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Biomedical subjects

Jin Xu

Publications and source records attributed to Jin Xu.

At least 19 recordsLinked to original sources
PubMed2026

Differential impacts of exon 1-associated and exon 11-associated variants of the rat mu opioid receptor gene, Oprm1, on buprenorphine- and morphine-induced analgesia and respiratory depression in male rats.

Buprenorphine has long been recognized as a mu opioid agonist with a distinctive and intricate pharmacological profile. It is a partial agonist at the mu opioid receptor, an antagonist at the kappa and delta opioid receptors, and an agonist at the nociception opioid receptor. Similar to other mu agonists such as morphine and fentanyl, buprenorphine can produce side effects, including tolerance, physical dependence, respiratory depression, and addiction. The mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, generating an array of splice variants or isoforms, which are conserved from rodents to humans. These splice variants can be categorized into 2 main types, exon 1 (E1)-associated variants and exon 11 (E11)-associated variants. E1-associated variants primarily consist of full-length, 7-transmembrane C-terminal variants, whereas E11-associated variants are typically truncated 6-transmembrane variants. Previous studies established that buprenorphine analgesia in mice is dependent on both E1- and E11-associated variants. However, the role of these variants in buprenorphine analgesia and respiratory depression in rats remains unclear. In this study, we used CRISPR/Cas9 technology to develop 2 rat Oprm1 gene-targeting models in which E1- and E11-associated variants were selectively disrupted, aiming to investigate their roles in buprenorphine and morphine's actions. The results showed that both E1- and E11-associated variants are essential for buprenorphine's analgesic and respiratory depressional effects in rats, whereas morphine's effects are solely attributed to the E1-associated variants. These findings provide new and important insights into the distinct contributions of the E1- and E11-associated variants to the pharmacological actions of buprenorphine and morphine. SIGNIFICANCE STATEMENT: Differential dependences of buprenorphine and morphine analgesia and respiratory depression on Oprm1 exon 1- and exon 11-associated variants revealed in rat gene-targeting models provide new and important insights into unique contributions of these variants to buprenorphine and morphine actions.

Animals↗
PubMed2025

Evolutionary Process Underlying Receptor Gene Expansion and Cellular Divergence of Olfactory Sensory Neurons in Honeybees.

Olfaction is crucial for animals' survival and adaptation. Unlike the strict singular expression of odorant receptor (OR) genes in vertebrate olfactory sensory neurons (OSNs), insects exhibit complex OR gene expression patterns. In honeybees (Apis mellifera), a significant expansion of OR genes implies a selection preference for the olfactory demands of social insects. However, the mechanisms underlying receptor expression specificity and their contribution to OSN divergence remain unclear. In this study, we used single-nucleus multiomics profiling to investigate the transcriptional regulation of OR genes and the cellular identity of OSNs in A. mellifera. We identified three distinct OR expression patterns, singular OR expression, co-expression of multiple OR genes with a single active promoter, and co-expression of multiple OR genes with multiple active promoters. Notably, ∼50% of OSNs co-expressed multiple OR genes, driven by polycistronic transcription of tandemly duplicated OR genes via a single active promoter. In these OSNs, their identity was determined by the first transcribed receptor. The divergent activation of the promoter for duplicated OR genes ensures the coordinated increased divergence of OSN population. By integrating multiomics data with genomic architecture, we illustrate how fundamental genetic mechanisms drive OR gene expansion and influence flanking regulatory elements, ultimately contributing to the cellular divergence of OSNs. Our findings highlight the interplay between gene duplication and regulatory evolution in shaping OSN diversity, providing new insights into the evolution and adaptation of olfaction in social insects. This study also sheds light on how genetic innovations contribute to the evolution of complex traits.

Animals↗
PubMed2006

Characterizing exons 11 and 1 promoters of the mu opioid receptor (Oprm) gene in transgenic mice.

BACKGROUND: The complexity of the mouse mu opioid receptor (Oprm) gene was demonstrated by the identification of multiple alternatively spliced variants and promoters. Our previous studies have identified a novel promoter, exon 11 (E11) promoter, in the mouse Oprm gene. The E11 promoter is located approximately 10 kb upstream of the exon 1 (E1) promoter. The E11 promoter controls the expression of nine splice variants in the mouse Oprm gene. Distinguished from the TATA-less E1 promoter, the E11 promoter resembles a typical TATA-containing eukaryote class II promoter. The aim of this study is to further characterize the E11 and E1 promoters in vivo using a transgenic mouse model. RESULTS: We constructed a approximately 20 kb transgenic construct in which a 3.7 kb E11 promoter region and an 8.9 kb E1 promoter region controlled expression of tau/LacZ and tau/GFP reporters, respectively. The construct was used to establish a transgenic mouse line. The expression of the reporter mRNAs, determined by a RT-PCR approach, in the transgenic mice during embryonic development displayed a temporal pattern similar to that of the endogenous promoters. X-gal staining for tau/LacZ reporter and GFP imaging for tau/GFP reporter showed that the transgenic E11 and E1 promoters were widely expressed in various regions of the central nervous system (CNS). The distribution of tau/GFP reporter in the CNS was similar to that of MOR-1-like immunoreactivity using an exon 4-specific antibody. However, differential expression of both promoters was observed in some CNS regions such as the hippocampus and substantia nigra, suggesting that the E11 and E1 promoters were regulated differently in these regions. CONCLUSION: We have generated a transgenic mouse line to study the E11 and E1 promoters in vivo using tau/LacZ and tau/GFP reporters. The reasonable relevance of the transgenic model was demonstrated by the temporal and spatial expression of the transgenes as compared to those of the endogenous transcripts. We believe that these transgenic mice will provide a useful model for further characterizing the E11 and E1 promoter in vivo under different physiological and pathological circumstances such as chronic opioid treatment and chronic pain models.

Animals↗
PubMed2006

[An improved operation approach for bipedal rat model construction].

OBJECTIVE: To explore an improved operation approach to make up the ethical deficiency of classical bipedal rat model. METHODS: 20 SD rats were randomly divided into an improved group and a traditional group averagely. Improved group were operated with plexus brachialis nerve amputation, while traditional group with forelimbs amputation close to shoulder joint. Forelimb and shoulder joint movements were observed and electromyography of the peripheral muscles around shoulder joint were recorded to make certain the paralytic scope. Operation duration and axillary artery hurt probability of both the improved and traditional operation were compared to evaluate the operation risk of improved approach. Mean total upright time on 2 d, 1 w, 2 w, 4 w and 6 w post-operation and upright posture on 6 w post-operation were recorded to evaluate the human-upright-posture-simulating effect of bipedal rats operated with improved approach. RESULTS: Compared with classical amputation approach, improved approach exhibited simpler operation procedure, shorter operation duration and lower axillary artery hurt probability. Electromyography revealed that all forelimb muscles and most shoulder-peripheral muscles were denervated, forelimbs of the improved bipedal rats were absolutely paralyzed and shoulder joint reserved only slight abduction function. The mean total upright time of improved bipedal rats was longer than the classical ones after 2 w post-operation, while upright posture showed no difference with classical bipedal rats. CONCLUSIONS: The improved operation approach not only simplified operation procedures, but also achieved even better effect than classical amputation operation and exempted bipedal rat model from the ethical shadow.

Animals↗
PubMed2006

Is delayed gastric emptying so terrible after pylorus-preserving pancreaticoduodenectomy? Prevention and management.

AIM: To explore some operative techniques to prevent the occurrence of delayed gastric emptying (DGE) after pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: One hundred and eighty-six patients in a single medical center who accepted PPPD were retrospectively studied. The incidence of DGE was investigated and the influence of some operative techniques on the prevention of DGE was analyzed. RESULTS: During the operative process of PPPD, the methods of detached drainage of pancreatic fluid and bile and gastric fistulization were used. Postoperatively, six patients suffered DGE among the 186 cases; the incidence was 3.23% (6/186). One of them was complicated with intraabdominal infection at the same time, and two with pancreatic leakage. CONCLUSION: Appropriate maneuvers during operation are essential to avoid postoperative DGE in PPPD. The occurrence of DGE is avoidable. It should not be used as an argument to advocate hemigastrectomy in PPPD.

Adult↗
PubMed2006

Comparison of round window and cochleostomy approaches with a prototype hearing preservation electrode.

INTRODUCTION: Preservation of residual hearing in cochlear implant recipients has been demonstrated to be possible and provides the potential benefit of combined electric and acoustic auditory stimulation. A prototype 16-mm multichannel array has been designed to facilitate placement of 22 electrodes without damage to intracochlear structures. The electrode array is suitable for insertion via the round window membrane (RWM) or a small cochleostomy. AIM: To evaluate the insertion trajectory and the presence of trauma to intracochlear structures with the prototype electrode inserted by either the RWM or a scala tympani cochleostomy. MATERIALS AND METHODS: Eighteen fresh frozen human temporal bones were prepared for cochlear implantation using a standard transmastoid facial recess technique. Twelve electrodes were implanted at the University of Melbourne and 6 at the Medizinische Hochschule Hannover. In Melbourne fluoroscopy was used to monitor the insertions. Twelve prototype electrodes were inserted via the RWM. A further 6 electrodes were inserted via a small scala tympani cochleostomy. The cochleostomy was sited inferior to the RWM to avoid trauma to the basilar membrane and spiral ligament. Specimens were embedded and fixed with acrylic resin and the cochleae then examined histologically at 200-mum intervals using a grinding and polishing technique. RESULTS: Full insertion of the electrode was achieved without significant resistance in all RWM and cochleostomy specimens. In two RWM specimens fold-over of the electrode tip occurred, and in one specimen the electrode penetrated the spiral ligament to lie in an 'endosteal 'position. In one cochleostomy specimen the electrode was rotated within the cochlea to face laterally rather than towards the modiolus. The final electrode position differed for the two groups, with the electrodes inserted via the RWM lying in a more perimodiolar position along the first part of the basal turn. The average depth of insertion was 240 degrees for the RWM electrodes and 255 degrees for the cochleostomy electrodes. Histologic examination showed no damage in any specimen to the modiolus, osseous spiral lamina or basilar membrane. CONCLUSIONS: A prototype hearing preservation electrode array was inserted by either a RWM or a scala tympani cochleostomy without evidence of significant intracochlear trauma.

Basilar Membrane↗
PubMed2006

Better prediction of the location of alpha-turns in proteins with support vector machine.

We have developed a novel method named AlphaTurn to predict alpha-turns in proteins based on the support vector machine (SVM). The prediction was done on a data set of 469 nonhomologous proteins containing 967 alpha-turns. A great improvement in prediction performance was achieved by using multiple sequence alignment generated by PSI-BLAST as input instead of the single amino acid sequence. The introduction of secondary structure information predicted by PSIPRED also improved the prediction performance. Moreover, we handled the very uneven data set by combining the cost factor j with the "state-shifting" rule. This further promoted the prediction quality of our method. The final SVM model yielded a Matthews correlation coefficient (MCC) of 0.25 by a 10-fold cross-validation. To our knowledge, this MCC value is the highest obtained so far for predicting alpha-turns. An online Web server based on this method has been developed and can be freely accessed at http://bmc.hust.edu.cn/bioinformatics/ or http://210.42.106.80/.

Amino Acid Sequence↗
PubMed2006

Clonorchis sinensis: molecular cloning and functional expression of a novel cytosolic glutathione transferase.

Glutathione transferases (GSTs) represent a large family of enzymes. In the high throughput sequencing of the cDNA library constructed from the adult stage of Clonorchis sinensis (Cs), we isolate another cDNA clone encoding a novel cytosolic GST enzyme. To discriminate with our former reported CsGST, we designated this GST as CsGST1. This new cDNA contains 744 bp with a putative open reading frame of 213 amino acids. The deduced amino acid sequence exhibits 88% identity to Opisthorchis viverrini 28GST (Ov28GST), 60 and 52% identity to C. sinensis cytosolic 28-kDa GST (Cs28GST) and CsGST, respectively. The CsGST1 was expressed in Escherichia coli BL21(DE3) as a His-tag fusion protein and was purified by Ni-NTA agarose. The recombinant CsGST1 showed moderate GST activity of 0.79 U mg(-1). The average K (m) of the CsGST1 for 1-chloro-2, 4-dinitrobenzene is 150 microM. Cibacron blue F3GA and albendazole inhibited the CsGST1 activity with average IC(50) values of 9.1 and 265.4 muM, respectively. The nucleotide sequence reported in this paper was submitted to the GenBank Database with accession number DQ342327.

Amino Acid Sequence↗
PubMed2006

The epidemiology and burden of rotavirus in China: a review of the literature from 1983 to 2005.

We reviewed studies of rotavirus in MEDLINE and the Chinese literature to get a preliminary estimate of the burden of rotavirus gastroenteritis in China and the epidemiology of the disease. Studies were selected if they were conducted for a period 1 year or more, had more than 100 patients enrolled, and used an accepted diagnostic test. Overall, in 27 reports of children hospitalized for diarrhea in urban areas and 3 in rural areas, 44 and 33%, respectively, had rotavirus identified as the etiologic agent. Rotavirus was less commonly detected in children with milder illness seen in clinics (26% in urban and 28% in rural areas) and those cared for in the community (9%). The four main strains of rotavirus in circulation worldwide were also found in China and while G1 was the predominant strain overall, G3 emerged to be the most common strain in 9 of the 12 most recent studies. The disease has a distinct winter seasonal pattern and affects most children in their first 2 years of life. Although further studies are required to fully assess the burden of rotavirus diarrhea before decisions can be made about vaccine use, this review suggests that development and implementation of rotavirus vaccines should be a national priority.

Age Factors↗
PubMed2006

Lead-induced apoptosis in PC 12 cells: involvement of p53, Bcl-2 family and caspase-3.

It has been reported that lead could induce apoptosis in a variety of cell types. Although mitochondrion is regarded as the most pertinent pathway in mediating apoptosis, the exact mechanisms of lead-induced apoptosis are still largely unknown. Furthermore, there is little information about expressions and regulations of Bax, Bcl-2, and p53 in lead-induced apoptosis, which are critical regulators of mitochondrial stability. The present study was undertaken to determine whether lead could induce DNA damage and apoptosis in PC 12 cells, and the involvement of Bax, Bcl-2, p53, and caspase-3 in this process. The results showed that lead could induce DNA damage and apoptosis in PC 12 cells, accompanying with upregulation of Bax and downregulation of Bcl-2. Additionally, the expression of p53 increased, and caspase-3 was activated. Therefore, it suggests that lead can induce activation of p53 by DNA damage, which may lead to imbalance of Bax/Bcl-2 and mitochondrial dysfunction. Subsequently, after activation of caspase-3, lead-induced apoptosis occurres.

Animals↗
PubMed2006

Prediction of pi-turns in proteins using PSI-BLAST profiles and secondary structure information.

Due to the structural and functional importance of tight turns, some methods have been proposed to predict gamma-turns, beta-turns, and alpha-turns in proteins. In the past, studies of pi-turns were made, but not a single prediction approach has been developed so far. It will be useful to develop a method for identifying pi-turns in a protein sequence. In this paper, the support vector machine (SVM) method has been introduced to predict pi-turns from the amino acid sequence. The training and testing of this approach is performed with a newly collected data set of 640 non-homologous protein chains containing 1931 pi-turns. Different sequence encoding schemes have been explored in order to investigate their effects on the prediction performance. With multiple sequence alignment and predicted secondary structure, the final SVM model yields a Matthews correlation coefficient (MCC) of 0.556 by a 7-fold cross-validation. A web server implementing the prediction method is available at the following URL: http://210.42.106.80/piturn/.

Amino Acid Sequence↗
PubMed2006

Using multifocal ERG responses to discriminate diabetic retinopathy.

PURPOSE: Increase the accuracy in classifying subjects with or without early diabetic retinopathy, by analyzing the multifocal electroretinogram (mfERG) responses. METHOD: The mfERG was recorded for 14 control subjects (Normal) and 26 non-insulin dependent diabetic patients, 16 of the patients had no apparent retinopathy (NDR), the other 10 had mild to moderate non-proliferative retinopathy (NPDR). The first order kernel (K1) and the first slice of second order kernel (K21) of the mfERG were summed across the field and exported as trace arrays. The feature subset was selected from the kernel arrays by criterion of inter-intra distance and sequential forward searching strategy. Based on the selected features, Fisher's linear classifiers were trained and the classification error rates were given. RESULT: With one feature selected, the error rates of the classifiers were bigger than 23% between the NDR and NPDR subjects. When six features were selected to train the classifiers, the classification error rate decreased to 6.5% between Normal and NDR, 0 between Normal and NPDR, and 9.6% between NDR and NPDR. The criterion function of inter-intra distance was calculated for each feature in the K1 and K21 arrays. According to rank of the function value, during early DR, deformations should be easier to find at the front limb of peaks N2 and P1 on the K1 trace, and at the front limb of peak N2 on the K21 trace. As a conclusion, the multifocal ERG responses have great potentials in exploring diabetic retinopathy, assisted with the pattern classification methods.

Adult↗
PubMed2006

Chiral layered zincophosphate [d-Co(en)3]Zn3(H0.5PO4)2(HPO4)2 assembled about d-Co(en)(3)3+ complex cations.

A new chiral layered zincophosphate [d-Co(en)3]Zn3(H(0.5)PO4)2(HPO4)2, designated ZnPO-CJ16, has been hydrothermally synthesized by using the optically pure chiral metal complex d-Co(en)3I3 as the template. It contains 4.6-net sheets which array in a helical fashion with an ABCDEF stacking sequence along the [001] direction. The chiral d-Co(en)3(3+) complex cations reside in the interlayer regions. Interestingly, there exist symmetrical O...H...O H-bonds between inorganic sheets, which results in a pseudo-three-dimensional open-framework structure stabilized by strong H-bonds. The crystal data are as follows: ZnPO-CJ16, [d-Co(en)3]Zn3(H(0.5)PO4)2(HPO4)2; M = 818.26; hexagonal; P6(5)22 (No. 179); a = 8.5832(12) A; c = 52.610(11) A; U = 3356.6(9) A(3); T = 293(2) K; Z = 6; R1 = 0.0415 (I > 2sigma(I)); wR2 = 0.1383 (all data); Flack parameter, 0.04(4).

Journal Article↗
PubMed2006

DJ-1 transcriptionally up-regulates the human tyrosine hydroxylase by inhibiting the sumoylation of pyrimidine tract-binding protein-associated splicing factor.

Loss-of-function mutations in DJ-1 cause a subset of familial Parkinson disease (PD). However, the mechanism underlying the selective vulnerability in dopaminergic pathway due to the inactivation of DJ-1 is unclear. Previously, we have reported that DJ-1 is a neuroprotective transcriptional co-activator interacting with the transcriptional co-repressor pyrimidine tract-binding protein-associated splicing factor (PSF). Here we show that DJ-1 and PSF bind and regulate the human tyrosine hydroxylase (TH) promoter. Inactivation of DJ-1 by small interference RNA (siRNA) results in decreased TH expression and l-DOPA production in human dopaminergic cell lines. Consistent with its role as a transcriptional regulator, DJ-1 specifically suppresses the global SUMO-1 modification. High molecular weight sumoylated protein species, including PSF, accumulate in the lymphoblast cells from the patients carrying pathogenic DJ-1 mutations. DJ-1 elevates the TH expression by inhibiting the sumoylation of PSF and preventing its sumoylation-dependent recruitment of histone deacetylase 1. Furthermore, siRNA silencing of DJ-1 decreases the acetylation of TH promoter-bound histones, and histone deacetylase inhibitors restore the DJ-1 siRNA-induced repression of TH. Therefore, our results suggest DJ-1 as a regulator of protein sumoylation and directly link the loss of DJ-1 expression and transcriptional dysfunction to impaired dopamine synthesis.

Humans↗
PubMed2006

Enzymatic and physico-chemical characteristics of recombinant cMDH and mMDH of Clonorchis sinensis.

The cytosol and mitochondrial malate dehydrogenases (MDHs, EC 1.1.1.37) of Clonorchis sinensis were expressed in Escherichia coli as a fusion protein with a 6xHis and GST tag, respectively. The cytosol MDH of Clonorchis sinensis (Cs-cMDH) has higher resistibility to acid than mitochondrial MDH (Cs-mMDH). The Cs-cMDH also has higher heat resistibility and thermal stability than Cs-mMDH. Although there is only 22.8% identity between the amino acid sequences of Cs-cMDH and Cs-mMDH, they share several conserved residues. There are some differences between the circular dichroism spectra of Cs-cMDH and Cs-mMDH, but they have approximate percentages of helix. 4,4'-Bisdimethylamino diphenylcarbinol can decrease the Cs-mMDH activity but not the Cs-cMDH activity. Paraziquantel, metronidazole and albendazole did not inhibit the enzymes' activity, but adenosine 5'-monophosphate showed competitive inhibition to enzyme, with the Ki for Cs-cMDH and Cs-mMDH being 2.81 and 0.49 mM, respectively.

Amino Acid Sequence↗
PubMed2006

Molecular cloning and characterization of a novel lactate dehydrogenase gene from Clonorchis sinensis.

From a Clonorchis sinensis adult worm cDNA library, we isolated a cDNA clone encoding a novel lactate dehydrogenase (LDH) gene which encoded a putative protein with a predicted molecular weight of 35.6 kDa. The optimum pH and temperature for the enzyme were 7.5 and 50 degrees C in the pyruvate reduction while 11 and 80 degrees C in the lactate oxidation reaction, respectively. CsLDH showed no substrate inhibition by high lactate and NAD(+) concentration, and the optimal pyruvate and optimal NADH concentrations were 10 and 0.5 mmol/l, respectively. The relative activities of these 2-oxocarboxylic acids were pyruvic acid>2-ketobutyrate>oxalacetic acid>alpha-ketoglutaric acid>phenylpyruvate. The cofactor 3-acetylpyridine adenine dinucleotide was much more effective than NAD(+). The cofactor analogs in which the nicotinamide ring is replaced by 3-pyridinealdehyde were lower activity cofactors, while the nicotinamide ring is replaced by nicotinic acid or thionicotinamide which is not a cofactor to CsLDH. The succinic acid and malic acid are not substrates of CsLDH. Cu(2+), Fe(2+), and Zn(2+) greatly inhibited the CsLDH activity both in the direction of pyruvate reduction and in the direction of lactate oxidation. The inhibition of CsLDH by gossypol may make gossypol a potential therapy drug or a lead compound for C. sinensis. Accordingly, the CsLDH may be a novel potential drug target.

Amino Acid Sequence↗
PubMed2006

Involvement of caspase-3 pathway in anti-apoptotic action of methionine enkephalin on CEM x 174 cells in prolonged infection with simian immunodeficiency virus in vitro.

The roles of methionine enkephalin, as an immunomodulator, on immunodeficiency virus-induced apoptosis of lymphocytes during prolonged infection are still unclear. In the present study, we evaluated the effects of methionine enkephalin on the viability, the profile of cell cycle and apoptosis, as well as the expression of apoptosis-related genes in CEM x 174 cells infected with simian immunodeficiency virus for 72 h. Our data demonstrated that methionine enkephalin maintains the viability of cells during the period of prolonged infection. Following co-incubation with the virus, CEM x 174 cells were arrested at S phase, with increased mortality as a result of apoptosis. Methionine enkephalin could abolish virus-induced over-expression of caspase-3. Taken together all findings, we conclude that methionine enkephalin may maintain the viability of SIV-infected cells via suppressing the expression of caspase-3, which may have clinical implications in opioid peptide therapy for AIDS.

Apoptosis↗