTS: Significantly different distributions of C/T and T/T genotypes were found between MMSE normal and abnormal subjects (OR=2.8, 95%CI 0.96-8.18, P=0.024), and between AD patients and healthy controls (OR=3.27, 95% CI 1.54-6.94, P=0.001), respectively. The frequencies of T allele of NQ01 C609T were significantly higher in MMSE abnormal subjects and AD patients (P=0.034 and 0.005) as compared to normal controls. CONCLUSION: The C609T polymorphism of NQ01 gene may be a genetic risk factor for cognitive dysfunction and sporadic AD in Chinese population.

Alzheimer Disease↗