Author Correction: Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment.
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Published Erratum↗
Biomedical subjects
Peng Du
Publications and source records attributed to Peng Du.
From population to individual: advocating personalised digital tools for heat-health early warning in a changing climate.
Escalating heat extremes under climate change are imposing substantial health burdens, with 2023 and 2024 consecutively breaking global temperature records. Mounting evidence suggests that heatwaves elevate the risks of hospitalisation and mortality across multiple disease categories, including ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and acute kidney injury. Nonetheless, most existing heat-health warning systems remain primarily reliant on population-level predictions, and considering individual differences and disease-specific considerations when defining warning levels would benefit the effectiveness of early prevention for high-risk groups. In this Viewpoint, which is based on the framework of precision public health-delivering the right intervention to the right population at the right time-we propose a framework for personalised digital heat-health early warning tools comprising three dimensions: individualised, risk-stratified prediction models that generate tiered early warnings; personalised health prompts coupled with theory-informed behavioural interventions; and adaptive, equity-oriented alert delivery mechanisms tailored to diverse populations. Such tools have the potential to bridge precision disease prevention and climate adaptation, thereby helping to mitigate heat exposure risks and disease burdens, particularly among high-risk populations. Future implementation research will be essential to address substantial challenges related to feasibility, validation, and equity.
Journal Article↗
Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment.
In the tumour microenvironment, accumulated lactic acid (LA) promotes tumour immune evasion by facilitating regulatory T cell (Treg) immunosuppressive function and restraining CD8+ T cell cytotoxicity, but the underlying mechanism remains elusive. Here we report that transcriptional factor MondoA-induced thioredoxin interacting protein (TXNIP) transcription is a common feature of both Treg and CD8+ T cells in response to lactic acid. In contrast to reduction in immunosuppressive capacity in MondoA-deficient Treg cells, loss of MondoA enhanced CD8+ T cell cytotoxic function in the lactic-acid-induced immunosuppressive microenvironment, by restoring glucose uptake and glycolysis. Mechanistically, lactic acid relied on sentrin/SUMO-specific protease 1 (SENP1) to stimulate the MondoA-TXNIP axis, which impaired TCR/CD28-signal-induced CD8+ T cell activation. Importantly, targeting the MondoA-TXNIP axis potentiated antitumour immunity in multiple cancer types and synergized with anti-PD-1 therapy to promote effective T cell responses in colorectal cancer. Our results demonstrate that the MondoA-TXNIP axis is a promising therapeutic target for improving cancer immunotherapy.
Tumor Microenvironment↗
Mouse totipotent blastomere-like cells model embryogenesis from zygotic genome activation to post implantation.
Embryo development begins with zygotic genome activation (ZGA), eventually generating blastocysts for implantation. However, in vitro systems modeling the pre-implantation development are still absent and challenging. Here, we used mouse totipotent blastomere-like cells (TBLCs) to develop spontaneous differentiation and blastoid formation systems, respectively. We found Wnt signaling enabled the rapid expansion of TBLCs and the optimization of their culture medium. We successfully developed a TBLC-spontaneous differentiation system in which mouse TBLCs (mTBLCs) firstly converted into two types of ZGA-like cells (ZLCs) distinguished by Zscan4 expression. Surprisingly, Zscan4-, but not Zscan4+, ZLCs further passed through intermediate 4-cell and then 8-cell/morula stages to produce epiblast, primitive endoderm, and trophectoderm lineages. Significantly, single TBLCs underwent expansion, compaction, and polarization to efficiently generate blastocyst-like structures and even post-implantation egg-cylinder-like structures. Conclusively, we established TBLC-based differentiation and embryo-like structure formation systems to model early embryonic development, offering criteria for evaluating and understanding totipotency.
Animals↗
Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats.
This study investigated the pharmacokinetic properties of crocin following oral administration in rats. After a single oral dose, crocin was undetected while crocetin, a metabolite of crocin, was found in plasma at low concentrations. Simultaneously, crocin was largely present in feces and intestinal contents within 24h. After repeated oral doses for 6 days, crocin remained undetected in plasma and plasma crocetin concentrations were comparable to the corresponding data obtained after the single oral dose. Furthermore, the absorption characteristics of crocin were evaluated in situ using an intestinal recirculation perfusion method. During recirculation, crocin was undetected and low concentrations of crocetin were detected in plasma. The concentrations of crocin in the perfusate were reduced through different intestinal segments, and the quantities of drug lost were greater throughout the colon. These results indicate that (1) orally administered crocin is not absorbed either after a single dose or repeated doses, (2) crocin is excreted largely through the intestinal tract following oral administration, (3) plasma crocetin concentrations do not tend to accumulate with repeated oral doses of crocin, and (4) the intestinal tract serves as an important site for crocin hydrolysis.
Administration, Oral↗
[Analysis of anisodine and its metabolites in rat plasma by liquid chromatography-tandem mass spectrometry].
AIM: To identify anisodine and its metabolites in rat plasma after ingestion of anisodine by combining liquid chromatography and tandem mass spectrometry (LC-MS(n)). METHODS: Plasma samples from rats after a single orally administration of 20 mg anisodine were added with methanol to precipitate protein. Then, it was analyzed by LC-MS(n). Identification and structural elucidation of the metabolites were performed by comparing their changes in molecular masses, retention-times and full scan MS(n) spectra with those of the parent drug and blank plasma. RESULTS: The results revealed that the parent drug and its four metabolites (norscopine, scopine, hydroxyanisodine, N-oxide anisodine) existed in rat plasma. CONCLUSION: This method is sensitive, rapid, simple, and it is suitable for the rapid identification of drug and its metabolits.
Administration, Oral↗
Sensitive and specific liquid chromatographic-tandem mass spectrometric assay for atropine and its eleven metabolites in rat urine.
A sensitive and specific method is described for the simultaneous determination of atropine and its metabolites in rat urine by combining liquid chromatography and tandem mass spectrometry (LC-MS(n)). Various extraction techniques (free fraction, acid hydrolyses and enzyme hydrolyses) and their comparison were carried out for investigation of the metabolism of atropine. After extraction procedure the pretreated samples were separated on a reversed-phase C18 column using a mobile phase of methanol/ammonium acetate (2 mM, adjusted to pH 3.5 with formic acid) (70: 30,v/v) and detected by an on-line LC-MS(n) system. Identification and structural elucidation of the metabolites were performed by comparing their changes in molecular masses (DeltaM), retention-times and full scan MS(n) spectra with those of the parent drug. The results revealed that at least eleven metabolites (N-demethyltropine, tropine, N-demethylatropine, p-hydroxyatropine, p-hydroxyatropine N-oxide, glucuronide conjugates and sulfate conjugates of N-demethylatropine, p-hydroxyatropine and the parent drug) and the parent drug existed in rat urine after ingesting 25 mg/kg atropine. p-Hydroxyatropine and the parent drug were detected in rat urine for up 106 h after ingestion of atropine.
Acetates↗
[Expression of melanoma antigen gene in urinary transitional cell carcinomas].
OBJECTIVE: To evaluate the significance of melanoma antigen (MAGE) gene expression in bladder transitional cell carcinoma (TCC). METHODS: MAGE-A1, A2, A3, A4 mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR) in 3 clusters bladder TCC cells and 20 samples of bladder TCC patients (T(1) 7 samples, T(2) 5 samples, T(3) 6 samples, T(4) 2 samples, G(1) 1 samples, G(2) 11 samples, G(3) 8 samples). MAGE-A4 protein was detected by immunohistochemistry in 105 samples of bladder TCC patients (T(1) 35 samples, T(2) 12 samples, T(3) 26 samples, T(4) 13 samples, G(1) 13 samples, G(2) 44 samples, G(3) 48 samples). RESULTS: Three clusters bladder TCC cells had MAGE gene mRNA expression. In detection of MAGE mRNA of 20 samples of bladder TCC patients, 12 samples (60%) expressed MAGE-A1, 16 samples (80%) expressed MAGE-A2, 11 samples (55%) expressed MAGE-A3, 18 samples (90%) expressed MAGE-A4, 8 samples (40%) expressed all of MAGE-A1--A4. In 105 bladder TCC samples, 53 samples (50%) expressed MAGE-A4 protein. Strong expression (++ or +++) was significant higher in higher grade (13 samples/48 samples) or stage (14 samples/51 samples) than in lower grade (2 samples/57 samples) or stage (0 samples/35 samples). CONCLUSION: MAGE gene highly expresses in bladder TCC. Bladder TCC of high grade or high stage has higher MAGE-A4 protein strong expression.
Adult↗
[Expression of SSX2 gene in human urologic neoplasms].
OBJECTIVE: To investigate the expression of SSX(2)gene in human renal cell carcinoma and urinary transitional cell carcinoma. METHODS: Reverse-transcription polymerase chain reaction (RT-PCR) was used for detecting SSX(2) gene in the specimens from renal cell carcinoma (n = 26), urinary transitional cell carcinoma (n = 27) and in 15 specimens taken from the tumor surrounding tissues. RESULTS: Positive expression of SSX(2) gene at mRNA was detected in 69% renal cell carcinomas (18/26), in 81% urinary transitional cell carcinomas (22/27). The mRNA of SSX(2) was not detected in the 15 specimens from tumor surrounding tissues. CONCLUSION: The SSX(2) gene is highly expressed in human renal cell carcinoma and urinary transitional cell carcinoma.
Adult↗
[Development of proteome two-dimensional electrophoresis technology].
Two-dimensional electrophoresis (2-DE) is the core technology of proteome study. This paper mainly introduces the 2-DE principle, sample preparation and usual methods to improve its resolving power. Furthermore, isoelectric focusing, SDS-PAGE electrophoresis and 2-DE staining methods are also reviewed.
Electrophoresis, Gel, Two-Dimensional↗
[HPLC-electrospray ionization ion trap tandem mass spectrometry analysis of oxymatrine and its metabolites in rat urine].
AIM: To identify the main metabolites of oxymatrine (OMT) in rats. METHODS: To optimize the conditions of LC/ESI-ITMS' chromatograms and spectra by oxymatrine and matrine (MT), and summarize their ionization and cleavage rules in ESIMS, then serving as the basis for the metabolite analyses of oxymatrine in rats. To collect the 0-24 h urine samples of the rats after ip 40 mg x kg(-1) oxymatrine, the samples were enriched and purified through C18 solid-phase extraction cartridge. The purified samples were analyzed by LC/ESI-ITMS. The structures of OMT metabolites were identified according to their retention times and ESI-ITMSn rules. RESULTS: Six phase I metabolites and the parent drug OMT were found in the rat urine, and the main metabolite was MT. No phase II metabolites were found. CONCLUSION: The developed LC/ESI-ITMSn methods to identify the metabolites of oxymatrine in rats is not only simple and rapid but also sensitive and specific. This technology is one of the most efficient methods for the analysis of drug metabolites.
Alkaloids↗
[Comparing studies on the differences of CCl4 liver injury and immunity liver injury mice models].
Comparison between CCl4 liver injury model and immunity liver injury model was studied through physiological, biochemical and gene expression profile methods, and the pathological mechanism of them were discussed. There are significant changes about the physiological, biochemical parameters including ALT,AST between two model groups and normal control group. Among the 14112 target genes, 379 and 293 differentially expressed genes were screened out from the both two model groups respectively in gene expression profile experiments, including 105 common, differentially expressed genes. The results indicate that the two models of CCl4 and immunity have some similarities. However, the differences between them are also obvious. It is useful for the further investigation on the liver-injury mechanism and pathological process of the two different liver-injury models.
Alanine Transaminase↗
[Changes of gene expression profiles in CCl4 injured liver of mice].
AIM: To study the gene expression profiles between the CCl4 injured liver and normal liver in mice, and to screen the differentially expressed genes that relate to liver injury by CCl4 on a large scale using cDNA microarrays. METHODS: Male Kunming strain mice were divided into two groups: one was control group and another was CCl4 injured liver group that was given 0.1% CCI4 oil solution ip at dose of 10 mL x kg(-1) every three days, totally for ten times. Then mRNA in livers of the two groups of mice was extracted, separately, and reversely transcribed to cDNA with the incorporation of different fluorescent-labeled dUTP as the hybridization probes. The mixed probes were hybridized to the cDNA microarrays. The fluorescent signal values were acquired by scanner and analyzed with statistical software. RESULTS: Among the 14 100 target genes, 379 genes were differentially expressed, in which 163 genes were up-regulated and the other 216 genes were down-regulated. They are closely related to a range of biological functions. CONCLUSION: Using the cDNA microarray and experimental animal modeling technique, the differentially expressed genes of CCl4 injured liver in mice on a large scale could be studied. It is useful for further investigation of the injury mechanism of CCl4.
Alanine Transaminase↗
Angiostatin production in cultivation of recombinant Pichia pastoris fed with mixed carbon sources.
A recombinant strain of Pichia pastoris with a phenotype of MutS was used to produce angiostatin. Due to the low methanol consumption rate of this strain, both methanol and glycerol feedings, that produced oscillation in dissolved O2 concentration, were used during the expression phase to improve cell growth and angiostatin expression. However, enhanced cell growth led to nitrogen limitation that suppressed further production of angiostatin, but addition of ammonia allowed angiostatin concentration to reach 108 mg l(-1) after an expression period of 96 h. The ratio of consumed glycerol to methanol of 1.5:1 (w/w) in the expression phase suggested that methanol played an important role in the metabolism of carbon sources.
Ammonia↗
Methylation and mutation analysis of p16 gene in gastric cancer.
AIM: To study methylation, frequencies of homozygous deletion and mutation of p16 gene in gastric carcinoma. METHODS: The methylation pattern in exon 1 and exon 2 of p16 gene was studied with polymerase chain reaction (PCR), using methylation sensitive restriction endonuclease HpaII and methylation insensitive restriction endonuclease MspI. PCR technique was used to detect homozygous deletions of exon 1 and exon 2 of p16 gene and single strand conformation polymorphism (SSCP) technique was used to detect the mutation of the gene. RESULTS: Hypermethylation changes in exon 1 and exon 2 of p16 gene were observed in 25 % and 45 % of 20 gastric cancer tissues, respectively, while no methylation abnormality was found in normal tissues. The homozygous deletion frequency of exon 1 and exon 2 of p16 gene in 20 gastric cancer tissues was 20 % and 10 %, respectively. No mutation was found in exon 1 of p16 gene, while abnormal single strands were found in 2 (10 %) cases in exon 2 as detected by SSCP. CONCLUSION: The results suggest that hypermethylation and abnormality of p16 gene may play a key role in the progress of gastric cancer. Hypermethylation of exon 2 of p16 gene may have effects on the carcinogenesis of gastric mucosa and may be a later event.
DNA Methylation↗
Studies on microsatellite instability in p16 gene and expression of hMSH2 mRNA in human gastric cancer tissues.
AIM: To detect the loss of heterozygosity (LOH) frequency of microsatellite sites D9s171, D9s1604 of p16 gene and expression of hMSH2 mRNA in various differentiated types of gastric cancer, adjacent cancer tissues and normal gastric mucosa. METHODS: LOH was detected by polymerase chain reaction (PCR)-denaturing polyacrylamide gel electrophoresis-silver staining. The expression of hMSH2 mRNA was examined with in situ hybridization. RESULTS: The frequency rate of LOH was significantly higher in gastric cancers than that in adjacent cancer tissues (P=0.032). No significant difference was noted among various differentiated types and various clinical stages of gastric cancers. The significantly reduced expression of hMSH2 mRNA positive signal cells exhibited in gastric cancers, in comparison with that in the adjacent cancer tissues and normal gastric mucosa, respectively (P=0.001). No significant difference was noted among various clinical stages of gastric cancers (P>0.05). The difference of positive signal cells in poorly differentiated cancers and those in well and moderately differentiated cancers were significant (P<0.001). CONCLUSION: The frequencies of LOH in two microsatellite sites, D9s171 and D9s1604, in p16 genome were associated with development of gastric cancer and no significant correlation was demonstrated between the LOH frequency and the cell differentiated types of tumor cells or clinical stages. There was a positive relationship between the expression of hMSH2 mRNA and the differentiated types of gastric cancer.
DNA-Binding Proteins↗
[Feeding of mixed-carbon-resource during the expression phase in cultivation of recombinant Pichia pastoris expressing angiostatin].
A recombinant strain of Pichia pastoris with a phenotype of Muts was used to produce angiostatin in a 5-L fermentor. The methanol utilization ability of the present strain was weak, which resulted in extremely low growth rate and angiostatin productivity during the expression phase with methanol as the sole carbon source. To enhance the cell density and angiostatin expression level, mixed-carbon-source of glycerol-methanol was used in the expression phase. The methanol concentration was well controlled at 5 g/L by a methanol sensor and control system, and glycerol was continuously fed into the fermentor to achieve a higher cell density. 120 g/L of cells and 39 mg/L of angiostatin were reached at the end of fermentation which lasted 110 h. The mean specific cell growth rate in the expression phase was 0.01 h(-1), and the mean specific angiostatin productivity was 0.006 mg/(g x h). According to the data obtained in several runs of fermentation in which glycerol was fed at different rates, a higher mean specific angiostatin productivity was reached at the mean specific cell growth rate of 0.012 h(-1). To avoid the repression of angiostatin expression caused by residual glycerol and ethanol accumulation due to overfeeding of glycerol, glycerol addition was controlled to produce continuous oscillations in dissolved oxygen, because the change of dissolved oxygen concentration could deliver the information of available carbon source in the fermentation broth. Controlled glycerol feeding also avoided the problem of oxygen limitation brought by high cell density, and thus decreased the cooling requirement of the fermentor. Cell density reached 150 g/L at the end of fermentation, and angiostatin level reached 108 mg/L after an expression period of 96 h when the mean specific growth rate was maintained at 0.012 h(-1) by using the glycerol feeding strategy to result in the oscillations in dissolved oxygen. The mean specific angiostatin productivity was improved to 0.02 mg/(g x h). The apparent cell yield on glycerol and methanol were respectively 0.69 g/g and 0.93 g/g, higher than those in the fermentation without using the feeding strategy with dissolved oxygen as the indicator of metabolism.
Angiostatins↗
High-level expression and secretion of recombinant mouse endostatin by Escherichia coli.
The expression of murine endostatin was achieved by placing its gene downstream of an alkaline phosphatase gene (phoA) promoter. To ensure proper folding and secretion of the recombinant protein, the mouse endostatin was fused with alkaline phosphatase signal peptide. SDS/polyacrylamide gel electrophoresis analysis of the culture medium of recombinant Escherichia coli cells revealed that endostatin was efficiently secreted. The signal peptide was efficiently cleaved during secretion as demonstrated by N-terminal amino acid sequencing. The maximum yield of secreted endostatin during fermentation was 40 mg/liter. Up to 28 mg of endostatin was purified from 1 liter of cell culture broth. The biological activity of recombinant protein was tested in a bovine aortic endothelial (BAE) cell proliferation assay. The recombinant endostatin inhibited the growth of BAE cells stimulated by basic fibroblast growth factor, and its ED50 was comparable to that from a previous report. Flow cytometric measurements of BAE cells cultivated in medium with endostatin demonstrated a cell cycle arrest mainly in the G0/G1 phase and a decrease in the S phase.
Adenosine Triphosphatases↗