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Ting Wang

Publications and source records attributed to Ting Wang.

At least 19 recordsLinked to original sources
PubMed2026

Paleogenomics and habitat modeling reveal temperate Eurasian origins of woolly rhinoceroses.

The woolly rhinoceros was a prominent Ice Age megafaunal species, and there is limited knowledge regarding its origin and responses to past glacial cycles. We sequenced 29 mitochondrial and 14 nuclear genomes from Pleistocene specimens across Eurasia and modeled the species' habitats over the past 500,000 years. Our results suggest that its maternal genetic diversity mainly evolved in temperate Eurasia around 460 thousand to 420 thousand years ago during a prolonged glacial-interglacial transition. We found that a ~170-thousand-year-old East Asian individual was ancestral to all later populations, indicating East Asia as one possible origin of Late Pleistocene ancestry. We also identified the Altai region as a major climatic refugium. These findings highlight the crucial role of temperate Eurasia in the evolution of woolly rhinoceroses and the diversification of cold-adapted megafauna.

Animals↗
PubMed2026

Building biofilms for saline hydrogenotrophic denitrification from contrasting origins: Convergent acclimation, divergent performance.

Hydrogenotrophic denitrification is promising for deep nitrogen removal from saline, low-C/N wastewaters, but rapid establishment of stable biofilms at high salinity remains challenging. Here, two saline-adapted inocula from two representative, functionally contrasting habitats-a functionally-diversified inoculum from mangrove sediment and a functionally-focused inoculum from seabed sediment-were acclimated in parallel H2-based membrane biofilm reactors at constant 3.5% salinity. The Diverse-derived biofilm required 80 d to reach steady state and achieved only partial denitrification with 61.1% nitrate removal and considerable nitrite accumulation. In contrast, the Focus-derived biofilm rapidly established complete denitrification within ∼40 d, which was maintained for >50 d, with effluent NOx- below 1 mg-N·L-1 and 98.7% nitrate removal. Microbiome analyses showed that identical operation promoted convergence in community structure and enriched similar community-level functional potentials. However, genome-resolved analysis revealed distinct source-dependent functional organization among dominant microbial populations. Complete denitrifiers co-encoding denitrifying, hydrogenotrophic, and autotrophic functions were preferentially enriched in the Focus-derived biofilm, whereas these functions remained partitioned among different dominant populations in the Diverse-derived biofilm, coinciding with less complete denitrification. These findings indicate that saline hydrogenotrophic denitrification performance depends not only on which functions are enriched at the community level, but also on how key functions become organized among microbial populations, providing a previously overlooked criterion for inoculum selection in saline biological nitrogen control.

Complete denitrification↗
PubMed2026

Essence: A benchmarking-validated transformer framework for early diagnosis of Parkinson's disease using cerebrospinal fluid protein biomarkers.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The lack of objective molecular biomarkers limits early diagnosis and personalized treatment. Here, we propose Essence, a benchmarking-validated framework integrating cerebrospinal fluid (CSF) proteomics with traditional and deep learning models to identify robust protein signatures for PD. Using data from two independent cohorts, 1266 high-confidence proteins are quantified, among which 178 exhibit differential abundance between PD and healthy controls (HC). Through systematic benchmarking of ten machine learning algorithms and four neural architectures, the Transformer model consistently outperforms alternatives across multiple feature selection strategies, achieving an area under the receiver operating characteristic curve (AUC) of 1.0000 with only 35 features. Functional analyses of the top-ranked 35 proteins reveal enrichment in neuroinflammatory, synaptic, and oxidative stress-related pathways. Importantly, spatial transcriptomic profiling based on the Allen Brain Atlas shows region-specific expression of these biomarkers in PD-relevant brain structures, including the striatum, subthalamic nucleus, hippocampus, and white matter tracts. This anatomical alignment supports the functional relevance of the identified markers and highlights their potential utility in early-stage diagnosis and mechanistic understanding of PD.

Benchmarking↗
PubMed2026

Mikania micrantha invasion restructures rhizosphere nitrogen cycling through enzyme activation, microbial recruitment, and allelopathic regulation.

BACKGROUND: Plant invasions profoundly influence terrestrial ecosystems by reshaping nutrient cycling processes. However, the mechanisms through which invasive plants such as Mikania micrantha modulate soil nitrogen (N) cycling and microbial communities remain insufficiently explored. Moreover, comparative studies with indigenous congener are scarce, limiting insights into whether such effects reflect species-specific strategies or genus-wide traits. This study investigates how M. micrantha modulates nitrogen metabolic pathways and rhizosphere microecology using combined metagenomic and metabolomic analyses. RESULTS: Integrated analyses revealed that M. micrantha established a distinctive "high total nitrogen-low mineral nitrogen" profile in the rhizosphere soil. Metagenomic profiling showed consistent enrichment of key ammonium assimilation enzymes, including glutamine synthetase and glutamate dehydrogenase, promoting enhanced incorporation of NH₄⁺ into organic nitrogen pools. In contrast, genes encoding nitrate reductase and nitrate transporters were significantly lower in relative abundance, limiting nitrate assimilation. Mikania micrantha also selectively enriched nitrogen-fixing microbes (notably rhizobia genera) and plant growth-promoting rhizobacteria (PGPR), thereby enhancing biological nitrogen fixation capacity. Metabolomic analysis further identified several allelopathic compounds in invaded soils at higher relative abundance, particularly epicatechin, which exhibited inhibitory effects on nitrifying bacteria. Compared with the congener Mikania cordata, which exerted weaker impacts on soil nitrogen cycling and microbial assembly, M. micrantha deployed a more comprehensive strategy integrating biochemical, microbial, and metabolic regulation. CONCLUSIONS: These findings demonstrate that under greenhouse-controlled conditions, M. micrantha reconfigures rhizosphere nitrogen cycling through a multi-dimensional strategy that couples biochemical regulation, microbial recruitment, and metabolite-mediated interference, thereby suggesting a potential mechanism that may contribute to its ecological advantage in natural settings. Video Abstract.

Rhizosphere↗
PubMed2026

Identification and evaluation of glutamine-related gene characteristics based on multi-omics to predict the prognosis of patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), a prevalent malignancy of the gastrointestinal tract, ranks among the leading causes of cancer-related morbidity and mortality. Its clinical course is marked by high fatality and poor prognosis. Elucidating the mechanisms underlying CRC initiation and recurrence is therefore critical for identifying novel therapeutic targets. METHODS: This study incorporated two datasets, TCGA-CRC and GSE17537. A total of 84 glutamine metabolism-related genes (GMRGs) were identified, and differential expression analysis was conducted using the TCGA-CRC dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to determine gene modules most strongly associated with GMRG scores. Single-cell RNA sequencing (scRNA-seq) was utilized to characterize key cellular clusters and to identify differentially expressed genes (DEGs) between high and low glutamine metabolism (GM) groups. Overlapping GMRGs were visualized using the ggVennDiagram package in R. A CRC risk prediction model was developed through Cox proportional hazards and LASSO regression analyses, with performance evaluated by ROC curves. Cell type enrichment across 64 immune and stromal populations was assessed via xCell, and intergroup differences were tested using the Wilcoxon rank-sum test. TIDE scores were used to estimate immunotherapy responsiveness, while oncoPredict facilitated drug sensitivity profiling. PCOLCE2 expression in CRC was validated by RT-qPCR and Western blotting. Its functional role was examined through CCK-8 assays, invasion and migration tests, flow cytometry, and glutamate quantification. RESULTS: ScRNA-seq analysis identified two key cell populations and 437 DEGs associated with GM status. WGCNA pinpointed the MEgreen module as most significantly correlated with GMRG scores, encompassing 1075 genes. Integration of DEGs, module genes, and GM-related DEGs yielded 60 candidate genes for downstream analysis. A GMRG-based prognostic model comprising six genes (SRPX, CXCL1, GPX3, PCOLCE2, CLU, SEMA3E) demonstrated strong predictive performance. Prognostic gene expression correlated with immune and stromal infiltration patterns, as indicated by Spearman correlation analysis. The high-risk group exhibited diminished predicted response to immunotherapy (TIDE scores). Drug sensitivity analysis identified four compounds—Dasatinib-51, WH-4-023-56, TWS-119-366, and LDN-193189-478—with elevated efficacy in high-risk CRC cases. PCOLCE2 expression was significantly reduced in CRC tissues. Functional assays revealed that PCOLCE2 knockdown did not substantially affect cell proliferation but significantly impaired invasion and migration in CRC cells, increased apoptosis, and suppressed both glutamine uptake and glutamate production—highlighting its oncogenic role. CONCLUSION: Six GMRGs—SRPX, CXCL1, GPX3, PCOLCE2, CLU, and SEMA3E—were identified as key components of a robust prognostic model for CRC. These findings offer valuable insights into CRC pathogenesis and potential therapeutic strategies. Notably, this study provides the first evidence implicating PCOLCE2 as a tumor-promoting factor in CRC.

Glutamine↗
PubMed2025

Non-canonical functions of DNMT3A in hematopoietic stem cells regulate telomerase activity and genome integrity.

DNMT3A is a critical regulator of hematopoietic stem cell (HSC) fate decisions and the most recurrently mutated gene in human clonal hematopoiesis (CH). DNMT3A is described as a DNA methyltransferase enzyme, but cells with DNMT3A loss of function show minor changes in DNA methylation that do not correlate with altered gene expression. To explore the possibility that Dnmt3a has DNA-methylation-independent functions in HSCs, we created an allelic series of mice with varying levels of DNA-methylation-impaired Dnmt3a. Clonal expansion of Dnmt3a-deficient HSCs was rescued by Dnmt3a proteins lacking DNA methylation capacity, suggesting that Dnmt3a has important non-canonical functions in HSCs. Dnmt3a-null HSCs can be transplanted indefinitely, implying the ability to circumvent mechanisms that limit the replicative lifespan of HSCs, such as telomere shortening. Dnmt3a-null HSCs show increased telomerase activity and sustain telomere length over serial transplantation, revealing a previously unidentified role for DNMT3A mutations in regulating HSC longevity that is unrelated to DNA methylation function.

Animals↗
PubMed2025

Genome-wide Parallelism Underlies Rapid Freshwater Adaptation Fueled by Standing Genetic Variation in a Wild Fish.

A fundamental focus of ecological and evolutionary biology is determining how natural populations adapt to environmental changes. Rapid parallel phenotypic evolution can be leveraged to uncover the genetics of adaptation. Using population genomic approaches, we investigated the genetic architecture underlying rapid parallel freshwater adaptation of Neosalanx brevirostris by comparing four freshwater-resident populations with their common ancestral anadromous population. We demonstrated that the rapid parallel adaptation to freshwater followed a complex polygenic architecture and was characterized by genomic-level parallelism, which proceeded predominantly through repeated selection on the preexisting standing genetic variations. Frequencies of the genome-wide adaptive standing variations were moderate in the ancestral anadromous population, which had pre-adapted to fluctuating salinities. Relatively large allele frequency shifts were observed at some adaptive single-nucleotide polymorphisms (SNPs) during parallel adaptation to freshwater environments, with a large fraction of freshwater-favored alleles being fixed or nearly fixed. These adaptive SNPs were involved in multiple biological functions associated with osmoregulation, immunoregulation, locomotion, metabolism, etc., which were highly consistent with the polygenic architecture of adaptive divergence between the two ecotypes involving multiple complex physiological and behavioral traits. This work provides insight into the mechanisms by which natural populations rapidly evolve to changes in the environment and highlights the importance of standing genetic variation for the evolutionary potential of populations facing global environmental changes.

Animals↗
PubMed2025

Metagenomic Analysis of the Tonsil Virome Highlights Its Diagnostic Potential for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease whose exact pathogenesis remains unclear, despite links to genetics, environmental factors, and microbial dysbiosis. Recent studies have highlighted the role of the microbiome in RA, yet the contribution of the tonsil virome remains unexplored. This study aims to investigate whether changes in the tonsil virome are associated with RA progression and assess its diagnostic potential. Using metagenomic data from 32 RA patients and 30 healthy controls (HCs), we identified 45 782 viral operational taxonomic units (vOTUs), with 14 341 classified as core vOTUs. RA patients exhibited significantly reduced virome richness and diversity, whereas Siphoviridae and Microviridae dominated both groups. Statistical analysis identified 235 RA-associated viral markers, including 13 enriched in RA and 222 in HCs. RA-enriched markers were primarily bacteriophages infecting Streptococcaceae, whereas HCs displayed more diverse viral-host interactions. Random forest models demonstrated strong discriminatory power of viral markers in distinguishing RA patients from HCs, achieving an AUC of 0.960, outperforming bacterial markers. Correlation analyses further linked viral markers to immune cell subsets, suggesting that tonsil virome alterations may influence immune dysregulation in RA. This study reveals significant changes in the tonsil virome of RA patients, highlighting its potential as a diagnostic tool and offering new insights into RA pathogenesis. These findings pave the way for future research into the virome's role in autoimmune diseases and therapeutic development.

Humans↗
PubMed2024

Transcriptome-wide N6-methyladenosine modification profiling of long non-coding RNAs in patients with recurrent implantation failure.

N6-methyladenosine (m6A) is involved in most biological processes and actively participates in the regulation of reproduction. According to recent research, long non-coding RNAs (lncRNAs) and their m6A modifications are involved in reproductive diseases. In the present study, using m6A-modified RNA immunoprecipitation sequencing (m6A-seq), we established the m6A methylation transcription profiles in patients with recurrent implantation failure (RIF) for the first time. There were 1443 significantly upregulated m6A peaks and 425 significantly downregulated m6A peaks in RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that genes associated with differentially methylated lncRNAs are involved in the p53 signalling pathway and amino acid metabolism. The competing endogenous RNA network revealed a regulatory relationship between lncRNAs, microRNAs and messenger RNAs. We verified the m6A methylation abundances of lncRNAs by using m6A-RNA immunoprecipitation (MeRIP)-real-time polymerase chain reaction. This study lays a foundation for further exploration of the potential role of m6A modification in the pathogenesis of RIF.

Humans↗
PubMed2007

[Construction and expression of eukaryotic coexpression plasmid containing human MUC1 gene and GM-CSF gene].

AIM: To construct an eukaryotic coexpression plasmid containing the coding region of human MUC1 tandem repeats gene and GM-CSF gene and to identify its expression in COS-7 cell. METHODS: MUC1 tandem repeats gene was obtained by synthesizing the segments. After identified by restriction endonuclease digestion analysis and DNA sequencing, MUC1 tandem repeats gene and GM-CSF gene were cloned into eukaryotic expression vector pcDNA3.1(+) to construct recombinant plasmid pcDNA3.1(+)-MUC1-GM-CSF. Then the recombinant plasmid was transfected into COS-7 cell by electroporation and the expression of target gene was detected by immunoflourescence and ELISA. RESULTS: Restriction analysis and DNA sequencing showed that the recombinant plasmid contained the coding region of human MUC1 tandem repeats gene and GM-CSF gene. The expression of MUC1 and GM-CSF was detected. CONCLUSION: The suuessful construction and expression of recombinant plasmid pcDNA3.1(+)-MUC1-GM-CSF lay a foundation for further development of DNA vaccine against breast cancer.

Animals↗
PubMed2006

GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS.

Understanding the mechanisms of hepatitis C virus (HCV) pathogenesis and persistence has been hampered by the lack of small, convenient animal models. GB virus B (GBV-B) is phylogenetically the closest related virus to HCV. It causes generally acute and occasionally chronic hepatitis in small primates and is used as a surrogate model for HCV. It is not known, however, whether GBV-B has evolved strategies to circumvent host innate defenses similar to those of HCV, a property that may contribute to HCV persistence in vivo. We show here in cultured tamarin hepatocytes that GBV-B NS3/4A protease, but not a related catalytically inactive mutant, effectively blocks innate intracellular antiviral responses signaled through the RNA helicase, retinoic acid-inducible gene I (RIG-I), an essential sensor molecule that initiates host defenses against many RNA viruses, including HCV. GBV-B NS3/4A protease specifically cleaves mitochondrial antiviral signaling protein (MAVS; also known as IPS-1/Cardif/VISA) and dislodges it from mitochondria, thereby disrupting its function as a RIG-I adaptor and blocking downstream activation of both interferon regulatory factor 3 and nuclear factor kappa B. MAVS cleavage and abrogation of virus-induced interferon responses were also observed in Huh7 cells supporting autonomous replication of subgenomic GBV-B RNAs. Our data indicate that, as in the case of HCV, GBV-B has evolved to utilize its major protease to disrupt RIG-I signaling and impede innate antiviral defenses. These data provide further support for the use of GBV-B infection in small primates as an accurate surrogate model for deciphering virus-host interactions in hepacivirus pathogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

[An improved operation approach for bipedal rat model construction].

OBJECTIVE: To explore an improved operation approach to make up the ethical deficiency of classical bipedal rat model. METHODS: 20 SD rats were randomly divided into an improved group and a traditional group averagely. Improved group were operated with plexus brachialis nerve amputation, while traditional group with forelimbs amputation close to shoulder joint. Forelimb and shoulder joint movements were observed and electromyography of the peripheral muscles around shoulder joint were recorded to make certain the paralytic scope. Operation duration and axillary artery hurt probability of both the improved and traditional operation were compared to evaluate the operation risk of improved approach. Mean total upright time on 2 d, 1 w, 2 w, 4 w and 6 w post-operation and upright posture on 6 w post-operation were recorded to evaluate the human-upright-posture-simulating effect of bipedal rats operated with improved approach. RESULTS: Compared with classical amputation approach, improved approach exhibited simpler operation procedure, shorter operation duration and lower axillary artery hurt probability. Electromyography revealed that all forelimb muscles and most shoulder-peripheral muscles were denervated, forelimbs of the improved bipedal rats were absolutely paralyzed and shoulder joint reserved only slight abduction function. The mean total upright time of improved bipedal rats was longer than the classical ones after 2 w post-operation, while upright posture showed no difference with classical bipedal rats. CONCLUSIONS: The improved operation approach not only simplified operation procedures, but also achieved even better effect than classical amputation operation and exempted bipedal rat model from the ethical shadow.

Animals↗
PubMed2006

[Distribution and expression of collagen type II, transforming growth factor beta1 and basic fibroblast growth factor in articular process cartilages of scoliosis].

OBJECTIVE: To look into the character of the expression of collagen type II and transforming growth factor beta1 (TGF-beta1), basic fibroblast growth factor (bFGF) in the apical articular process cartilages of adolescent idiopathic scoliosis (AIS) and congenital scoliosis (CS) patients. METHODS: The articular processes of 22 AIS and 18 CS were collected. The techniques of HE staining, immunohistochemistry and in situ hybridization were adopted in this research. By comparing the apical processes with the end processes, the convex processes with the concave processes, the AIS processes with CS processes, the pathological changes of the articular process cartilages of these patients and the distribution of collagen type II and TGF-beta1, bFGF in them were studied. The images of immunohistochemistry and in situ hybridization were input into the image analysis system and were analyzed semi-quantitatively. The SAS software (8.01) was adopted, and P < 0.05 was defined as the significant level. RESULTS: The expression of collagen type II and TGF-beta1, bFGF in AIS was similar to CS: the concave sides of apexes were higher than the convex sides. The comparisons had statistical significance. There was no statistical significance between upper and lower end vertebrae in convex and concave sides, between convex and concave sides in upper and lower end vertebrae. The apical vertebrae were significantly higher than the ipsilateral sides of upper or lower end vertebrae for collagen type II. There was no statistical difference of the expression at the concave, convex, upper, lower end vertebrae between AIS and CS. CONCLUSIONS: The cartilages of the apical processes show some signs of regression and hypoplasia in scoliosis. The concave side is more severe than the convex side. Increase of collagen type II and TGF-beta1, bFGF in the concave sides of apical processes in scoliosis may be the results of reconstruction of extracellular matrix and the compensation reactions which are caused by abnormal biomechanical forces such as compressive stresses. Compressive stress on the concave sides has more influences on the expression of collagen type II than tensile stress on the convex sides.

Adolescent↗
PubMed2006

Evaluation of a nutrition education intervention for women residents of Washington, DC, public housing communities.

We designed, implemented and evaluated an educational intervention to increase fruit and vegetable consumption among urban African-American women. Women aged 20-50 years (n=212) from 11 public housing communities participated in seven 90-min classes with a professional nutritionist. Our prospective pre- and post-test design, with 4-month follow-up, assessed the relationship between attendance and dietary change, using three 24-hour recalls per time point. Mean change in average daily dietary values for fruits and vegetables, calories and percent calories from fat (post-test versus pre-test, follow-up versus pre-test) was compared by class attendance, to evaluate the impact of class attendance on dietary change. Attendance varied from zero (35%) to five to seven classes (42%). Baseline dietary recalls showed average daily consumption of 3.05 servings of fruits and vegetables, 2416 calories and 35.8% calories from fat. No improvements in fruit and vegetable consumption, but statistically significant decreases in total calories and percent calories from fat, were seen at both endpoints. Women attending five to seven classes had the greatest dietary improvements, averaging, at post-test and follow-up, respectively, 246.2 and 324.5 fewer calories and 3.08 and 2.97% fewer calories from fat. Results suggest that, for some residents of low-resource communities, small group interventions are popular, effective vehicles for nutrition education.

Adult↗
PubMed2006

Inactive full-length p53 mutants lacking dominant wild-type p53 inhibition highlight loss of heterozygosity as an important aspect of p53 status in human cancers.

Over 1000 different mutants of the tumor suppressor protein p53 with one amino acid change in the core domain have been reported in human cancers. In mouse knock-in models, two frequent mutants displayed loss of wild-type (wt) p53 function, inhibition of wt p53 and wt p53-independent gain of function. The remaining mutants have been systematically characterized for loss of wt p53 function, but not other phenotypes. We report the concomitant assessment of loss of function and interference with wt p53 using URA3-based p53 yeast and confirmatory mammalian assays. We studied 76 mutants representing 54% of over 15 000 reported missense core domain mutations. The majority showed the expected complete loss of wt p53 function and dominant p53 inhibition. A few infrequent p53 mutants had wt p53-like activity. Remarkably, one-third showed no interference with wt p53 despite loss of wt p53 function at 37 degrees C. Half of this group consisted of temperature-sensitive p53 mutants, but the other half was surprisingly made up of mutants with complete loss of wt p53 function. Our findings illustrate the diverse behavior of p53 mutants and mechanisms of malignant transformation by p53 mutants. The identification of full-length p53 mutants without dominant inhibition of wt p53 highlights the importance of determining the status of the wt p53 allele in human cancers, in particular in the context of clinical studies. In the case of p53 mutants with no or weak dominant p53 inhibition, presence of the wt allele may indicate a good prognosis cancer, whereas loss of heterozygosity may spell an aggressive, therapy-resistant cancer.

Cell Line, Tumor↗
PubMed2006

High performance liquid chromatographic analysis of MS23 piperidine analog MSP001 in rat plasma.

MSP001 is a newly synthesized piperidine analog of the lead antihypertensive compound MS23 that dually targets cAMP-specific type 4 phosphodiesterase and L-type calcium channels. We validated an analytical protocol for MSP001 in rat plasma using high performance liquid chromatographic method. A C18 column and a phosphate/acetonitrile buffer were used to perform the chromatographic separation. UV detection was carried out at 307 nm, a wavelength at which an absorption peak was detected for this group of compounds. The calibration curve for MSP001 was linear in the range from 25 to 10,000 ng/ml. The limit of quantification (LOQ) was 25 ng/ml. The results demonstrate that this method has high linearity (R=0.99995), compound specificity, and acceptable precision/accuracy. The protocol is suitable for in vivo pharmacokinetic studies on the compound.

Animals↗
PubMed2006

Indole-3-carbinol alters placental cytochrome P450 1A1 and P-glycoprotein levels in rats: a potential role in intensifying fetal intrauterine growth-retardation produced by tobacco smoke.

To investigate the deleterious effects and possible mechanism of prenatal indole-3-carbinol (I3C) treatment on normal and tobacco-induced intrauterine growth restriction (IUGR) in rats, prenatal development toxicity in rats was studied. Expression of rat placental cytochrome P4501A1 (CYP1A1) and P-glycoprotein (Pgp), including mdr1a and mdr1b, were detected using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Results showed that prenatal oral I3C had no significant effects on corpora lutea counts, implantation or the number of live, dead and resorbed fetuses in normal rats. Fetal malformations, sex ratio, neonatal body weights and physical developmental indices were also unchanged after prenatal I3C treatment. However, the offspring in the tobacco + I3C (4 mg kg(-1)) group showed lower average body weights (3.98+/-0.29 g) than tobacco control (4.48+/-0.11 g), and body and tail lengths lagged significantly behind those of the tobacco-smoke exposure only group. Expression of placental CYP1A1 mRNA by RT-PCR was not detected in the normal group, but was detected in the I3C, tobacco and tobacco + I3C groups. The level of CYP1A1 mRNA expression in the tobacco + I3C group was higher than in tobacco control. The level of mdr1a mRNA increased significantly in the I3C group when compared to normal control, and no obvious difference was detected between tobacco and tobacco + I3C groups. Expression of mdr1b mRNA was increased in the I3C and tobacco + I3C groups compared to their respective controls. Immunohistochemistry results showed that placental Pgp expression was enhanced in the I3C, tobacco and tobacco + I3C groups when compared to the normal control. The results suggest that prenatal oral I3C had no developmental toxicity but intensified fetal IUGR produced by prenatal tobacco-smoke exposure in rats. Up-regulations of placental CYP1A1 and Pgp by I3C might underlie the toxic mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗