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Jian-Jun Liu

Publications and source records attributed to Jian-Jun Liu.

At least 19 recordsLinked to original sources
PubMed2025

Integrative metabolomic and proteomic analysis of diabetic kidney disease progression with younger-onset type 2 diabetes.

AIM: Younger-onset type 2 diabetes (YT2D) confers a disproportionately high risk of diabetic kidney disease (DKD), yet early biomarkers and underlying mechanisms remain poorly defined. We aimed to identify metabolites associated with DKD progression and integrate metabolomic and proteomic data to elucidate pathways involved in a multi-ethnic Asian cohort. MATERIALS AND METHODS: In this prospective study, 787 YT2D patients (diagnosed at ≤ age 40) were followed for a median of 5.7 years. DKD progression was defined as an annual decline in estimated glomerular filtration rate (eGFR) of ≥3 mL/min/1.73 m2 or ≥ 40% reduction in eGFR from baseline. Plasma metabolites were measured by nuclear magnetic resonance spectroscopy. Multivariable regression analysis was performed in a discovery (N = 550) and internal validation cohort (N = 237). Integrative metabolomic-proteomic analysis (N = 428) was performed using sparse partial least squares discriminant analysis (sPLS-DA). RESULTS: Ninety-eight metabolites were differentially expressed between DKD progressors and non-progressors, of which total branched-chain amino acids (BCAAs) (OR = 0.60, 95% CI 0.46-0.79), valine (OR = 0.62, 95% CI 0.48-0.81), and leucine (OR = 0.56, 95% CI 0.43-0.74) associated with DKD progression, independent of metabolic risk factors. Integrative analysis identified three components comprising 23 proteins and 30 metabolites, involved in the citrate cycle and apoptosis, which improved prediction of DKD progression beyond clinical risk factors (AUC 0.69-0.83). CONCLUSION: Lower plasma BCAA levels are independently associated with DKD progression in YT2D. Integrative multi-omics analysis highlights disruptions in metabolic and apoptotic pathways, providing insights into DKD pathophysiology and potential biomarkers for early risk stratification.

Humans↗
PubMed2007

Evidence for a novel psoriasis susceptibility locus at 9q33-9q34 in Chinese Hans.

Psoriasis is a heterogeneous disease for which nine linkage loci (PSORS loci 1-5 and PSORS7-10) have been accepted by the Human Genome Nomenclature Committee and an additional 16 potential susceptibility loci have been reported so far. Our previous genome-wide scan in 61 Chinese Han psoriasis vulgaris families found two susceptibility loci at 6p21.3 and 4q31 and additional suggestive linkage evidence at other regions, including 9q33. In this follow-up study, the linkage evidence at 9q33 was further investigated using an expanded sample of 160 families and improved marker coverage. Our follow-up linkage analysis of the 160 families demonstrated strong linkage evidence (P < or = 0.000022) throughout a region between 133.38 and 146.23 cM with a maximum nonparametric linkage (NPL) score of 4.64 (P = 0.00000023) and a heterogeneity LOD (HLOD) score of 5.03 (alpha = 46%) at 142.39 cM near the marker D9S290. By stratifying the 160 families into the subtypes of 130 early-onset and 30 late-onset families, we revealed stronger linkage evidence in the early-onset psoriasis families with a maximum multipoint HLOD score of 6.48 (alpha = 58%) and a maximum NPL score of 4.69 (P = 0.00000012) near marker D9S290. Our follow-up study has confirmed a novel susceptibility locus at 9q33-34 for early-onset psoriasis in the Chinese population.

Age of Onset↗
PubMed2007

LRRK2 G2019S founder haplotype in the Chinese population.

The G2019S mutation in the LRRK2 (leucine-rich repeat kinase) gene appears very rarely in the Chinese population. Among Chinese subjects who were non-G2019S carriers, we demonstrated the frequency of the LRRK2 G2019S founder haplotype (T-254-A-G-A-154) in Parkinson's disease and controls to be 33% and 30%. This rate is similar to the frequency in European noncarriers, indirectly supporting the association of this haplotype with G2019S carriers. The haplotype is likely to be more ancient than the G2019S mutation because it is also found in a population with a very low carrier rate.

Asian People↗
PubMed2006

Follow-up analysis of PSORS9 in 151 Chinese families confirmed the linkage to 4q31-32 and refined the evidence to the families of early-onset psoriasis.

Psoriasis linkage to 4q28-32 (PSORS9) was initially identified by our genome-wide scan in 61 Chinese families and subsequently supported by a meta-analysis of five genome-wide linkage scans of European populations. In this study, we performed a follow-up analysis of PSORS9 using an additional 90 families and improved marker coverage. Joint analysis of all 151 families obtained significant linkage evidence (HLOD=4.53, nonparametric linkage (NPL)=4.03 (P=0.000003)) at the marker interval D4S2997-D4S3033, and the same was obtained for the analysis of the independent new families (HLOD=4.33, NPL=3.15 (P=0.00004)). The linkage evidences from the whole families and the new families exceeded the genome-wide criteria for significant linkage. Furthermore, by performing an ordered subset analysis using mean age at onset as a covariate, we demonstrated that evidence for linkage to PSORS9 is concentrated in the early-onset families and suggested that further study of PSORS9 should focus on early-onset patients. This finding is contradictory to what was found in the Icelandic population and, together with other linkage results, suggests that Chinese and European populations are genetically different for linkage to PSORS9, which may partially explain the influence of ethnic factors on the varying prevalence of psoriasis.

Age of Onset↗
PubMed2006

Acetyl-keto-beta-boswellic acid inhibits cellular proliferation through a p21-dependent pathway in colon cancer cells.

1. Although there is increasing evidence showing that boswellic acid might be a potential anticancer agent, the mechanisms involved in its action are unclear. 2. In the present study, we showed that acetyl-keto-beta-boswellic acid (AKBA) inhibited cellular growth in several colon cancer cell lines. Cell cycle analysis by flow cytometry showed that cells were arrested at the G1 phase after AKBA treatment. 3. Further analysis showed that cyclin D1 and E, CDK 2 and 4 and phosphorylated Rb were decreased in AKBA-treated cells while p21 expression was increased. 4. The growth inhibitory effect of AKBA was dependent on p21 but not p53. HCT-116 p53(-/-) cells were sensitized to the apoptotic effect of AKBA, suggesting that p21 may have protected cells against apoptosis by inducing a G1 arrest.5. In conclusion, we have demonstrated that AKBA inhibited cellular growth in colon cancer cells. These findings may have implications to the use of boswellic acids as potential anticancer agents in colon cancer.

Apoptosis↗
PubMed2006

Systematic evaluation of association between the microsomal glutathione S-transferase 2 common variation and psoriasis vulgaris in Chinese population.

Several recent studies have demonstrated the possible involvement of the microsomal glutathione S-transferase 2 (MGST2) gene in the pathogenesis of psoriasis. The objectives of this work are to determine whether the genetic polymorphisms of the MGST2 gene were associated with an increased risk of psoriasis in Chinese patients. We first characterized the linkage disequilibrium pattern within MGST2 and identified single-nucleotide polymorphisms (SNPs) for tagging common genetic variants. Genotype- and haplotype-based analyses were then performed by genotyping the Tag SNPs in a large-scale sample of cases and controls. We characterized the linkage disequilibrium pattern within MGST2 using 12 densely distributed SNPs and identified 6 SNPs for tagging common genetic variants. We then performed an association analysis by genotyping the six SNPs in 552 cases and 384 controls, but none of the genotype- and haplotype-based analyses revealed significant evidence for association. We also performed family-based association analysis by genotyping the six SNPs in 95 trios; no evidence for association was identified. Our comprehensive genetic analysis of MGST2 common variants in a large Chinese sample of psoriasis did not provide any supporting evidence for MGST2 to be the susceptibility gene within the PSORS9 locus.

Adolescent↗
PubMed2006

Repression of HIP/RPL29 expression induces differentiation in colon cancer cells.

We had previously shown that the expression of heparin/heparan sulfate interacting protein/ribosomal protein L29 (HIP/RPL29) was upregulated in colon cancer tissues. The present study investigated the role of HIP/RPL29 in differentiation in colon cancer cells. Inducing cellular differentiation in HT-29 cells by both sodium butyrate and glucose deprivation resulted in a significant downregulation of HIP/RPL29 expression. The beta-catenin/Tcf-4 pathway is the most important pathway controlling the switch between cellular differentiation and proliferation in intestinal epithelial cells. Inducing differentiation by dominant-negative inhibition of the beta-catenin/Tcf-4 complexes in LS174T cells also resulted in downregulation of HIP/RPL29. To determine whether a lower expression of HIP/RPL29 could induce differentiation in cancer cells, small interfering RNA (siRNA) targeting HIP/RPL29 was transfected into LS174T cells. The resultant knockdown of HIP/RPL29 expression induced cellular differentiation, as shown by the increased expression of two known markers of differentiation in LS174T cells, galectin-4 and mucin-2. In addition, the differentiation process induced by repression of HIP/RPL29 expression was accompanied by the upregulation of p21 and p53. In conclusion, HIP/RPL29 plays a role in the cellular differentiation process in colon cancer cells. The differentiation process is at least partially mediated by the upregulation of p21 and p53 pathways.

Alkaline Phosphatase↗
PubMed2006

Analysis of 14 LRRK2 mutations in Parkinson's plus syndromes and late-onset Parkinson's disease.

The pleomorphic pathology of postmortem LRRK2-positive patients and the frequent association with late-onset Parkinson's disease (LOPD) symptoms suggest that LRRK2 mutations may play a role in Parkinson's Plus disorders and LOPD. Published studies primarily focus on the common G2019S mutation. Analysis of a spectrum of LRRK2 mutations in Parkinson's Plus disorders has yet to be reported. We investigated 14 leucine-rich repeat kinase 2 (LRRK2) mutations in a cohort of Parkinson's Plus disorders and LOPD. A total of 458 patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal ganglionic degeneration (CBGD), atypical Parkinsonism (AP), and LOPD were screened for 14 mutations that span exons 19 to 41 of the LRRK2 gene. Among the LOPD cases, 1 patient was found to harbor the R1441C mutation. He presented with typical features of PD at age of 58 years old and responded well to levodopa. We did not detect any of the 14 mutations in PSP, MSA, CBGD, and AP patients. We highlight the first case of LRRK2 R1441C mutation in late onset sporadic PD of non-European ancestry. Furthermore, extensive mutational screen found LRRK2 mutations to be rare among patients who presented with PSP, MSA, CBGD, and AP.

Age Factors↗
PubMed2006

A novel MGST2 non-synonymous mutation in a Chinese pedigree with psoriasis vulgaris.

A balanced translocation was recently identified in a German psoriasis patient. One of the breakpoints was mapped immediately upstream of the microsomal glutathione S-transferase 2 (MGST2) gene, suggesting it as a candidate gene. Here, we report the identification of a novel non-synonymous mutation in MGST2 by a comprehensive sequence analysis of MGST2's coding region in Chinese psoriasis samples. We demonstrate that this mutation co-segregated with the disease phenotype within a Chinese family affected with psoriasis vulgaris and is predicted to have an impact on the normal function of MGST2 protein. However, the mutation was absent in 551 additional cases and 384 healthy Chinese controls. While requiring independent confirmation, our results suggest that this rare mutation could play a causal role in a small subset of psoriasis individuals.

Adult↗
PubMed2006

Therapeutic angiogenesis by intramuscular injection of fibrin particles into ischaemic hindlimbs.

1. Fibrin gel has been used as a carrier of angiogenic molecules to promote neovascularization in animal models of limb ischaemia. However, little is known about the effects of fibrin itself under such pathological conditions. Accordingly, the present study tested the efficacy of fibrin in a rabbit model of acute hindlimb ischaemia. 2. Unilateral ischaemia was induced by resection of the left femoral artery. Seven days after surgery, fibrin particles (FP), which were free of fibrinogen, thrombin and vascular endothelial growth factor, were injected directly into the ischaemic thigh muscles. Twenty-four rabbits were divided into four groups, namely a control group receiving phosphate-buffered saline and three FP-treated groups receiving 5, 10 or 20 mg FP. 3. Collateral vessel development and limb perfusion were assessed by angiography, measuring the calf blood pressure ratio (BPR), thermographic scanning and the histological determination of capillary density. 4. At day 35 post-surgery, the treatment with 5 mg FP produced an augmentation of collateral vessel development (P < 0.01), increased numbers of capillaries (P < 0.05) and improved perfusion manifested by a higher blood flow (P < 0.01) and calf BPR (P < 0.05) compared with controls. Treatment with 10 and 20 mg FP had similar effects to those observed with 5 mg FP. 5. The present study reveals that FP promotes angiogenesis in a rabbit model of hindlimb ischaemia, thus providing a feasible approach to therapeutic angiogenesis in ischaemic diseases.

Angiogenesis Inducing Agents↗
PubMed2006

Polymorphisms in candidate genes: implications for the current treatment of Parkinson's disease.

Pharmacological treatment remains the cornerstone of therapy in Parkinson's disease. A number of clinical and genetic factors may influence the therapeutic response and treatment-related complications. Some exploratory studies have suggested that genetic polymorphisms may influence an individual's response to dopaminergic therapy and susceptibility to drug-related complications, such as hallucinations, dyskinesias, motor fluctuations and sudden onset of sleep episodes. This article provides a concise summary and discussion of the potential utility and limitation of studies that have examined the influence of genetic polymorphisms on drug-related response and complications in Parkinson's disease.

Animals↗
PubMed2005

The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson's disease patients.

A common heterozygous leucine-rich repeat kinase 2 (LRRK2) mutation 6055G > A transition (G2019S) accounts for about 3-7% of familial Parkinson's disease (PD) and 1-1.6% sporadic PD in a number of European populations. To determine the prevalence of the G1019S mutation in our Asian population, we conducted genetic analysis of this mutation in 1000 PD and healthy controls. The G2019S mutation was not detected in any of our study subjects. The prevalence of G2019S mutation is rare (< 0.1%) in our population, suggesting that occurrence of this mutation may vary amongst different ethnic races. This has important clinical implication when implementing guidelines for genetic testing.

Adolescent↗
PubMed2005

A novel linkage to generalized vitiligo on 4q13-q21 identified in a genomewide linkage analysis of Chinese families.

Generalized vitiligo is a common, autoimmune, familial-clustering depigmentary disorder of the skin and hair that results from selective destruction of melanocytes. Generalized vitiligo is likely a heterogeneous disease, with five susceptibility loci reported so far--on chromosomes 1p31, 6p21, 7q, 8p, and 17p13--in white populations. To investigate vitiligo susceptibility loci in the Chinese population, we performed a genomewide linkage analysis in 57 multiplex Chinese families, each with at least two affected siblings, and we identified interesting linkage evidence on 1p36, 4q13-q21, 6p21-p22, 6q24-q25, 14q12-q13, and 22q12. Subsequently, to extract more linkage information, we investigated our initial genomewide linkage findings in a follow-up analysis of 49 new families and additional markers. Our initial genomewide linkage analysis and our subsequent follow-up analysis have identified a novel linkage to vitiligo on 4q13-q21, with highly significant linkage evidence (a nonparametic LOD score of 4.62 [P=.000003] and a heterogeneity LOD score of 4.01, under a recessive inheritance model), suggesting that 4q13-q21 likely harbors a major susceptibility locus for vitiligo in the Chinese population. We observed a minimal overlap between the linkage results of our current genomewide analysis in the Chinese population and the results of previous analyses in white populations, and we thus hypothesize that, as a polygenic disorder, vitiligo may be associated with great genetic heterogeneity and a substantial difference in its genetic basis between ethnic populations.

China↗
PubMed2005

Effective algorithms for tag SNP selection.

Single nucleotide polymorphisms (SNPs), due to their abundance and low mutation rate, are very useful genetic markers for genetic association studies. However, the current genotyping technology cannot afford to genotype all common SNPs in all the genes. By making use of linkage disequilibrium, we can reduce the experiment cost by genotyping a subset of SNPs, called Tag SNPs, which have a strong association with the ungenotyped SNPs, while are as independent from each other as possible. The problem of selecting Tag SNPs is NP-complete; when there are large number of SNPs, in order to avoid extremely long computational time, most of the existing Tag SNP selection methods first partition the SNPs into blocks based on certain block definitions, then Tag SNPs are selected in each block by brute-force search. The size of the Tag SNP set obtained in this way may usually be reduced further due to the inter-dependency among blocks. This paper proposes two algorithms, TSSA and TSSD, to tackle the block-independent Tag SNP selection problem. TSSA is based on A* search algorithm, and TSSD is a heuristic algorithm. Experiments show that TSSA can find the optimal solutions for medium-sized problems in reasonable time, while TSSD can handle very large problems and report approximate solutions very close to the optimal ones.

Algorithms↗
PubMed2005

[Adaptive response induced by low concentration of hydroquinone in human embryonic fibroblasts cells].

OBJECTIVE: To study the adaptive response induced by hydroquinone(HQ) on eukaryocyte and its possible mechanism. METHODS: After hydroquinone treatment, AlamarBlue reduce rate, LDH release rate were observed to determine the cell proliferation and death. Annexin V/propidium iodide (PI) staining was performed for each treatment to distinguish viable, early, and late apoptosis or dead cells. The total cellular proteins were separated using two- dimensional gel electrophoresis and visualized by sliver staining. Digital images were analyzed using ImageMaster 2D platinum 5.0 software. The differentially expressed protein spots were picked and digested in gel then identified by tandem mass spectrum. RESULTS: The results of AlamarBlue reduce rate, LDH leakage and Annexin V-FITC/PI staining showed that no effect on cell viability was observed at a concentration of 10 micromol/L HQ while 250 micromol/L HQ significantly decreased cell viability. Cells pretreated with 10 micromol/L HQ for 12h show increasing survival to the following expose to 250 micromol/L HQ. In control MRC-5 cells 1429 +/- 369 protein spots were detected and, 1453 +/- 307 in low HQ group, 1191 +/- 393 in high HQ group, and 1107 +/- 247 in adaptive group by two dimensional gel electrophoresis. Twenty-four protein spots showed significant change after HQ stimulation and 22 protein spots were identified by tandems mass spectra. These identified proteins involved in energy metabolism, translation and RNA processing, protein folding, redox regulation, cell structure and cell signaling. CONCLUSION: Adaptive response can be induced by low concentration of HQ on MRC-5 cells and cellular adaptation is a complex process involving in a modulation of diverse cellular functions.

Apoptosis↗
PubMed2004

In vitro cultivation of human fetal pancreatic ductal stem cells and their differentiation into insulin-producing cells.

AIM: To isolate, culture and identify the human fetal pancreatic ductal stem cells in vitro, and to observe the potency of these multipotential cells differentiation into insulin-producing cells. METHODS: The human fetal pancreas was digested by 1 g/L collagease type IV and then 2.5 g/L trypsin was used to isolate the pancreatic ductal stem cells, followed by culture in serum-free, glucose-free DMEM media with some additional chemical substrates in vitro (according to the different stage). The cells were induced by glucose-free (control), 5 mmol/L, 17.8 mmol/L and 25 mmol/L glucose, respectively. The cell types of differentiated cells were identified using immunocytochemical staining. RESULTS: The shape of human fetal pancreatic ductal stem cells cultured in vitro was firstly fusiform in the first 2 wk, and became monolayer and cobblestone pattern after another 3 to 4 wk. After induced and differentiated by the glucose of different concentrations for another 1 to 2 wk, the cells formed the pancreatic islet-like structures. The identification and potency of these cells were then identified by using the pancreatic ductal stem cell marker, cytokeratin-19 (CK-19), pancreatic beta cell marker, insulin and pancreatic alpha cell marker, glucagons with immunocytochemical staining. At the end of the second week, 95.2% of the cells were positive for CK-19 immunoreactivity. Up to 22.7% of the cells induced by glucose were positive for insulin immunoreactivity, and less than 3.8% of the cells were positive for glucagon immunoreactivity in pancreatic islet-like structures. The positive ratio of immunoreactive staining was dependent on the concentration of glucose, and it was observed that the 17.8 mmol/L glucose stimulated effectively to produce insulin- and glucagons-producing cells. CONCLUSION: The human fetal pancreatic ductal stem cells are capable of proliferation in vitro. These cells have multidifferentiation potential and can be induced by glucose and differentiated into insulin-producing cells in vitro.

Cell Culture Techniques↗
PubMed2004

Crystallization of glycosylated human BACE protease domain expressed in Trichoplusia ni.

Human beta-amyloid precursor protein cleaving enzyme (beta-secretase, or BACE) belongs to the aspartyl protease family, and is responsible for generating the N-terminus of beta-amyloid peptide (Abeta). BACE is a type I transmembrane glycoprotein with pre-, pro- and catalytic domains, a short transmembrane helix and a cytoplasmic region. In this study, a truncated form was engineered to produce the authentic catalytic domain of BACE in Trichoplusia ni (High 5) cells. The glycosylated BACE zymogen (proBACE) was secreted into the conditioned medium for facile purification by metal chelate and gel filtration chromatographies. The mature catalytic domain was obtained by a trans cleavage event under acidic conditions and crystallized in the absence of a bound inhibitor. A complete 3.4 A data set was collected on a single orthorhombic crystal with unit cell parameters a=74 A, b=130 A, c=134A. Successful molecular replacement shows two BACE molecules in the asymmetric unit.

Amyloid Precursor Protein Secretases↗