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"Li, Liang-Cheng"
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Alternative splicing as a biomarker and potential target for drug discovery
by
Kai-qin LE Bellur S PRABHAKAR Wan-jin HONG Liang-cheng LI
in
Alternative Splicing - drug effects
,
Animals
,
Biomedical and Life Sciences
2015
Alternative splicing is a key process of multi-exonic gene expression during pre-mRNA maturation. In this process, particular exons of a gene will be included within or excluded from the final matured mRNA, and the resulting transcripts generate diverse protein isoforms. Recent evidence demonstrates that approximately 95% of human genes with multiple exons undergo alternative splicing during pre-mRNA maturation. Thus, alternative splicing plays a critical role in physiological processes and cell development programs, and.dysregulation of alternative splicing is highly associated with human diseases, such as cancer, diabetes and neurodegenerative diseases. In this review, we discuss the regulation of alternative splicing, examine the relationship between alternative splicing and human diseases, and describe several approaches that modify alternative splicing, which could aid in human disease diagnosis and therapy.
Journal Article
Immunological Safety Evaluation of Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells in Mice
2025
Mounting evidence indicates that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs‐exosomes) combine the advantages of hucMSC pluripotency with their nanoscale dimensions, enhancing their clinical potential through prolonged circulation half‐life. Despite these promising characteristics, research on their immunological toxicity remains insufficient. This study focuses on the impact of hucMSC‐exosomes on the general toxicity and immunopathological indicators. When mice received tail vein injections of 6 × 10 10 hucMSC‐exosomes particles, we observed no significant changes in body weight, feed intake, blood composition, organ indices, or histopathological findings throughout the 14 days observation period. Similarly, blood levels of immunoglobulins, cytokines, and lymphocyte subpopulations remained stable. The hucMSC‐exosomes produced no detectable negative effects on immune organs including the thymus, spleen, and bone marrow. These findings indicate that intravenous administration of 6 × 10 10 particles of hucMSC‐exosomes appears relatively safe at the murine level. This assessment of safety and immunological impact following intravenous hucMSC‐exosomes infusion offers experimental support for potential clinical applications and future analyses in this field.
Journal Article
Time-series metabolomic analysis revealed altered metabolism of cynomolgus monkeys after injecting exosomes
2024
Background
Recent years, exosomes have been increasing used to treat diseases, but there is little research on how exosomes affect the metabolism of the body after entering. Therefore, in this study, we discussed the changes of metabolic spectrum and determined the differentially expressed metabolites in the serum of cynomolgus monkeys after injecting exosomes. Six cynomolgus monkeys were divided into control group and exosomes group. After intravenous injection of exosomes, the peripheral blood serum of cynomolgus monkeys was collected at baseline, day 1, day 7 and day 14 respectively. An ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based non-targeted metabolomics platform was used to detect the metabolites. The metabolic spectra of two groups of cynomolgus monkeys were identified and compared, and the time series changes of metabolites in exosomes were described.
Results
The results showed that there was significant difference in metabolic spectrum between the two groups. 45, 114, 49, 39 differentially expressed metabolites were identified in baseline, day 1, day 7, and day 14, respectively. 6-hydroxydopamine, a metabolite related to the regulation of nerve function, was also found. Tryptophan metabolism, choline metabolism in cancer, porphyrin and chlorophyll metabolism were involved in day 1. Sphingolipid metabolism and histidine metabolism were involved in day 7. Three pathways, including choline metabolism, sphingolipid metabolism and biotin metabolism in cancer were involved in day 14. Through time series analysis, it was found that the level of propionylcarnitine and biliverdin increased on day 1 after inoculation with exosomes, while the level of hippuric acid decreased. These changes of immune-related metabolites suggested that exosomes might participate in the immunoregulation reaction after entering the body of cynomolgus monkeys.
Conclusions
In our current study, we found that exosomes injected intravenously affect the changes of metabolites and metabolic pathways in cynomolgus monkeys. Intravenous injection of exosomes may affect the metabolite 6-hydroxydopamine, sphingolipid metabolic pathway, and choline metabolic in cancer pathway, which is of some significance for the treatment of Parkinson’s disease. In addition, exosomes may also affect the immune-related metabolites in vivo, such as propionylcarnitine, biliverdin, hippuric acid metabolites, as well as tryptophan metabolism pathway, sphingolipid metabolism pathway involved in immune regulation, which is of great significance for the future study of immune-regulatory mechanisms of exosomes.
Journal Article
Menopausal symptoms and risk of coronary heart disease in middle-aged women: A nationwide population-based cohort study
by
Huang, Ching-Hui
,
Li, Cheng-Liang
,
Kor, Chew-Teng
in
Biology and Life Sciences
,
Cardiovascular disease
,
Cardiovascular diseases
2018
To assess the relationship between coronary heart disease (CHD) and menopausal symptoms in middle-aged women in Taiwan.
The present study identified 14,340 symptomatic menopausal women without a history of CHD from the Taiwan National Health Insurance Research Database from January 1, 2000, to December 31, 2013. A total of 14,340 age- and Charlson-comorbidity-index-score-matched asymptomatic women were used as controls. Possible comorbidity-attributable risks of CHD were surveyed to assess whether the symptomatic menopausal cohort had a higher incidence of CHD.
The incidence of CHD was higher in the symptomatic menopausal cohort than in the control cohort (17.18 vs. 12.05 per 1000 person-years). After adjustment in multivariate Cox analysis, the risk of CHD was significantly higher in the symptomatic menopausal cohort (adjusted hazard ratio = 1.344, 95% confidence interval [CI] = 1.262-1.43, P < 0.001) than in the control cohort. In the symptomatic menopausal cohort, the risk of CHD was significantly higher in all subgroups, except for the hormone therapy (HT) subgroup. Patients undergoing HT had a nonsignificantly higher risk of CHD, regardless of the presence or absence of menopausal symptoms.
This large-scale longitudinal retrospective cohort study revealed that menopausal symptoms are an independent risk factor for CHD. Moreover, our findings indicate that HT has a nonsignificant effect on the risk of CHD.
Journal Article
Effects of nitrogen application rate and topdressing times on yield and quality of Chinese cabbage and soil nitrogen dynamics
2019
A good understanding of the relationship between vegetable quality and soil N balance is very important for proper nitrogen (N) management for crop productions. In this study, a field experiment was carried out to investigate the N application rate and times on Chinese cabbage yield and quality, N use efficiency, soil nitrate-N concentration, and soil pH. The experiment was implemented in a two-way factorial design and the two factors comprises of number of N applications (once, twice and three times, denoted as T1, T2 and T3) and N rates (15%, 30% and 45% less than conventional rates (CF), denoted as F1, F2 and F3, respectively). The treatments were also compared with a no-fertilizer blank and a control (CF) with a conventional N management practice. The results showed that the highest yield of cabbage (164.65 t hm
−2
), Vitamine C content (14.80 g 100 g
−1
fresh mass), soluble sugar content (2.33 mg kg
−1
), plant N uptake (119.2 kg hm
−2
) were obtained under T3F1 treatment. Compared with CF treatment, T3F1 treatment significantly increased vegetable yield, vitamin C and soluble sugar content in fruit, and nitrogen use efficiency by 10.97%, 13.76% and 17.68%, and 18.76%, respectively. Nitrate-N content in cabbage was reduced by 7.55% in T3F1 treatment. With the reduced N application rate, soil pH gradually changed from 6.25 to 7.26. T3F1 treatment is a most suitable N management practice for vegetable production, in terms of higher vegetable yield and quality, soil N content, depressed soil acidification and nutrient uptake by Chinese cabbage.
Journal Article
MADD Knock-Down Enhances Doxorubicin and TRAIL Induced Apoptosis in Breast Cancer Cells
by
Qian, Lixia
,
Prabhakar, Bellur S.
,
Ganesh, Lakshmy
in
Amino Acid Sequence
,
Analysis
,
Anthracyclines
2013
The Map kinase Activating Death Domain containing protein (MADD) isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.
Journal Article
Soil microbial community structure, metabolic potentials and influencing factors in a subtropical mountain forest ecosystem of China
by
Yang, Xiaolu
,
Zhao, Rudong
,
Tian, Qiuxiang
in
Biolog
,
Chemicophysical properties
,
Community structure
2020
This study investigated the variances in soil microbial community (SMC) structure and metabolic potentials in subtropical mountain forest ecosystem. Soil samples (0-10, 10-30 and 30-60 cm) were collected within 27 plots (20×20 m
2
) that were randomly assigned. Changes in SMC structure were mainly regulated by soil physicochemical property and tree diversity in 0-10 cm depth, by total nitrogen (TN) and clay in 10-30 cm depth, and by soil organic carbon (SOC) and pH in 30-60 cm depth. Metabolic potential variance was mainly driven by soil chemical property in 0-10 cm depth, by SOC and TN in 10-30 cm depth, and by TN in 30-60 cm depth. Collectively, soil physicochemical properties were the primary factors influencing SMC structure and its metabolic potentials along the soil profile, but the expected effects of tree diversity and topography were not evident.
Journal Article
Addition of organic fertilizer affects soil nitrogen availability in a salinized fluvo-aquic soil
2019
Organic matter application was one of the suitable ways to improve soil nitrogen availability in saline soils. In this study, two soils of different levels of total soluble salts, 2.45 g kg
−1
(LS) and 4.03 g kg
−1
(HS), were used in a pot experiment with eight treatments: bio-organic fertilizer (prepared with cow dung) and farmyard manure (fowl manure) each at three dosages (3350, 6700, and 13,400 kg ha
−1
), chemical fertilizer control (DAP: 1675 kg ha
−1
), no fertilizer blank. At the same time, an indoor nitrogen mineralization incubation experiment with the same treatments without alfalfa planting was carried out. We aimed to explore the effects of the types and application amounts of organic fertilizers on soil nitrogen mineralization in saline soils and to improve its quality and finally realize its sustainable utilization. The main conclusions are as follows: the biomass of alfalfa treated with medium dose of organic fertilizer was higher than that of alfalfa treated with low or high dose of organic fertilizer. Compared with farmyard manure, bio-organic manure was more effective in increasing the biomass of alfalfa. The nitrogen uptake of alfalfa in high-dose treatment was significantly higher than that in low-dose treatment. The effects of the fertilizer treatments on soil nitrogen availability were in the increasing order of: medium dose, high or low dose of fertilizer treatment, single chemical fertilizer, and fertilizer free treatments by principal component analysis. For possible potential application, medium dosage of bio-organic fertilizer was recommended to apply in the region with saline fluvo-aquic soil.
Journal Article
An Efficient Bifunctional Core–Shell MIL-101(Cr)@MOF-867 Composite to Catalyze Deacetalization–Knoevenagel Tandem Reaction
by
Zhang, Yu-Yang
,
Meng, Ling-Xu
,
Liu, Wei
in
Cascade chemical reactions
,
Catalysis
,
Core-shell structure
2023
By growing one metal organic frameworks (MOFs) on different metal organic frameworks plays an important role in catalytic reaction, but its cooperative catalysis in tandem reaction is an undeveloped field yet, and the reports are very limited. In this work, the material MIL-101(Cr)@MOF-867 with core–shell structure was constructed by growing MOF-867 on the ultra-stable MIL-101(Cr). The synthesized core–shell material had acid–base sites at the same time. Thus, the synergistic catalysis of deacetalization-Knoevenagel tandem reaction showed good catalytic performance and obtained ultra-high yield. In addition, all experiments showed that the core–shell catalyst MIL-101(Cr)@MOF-867 had high stability and under the same conditions, the activity remained still high after five cycles. At the same time, this is the first time to apply MIL-101(Cr)@MOF-867 catalyzing deacetalization-Knoevenagel tandem reaction.A bifunctional material with core–shell structure was successfully synthesized. The obtained MIL-101(Cr)@MOF-867 with both acid and base sites showed ultra-high conversion in the deacetalization-Knoevenagel tandem reaction, thanks to the Lewis acid sites catalytic deacetalization reaction provided by Cr and Zr clusters and the Brönsted base sites to catalyze Knoevenagel reaction provided by pyridine. Fortunately, after five cycles of experiments, all the characterization showed that it still maintained ultra-high catalytic performance and stability. In addition, this is the first time to catalyze the deacetalization-Knoevenagel tandem reaction by MIL-101(Cr)@MOF-867.
Journal Article