Biomedical subjects

Lili Liu

Publications and source records attributed to Lili Liu.

At least 19 recordsLinked to original sources

PubMed2026

Antibody diversification in cartilaginous fishes: Mechanistic insights from the nurse shark and comparative perspectives across jawed vertebrates.

Antibody diversity in vertebrates arises through the coordinated actions of V(D)J recombination and somatic hypermutation (SHM). Cartilaginous fishes occupy a key phylogenetic position as the sister lineage to bony vertebrates and therefore provide important comparative insights into the evolution of adaptive immunity. This review focuses on the nurse shark (Ginglymostoma cirratum) as a representative model for examining antibody-diversification mechanisms in cartilaginous fishes. Shark immunoglobulin genes exhibit a multicluster organization, while immunoglobulin new antigen receptor (IgNAR), a heavy-chain-only isotype, contains a single variable domain with an extended complementarity-determining region 3 (CDR3) that can be stabilized by non-canonical disulfide bonds. These structural features, together with intracluster multi-D V(D)J recombination and distinctive SHM characterized by single and tandem substitutions and insertions/deletions, contribute to antibody diversification in sharks. By comparing cartilaginous fishes, ray-finned fishes, and mammals, this review highlights lineage-specific combinations of immunoglobulin gene organization, recombination, mutational processing, and affinity maturation. Within the heuristic framework proposed here, shark and mammalian systems are described as emphasizing "breadth-first" repertoire generation and "precision-first" affinity optimization, respectively. These terms indicate relative mechanistic emphases rather than mutually exclusive categories or sequential evolutionary stages, while ray-finned fishes exhibit a distinct combination of genomic organization and mutational features. Investigating antibody diversification in cartilaginous fishes not only advances our understanding of vertebrate immune evolution but also provides structural and mechanistic insights that may inform the development of engineered antibodies based on the IgNAR scaffold.

Antibody diversity↗

PubMed2026

Comparison of clinical efficacy and gut microbiota characteristics in children with ASD treated with fecal microbiota transplantation and ketogenic diet.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, along with restricted, repetitive patterns of behavior. It is often accompanied by gastrointestinal dysfunction and gut microbiota dysbiosis. Fecal Microbiota Transplantation (FMT) and the Ketogenic Diet (KD) are interventions targeting the gut microbiota for ASD. METHODS: 30 participants were diagnosed with ASD according to DSM-5 and ADOS-2. ASD core symptoms were evaluated with CARS and ABC. Gut microbiota composition was analyzed by shotgun metagenomic sequencing. RESULTS: Both groups demonstrated significant improvements in core symptoms. In the FMT group, the mean CARS score significantly decreased from 34.87 to 33.53 (p < 0.01); in the KD group, it declined from 35.13 to 33 (p < 0.01). The mean ABC score reduced from 79.93 to 69.33 (p = 0.064) in the FMT group and from 63.07 to 42.73 (p < 0.01) in the KD group. Following the intervention, no statistically significant changes were observed in α-diversity or β-diversity within either group. LEfSe analysis revealed distinct post-intervention microbial signatures: FMT significantly enriched butyrate-producing taxa (Wujia chipingensis, Eubacterium sp. MSJ-33, and Butyrivibrio crossotus), while KD elevated Blautia massiliensis and decreased propionate metabolism -associated taxa (Veillonella sp. S12025-13 and Veillonella nakazawae). KEGG enrichment analysis revealed that KD enriched propionate metabolism (Fold enrichment = 3.747, q = 0.010) and aromatic compound degradation (Fold enrichment = 3.591, q = 0.010). CONCLUSIONS: Both interventions significantly improved clinical symptoms among children with ASD, potentially through distinct patterns of gut microbiota modulation. CLINICAL TRIALS NUMBER: NCT06348433 (03/21/2024).

Child↗

PubMed2026

Immune Cell-Stratified Regulatory Contexts Associated With BMI-Related Multi-System Disease Risk: A Cell-Stratified Mendelian Randomization Study Using Single-Cell eQTL Data.

AIMS: Body mass index (BMI) is associated with multisystem disease risk, but the immune cell-specific regulatory contexts underlying BMI-related genetic associations with disease outcomes remain unclear. METHODS: We applied a cell-stratified Mendelian randomization framework integrating European-ancestry BMI GWAS data, GWAS datasets for 33 disease outcomes across five disease systems, single-cell cis-eQTL data from 28 peripheral blood immune cell types, and dynamic CD4+ T cell eQTL data. SuSiE-based colocalization was used to identify BMI-associated loci sharing causal variants with immune-cell gene expression. These variants were used as cell-stratified instruments for Mendelian randomization. RESULTS: Across 28 immune cell types, 1326 colocalized variants regulating 1426 genes were identified. In primary MR analyses, genetically predicted BMI showed Bonferroni-significant associations with 26 disease outcomes. Cell-stratified analyses identified 87 Bonferroni-significant associations across 17 disease outcomes. Cardiovascular diseases showed the broadest cell-stratified associations, followed by respiratory and metabolic diseases. CD4+ T cell regulatory contexts contributed one of the largest shares of prioritized associations, and BMI-related effects varied across CD4+ T cell activation states. Cross-disease prioritization highlighted recurrent immune feature genes, including TRAF3 and FGFR1. CONCLUSION: These findings prioritize CD4+ T cell regulatory contexts as potential immunogenetic links between BMI and multi-system disease risk, while requiring further validation in diverse populations and mechanistic models.

Humans↗

PubMed2025

Cross-Phenotype Genome-Wide Association Study on the Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis.

OBJECTIVE: An increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross-phenotype genome-wide association study (GWAS) meta-analysis. METHODS: We performed cross-phenotype GWAS meta-analysis and Bayesian colocalization analysis for patients with SSc and patients with PBC. We performed both genome-wide and locus-based analysis, including tissue and pathway enrichment analyses, fine-mapping, Bayesian colocalization analyses with expression quantitative trait loci and protein quantitative trait loci (pQTL) datasets, and phenome-wide association studies. Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci. RESULTS: We detected a strong genetic correlation between SSc and PBC (global genetic correlation = 0.84, P = 1.7 × 10-6). In the cross-phenotype GWAS meta-analysis, we identified 44 nonhuman leukocyte antigens loci that reached genome-wide significance (P < 5 × 10-8). Evidence of shared causal variants between patients with SSc and patients with PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40, ERAP1, PLD4, SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans-pQTLs of multiple plasma proteins involved in B cell function. CONCLUSION: Our study supports a strong shared genetic susceptibility between SSc and PBC. Using cross-phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.

Humans↗

PubMed2006

Compression-inhibited pore formation of polyelectrolyte multilayers containing weak polyanions: a scanning force microscopy study.

Morphological changes of poly(acrylic acid)/poly(diallyldimethylammonium chloride) multilayers induced by low pH were investigated by scanning force microscopy. The weakened interaction between the charged polymer chains in the protonation process is believed to be the reason for this variation. Kinetic studies have shown that during protonation phase separation and dissociation of the multilayers took place successively. The compression of the multilayers, however, caused a transition of the multilayers from a rubbery state to a glassy state. As a result, the closely compacted multilayers lost their sensitivity to pH change. An increase of electrostatic and hydrophobic interactions, can decrease the free energy of the multilayers, and stabilize the films. By compression of the multilayers with a rubber stamp having geometric patterns, films with spatially localized pores were produced.

Journal Article↗

PubMed2006

Targeted modulation of MGMT: clinical implications.

O(6)-Methylguanine DNA methyltransferase (MGMT) has been studied for >20 years as a gene that is associated with the mutagenicity and cytotoxicity induced by either methylating carcinogens or alkylating (methylating and chloroethylating) therapeutic agents. Pioneering studies of alkylating agents identified alkylated guanine at the O(6) position, the substrate of MGMT, as a potentially promutagenic and lethal toxic DNA lesion. MGMT plays a prominent role in DNA adduct repair that limits the mutagenic and cytotoxic effect of alkylating agents. Because of its role in cancer etiology and chemotherapy resistance, MGMT is of particular interest. In this article, the clinical effect of MGMT expression and targeted modulation of MGMT will be summarized.

Antineoplastic Agents, Alkylating↗

PubMed2006

Reliability and validity of the Safety Assessment Scale for people with dementia living at home.

BACKGROUND: With the recent funding changes in health care services, more seniors with dementia are cared for in their homes and the nature of their condition puts them at higher risk for accidents and injuries. PURPOSE: The Safety Assessment Scale (SAS) was developed for use by community healthcare providers to evaluate and lower the risk of accidents, provide recommendations to family caregivers and enhance case management. Method. The scale was assessed in terms of the reliability as well as content, criterion and construct validity with 176 community-residing people with dementia in Quebec, Alberta and British Columbia. The Safety Assessment Scale was validated in French and English. RESULTS: The SAS demonstrated an excellent test-retest (ICC=.91) and inter-rater (ICC=.88) reliability. Results for validity were also extremely good. PRACTICE IMPLICATIONS: The scale is available in French and English. The short version of the SAS is a screening tool and the longer version provides an in-depth evaluation of safety and intervention planning. The SAS can be used by a variety of health care professionals who work with individuals who have dementia.

Accidents, Home↗

PubMed2006

Accessible support for family caregivers of seniors with chronic conditions: from isolation to inclusion.

Accessible support programs can improve health outcomes for family caregivers of older relatives with a chronic condition. Over the course of 6 months, 27 experienced family caregivers provided weekly support via the telephone to 66 individuals, either new family caregivers of seniors recently diagnosed with stroke or newly vulnerable family caregivers (i.e., facing increasing demands from the deterioration of their senior relative's condition) of seniors with Alzheimer's disease. Qualitative data documented the perceived impact of the intervention, including increased satisfaction with support, coping skills, caregiving competence and confidence, and decreased caregiver burden and loneliness. Caregivers identified varied support processes that overcame support deficits in their social networks. These processes can facilitate replication in future research and inform practice, programs, and policies.

Adaptation, Psychological↗

PubMed2005

Poly(ethylene glycol) micro-patterns as environmentally sensitive template for selective or non-selective adsorption.

Poly(ethylene glycol) (PEG), a hydrophilic and repulsive polymer to non-specific adsorption, was stamped onto carboxylic acid-enriched polymer surfaces using the micro-contact printing technique. The patterns are stabilized via hydrogen bonds. Areas printed with PEG were then shown to be non-adsorbed with fluorescein isothiocyanate (FITC)-labeled dextran, while the poly(methacrylic acid) (PMAA) regions could via hydrogen bonding. Due to this contrast, well defined dextran patterns were obtained. Tuned with pH and temperature, the PEG molecules could be detached from the surfaces, erasing the template. Moreover, ionization of PMAA at higher pH induced an abrupt transition to an extended conformation, weakening the interactions between PMAA and dextran. Not only the dextran patterns lose their spatial selectivity, but also the overall adsorption amount is much lower. The pH sensitivity was in a quite narrow range, i.e. around pH 5. As the hydrogen bonds are also temperature sensitive, the attach points of PEG molecules on the surfaces disappeared at higher temperature. For poly(acrylic acid) (PAA) photografted surfaces, the pH sensitivity was more complicated due to the formation of the compact complexes of PEG and PAA molecules.

Adsorption↗

PubMed2005

Effects of extracellular polymeric substances on aerobic granulation in sequencing batch reactors.

The effects of extracellular polymeric substances on aerobic granulation in sequencing batch reactors were investigated by evaluating the content and compositions of extracellular polymeric substances, and the relationship between extracellular polymeric substances composition and surface properties of glucose-fed aerobic granules. The results showed that extracellular polymeric substances could affect surface properties of cells, such as surface charge and hydrophobicity, enhance polymeric interaction and promote aerobic granulation. Moreover, extracellular polymeric substances were produced mainly in the exponential phase, and served as carbon and energy source in starvation phase during granulation process, thus regulating the growth of bacteria in the interior and exterior of granules, and maintaining the integrality of granules.

Aerobiosis↗

PubMed2005

Phase II trial of the O6-alkylguanine DNA alkyltransferase inhibitor O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea in advanced melanoma.

PURPOSE: 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) induces DNA damage via a chloroethyl adduct at the O(6) position of guanine, which can be repaired by O(6)-alkylguanine DNA alkyltransferase (AGT) expressed in melanoma. We postulated that the addition of O(6) benzylguanine (O(6)BG), a potent inactivator of AGT, would improve the clinical response to BCNU in melanoma. EXPERIMENTAL DESIGN: Patients had measurable disease, adequate organ function, and a corrected Diffusing capacity of the lung for carbon monoxide (DLCO) of > or =70% predicted. They were accrued into two cohorts based on prior chemotherapy. O(6)BG (120 mg/m(2)) was administered i.v. followed by BCNU (40 mg/m(2)) on an outpatient basis. Peripheral blood mononuclear cells (PBMC) were collected pre- and 18 hours post-O(6)BG to analyze AGT depletion. Treatment was every 6 weeks, and clinical response was assessed after every two cycles. RESULTS: Forty-two patients were enrolled, 22 of these patients were chemotherapy-naïve. In the chemotherapy-naïve cohort, there was a patient with a complete response (CR), 4 with stable disease (SD), 13 with progressive disease (PD), and 4 nonevaluable patients; the median time to progression was 80 days and the median survival was 211 days. In the prior-chemotherapy cohort, there were no responses, 3 SD, 15 PD, and 2 nonevaluable patients; median time to progression was 54 days and median survival was 120 days. AGT was depleted from PBMC in the 15 patients tested. Grades 3 to 4 myelosuppression was seen in 57% of patients; toxicities were similar between the two cohorts. CONCLUSIONS: O(6)BG/BCNU was successfully administered on an outpatient basis and depleted AGT from PBMC. However, significant myelosuppression was observed and the clinical outcome was not improved. Alternative mechanisms of resistance to melanoma cell death need to be investigated.

Adult↗

PubMed2005

Loading and release behaviors of compressed polyelectrolyte multilayers for small dye molecules.

Loading and release behaviors of compressed polyelectrolyte multilayers composed of poly(styrenesulfonate sodium salt) and poly(diallyldimethylammonium chloride) were investigated using fluorescein and rhodamine 6G as indicators by confocal laser scanning microcopy, fluorescence spectroscopy, and UV-vis spectroscopy. Compression of the multilayers resulted in a more densely packed microstructure, leading to the decrease of fluorescence intensity of the incorporated probes to 80% of its initial value, and much slower releasing rate as well as smaller releasing amount regardless of the types of the probes and the presence of salt. Utilizing the difference of loading and release rates between the compressed and the uncompressed regions, arrays of dye reservoirs have been fabricated on a chemical homogeneous but physical heterogeneous multilayer film.

Coloring Agents↗

PubMed2005

Inactivated MGMT by O6-benzylguanine is associated with prolonged G2/M arrest in cancer cells treated with BCNU.

HCT116 and HCT15 cells that highly express O(6)-methylguanine-DNA-methyltransferase (MGMT) displayed a transient cell cycle G2/M arrest in response to exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) alone; however, 70-80% of cells were arrested in G2/M after treatment with O(6)-benzylguanine (BG) and BCNU. Cells accumulated in G2/M showed elevated levels of an inactive form of cyclin B1/p-Cdc2 (Tyr15) complex that was not associated with activation of Chk1/p-Cdc25C and was independent of p53/p21 status. The most prominent feature of cell death was the appearance of enlarged and multinucleated cells that was related to the inhibition of mitotic entry. In contrast, BG-resistant cell lines, HCT116 BBR and HCT15 BBR cells that contain mutations K165E and K165N of MGMT, respectively, displayed a normal cell cycle progression with a slight and transient increase in G2/M arrest at 24 h after treatments with either BCNU alone or BG combined with BCNU. The differences in the ability to progress toward G2/M after treatment with BG and BCNU between cells expressing wild-type MGMT and mutated MGMT were confirmed in CHO cells transfected with human wild type and K165E mutant MGMT cDNA, respectively. Thus, our findings suggest that BG-inactivated MGMT may be linked to cell signaling events, forcing cells into a permanent G2/M arrest in response to the DNA damages induced by BCNU.

Amino Acid Substitution↗

PubMed2005

Use of Ssp dnaB derived mini-intein as a fusion partner for production of recombinant human brain natriuretic peptide in Escherichia coli.

To prevent in vivo degradation, small peptides are usually expressed in fusion proteins from which target peptides can be released by proteolytic or chemical reagents. In this report, a modified Ssp dnaB mini-intein linked with a chitin binding domain tag was used as a fusion partner for production of human brain natriuretic peptide (hBNP), a hormone for the treatment of congestive heart failure. The fusion protein was expressed as an inclusion body in Escherichia coli. After refolding, the fusion protein was purified with a chitin affinity column, and dnaB mini-intein mediated peptide-bond hydrolysis was triggered by shifting the pH in the chitin column to 7.0 at 25 degrees C for 16 h, which led to the release and separation of hBNP from its fusion partner. The hBNP sample was further purified with reverse phase HPLC and its biological activity was assayed in vitro. It was found that hBNP had a potent vasodilatory effect on rabbit aortic strips with an EC(50) of (1.24+/-0.32)x10(-6)mg/ml, which was similar to that of the synthetic BNP standard. The expression strategy described here promises to produce small peptides without use of proteolytic or chemical reagents.

Adenosine Triphosphatases↗

PubMed2005

Continuing professional education and the Internet: views of Alberta occupational therapists.

BACKGROUND: Occupational therapists have identified barriers to accessing continuing professional education (CPE) in the traditional face-to-face formats. One alternative to traditional, centrally located, face-to-face CPE is course delivery through the Internet. PURPOSE: This study examined Alberta occupational therapists' perceptions of Internet-based CPE. METHOD: A questionnaire was mailed to 800 randomly sampled Alberta occupational therapists (response rate = 35.5%; n = 281). RESULTS: Respondents pursued CPE to increase skills, knowledge and maintain clinical competency. They reported that a face-to-face CPE course was more useful than distance courses. Although almost 90% of respondents had access to computers with an Internet connection at home or at work, and nearly 65% thought that their computer knowledge was sufficient, only 2.9% had previously taken Internet-based CPE. PRACTICE IMPLICATIONS: In order for the Internet to be accepted as a common, useful and alternative delivery tool for CPE in occupational therapy, the perceived barriers such as the lack of personal time, cost, and limited interaction with other learners and instructors will need to be addressed.

Adult↗

PubMed2004

Biological pacemaker implanted in canine left bundle branch provides ventricular escape rhythms that have physiologically acceptable rates.

BACKGROUND: We hypothesized that administration of the HCN2 gene to the left bundle-branch (LBB) system of intact dogs would provide pacemaker function in the physiological range of heart rates. METHODS AND RESULTS: An adenoviral construct incorporating HCN2 and green fluorescent protein (GFP) as a marker was injected via catheter under fluoroscopic control into the posterior division of the LBB. Controls were injected with an adenoviral construct of GFP alone or saline. Animals were monitored electrocardiographically for up to 7 days after surgery, at which time they were anesthetized and subjected to vagal stimulation to permit emergence of escape pacemakers. Hearts were then removed and injection sites visually identified and removed for microelectrode study of action potentials, patch clamp studies of pacemaker current, and/or immunohistochemical studies of HCN2. For 48 hours postoperatively, 7 of 7 animals subjected to 24-hour ECG monitoring showed multiple ventricular premature depolarizations and/or ventricular tachycardia attributable to injection-induced injury. Thereafter, sinus rhythm prevailed. During vagal stimulation, HCN2-injected dogs showed rhythms originating from the left ventricle, the rate of which was significantly more rapid than in the controls. Excised posterior divisions of the LBB from HCN2-injected animals manifested automatic rates significantly greater than the controls. Isolated tissues showed immunohistochemical and biophysical evidence of overexpressed HCN2. CONCLUSIONS: A gene-therapy approach for induction of biological pacemaker activity within the LBB system provides ventricular escape rhythms that have physiologically acceptable rates. Long-term stability and feasibility of the approach remain to be tested.

Action Potentials↗

PubMed2004

Pre-UV-treatment of cells results in enhanced host cell reactivation of a UV damaged reporter gene in CHO-AA8 chinese hamster ovary cells but not in transcription-coupled repair deficient CHO-UV61 cells.

We have used a non-replicating recombinant adenovirus, Ad5MCMVlacZ, which expresses the beta-galactosidase reporter gene, to examine both constitutive and inducible repair of UV-damaged DNA in repair proficient CHO-AA8 Chinese hamster ovary cells and in mutant CHO-UV61 cells which are deficient in the transcription-coupled repair (TCR) pathway of nucleotide excision repair. Host cell reactivation (HCR) of beta-galactosidase activity for UV-irradiated Ad5MCMVlacZ was significantly reduced in non-irradiated CHO-UV61 cells compared to that in non-irradiated CHO-AA8 cells suggesting that repair in the transcribed strand of the UV-damaged reporter gene in untreated cells utilizes TCR. Prior UV-irradiation of cells with low UV fluences resulted in a transient enhancement of HCR for expression of the UV-damaged reporter gene in CHO-AA8 cells but not in TCR deficient CHO-UV61 cells. These results suggest the presence of an inducible DNA pathway in CHO cells that results from an enhancement of TCR or a mechanism that involves the TCR pathway.

Adenoviridae↗

PubMed2004

Rehabilitation professionals' satisfaction with continuing education delivered at a distance using different technologies.

This paper examines learner satisfaction with technologies used for distance delivery of continuing education across 10 Canadian sites: nine within the province of Alberta and one in Nunavut Territory. The technologies were satellite (or videotapes of) broadcasts, videoconferencing, and web-based technology. Learner satisfaction was evaluated using questionnaires. A survey on general issues related to continuing education was developed and mailed to random samples of health professionals and a convenience sample of stakeholders. The learners (n = 1,141) represented 20 types of health service providers who had attended at least one session delivered via satellite, videotape, or videoconferencing. Seven individuals completed the web-based course. Overall, the majority of participants were satisfied or very satisfied. In general, satellite delivery was received more favorably compared with videotapes of the same content. A total of 350 (33% response rate) health professionals and 37 (50% response rate) stakeholders returned the surveys. Nearly 50% of health professionals thought that clinical case presentations (rounds) were valuable to them, but over half of the stakeholders perceived that videotapes, rounds, and research seminars were valuable to health professionals. Ratings for the web-based course varied, indicating different learner characteristics. We conclude that it is possible to utilize multiple technologies to meet the continuing education needs of an interdisciplinary group of health service providers, but future research is needed to develop a framework for evaluating the usability of multiple existing and emerging technologies for distance education.

Alberta↗