Biomedical subjects

Zhiqiang Chen

Publications and source records attributed to Zhiqiang Chen.

At least 19 recordsLinked to original sources

PubMed2026

Identification and expression validation of key genes of Xiaozhengtongluo formula in the treatment of diabetic nephropathy by Mendelian randomization.

Xiaozhengtongluo formula (XZTL) has a positive effect on the treatment of diabetic nephropathy (DN), but its mechanism is not fully understood. Therefore, it is important to explore the key genes of XZTL in the treatment of DN. Differentially expressed genes (DEGs) between DN and control obtained from GSE96804, drug target genes of XZTL, and disease target genes of DN obtained from public databases were intersected. Genes of intersection were defined as candidate genes. Next, Mendelian randomization (MR) analysis was used to ascertain the causal associations between candidate genes and DN. Afterwards, key genes were confirmed through receiver operating characteristic (ROC) curve analysis and expression validation. Subsequently, enrichment analysis, molecular regulatory network analysis, and molecular docking were conducted. Finally, experimental verification of the expression levels of key genes was performed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Altogether, 29 candidate genes were screened via MR analysis, identifying APOD, IGFBP3, and LPL as significantly associated with DN. IGFBP3 and APOD were risk factors, whereas LPL was protective. Consistent expression trends across training and validation datasets defined them as key genes. All three were co-enriched in 26 pathways, including oxidative phosphorylation. Regulatory networks showed MIR497HG/hsa-miR-19a-3p regulated IGFBP3, and NEAT1/hsa-miR-29a-3p regulated LPL; IGFBP3 and LPL were co-targeted by SP3 and SP1. Molecular docking revealed APOD-baicalein, LPL-oleic acid, and IGFBP3-quercetin binding, suggesting therapeutic potential. RT-qPCR confirmed aberrant expression of these genes in DN, which was normalized by XZTL intervention. In this study, three key genes (APOD, IGFBP3, and LPL) of XZTL in the treatment of DN were finally obtained, providing mechanistic clues for understanding XZTL's multi-target mechanism and providing experimentally tractable candidate targets for DN molecular subtyping, targeted therapeutic development, and precision medicine approaches in TCM.

Diabetic Nephropathies↗

PubMed2006

Deprotonations and charges of well-defined {Mo72Fe30} nanoacids simply stepwise tuned by pH allow control/variation of related self-assembly processes.

The solution behavior of the largest inorganic acid known thus far, the neutral, spherical iron/molybdenum/oxide nanocluster {Mo72Fe30} ([triple bond{(MoVI) MoVI5}12FeIII30 1a), including the pH-controlled deprotonation, is reported. The acidic properties are due to the 30 peripheral, weakly acidic FeIII(H2O) groups that form a unique Archimedean solid with all edges and dihedral angles being equal, the icosidodecahedron, and therefore an "isotropic" surface. Interestingly, the aqueous solutions are stable even for months because of the inertness of the spherical solutes and the presence of the hard FeIII and MoVI centers. The stability can be nicely proven by the very characteristic Raman spectrum showing, because of the (approximately) icosahedral symmetry, only a few lines. Whereas the {Mo72Fe30} clusters exist as discrete, almost neutral, molecules in aqueous solution at pH < 2.9, they get deprotonated and self-associate into single-layer blackberry-type structures at higher pH while the assembly process (i.e., the size of the final species) can be controlled by the pH values; this allows the deliberate generation of differently sized nanoparticles, a long-term goal in nanoscience. The average hydrodynamic radius (Rh) of the self-assembled structures decreases monotonically with increasing number of charges on the {Mo72Fe30} macroanions (from approximately 45 nm at pH approximately 3.0 to approximately 15 nm at pH approximately 6.6), as studied by laser light scattering and TEM techniques. The {Mo72Fe30} macroions with high-stability tunable charges/surfaces, equal shape, and masses provide models for the understanding of more complex polyelectrolyte solutions while the controllable association and dissociation reported here of the assembled soft magnetic materials with tuneable sizes could be interesting for practical applications.

Journal Article↗

PubMed2006

A general exact method for synthesizing parallel-beam projections from cone-beam projections via filtered backprojection.

In recent years, image reconstruction methods for cone-beam computed tomography (CT) have been extensively studied. However, few of these studies discussed computing parallel-beam projections from cone-beam projections. In this paper, we focus on the exact synthesis of complete or incomplete parallel-beam projections from cone-beam projections. First, an extended central slice theorem is described to establish a relationship between the Radon space and the Fourier space. Then, data sufficiency conditions are proposed for computing parallel-beam projection data from cone-beam data. Using these results, a general filtered backprojection algorithm is formulated that can exactly synthesize parallel-beam projection data from cone-beam projection data. As an example, we prove that parallel-beam projections can be exactly synthesized in an angular range in the case of circular cone-beam scanning. Interestingly, this angular range is larger than that derived in the Feldkamp reconstruction framework. Numerical experiments are performed in the circular scanning case to verify our method.

Algorithms↗

PubMed2006

A BPF-type algorithm for CT with a curved PI detector.

Helical cone-beam CT is used widely nowadays because of its rapid scan speed and efficient utilization of x-ray dose. Recently, an exact reconstruction algorithm for helical cone-beam CT was proposed (Zou and Pan 2004a Phys. Med. Biol. 49 941-59). The algorithm is referred to as a backprojection-filtering (BPF) algorithm. This BPF algorithm for a helical cone-beam CT with a flat-panel detector (FPD-HCBCT) requires minimum data within the Tam-Danielsson window and can naturally address the problem of ROI reconstruction from data truncated in both longitudinal and transversal directions. In practical CT systems, detectors are expensive and always take a very important position in the total cost. Hence, we work on an exact reconstruction algorithm for a CT system with a detector of the smallest size, i.e., a curved PI detector fitting the Tam-Danielsson window. The reconstruction algorithm is derived following the framework of the BPF algorithm. Numerical simulations are done to validate our algorithm in this study.

Algorithms↗

PubMed2006

Dimeric organization of the yeast oligosaccharyl transferase complex.

The enzyme complex oligosaccharyl transferase (OT) catalyzes N-glycosylation in the lumen of the endoplasmic reticulum. The yeast OT complex is composed of nine subunits, all of which are transmembrane proteins. Several lines of evidence, including our previous split-ubiquitin studies, have suggested an oligomeric organization of the OT complex, but the exact oligomeric nature has been unclear. By FLAG epitope tagging the Ost4p subunit of the OT complex, we purified the OT enzyme complex by using the nondenaturing detergent digitonin and a one-step immunoaffinity technique. The digitonin-solubilized OT complex was catalytically active, and all nine subunits were present in the enzyme complex. The purified OT complex had an apparent mass of approximately 500 kDa, suggesting a dimeric configuration, which was confirmed by biochemical studies. EM showed homogenous individual particles and revealed a dimeric structure of the OT complexes that was consistent with our biochemical studies. A 3D structure of the dimeric OT complex at 25-A resolution was reconstructed from EM images. We suggest that the dimeric structure of OT might be required for effective association with the translocon dimer and for its allosteric regulation during cotranslational glycosylation.

Animals↗

PubMed2006

Bioactivation of nitroglycerin by the mitochondrial aldehyde dehydrogenase.

The mitochondrial aldehyde dehydrogenase (ALDH2, mtALDH) was recently found to catalyze the reduction of nitroglycerin (glyceryl trinitrate [GTN]) to generate nitrite and 1,2-glyceryl dinitrate. The nitrite generated within the mitochondria is metabolized further to generate nitric oxide (NO)-based bioactivity, by reduction to NO and/or by conversion to S-nitrosothiol, as revealed by a series of biochemical, pharmacologic, and genetic studies. These studies also demonstrated that mechanism-based inactivation of mtALDH is involved in the development of GTN tolerance. In mice in which the mtALDH gene was selectively deleted (mtALDH(-/-)), vascular responsiveness to low but not to high GTN concentrations was eliminated, indicating the existence of an additional mechanism of GTN biotransformation ("high K(m)" pathway). In addition, bioactivation of isosorbide dinitrate/mononitrate vasodilators is independent of mtALDH. Induction of GTN tolerance in vitro in aortae from normal mice selectively affected responsiveness to low doses of GTN, and the remaining responsiveness to high doses of GTN in mtALDH(-/-) vasculature did not exhibit tolerance. These findings suggest strongly that the high K(m) pathway is not involved in the development of GTN tolerance that is mechanism-based. Notably, recent studies indicate that individuals of East Asian origin with the common E487K mutation of mtALDH, which results in decreased mtALDH activity, are significantly less responsive to GTN. These observations in toto provide strong support for the conclusion that mtALDH provides the necessary and sufficient enzymatic mechanism for biotransformation of clinically relevant concentrations of GTN to NO-based vasoactivity and indicate in addition that inactivation of mtALDH plays a significant role in the development of mechanism-based GTN tolerance.

Aldehyde Dehydrogenase↗

PubMed2006

Low-dose, long-term caroverine administration attenuates impulse noise-induced hearing loss in the rat.

CONCLUSION: Physiological and morphological assessments indicated that low-dose and long-term caroverine delivery might be a new approach to protect against impulse noise-induced hearing loss. BACKGROUND: Although the exact mechanisms by which impulse noise causes hearing loss are still unclear, there is accumulating evidence that increased reactive oxygen species (ROS) production and excessive glutamate released from the inner hair cells lead to hair cell loss and consequently hearing loss. Caroverine is an antagonist of two glutamate receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the inner ear, as well as an antioxidant. MATERIALS AND METHODS: In this study, caroverine was delivered subcutaneously using an osmotic pump. This kind of delivery has the advantage, via continuous, long-term and low dose drug administration, of avoiding systemic side effects. RESULTS: It was shown that caroverine could significantly protect the cochlea against impulse noise trauma.

Animals↗

PubMed2006

Mycobacterium tuberculosis prcBA genes encode a gated proteasome with broad oligopeptide specificity.

Genes predicted to be associated with the putative proteasome of Mycobacterium tuberculosis (Mtb) play a critical role in defence of the bacillus against nitrosative stress. However, proteasomes are uncommon in eubacteria and it remains to be established whether Mtb's prcBA genes in fact encode a proteasome. We found that coexpression of recombinant PrcB and PrcA in Escherichia coli over a prolonged period at 37 degrees C allowed formation of an alpha(7)beta(7)beta(7)alpha(7), 750 kDa cylindrical stack of four rings in which all 14 beta-subunits were proteolytically processed to expose the active site threonine. In contrast to another Actinomycete, Rhodococcus erythropolis, Mtb's beta-chain propeptide was not required for particle assembly. Peptidolytic activity of the 750 kDa particle towards a hydrophobic oligopeptide was nearly two orders of magnitude less than that of the Rhodococcus 20S proteasome, and unlike eukaryotic and archaeal proteasomes, activity of the Mtb 750 kDa particle could not be stimulated by SDS, Mg(2+) or Ca(2+). Electron microscopy revealed what appeared to be obstructed alpha-rings in the Mtb 750 kDa particle. Deletion of the N-terminal octapeptide from Mtb's alpha-chain led to disappearance of the apparent obstruction and a marked increase of peptidolytic activity. Unlike proteasomes isolated from other Actinomycetes, the open-gate Mtb mutant 750 kDa particle cleaved oligopeptides not only after hydrophobic residues but also after basic, acidic and small, neutral amino acids. Thus, Mtb encodes a broadly active, gated proteasome that may work in concert with an endogenous activator.

Bacterial Proteins↗

PubMed2006

Cell death-inducing DFF45-like effector may take part in neuronal apoptosis of the lumbar spinal cord after sciatic nerve injury caused by a firearm.

OBJECTIVE: To investigate neuronal apoptosis and gene regulation after peripheral nerve injury caused by a firearm. METHODS: A rabbit model of sciatic nerve injury caused by a firearm was used. Neuronal apoptosis was determined by using terminal transferase-mediated dUTP nick end-labeling and flow cytometry. Differentially expressed genes were screened with mouse_8192S GeneChips. Cell death-inducing DFF45-like effector (CIDE-B) gene expression in spinal cord after sciatic nerve injury was detected with reverse transcription-polymerase chain reaction. RESULTS: The size of the injury caused by the firearm was widely extended. Neuronal apoptosis was found in days 1, 3, and 7 groups. The expression of apoptosis-related gene CIDE-B was high according to analysis of the GeneChips and reverse transcription-polymerase chain reaction detection. The trend of CIDE-B expression was consistent with neuronal apoptosis after nerve injury. CONCLUSIONS: Neuronal apoptosis is an important pathological change after peripheral nerve injury caused by firearms, and CIDE-B may be an important regulator.

Animals↗

PubMed2005

Inner ear drug delivery via a reciprocating perfusion system in the guinea pig.

Rapid progress in understanding the molecular mechanisms associated with cochlear and auditory nerve degenerative processes offers hope for the development of gene-transfer and molecular approaches to treat these diseases in patients. For therapies based on these discoveries to become clinically useful, it will be necessary to develop safe and reliable mechanisms for the delivery of drugs into the inner ear, bypassing the blood-labyrinthine barrier. Toward the goal of developing an inner ear perfusion device for human use, a reciprocating microfluidic system that allows perfusion of drugs into the cochlear perilymph through a single inlet hole in scala tympani of the basal turn was developed. The performance of a prototype, extracorporeal reciprocating perfusion system in guinea pigs is described. Analysis of the cochlear distribution of compounds after perfusion took advantage of the place-dependent generation of responses to tones along the length of the cochlea. Perfusion with a control artificial perilymph solution had no effect. Two drugs with well-characterized effects on cochlear physiology, salicylate (5 mM) and DNQX (6,7-Dinitroquinoxaline-2,3-dione; 100 and 300 microM), reversibly altered responses. The magnitude of drug effect decreased with distance from the perfusion pipette for up to 10 mm, and increased with dose and length of application.

Animals↗

PubMed2005

An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation.

The identity of the cellular mechanisms through which nitroglycerin (glyceryl trinitrate, GTN) elicits nitric oxide (NO)-based signaling to dilate blood vessels remains one of the longest standing foci of investigation and sources of controversy in cardiovascular biology. Recent evidence suggests an unexpected role for mitochondria. We show here that bioconversion by mitochondria of clinically relevant concentrations of GTN results in activation of guanylate cyclase, production of cGMP, vasodilation in vitro, and lowered blood pressure in vivo, which are eliminated by genetic deletion of the mitochondrial aldehyde dehydrogenase (mtALDH). In contrast, generation of vasoactivity from alternative nitro(so)-vasodilators is unaffected. In mtALDH(-/-) mice and their isolated vascular tissue, GTN bioactivity can still be generated, but only at substantially higher concentrations of GTN and by a mechanism that does not exhibit tolerance. Thus, mtALDH is necessary and sufficient for vasoactivity derived from therapeutic levels of GTN, and, more generally, mitochondria can serve as a source of NO-based cellular signals that may originate independently of NO synthase activity.

Aldehyde Dehydrogenase↗

PubMed2005

Dimethyl sulfoxide targets phage RNA polymerases to promote transcription.

Dimethyl sulfoxide (DMSO) is a "universal" solvent in pharmaceutical sciences and cell biology. DMSO was previously reported to facilitate in vitro transcription of chromatin and supercoiled plasmid, with the underlying mechanism being attributed to the alteration of the template structure. Here, we demonstrated that low concentrations of DMSO significantly increase the phage polymerase-catalyzed RNA synthesis when the naked and short PCR products were used as templates, suggesting that DMSO promotes transcription through additional mechanism(s). Interestingly, SP6 RNA polymerase was more sensitive to the DMSO stimulation than T7 RNA polymerase, suggesting that the polymerase is an important target for DMSO stimulation of RNA synthesis. Consistent with this finding, we also showed that DMSO dramatically elevated the RNA polymerase activity. This elevated activity is explained by altered polymerase structure as reflected by a change in intrinsic fluorescence. Furthermore, DMSO was shown to simultaneously accumulate both the abortive and full-length transcripts, leading us to conclude that the DMSO-altered polymerase structure primarily encodes an enhanced activity at the stage of transcription initiation. DMSO-induced alteration of the polymerase structure and function highlights a potentially generalized mechanism in interpreting the molecular action of this popular solvent.

DNA-Directed RNA Polymerases↗

PubMed2005

A method for intracochlear drug delivery in the mouse.

The confluence of two rapidly emerging research arenas - development of mouse models of human deafness and inner ear drug therapy for treatment and prevention of hearing loss - provides an opportunity for unprecedented approaches to study and treat deafness. Toward such goals, we have developed a method for intracochlear drug delivery in the mouse. The bulla was exposed using a ventral approach and the stapedial artery cauterized. An opening made into the inferior-medial aspect of the bulla, where the basal cochlear wall fuses with tympanic bulla, provided direct access to the scala tympani without separately opening the bulla or elevating auditory response thresholds. Cochlear responses, assayed by frequency-specific effects on ABRs and DPOAEs, were stable with infusion (1 microl/h) of an artificial perilymph solution (80 min). The glutamate receptor antagonist, CNQX (100 microM; 175 min), reduced ABR responses without affecting DPOAEs. Salicylate (5mM; 165 min) altered both. Both drugs had greatest effects at high frequencies, but distributed throughout the cochlea and were reversible. The safe delivery of drugs into the cochlea by this approach has immediate application in the study and treatment of various forms of human hearing loss that can be modeled in the mouse.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2005

Dissolution of ureteral uric acid calculi with local litholytic irrigation.

This study was designed to evaluate the efficacy of local litholytic irrigation (LLI) in the treatment of ureteral uric acid calculi. Fourteen cases of ureteral uric acid calculi were diagnosed by abdominal plain radiography (KUB), retrograde urography, ultrasonography (B-mode ultrasound), spiral computerized tomography(CT) and blood biochemical examinations. A ureteral catheter was passed retrogradely across ureteral calculi by cystoscopy. LLI with tromethamine-E (THAM-E) was performed via the ureteral catheter after the improvement of renal function and general situation and the control of urinary tract infection under the condition of intravenous application of antibiotics. The irrigation rate varied from 1000 to 1500 ml per day. Retrograde pyelography demonstrated complete dissolution of all the stones, 13 cases within 10 days and 1 within 12 days. Mild hematuria was observed in the majority of the cases and temporary aggravated lumbago in 1 case, with no other side effects. It is concluded that LLI is a practical and effective method in the treatment of ureteral uric acid calculi for its advantages of shorter duration,lower cost, less physical suffering and no severe complications.

Adult↗

PubMed2005

ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA.

Binding of Cdc6 to the origin recognition complex (ORC) is a key step in the assembly of a pre-replication complex (pre-RC) at origins of DNA replication. ORC recognizes specific origin DNA sequences in an ATP-dependent manner. Here we demonstrate cooperative binding of Saccharomyces cerevisiae Cdc6 to ORC on DNA in an ATP-dependent manner, which induces a change in the pattern of origin binding that requires the Orc1 ATPase. The reaction is blocked by specific origin mutations that do not interfere with the interaction between ORC and DNA. Single-particle reconstruction of electron microscopic images shows that the ORC-Cdc6 complex forms a ring-shaped structure with dimensions similar to those of the ring-shaped MCM helicase. The ORC-Cdc6 structure is predicted to contain six AAA+ subunits, analogous to other ATP-dependent protein machines. We suggest that Cdc6 and origin DNA activate a molecular switch in ORC that contributes to pre-RC assembly.

Amino Acid Sequence↗

PubMed2005

Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue.

A screen for Mycobacterium tuberculosis (Mtb) mutants sensitive to reactive nitrogen intermediates identified transposon insertions in the presumptive proteasomal ATPase gene mpa (mycobacterium proteasome ATPase; Rv2115c). mpa mutants are attenuated in both wild type and nitric oxide synthase 2 deficient mice. In this work, we show that attenuation of mpa mutants is severe, and that Mpa is an ATPase associated with various cellular activities (AAA) ATPase that forms hexameric rings resembling the eukaryotic complex p97/valosin-containing protein (VCP). Point mutations in the conserved Walker box ATPase motifs of Mpa greatly reduced or abolished ATPase activity in vitro and abrogated protection of Mtb against acidified nitrite. A mutant Mpa protein missing only its last two amino acids retained ATPase activity, yet failed to protect Mtb against nitrite. The corresponding strain was attenuated in mice. Thus, Mpa is an ATPase whose enzymatic activity is necessary but not sufficient to protect against reactive nitrogen intermediates.

Adenosine Triphosphatases↗

PubMed2005

[Visualization of regenerated sciatic nerve of rat after injury].

There is close relationship between the morphologic changes of peripheral nerve after injury and its function recovery during regeneration. In our experiment, the sciatic nerve of rats was transected and bridge-connected with silicone tube, and the images of serial slices of different time and different injury parts were taken by micro-photograph system. The volume unit model was applied to rendering the three dimensional (3D) structure of degenerative and regenerative sciatic nerve fiber and its affiliated structure after injury. The 3D images showed that node of Ranvier had not formed and its array was turbulent, both the myelin sheath and the axis-cylinder were thinner, and the collagen fibres had proliferated.

Animals↗

PubMed2004

The outer membrane usher forms a twin-pore secretion complex.

The PapC usher is an outer membrane protein required for assembly and secretion of P pili in uropathogenic Escherichia coli. P pilus biogenesis occurs by the chaperone/usher pathway, a terminal branch of the general secretory pathway. Periplasmic chaperone-subunit complexes target to the PapC usher for fiber assembly and secretion through the usher to the cell surface. The molecular details of pilus biogenesis at the usher, and protein secretion across the outer membrane in general, are unclear. We studied the structure and oligomeric state of PapC by gel filtration, dynamic light scattering, and electron microscopy and image analysis. Two-dimensional crystals of wild-type PapC and a C-terminal deletion mutant of PapC were produced by reconstituting detergent purified usher into E.coli lipids. PapC formed a dimer both in detergent solution and in the phospholipid bilayer. Cryo-electron microscopy revealed that the usher forms a twin-pore complex. Removal of the C-terminal domain did not change the basic shape of the PapC molecule, but altered the dimeric association of the usher, suggesting that the C terminus forms part of the dimerization interface. The overall molecular size (11 nm), pore size (2 nm), and twin-pore configuration of PapC resemble that of the Tom40 complex, a mitochondrial outer membrane protein translocase.

Cell Membrane↗