Biomedical subjects

Junwei Zhang

Publications and source records attributed to Junwei Zhang.

10 recordsLinked to original sources

PubMed2026

Adaptive Evolution of the PFK Gene Family in Chinese Longsnout Catfish, Leiocassis longirostris.

The Chinese longsnout catfish is a typical carnivorous fish with a relatively weak ability to utilize glucose. However, the genomic basis for its glucose metabolic adaptation remains unclear. In this study, we used comparative genomics methods to systematically analyze the evolutionary characteristics of glucose metabolism-related genes in the Chinese longsnout catfish, focusing on gene family evolution, patterns of expansion and contraction, and selective pressures. The results indicate that glucose metabolism-related genes have undergone significant reshaping during evolution. Genes involved in glucose digestion, absorption, and insulin signaling pathways demonstrate a tendency toward contraction, while those associated with protein and lipid metabolism exhibit expansion. This pattern is consistent with the species' long-term adaptation to a high-protein, high-fat diet. Comparative analysis further revealed that, compared to fish with different dietary habits, certain key genes involved in glycolysis in the Chinese longsnout catfish exhibit a reduction in copy number. Molecular evolutionary analysis showed that key genes involved in glycolysis and gluconeogenesis (including hexokinase 2 (hk2), phosphofructokinase, muscle/platelet (pfkm/p)) exhibit signs of accelerated evolution or positive selection. Notably, the PFK gene family exhibits complex evolutionary characteristics resulting from the combined effects of gene contraction, rapid evolution, and positive selection. In summary, this study reveals the genomic evolutionary basis for the glucose metabolic adaptation of the Chinese longsnout catfish and identifies the PFK gene family as a key candidate for elucidating its unique glucose metabolic characteristics.

Leiocassis longirostris↗

PubMed2005

Effectiveness of multiple-level decompression in laminoplasty and simultaneous C1 laminectomy for patients with cervical myelopathy.

A retrospective study to investigate the relationship between the surgical levels and decompression effects was performed in patients with cervical myelopathy who had undergone Tension-band laminoplasty (TBL) with/without simultaneous C1 laminectomy. One hundred and sixty-eight patients (115 males, 53 females; age: 31-80 years, average 58.9 years; follow-up period: 12-120 months, average 20 months) were divided into three groups according to the range of the surgical levels: seventy-two patients in group A underwent TBL at the C2-C7 levels with C1 laminectomy; 60 patients in group B underwent TBL at the C2-C7 levels; 36 patients in group C underwent TBL at the C3-C7 levels. Neurological evaluation was performed by using the Japanese Orthopedic Association (JOA) scoring system. The alignment changes of the spinal column and the spinal cord were analyzed using pre- and post-operative roentgenograms and MRIs. The differences in the pre- and post-operative anterior subarachnoid spaces (D-ASAS), the spinal cord diameters (D-CORD), and the dural sleeve diameters (D-DURA) at the C1-C7 levels were also analyzed by using MRIs. The JOA scores improved in all groups. As for the spinal alignment, neither significant changes between pre- and post-operation in any group nor significant differences among the three groups were found. The lordosis of the cervical spinal cord was decreased in all groups. D-ASAS of group A was larger than that of group B at the C1-C5 levels (P<0.05), as were those of D-CORD and D-DURA at the C1-C2 and C4-C5 levels (P<0.05). D-ASAS of group A was larger than that of group C at the C1-C4 levels (P<0.05), as were those of D-CORD and D-DURA at the C1-C5 levels (P<0.05). In conclusion, laminoplasty including the C2-C7 levels with simultaneous C1 laminectomy was proven to allow the most posterior shift of the spinal cord within the widened dural sleeve at C5 or higher levels without significantly changing the spinal alignment.

Adult↗

PubMed2005

A new method for measurement of (-)-sophocarpine, a candidate therapeutic for viral myocarditis, in plasma: application to a toxicokinetic study in beagle dogs.

The naturally occurring alkaloid (-)-sophocarpine (SC) has been developed as a novel anti-coxsackieviral agent for potential treatment of viral myocarditis. However, there is currently no rapid, sensitive method available for ascertaining systemic exposure during the course of SC toxicity studies. The development and full validation of the first rapid and sensitive method, based on liquid chromatography with tandem mass spectrometry (LC/MS/MS), for determination of SC in plasma is reported here. This new assay increases sample throughput by using minimal sample clean-up procedures and short chromatographic analysis times. The bio-matrix effect on the ionization of SC and the internal standard, (-)-stepholidine, was investigated for method development and validation, and two organic solvents (methyl tert-butyl ether and ethyl acetate) were found for sample preparation that led to low matrix effects. The new analytical method was used to analyze plasma samples obtained from a repeated-dose toxicity study of SC in beagle dogs. The results of the toxicokinetic analysis indicated that the systemic exposure to SC was proportional to the dose, and that no significant accumulation of SC was observed after 3 months of repeated treatments with intravenous SC at 7.5, 15, or 30 mg/kg/day. This sensitive and specific LC/MS/MS technique can form the basis for accurate quantification of SC in various biological fluids for preclinical and clinical pharmacokinetic evaluation.

Alkaloids↗

PubMed2004

Development of KiBank, a database supporting structure-based drug design.

KiBank is a database of inhibition constant (Ki) values with 3D structures of target proteins and chemicals. Ki values were accumulated from peer-reviewed literature searched via PubMed. The 3D structure files of target proteins were originally from Protein Data Bank (PDB), while the 2D structure files of the chemicals were collected together with the Ki values and then converted into 3D ones. In KiBank, the chemical and protein 3D structures with hydrogen atoms were optimized by energy minimization and stored in MDL MOL and PDB format, respectively. KiBank is designed to support structure-based drug design. It provides structure files of proteins and chemicals ready for use in virtual screening through automated docking methods, while the Ki values can be applied for tests of docking/scoring combinations, program parameter settings, and calibration of empirical scoring functions. Additionally, the chemical structures and corresponding Ki values in KiBank are useful for lead optimization based on quantitative structure-activity relationship (QSAR) techniques. KiBank is updated on a daily basis and is freely available at . As of August 2004, KiBank contains 8000 Ki values, over 6000 chemicals and 166 proteins covering the subtypes of receptors and enzymes.

Binding Sites↗

PubMed2004

[KiBank: a database for computer-aided drug design based on protein-chemical interaction analysis].

KiBank is a database for computer-aided drug design and consists of binding affinities and chemical and target protein structures. Each chemical or protein structure with hydrogen atoms added was optimized by energy minimization and stored in PDB or MDL MOL file format, so that the structural data can be directly used for in silico binding studies. To describe the extent of inhibition, the inhibition constant (K(i)) value is used to simplify comparisons of strengths among chemical-protein bindings. As of April 2004, KiBank contained 142 proteins, over 5000 chemicals, and over 6000 binding affinity values that were published in peer-reviewed journals. The binding affinity values are currently mostly for membrane and nuclear receptors but are soon being expanded to other drug targets. KiBank is updated daily and can be accessed on the Web at http://kibank.iis.u-tokyo.ac.jp/at no charge.

Computer-Aided Design↗

PubMed2003

RMRP mutations in Japanese patients with cartilage-hair hypoplasia.

We examined 12 Japanese patients with metaphyseal chondrodysplasia (MCD) for mutations in the ribonuclease mitochondrial RNA processing gene (RMRP), and identified four novel mutations in two patients with typical and atypical cartilage-hair hypoplasia (CHH), a form of MCD characterized by extra-skeletal manifestations including hypoplastic hair and defective immunity. A patient with typical CHH had a 17-bp duplication at +3 and a de novo 182G > A. The other patient with atypical CHH had a 17-bp insertion at -20 and a 218A > G. Expression analysis revealed that the allele with this insertion mutation in the promoter region silenced the gene. Spectrum analysis of the mutations and polymorphisms in RMRP showed marked difference between the Japanese and other ethnic groups. Such ethnic and phenotypic difference should be taken into account in mutation analysis of the gene.

Adolescent↗

PubMed2003

Surgical anatomy of the nerves and muscles in the posterior cervical spine: a guide for avoiding inadvertent nerve injuries during the posterior approach.

STUDY DESIGN: An anatomic study investigated the cervical dorsal rami and major cervical paravertebral muscles. OBJECTIVE: To provide a detailed description of the cervical dorsal rami and important paravertebral muscles as a way of avoiding inadvertent injuries during the posterior approach. SUMMARY OF BACKGROUND DATA: No detailed anatomic studies of the nerves and the muscles in the posterior neck useful for the posterior approach have been reported previously. METHODS: Running courses of the cervical dorsal rami of spinal nerves and the morphology of cervical major paravertebral muscles were studied using 14 cadavers. In four posterior approaches of cervical laminoplasty, subcutaneous facial exits of cutaneous nerves and the running course of the right C3 medial branches around facet joint were exposed for observation of living anatomy. RESULTS: Every medial branch from the dorsal rami of the C3-C8 spinal nerves passed through an anatomic tunnel dorsolateral to the facet joint. The base of the tunnel was a bony gutter between neighboring facet joint capsules, and the roof was the tendon of the semispinalis capitis. In this tunnel, the medial branch had a little laxity in moving, and was assumed to be the most susceptible to iatrogenic injury during the operation. The semispinalis cervicis was composed with long muscle bundles. Each of these had only one or two innervating nerves from the dorsal rami of cervical spinal nerves. Cutaneous branches from the dorsal rami were found adjacent to every spinous process below the C2 spinous process in cadaveric studies. However, only two or three larger cutaneous nerves were discernible below the C5 or C6 spinous process in surgical approaches. CONCLUSIONS: With the posterior approach to the cervical spine, a precise knowledge of the cervical dorsal rami anatomy and the innervating patterns of the paravertebral muscles is necessary for avoidance of inadvertent injuries to the nerves.

Adolescent↗

PubMed2003

A pair of sibs with tibial hemimelia born to phenotypically normal parents.

Tibial hemimelia is a rare congenital anomaly characterized by deficiency of the tibia with relatively intact fibula. Tibial hemimelia is identified as a solitary disorder, or a part of more complex malformation syndromes. Although the majority of cases with tibial hemimelia are sporadic, affected families with possible autosomal dominant or autosomal recessive inheritance have been reported. Here we report a pair of sibs, 6- and 2-year-old Japanese boys, with tibial hemimelia born to unrelated, phenotypically normal parents. The type of tibial hemimelia and associated malformations of hands and feet was quite different between the brothers. The elder brother was compatible with the Gollop-Wolfgang complex, and the younger brother with tibial agenesis-ectrodactyly syndrome. Screening of mutation by direct sequencing of candidate genes including Sonic hedgehog, HOXD-11, and HOXD-12 was unable to identify a disease-causing mutation.

Child↗

PubMed2002

Identification and characterization of the human long form of Sox5 (L-SOX5) gene.

The Sox (Sry-type HMG box) group of transcription factors, which is defined by a high-mobility group (HMG) DNA-binding domain, is categorized into six subfamilies. Sox5 and Sox6 belong to the group D subfamily, which is characterized by conserved N-terminal domains including a leucine-zipper, a coiled-coil domain and a Q-box. Group D Sox genes are expressed as long and short transcripts that exhibit differential expression patterns. In mouse, the long form of Sox5, L-Sox5, is co-expressed and interacts with Sox6; together, these two proteins appear to play a key role in chondrogenesis and myogenesis. In humans, however, only the short form of Sox5 has previously been identified. To gain insight into Sox5 function, we have identified and characterized human L-SOX5. The human L-SOX5 cDNA encodes a 763-amino-acid protein that is 416 residues longer than the short form and contains all of the characteristic motifs of group D Sox proteins. The predicted L-SOX5 protein shares 97% amino acid identity with its mouse counterpart and 59% identity with human SOX6. The L-SOX5 gene contains 18 exons and shows similar genomic structure to SOX6. We have identified two transcription start sites in L-SOX5 and multiple alternatively spliced mRNA variants that are distinct from the short form. Unlike the short form, which shows testis-specific expression, L-SOX5 is expressed in multiple tissues. Like SOX6, L-SOX5 shows strong expression in chondrocytes and striated muscles, indicating a likely role in human cartilage and muscle development.

Alternative Splicing↗

PubMedDate not supplied

VISCANA: visualized cluster analysis of protein-ligand interaction based on the ab initio fragment molecular orbital method for virtual ligand screening.

We have developed a visualized cluster analysis of protein-ligand interaction (VISCANA) that analyzes the pattern of the interaction of the receptor and ligand on the basis of quantum theory for virtual ligand screening. Kitaura et al. (Chem. Phys. Lett. 1999, 312, 319-324.) have proposed an ab initio fragment molecular orbital (FMO) method by which large molecules such as proteins can be easily treated with chemical accuracy. In the FMO method, a total energy of the molecule is evaluated by summation of fragment energies and interfragment interaction energies (IFIEs). In this paper, we have proposed a cluster analysis using the dissimilarity that is defined as the squared Euclidean distance between IFIEs of two ligands. Although the result of an ordered table by clustering is still a massive collection of numbers, we combine a clustering method with a graphical representation of the IFIEs by representing each data point with colors that quantitatively and qualitatively reflect the IFIEs. We applied VISCANA to a docking study of pharmacophores of the human estrogen receptor alpha ligand-binding domain (57 amino acid residues). By using VISCANA, we could classify even structurally different ligands into functionally similar clusters according to the interaction pattern of a ligand and amino acid residues of the receptor protein. In addition, VISCANA could estimate the correct docking conformation by analyzing patterns of the receptor-ligand interactions of some conformations through the docking calculation.

Binding Sites↗