Biomedical subjects

Ke Li

Publications and source records attributed to Ke Li.

At least 19 recordsLinked to original sources

PubMed2026

Mechanistic insights into flavor deterioration in bitter sturgeon caviar: Evidence from lipidomics and metagenomics.

This study systematically compared the flavor and multi-omics differences between normal caviar and bitter caviar based on quantitative descriptive analysis (QDA), volatile compounds (VOCs) analysis, untargeted lipidomics, and metagenomics. The results showed that bitter caviar was characterized not only by increased bitterness, but also by decreased positive sensory attributes, including buttery, nutty, and marine fresh. VOCs analysis indicated that the volatile profile of bitter caviar was reorganized. Compounds such as 3-hydroxy-2-butanone, 1-octen-3-ol, and (E, Z)-2,6-nonadienal showed higher relative odor activity values (rOAVs); however, these changes did not improve its overall sensory experience. Untargeted lipidomics identified 492 differential lipids. These changes were mainly characterized by decreased PC and increased DG and LPC in bitter caviar. KEGG pathways analysis showed that these differential lipids were mainly associated with glycerophospholipid metabolism, choline metabolism in cancer, and retrograde endocannabinoid signaling. Metagenomic analysis showed that bacteria dominated the microbial community of caviar. Among them, Bacillus and Micromonospora showed relatively high abundance in the caviar microbiota. They were also closely associated with lipid metabolic changes involving PC, DG, and LPC, suggesting their potential as candidate targets for future microbiota-directed regulation of caviar quality. These findings provide new insights into the mechanisms underlying sensory deterioration and flavor formation in bitter caviar, and offer a theoretical basis for improving caviar quality in industrial production.

Animals↗

PubMed2026

Genomic surveillance of a deeply sampled local population reveals age-specific drivers of RSV transmission.

Respiratory syncytial virus (RSV) disproportionately causes severe infections among infants and older adults, yet the key age group responsible for viral spread to other age groups remains poorly defined. While current immunization approaches effectively reduce disease severity among the most vulnerable, identifying the core drivers of infection is essential to effectively disrupt population-level transmission. By generating 910 whole-genome viral sequences of RSV from all age groups (<1 to 65+ years) in Connecticut, we identified that children aged 12-35 months are the primary drivers of viral transmission to other age groups. This group significantly shapes the genetic diversity of circulating strains. Furthermore, we found that RSV is introduced into the community through frequent and independent entries from other US regions throughout the year, rather than through a single explosive seasonal introduction or long-term local persistence. Ultimately, our findings justify prevention strategies that expand beyond reducing disease burden to actively prioritizing the reduction of transmission and infection.

Journal Article↗

PubMed2026

TRIM49 Deficiency Stabilizes a Galectin-3/EGR1 Transcriptional Complex That Drives Invasiveness of Gastric Adenocarcinoma.

UNLABELLED: Tissue invasion is an initiating step of the cancer metastatic cascade. Unraveling the mechanisms underlying intracellular signaling pathway rewiring that activates downstream transcriptional machinery to drive invasiveness could help identify improved strategies to prevent and treat metastasis. Through an unbiased genome-wide CRISPR screen in a mouse model of gastric adenocarcinoma (GAC), an E3 ubiquitin ligase, tripartite motif-containing protein 49 (TRIM49), was identified as a potent suppressor of cancer invasiveness. In two thirds of GAC, TRIM49 expression was downregulated in invading cancer cells, in which TRIM49 deficiency correlated with deeper tumor infiltration and lymph node metastasis and was indicative of shorter overall patient survival. In multiple orthotopic GAC mouse models, TRIM49-deficient cancer cells were highly infiltrative, leading to multiorgan metastasis. Mechanistically, galectin-3, a putative regulator of cancer invasion, was stabilized in TRIM49-deficient cancer, largely because of the failure to undergo TRIM49-mediated polyubiquitination and proteasomal degradation. Consequently, galectin-3 assembled a complex with EGR1, thereby regulating transcriptional activities of a proinvasive gene module. As the galectin-3/EGR1 complex acted as a key node relaying proinvasive signaling, its disruption using GB1107, an oral galectin-3 inhibitor, suppressed tissue infiltration and metastasis of patient-derived xenografts. Taken together, a proinvasive galectin-3/EGR1 transcriptional complex was exploited by TRIM49-deficient GAC to fuel tissue invasion, representing an Achilles' heel that is potentially targetable to prevent metastasis. SIGNIFICANCE: A proinvasion galectin-3/EGR1 transcriptional complex is a therapeutic vulnerability in the highly invasive TRIM49-deficient gastric adenocarcinoma, which can be disrupted by the oral galectin-3 inhibitor GB1107 to prevent cancer spreading.

Stomach Neoplasms↗

PubMed2025

Donor MHC-specific thymus vaccination allows for immunocompatible allotransplantation.

Organ transplantation is the last-resort option to treat organ failure. However, less than 10% of patients benefit from this only option due to lack of major histocompatibility complex (MHC)-matched donor organs and 25%-80% of donated organs could not find MHC-matched recipients. T cell allorecognition is the principal mechanism for allogeneic graft rejection. We herein present a "donor MHC-specific thymus vaccination" (DMTV) strategy to induce T cell tolerance to both autologous and allogeneic donor MHC. Allogeneic MHC molecules were expressed in the recipient thymus through adeno-associated virus-mediated delivery, which led to stable expression of allogeneic MHC together with the autologous MHC in the engineered thymus. During local T cell education, those T cells recognizing either autologous MHC or allogeneic MHC were equally depleted. We constructed C57BL/6-MHC and BALB/c-MHC dual immunocompatible mice via thymus vaccination of C57BL/6-MHC into the BALB/c thymus and observed long-term graft tolerance after transplantation of C57BL/6 skin and C57BL/6 mouse embryonic stem cells into the vaccinated BALB/c mice. We also validated our DMTV strategy in a bone marrow, liver, thymus (BLT)-humanized mouse model for immunocompatible allotransplantation of human embryonic stem cells. Our study suggests that the DMTV strategy is a potent avenue to introduce a donor compatible immune system in recipients, which overcomes the clinical dilemma of the extreme shortage of MHC-matched donor organs for treating patients with end-stage organ failure.

Animals↗

PubMed2025

Clinical and Multiorgan Proteomics Characteristics of the Diverse Fatal Phase in Super Elderly Patients With SARS-CoV-2 Infection: A Descriptive Study.

This study aims to identify the risk factors associated with clinical outcomes and the proteomic changes in organs related to fatal SARS-CoV-2 infection within the super-elderly population. This retrospective analysis included all elderly individuals with COVID-19 admitted to the Second Medical Center of PLA General Hospital from December 2022 to January 2023. The follow-up period ended on March 30, 2023. During this time, epidemiological, demographic, laboratory, and outcome data were analyzed descriptively. Proteomic sequencing was performed on super-elderly patients who died from COVID-19 at different stages of the disease. A total of 352 elderly COVID-19 patients, with a mean age of 89.84 ± 8.54 years, were included in this study. During a median follow-up period of 98 days, 79 patients died. Deceased patients were older and more likely to have cardiovascular and cerebrovascular diseases, with a lower prevalence of lipid-lowering therapy. The number of deaths in the acute and post-acute phases were 34 and 45, respectively. Proteomics data suggest that the immune systems of patients who died in the acute phase underwent a more rapid and severe onslaught. Patients in the post-acute phase showed higher levels of viral genome replication and a more robust immune response. However, the over-activation of the immune system led to systemic organ dysfunction. Effective management of comorbidities may improve the prognosis of COVID-19 in super-elderly patients. The continuous replication of the SARS-CoV-2 virus and its subsequent impact on the immune system are critical determinants of survival time in this demographic.

Humans↗

PubMed2006

High-fat- and lipid-induced insulin resistance in rats: the comparison of glucose metabolism, plasma resistin and adiponectin levels.

AIMS: In animal models, both an acute elevation in plasma free fatty acid (FFA) via intravenous infusion of a lipid emulsion and a chronic elevation in plasma FFA via high-fat feeding have been shown to induce skeletal muscle and liver insulin resistance. However, there have been very few studies comparing the effects of high-fat- and lipid-induced insulin resistance on glucose metabolism and adipocytokines. METHODS: In the current study, we used lipid infusion and a high-fat feed in combination with the hyperinsulinemic-euglycemic clamp technique to assess the impact of acute and chronically elevated FFA levels on overall glucose metabolism and insulin action; two adipocytokines, resistin and adiponectin, were used. RESULTS: At baseline, plasma FFA levels were significantly increased in the high-fat diet (HF) group compared to the control group (p < 0.05). During clamp steady-state, the FFA levels were reduced by approximately 25% in the control and approximately 48% in the HF groups. In contrast, there was a significant increase in the plasma FFA level in the lipid-infused group (from 0.82 +/- 0.03 to 2.87 +/- 0.18 mmol/l). The glucose infusion rates (GIRs) in the HF and lipid groups were obviously lower than in the control group (p < 0.01). Moreover, GIR was lower in the lipid group compared with the HF group (p < 0.05). The rate of glucose disappearance (G(Rd)) was significantly lower in the lipid group compared with the control group. Hepatic glucose production in the control group was suppressed by approximately 15% compared with the HF and lipid groups where it was suppressed by only approximately 72 and approximately 91%, respectively. The resistin level of muscle tissues in the lipid group was significantly higher compared with the control and HF groups (both p < 0.05). After the insulin clamp, the circulating adiponectin level was significantly decreased in the lipid group compared with the control and HF groups (p < 0.05). CONCLUSIONS: Lipid infusion, which was more effective than a high-fat diet, can induce peripheral and hepatic insulin resistance in rats. Insulin-induced resistance might be associated with elevated resistin and decreased adiponectin.

Adiponectin↗

PubMed2006

Sensitive quantification of rifaximin in human plasma by liquid chromatography-tandem mass spectrometry.

A liquid chromatography-mass spectrometry method (LC-MS/MS) for the quantitative determination of rifaximin in human plasma was developed and validated. In the developed procedure, metoprolol was added to human plasma as an internal standard (IS) and acetonitrile was used to precipitate the plasma proteins before LC-MS/MS analysis. Chromatographic separation was obtained on a RESTEK Pinnacle C18 column (50 mm x 2.1mm, 5 microm) with a mobile phase consisted of ammonium acetate solution (15 mM, pH 4.32) as buffer A and methanol as mobile phase B. Quantification was performed in positive mode using multiple reaction monitoring (MRM) of the transitions m/z 786.1-->754.1 for rifaximin and m/z 268.3-->116.1 for the IS. The assay has been validated over the concentration range of 0.5-10 ng/ml (r=0.9992) based on the analysis of 0.2 ml of plasma. The assay accuracy was between 98.2% and 109%. The within-day and between-day precision was better than 3.9% and 8.9% at three concentration levels. The freeze-thaw stability was also investigated and it was found that both rifaximin and the IS were quite stable. This method provides a rapid, sensitive, specific and robust tool for the quantitative determination of rifaximin in human plasma, which is especially useful for the pharmacokinetic study of rifaximin.

Anti-Infective Agents↗

PubMed2006

Determination of free L-carnitine in human seminal plasma by high performance liquid chromatography with pre-column ultraviolet derivatization and its clinical application in male infertility.

BACKGROUND: To develop and validate a simple and reliable high performance liquid chromatographic (HPLC) method for the analysis of free L-carnitine in human seminal plasma and to investigate its clinical significance as a potentially additional means of evaluating the infertile male. METHODS: After proteins in seminal plasma are precipitated with a mixture of acetonitrile and methanol (9:1; v/v), free L-carnitine in seminal plasma was derivatized to form its UV-absorbing ester. HPLC separation of the sample solution was performed on a Lichrospher SiO2 column and detected by ultraviolet absorbance at 260 nm. A mobile phase composed of acetonitrile-citric acid buffer (containing 12 mmol/L triethanolamine, pH 5.0) was found to be the most suitable for this separation at a flow rate of 1.2 mL/min and enabled the baseline separation of the free L-carnitine from interferences with isocratic elution. The free L-carnitine levels in seminal plasma were studied in both 30 control subjects and 87 patients with infertility. Ejaculates were classified into studied subgroups and defined as: asthenozoospermia (n=29), oligozoospermia (n=19) and oligoasthenoteratozoospermia (n=39). RESULTS: Under the chromatographic conditions described, the free L-carnitine derivative had a retention time of approximately 13 min. Good separation and detectability of free L-carnitine in human seminal plasma sample were obtained. The method proved to be linear in the range of L-carnitine from 0 micromol/L to 1000 micromol/L. The relative standard deviations of within- and between-assay for free L-carnitine analysis were 1.23 and 1.36 %, respectively. The recoveries were 91.6-96.5% for the human seminal plasma samples. Free L-carnitine concentrations in the populations were 392.66+/-107.18 micromol/L in the fertile group (n=30), 270.00+/-83.92 micromol/L in asthenozoospermia group, 187.97+/-43.90 micromol/L in oligozoospermia group and 175.65+/-67.07 micromol/L in oligoasthenozoospermia group. The large difference (P<0.01) between the fertile and infertile populations is evident and the difference between the subdivided groups in the infertile group is not significant (P>0.05). CONCLUSION: The determination of free L-carnitine level in seminal plasma may prove useful as a potentially biochemical marker of fertility and this is a useful guidance for the clinic therapy and the mechanismic study on the male reproduction.

Adult↗

PubMed2006

CD46 (membrane cofactor protein) acts as a human epithelial cell receptor for internalization of opsonized uropathogenic Escherichia coli.

Escherichia coli is a common urinary pathogen whose uptake into epithelial cells is mediated by attachment through type 1 fimbriae. In this study, we show by using using human urinary tract epithelial cells that maximal internalization of E. coli is achieved only when bacteria are opsonized with complement. The concentrations of complement proteins in the urine rise sufficiently during infection to allow bacterial opsonization. The complement regulatory protein, CD46 (membrane cofactor protein), acts in cohort with fimbrial adhesion to promote the uptake of pathogenic E. coli. This uptake is inhibited by RNA interference to lower the expression of CD46 and by soluble CD46 that will competitively inhibit opsonized bacteria binding to cell surface CD46. We propose that efficient internalization of uropathogenic E. coli by the human urinary tract depends on cooperation between fimbrial-mediated adhesion and C3 receptor (CD46)-ligand interaction. Complement receptor-ligand interaction could pose a new target for interrupting the cycle of reinfection due to intracellular bacteria.

Antibodies, Bacterial↗

PubMed2006

Role of dendritic cell synthesis of complement in the allospecific T cell response.

Although extrahepatic synthesis of complement and particularly C3 has been widely studied in most cells and tissues, new information is emerging on dendritic cells (DCs). This research has shown that mouse bone marrow (BM) derived DCs are able to synthesise C3 and this synthesis has a substantial impact on DC activation, affecting the diverse range of DC functions relevant to the allospecific T cell response. Thus, local production of C3 appears to regulate the capacity of DCs to trigger the primary T cell response against donor alloantigen. Understanding of the key mechanisms by which complement activation modulates DC maturation could lead to the development of therapeutic strategies to down regulate DC activation thus reduce allograft rejection.

Animals↗

PubMed2006

Dendritic cell synthesis of C3 is required for full T cell activation and development of a Th1 phenotype.

Previous studies have found that deficiency of complement component C3 is associated with reduced T cell responses in several disease models including viral infection, autoimmune disease, and transplantation. However, the underlying mechanism is unclear. In this study, we demonstrate that dendritic cells (DCs) are able to synthesize C3 and this synthesis is required for the capacity of DCs to stimulate alloreactive T cell responses in vitro and in vivo. Compared with C3-producing DCs, C3-nonproducing DCs exhibit reduced potency to stimulate an alloreactive T cell response, favor the polarization of CD4(+) T cells toward Th2 phenotype, and have regulatory T cell-driving capacity. In addition, priming mice with C3-deficient DCs compared with wild-type DCs led to delayed skin allograft rejection. Our findings that nonproduction of C3 by DCs significantly reduced T cell stimulation and impaired allograft rejection provide a potentially important explanation of how C3-deficient mice develop reduced T cell responses and of how C3-deficient donor kidney is protected from T cell-mediated graft rejection.

Animals↗

PubMed2006

Construction of eukaryotic expression plasmid containing HCV NS3 segment and protein expression in human HL-7702 hepatocytes.

AIM: To construct the eukaryotic expression plasmid containing HCV NS3 segment and to analyze the expression of NS3 protein in normal human hepatocyte HL-7702. METHODS: We amplified HCV NS3 fragment from plasmid pBRTM/HCV 1-3011 containing the whole length of HCV genome, recombined it with expression vector pcDNA3.1(-) to form the eukaryotic expression vector pcDNA3.1(-)/NS3, and transfected human HL-7702 hepatocytes with the recombined plasmid by cationic polymers. The expressed HCV NS3 protein was detected and analyzed by immunohistochemical method and Western blot. RESULTS: The amplified NS3 fragments had correct molecule weight and sequence. The successfully constructed eukaryotic expression plasmids were transfected to HL-7702 cells. The expressed NS3 proteins had correct molecular weight 70000. CONCLUSION: Eukaryotic expression vector pcDNA3.1 (-)/NS3 containing NS3 segment of HCV can be constructed, the sequence of NS3 fragments is consistent with the template. Normal human HL-7702 hepatocytes can efficiently express specific HCV NS3 protein in vitro.

Blotting, Western↗

PubMed2006

Determination of coenzyme Q10 in human seminal plasma by high-performance liquid chromatography and its clinical application.

A high-performance liquid chromatographic (HPLC) method for the analysis of coenzyme Q10 (CoQ10) in human seminal plasma was developed and applied to investigate its clinical significance as a reference index relating to oxidative stress and infertile status of spermatozoa. After precipitation of proteins in seminal plasma with methanol, CoQ10 and coenzyme Q9 (CoQ9; internal standard) were extracted with hexane. The supernatant after centrifugation was evaporated to dryness with nitrogen at 45 degrees C. The residue was re-dissolved in isopropanol. HPLC separation of the sample solution was performed on a Lichrospher C(18) column with a mobile phase composed of isopropanol-methanol-tetrahydrofuran in the ratio of 55:39:6 (v/v/v) at a flow rate of 1.0 mL/min. Under the chromatographic conditions described, the CoQ10 and CoQ9 had retention times of approximately 5.83 and 4.97 min, respectively. The peaks were detected at UV 275 nm. Good separation and detectability of CoQ10 in human seminal plasma were obtained. The method was linear in the range 0.01-10.00 microg/mL. The relative standard deviations within- and between-assay for CoQ10 analysis were 0.85 and 1.86%, respectively. The average recoveries were 94.1-99.0% for the human seminal plasma samples. The CoQ10 levels in seminal plasma of 195 patients and 23 control subjects were studied. CoQ10 concentrations in the two populations were: 37.1 +/- 12.2 ng/mL in the fertile group and 48.5 +/- 20.4 ng/mL in the infertile group. The large difference (p < 0.01) between the fertile and infertile populations is evident.

Adult↗

PubMed2006

Improved temporal clustering analysis method for detecting multiple response peaks in fMRI.

PURPOSE: To develop an improved temporal clustering analysis (TCA) method for detecting multiple active peaks by running the method once. MATERIALS AND METHODS: Two cases of simulation data and a set of actual fMRI data from nine subjects were used to compare the traditional TCA method with the new method, termed extremum TCA (ETCA). The first case of simulation data simulated event-related activation and block activation in one cerebral area, and the second case simulated event-related activation and block activation in two cerebral areas. An in vivo visual stimulating experiment was performed on a 1.5T MR scanner. All imaging data were processed using both traditional TCA and the new method. RESULTS: The results of both the simulated and actual fMRI data show that the new method is more sensitive and exact than traditional TCA in detecting multiple response peaks. CONCLUSION: The new method is effective in detecting multiple activations even when the timing and location of the brain activation are completely unknown.

Brain Mapping↗

PubMed2006

Changes in FMRI in the human brain related to different durations of manual acupuncture needling.

OBJECTIVES: The present study is aimed at evaluating the effects of manual acupuncture with different durations on the human brain using functional magnetic resonance imaging. MATERIALS AND METHODS: Eighteen healthy right-handed volunteers were divided into three groups randomly. Each group received only one kind of acupuncture on the right LI4 (Hegu) point, which lasted 30 sec, 60 sec, or 180 sec, respectively. Fix-effect and conjunction analysis were used to compare the effects of the three kinds of acupunctures. RESULTS: The results indicated that the stimulation of manual acupuncture with different durations could induce different effects in the central nervous system on the human brain. The longer duration of manual acupuncture might induce more significant areas. CONCLUSIONS: The present study provided not only neuroimaging evidence for manual acupuncture, but also a useful guide for clinical applications of acupuncture. In addition, the results might be helpful to understand the relationship between the central nervous system responses and the durations of acupuncture.

Acupuncture Points↗

PubMed2006

[Identification and evaluation promoter sequence and the transcription activation of Hcbp6 interaction with core protein of hepatitis C virus].

OBJECTIVE: To clarify the expression and regulation mechanism of the new target gene (human hepatitis C virus binding protein 6, Hcbp6) interaction with the core protein of hepatitis C virus (HCV). METHODS: Referring to the prediction online of the promoter region, 3256 base pairs (bp) upstream and downstream of the translation start site were selected as 5 putative promoter sequences which were amplified from the hepatoblastoma cell line-HepG2 cell genomic DNA by polymerase chain reaction (PCR). The amplified products were cloned into a pCAT3 vector. The HepG2 and NIH3T3 cell lines were transfected by pCAT3-Hcbp6-promoters. The CAT activity was detected using an enzyme-linked immunoassay (ELISA) kit. RESULTS: We found that 2 kinds of pCAT3-Hcbp6-promoters (1066 and 240) could direct the reporter gene expression. The expression of CAT was 3.1 times and 6.4 times higher than that of the pCAT3-basic control vector. CONCLUSION: These results indicated that pCAT3-Hcbp6-promoters have promoter activity.

3T3 Cells↗

PubMed2006

The KOJACH food frequency questionnaire for Chaoshan, China: development and description.

This paper aims to develop a data-based Semi-Quantitative Food Frequency Questionnaire (SQFFQ) covering both urban and rural areas in the Chaoshan region of Guangdong Province, China, for the investigation of relationships between food intake and lifestyle-related diseases among middle-aged Chinese. We recruited 417 subjects from the general population and performed an assessment of the diet, using a 3-day weighed dietary record survey. We employed contribution analysis (CA) and multiple regression analysis (MRA) to select food items covering up to a 90% contribution and a 0.90 R2, respectively. The total number of food items consumed was 523 (443 in the urban and 417 in the rural population) and the intake of 29 nutrients was calculated according to the actual consumption by foods/recipes. The CA selected 233, 194 and 183 foods/recipes for the combined, the urban and the rural areas, respectively, and then 196, 157 and 160 were chosen by the MRA. Finally, 125 foods/recipes were selected for the final questionnaire. The frequencies were classified into eight categories and standard portion sizes were also calculated. For adoption of the area-specific SQFFQ, Validity and reproducibility tests are now planned to determine how the combined SQFFQ performs in actual assessment of disease risk and benefit.

Adult↗

PubMed2006

[Roles of vasodilator-stimulated phosphoprotein in the regulation of cytoskeleton].

Regulation of cytoskeletal dynamics is required to coordinate cell adhesion, morphology change and cell motility. Vasodilator-stimulated phosphoprotein (VASP) is an actin-binding protein which is composed of EVH1, EVH2 domains and PRR. It has been implicated in actin-based processes such as axon guidance, T cell polarization and fibroblast migrations. The regulation of VASP phosphorylation, which is controlled by PKG (cGMP-dependent protein kinase) and PKA (cAMP-dependent protein kinase), could correspond to the "switch" process in its communication with cytoskeleton during modification of focal adhesion.

Animals↗