The Effect of Oxidative Stress and Antioxidants Treatment on Gestational Diabetes Mellitus Outcome: A Scoping Review.

Diagnosing a pregnant woman's glucose intolerance is referred to as gestational diabetes mellitus (GDM). Diabetes has been linked to enhanced oxidative stress. In this condition, oxidative stress may damage nucleic acids, fats, and proteins, which in turn affects cell and tissue functions. The present study highlights the relationship between oxidative stress and GDM, with a particular focus on the role of hyperglycemia-induced processes during reactive oxygen species (ROS) oversupply, followed by it discusses the oxidative stress biomarkers and assesses the effects of antioxidant supplements on glycemic control, inflammatory processes, and oxidative stress among individuals with GDM. Two reviewers conducted a comprehensive literature search utilizing the PubMed®, Web of Science™, and Scopus® databases. Only items published in the English language up until June 2024 were taken into account. We conducted a thorough search of research databases to identify articles that had the terms "oxidative stress" or "antioxidant" and "GDM". From this search, we selected 55 relevant papers to be included in this narrative review. Pregnancy-induced hypertension, postpartum bleeding, lower birth weight, a higher risk of hyperbilirubinemia in their neonates, fetal growth retardation, and birth asphyxia were revealed to be outcomes of women enduring major oxidative stress during pregnancy. Furthermore, tight glycemic control both before and throughout pregnancy as well as oxidative stress treatment may help women highly prone to GDM.

Excited-state quantum phase transitions and the entropy of the work distribution in the anharmonic Lipkin-Meshkov-Glick model.

Studying the implications and characterizations of the excited-state quantum phase transitions (ESQPTs) would enable us to understand various phenomena observed in quantum many-body systems. In this work, we delve into the affects and characterizations of the ESQPTs in the anharmonic Lipkin-Meshkov-Glick (LMG) model by means of the entropy of the quantum work distribution. The entropy of the work distribution measures the complexity of the work distribution and behaves as a valuable tool for analyzing nonequilibrium work statistics. We show that the entropy of the work distribution captures salient signatures of the underlying ESQPTs in the model. In particular, a detailed analysis of the scaling behavior of the entropy verifies that it not only acts as a witness of the ESQPTs but also reveals the difference between different types of ESQPTs. We further demonstrate that the work distribution entropy also behaves as a powerful tool for understanding the features and differences of ESQPTs in the energy space. Our results provide further evidence of the usefulness of the entropy of the work distribution for investigating various phase transitions in quantum many-body systems and open up a promising way for experimentally exploring the signatures of ESQPTs.

Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

A Girl with PRRT2 Mutation Presenting with Benign Familial Infantile Seizures Followed by Autistic Regression.

Benign familial infantile seizure (BFIS) is an autosomal dominant infantile-onset epilepsy syndrome with a typically benign prognosis. It is commonly associated with heterozygous mutations of the PRRT2 gene located on chromosome 16p11.2. The frameshift heterozygous mutation (c.649dupC, p.Arg217Profs∗8) in PRRT2 is responsible for the majority of BFIS cases. In this report, we present a rare case of a girl with a confirmed clinical and genetic diagnosis of BFIS due to a frameshift heterozygous mutation in PRRT2 (c.649dupC). She exhibited typical neurodevelopment until 15 months of age, followed by an unexpected severe autistic regression. In addition to BFIS, PRRT2 mutations are also associated with paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions and paroxysmal choreoathetosis (ICCA), indicating a complex genotype-phenotype heterogeneity in PRRT2 mutations. This clinical observation highlights the possibility that BFIS patients with PRRT2 mutations may not always have a benign neurodevelopmental prognosis, emphasizing the need for long-term clinical follow-up.

EndoQuad: a comprehensive genome-wide experimentally validated endogenous G-quadruplex database.

G-quadruplexes (G4s) are non-canonical four-stranded structures and are emerging as novel genetic regulatory elements. However, a comprehensive genomic annotation of endogenous G4s (eG4s) and systematic characterization of their regulatory network are still lacking, posing major challenges for eG4 research. Here, we present EndoQuad (https://EndoQuad.chenzxlab.cn/) to address these pressing issues by integrating high-throughput experimental data. First, based on high-quality genome-wide eG4s mapping datasets (human: 1181; mouse: 24; chicken: 2) generated by G4 ChIP-seq/CUT&Tag, we generate a reference set of genome-wide eG4s. Our multi-omics analyses show that most eG4s are identified in one or a few cell types. The eG4s with higher occurrences across samples are more structurally stable, evolutionarily conserved, enriched in promoter regions, mark highly expressed genes and associate with complex regulatory programs, demonstrating higher confidence level for further experiments. Finally, we integrate millions of functional genomic variants and prioritize eG4s with regulatory functions in disease and cancer contexts. These efforts have culminated in the comprehensive and interactive database of experimentally validated DNA eG4s. As such, EndoQuad enables users to easily access, download and repurpose these data for their own research. EndoQuad will become a one-stop resource for eG4 research and lay the foundation for future functional studies.

Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development.

Men demonstrate higher incidence and mortality rates of colorectal cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex-biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both ApcMin/ + mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo-germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo-germ mice receiving fecal sample from male mice. Sex-biased gut metabolites in pseudo-germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex-biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex-biased gut microbiota and metabolites could be a potential sex-targeting therapeutic strategy of CRC.

In vivo dynamics and regulation of DNA G-quadruplex structures in mammals.

G-quadruplex (G4) is a four-stranded helical DNA secondary structure formed by guanine-rich sequence folding, and G4 has been computationally predicted to exist in a wide range of species. Substantial evidence has supported the formation of endogenous G4 (eG4) in living cells and revealed its regulatory dynamics and critical roles in several important biological processes, making eG4 a regulator of gene expression perturbation and a promising therapeutic target in disease biology. Here, we reviewed the methods for prediction of potential G4 sequences (PQS) and detection of eG4s. We also highlighted the factors affecting the dynamics of eG4s and the effects of eG4 dynamics. Finally, we discussed the future applications of eG4 dynamics in disease therapy.

Integrating massive RNA-seq data to elucidate transcriptome dynamics in Drosophila melanogaster.

The volume of ribonucleic acid (RNA)-seq data has increased exponentially, providing numerous new insights into various biological processes. However, due to significant practical challenges, such as data heterogeneity, it is still difficult to ensure the quality of these data when integrated. Although some quality control methods have been developed, sample consistency is rarely considered and these methods are susceptible to artificial factors. Here, we developed MassiveQC, an unsupervised machine learning-based approach, to automatically download and filter large-scale high-throughput data. In addition to the read quality used in other tools, MassiveQC also uses the alignment and expression quality as model features. Meanwhile, it is user-friendly since the cutoff is generated from self-reporting and is applicable to multimodal data. To explore its value, we applied MassiveQC to Drosophila RNA-seq data and generated a comprehensive transcriptome atlas across 28 tissues from embryogenesis to adulthood. We systematically characterized fly gene expression dynamics and found that genes with high expression dynamics were likely to be evolutionarily young and expressed at late developmental stages, exhibiting high nonsynonymous substitution rates and low phenotypic severity, and they were involved in simple regulatory programs. We also discovered that human and Drosophila had strong positive correlations in gene expression in orthologous organs, revealing the great potential of the Drosophila system for studying human development and disease.

The impact of pharmacist practice of medication therapy management in ambulatory care: an experience from a comprehensive Chinese hospital.

BACKGROUD: With the reform of medical system in China, Beijing municipal hospitals explored a new pharmaceutical care model and set up medication therapy management services (MTMs) in ambulatory care since 2019. We were one of the first hospitals to set up this service in China. At the present, there were relatively few reports about the effect of MTMs in China. In this study, we summarized the implementation of MTMs in our hospital, explore the feasibility of pharmacist-led MTMs in ambulatory care and the impact of MTMs on patients' medical costs. METHODS: A retrospective study was conducted in a university-affiliated, tertiary comprehensive hospital in Beijing, China. The patients who received at least one MTMs and with complete medical records and pharmaceutical documents from May 2019 to February 2020 were included. Pharmacists provided pharmaceutical care for patients according to the MTMs standards issued by the American Pharmacists Association, identified the numbers and classification of the patients' perceived medication-related demands, identified medication-related problems (MRPs), and developed the medication-related action plans (MAPs). All MRPs found by pharmacists, pharmaceutical interventions, and resolving recommendations were documented, and calculate the cost of treatment drugs that patients can reduce. RESULTS: A total of 112 patients received MTMs in ambulatory care, among them 81 cases with the completed record were included in this study. 67.9% of patients had five or more diseases, 83% of them co-took over 5 drugs. While performing MTMs, 128 patients' perceived medication-related demands were recorded in all, monitoring and judgment of adverse drug reaction (ADR) (17.19%) was the most common demand. 181 MRPs were found, with an average of 2.55 MPRs per patient. Nonadherence (38%), excessive drug treatment (20%), and adverse drug events (17.12%) were the top three MRPs. Pharmaceutical care (29.77%), adjustment of drug treatment plan (29.10%) and referral to the clinical department (23.41%) were the top three MAPs. Whereby the MTMs provided by pharmacists, the cost-saving of each patient was about $ 43.2 monthly. CONCLUSION: By participating in the MTMs of outpatients, the pharmacists could identify more MRPs and develop personalized MAPs timely for patients, thereby promoting rational drug use and reducing medical expenses.

[Key quality attributes of benchmark samples of famous classical formula Kaixin Powder].

We prepared 15 batches of Kaixin Powder benchmark samples with the decoction pieces of different batches. Further, we established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples and analyzed the peaks and similarity of the chromatograms. With sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, ß-asarone, α-asarone, and dehydropachymic acid as index components, the index component content determination method was established and 70%-130% of the mean content of each component was set as the range. The chromatograms of 15 batches of Kaixin Powder benchmark samples had a total of 22 characteristic peaks, among which 8 peaks were identified, which represented sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, ß-asarone, α-asarone, and dehydropachymic acid, respectively. The chromatograms shared the similarity of 0.992-0.999. The 15 batches of benchmark samples had sibiricose A5 of 0.34-0.55 mg·g~(-1), sibiricose A6 of 0.43-0.57 mg·g~(-1), polygalaxanthone Ⅲ of 0.12-0.19 mg·g~(-1), 3,6'-disinapoyl sucrose of 1.08-1.78 mg·g~(-1), ginsenoside Rb_1 of 0.33-0.62 mg·g~(-1), ß-asarone of 2.34-3.72 mg·g~(-1), α-asarone of 0.11-0.22 mg·g~(-1), and dehydropachymic acid of 0.053-0.079 mg·g~(-1). This study established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples, and the method was simple, feasible, reproducible, and stable. This study provides a scientific basis for further research on the key chemical properties of the benchmark samples and preparations of Kaixin Powder.

Key quality attributes of benchmark samples of famous classical formula Kaixin Powder / 中国中药杂志

We prepared 15 batches of Kaixin Powder benchmark samples with the decoction pieces of different batches. Further, we established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples and analyzed the peaks and similarity of the chromatograms. With sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid as index components, the index component content determination method was established and 70%-130% of the mean content of each component was set as the range. The chromatograms of 15 batches of Kaixin Powder benchmark samples had a total of 22 characteristic peaks, among which 8 peaks were identified, which represented sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid, respectively. The chromatograms shared the similarity of 0.992-0.999. The 15 batches of benchmark samples had sibiricose A5 of 0.34-0.55 mg·g~(-1), sibiricose A6 of 0.43-0.57 mg·g~(-1), polygalaxanthone Ⅲ of 0.12-0.19 mg·g~(-1), 3,6'-disinapoyl sucrose of 1.08-1.78 mg·g~(-1), ginsenoside Rb_1 of 0.33-0.62 mg·g~(-1), β-asarone of 2.34-3.72 mg·g~(-1), α-asarone of 0.11-0.22 mg·g~(-1), and dehydropachymic acid of 0.053-0.079 mg·g~(-1). This study established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples, and the method was simple, feasible, reproducible, and stable. This study provides a scientific basis for further research on the key chemical properties of the benchmark samples and preparations of Kaixin Powder.

Attention to the prevention and control of allergic diseases in the elderly / 中华预防医学杂志

With the global increase in the prevalence of allergic diseases and the rising life expectancy, it is anticipated that the number of elderly patients affected by allergies will also increase. While it was previously believed that allergies primarily affected children and adolescents and diminished with age, epidemiological studies indicate a growing prevalence of allergies in the elderly. Various allergic diseases have similar prevalence rates in the elderly as in the general population, and some, like drug allergies, are even more prevalent in this age group. Allergic diseases in the elderly often present with atypical symptoms, leading to challenges in differential diagnosis and treatment. This paper discusses immunosenescence and the distinct features of allergic diseases in older individuals. The goal is to raise awareness among healthcare providers about allergies in older adults, encourage preventive measures, and improve the quality of life for elderly patients with allergies. By managing allergies better, it can also help with the management of other chronic diseases in the elderly and contribute to better overall health for everyone.

Attention to the prevention and control of allergic diseases in the elderly / 中华预防医学杂志

With the global increase in the prevalence of allergic diseases and the rising life expectancy, it is anticipated that the number of elderly patients affected by allergies will also increase. While it was previously believed that allergies primarily affected children and adolescents and diminished with age, epidemiological studies indicate a growing prevalence of allergies in the elderly. Various allergic diseases have similar prevalence rates in the elderly as in the general population, and some, like drug allergies, are even more prevalent in this age group. Allergic diseases in the elderly often present with atypical symptoms, leading to challenges in differential diagnosis and treatment. This paper discusses immunosenescence and the distinct features of allergic diseases in older individuals. The goal is to raise awareness among healthcare providers about allergies in older adults, encourage preventive measures, and improve the quality of life for elderly patients with allergies. By managing allergies better, it can also help with the management of other chronic diseases in the elderly and contribute to better overall health for everyone.

Gut microbiome in tumorigenesis and therapy of colorectal cancer.

Colorectal cancer (CRC) is the malignant tumor with the highest incidence in the digestive system, and the gut microbiome plays a crucial role in CRC tumorigenesis and therapy. The gastrointestinal tract is the organ harboring most of the microbiota in humans. Changes in the gut microbiome in CRC patients suggest possible host-microbe interactions, thereby hinting the potential tumorigenesis, which provides new perspective for preventing, diagnosing, or treating CRC. In this review, we discuss the effects of gut microbiome dysbiosis on CRC, and reveal the mechanisms by which gut microbiome dysbiosis leads to CRC. Gut microbiome modulation with the aim to reverse the established gut microbial dysbiosis is a novel strategy for the prevention and treatment of CRC. In addition, this review summarizes that probiotic antagonize CRC tumorigenesis by protecting intestinal barrier function, inhibiting cancer cell proliferation, resisting oxidative stress, and enhancing host immunity. Finally, we highlight clinical applications of the gut microbiome, such as gut microbiome analysis-based biomarker screening and prediction, and microbe modulation-based CRC prevention, treatment enhancement, and treatment side effect reduction. This review provides the reference for the clinical application of gut microbiome in the prevention and treatment of CRC.

[Comparison of clear aligners and customized lingual appliance for bimaxillary dentoalveolar protrusion: a retrospective study].

PURPOSE: To compare the treatment effects of clear aligners and customized lingual appliance on treating bimaxillary dentoalveolar protrusion patients with first premolar extractions. METHODS: Fifty-four patients with bimaxillary dentoalveolar protrusion treated in Shanghai Ninth People Hospital were involved in the retrospective study. Twenty-five cases used clear aligners and 29 cases used customized lingual appliance. All of them were treated by extracting 4 first premolars and retracting anterior teeth with strong anchorage. The changes of anterior tooth and soft tissue adduction before and after treatment were compared by lateral cephalometric measurements. SPSS 26.0 software package was used for data analysis. RESULTS: The total course of treatment in the clear aligners group (46.32±7.37 months) was about 10.8 months longer than that in the customized lingual appliance group (35.55±5.90 months) (P＜0.05). There was no significant difference in upper incisor retraction, lower incisor inclination and overjet reduction between the two groups(P＞0.05). There were significant differences in upper lip retraction, lower lip retraction, upper incisor torque reduction, and overbite reduction between the two groups(P＜0.05). Customized lingual appliance group showed a significant improvement of lips retraction and overbite reduction in orthodontic treatment. For the correction of overjet, there was no significant difference between the two groups (P=0.337). The data of U1-OP (the distance between edge of the upper central incisor and the functional occlusal plane) was not in normal distribution, and there was no significant difference between the two groups(P=0.184). CONCLUSIONS: The two techniques can both retract the anterior teeth and lips to improve the profile. However, the customized lingual appliance was more effective in improving the soft tissue profile of patients with bimaxillary dentoalveolar protrusion, with shorter treatment course.

Sexually Dimorphic Gene Expression in X and Y Sperms Instructs Sexual Dimorphism of Embryonic Genome Activation in Yellow Catfish (Pelteobagrus fulvidraco).

Paternal factors play an important role in embryonic morphogenesis and contribute to sexual dimorphism in development. To assess the effect of paternal DNA on sexual dimorphism of embryonic genome activation, we compared X and Y sperm and different sexes of embryos before sex determination. Through transcriptome sequencing (RNA-seq) and whole-genome bisulfite sequencing (WGBS) of X and Y sperm, we found a big proportion of upregulated genes in Y sperm, supported by the observation that genome-wide DNA methylation level is slightly lower than in X sperm. Cytokine-cytokine receptor interaction, TGF-beta, and toll-like receptor pathways play important roles in spermatogenesis. Through whole-genome re-sequencing (WGRS) of parental fish and RNA-seq of five early embryonic stages, we found the low-blastocyst time point is a key to maternal transcriptome degradation and zygotic genome activation. Generally, sexual differences emerged from the bud stage. Moreover, through integrated analysis of paternal SNPs and gene expression, we evaluated the influence of paternal inheritance on sexual dimorphism of genome activation. Besides, we screened out gata6 and ddx5 as potential instructors for early sex determination and gonad development in yellow catfish. This work is meaningful for revealing the molecular mechanisms of sex determination and sexual dimorphism of fish species.

Evolution and function of developmentally dynamic pseudogenes in mammals.

BACKGROUND: Pseudogenes are excellent markers for genome evolution, which are emerging as crucial regulators of development and disease, especially cancer. However, systematic functional characterization and evolution of pseudogenes remain largely unexplored. RESULTS: To systematically characterize pseudogenes, we date the origin of human and mouse pseudogenes across vertebrates and observe a burst of pseudogene gain in these two lineages. Based on a hybrid sequencing dataset combining full-length PacBio sequencing, sample-matched Illumina sequencing, and public time-course transcriptome data, we observe that abundant mammalian pseudogenes could be transcribed, which contribute to the establishment of organ identity. Our analyses reveal that developmentally dynamic pseudogenes are evolutionarily conserved and show an increasing weight during development. Besides, they are involved in complex transcriptional and post-transcriptional modulation, exhibiting the signatures of functional enrichment. Coding potential evaluation suggests that 19% of human pseudogenes could be translated, thus serving as a new way for protein innovation. Moreover, pseudogenes carry disease-associated SNPs and conduce to cancer transcriptome perturbation. CONCLUSIONS: Our discovery reveals an unexpectedly high abundance of mammalian pseudogenes that can be transcribed and translated, and these pseudogenes represent a novel regulatory layer. Our study also prioritizes developmentally dynamic pseudogenes with signatures of functional enrichment and provides a hybrid sequencing dataset for further unraveling their biological mechanisms in organ development and carcinogenesis in the future.

A Germline-Specific Regulator of Mitochondrial Fusion is Required for Maintenance and Differentiation of Germline Stem and Progenitor Cells.

Maintenance and differentiation of germline stem and progenitor cells (GSPCs) is important for sexual reproduction. Here, the authors identify zebrafish pld6 as a novel germline-specific gene by cross-analyzing different RNA sequencing results, and find that pld6 knockout mutants develop exclusively into infertile males. In pld6 mutants, GSPCs fail to differentiate and undergo apoptosis, leading to masculinization and infertility. Mitochondrial fusion in pld6-depleted GSPCs is severely impaired, and the mutants exhibit defects in piRNA biogenesis and transposon suppression. Overall, this work uncovers zebrafish Pld6 as a novel germline-specific regulator of mitochondrial fusion, and highlights its essential role in the maintenance and differentiation of GSPCs as well as gonadal development and gametogenesis.

Dynamic Spatial-temporal Expression Ratio of X Chromosome to Autosomes but Stable Dosage Compensation in Mammals.

In the evolutionary model of dosage compensation, per-allele expression level of the X chromosome has been proposed to have twofold up-regulation to compensate its dose reduction in males (XY) compared to females (XX). However, the expression regulation of X-linked genes is still controversial, and comprehensive evaluations are still lacking. By integrating multi-omics datasets in mammals, we investigated the expression ratios including X to autosomes (X:AA ratio) and X to orthologs (X:XX ratio) at the transcriptome, translatome, and proteome levels. We revealed a dynamic spatial-temporal X:AA ratio during development in humans and mice. Meanwhile, by tracing the evolution of orthologous gene expression in chickens, platypuses, and opossums, we found a stable expression ratio of X-linked genes in humans to their autosomal orthologs in other species (X:XX ≈ 1) across tissues and developmental stages, demonstrating stable dosage compensation in mammals. We also found that different epigenetic regulations contributed to the high tissue specificity and stage specificity of X-linked gene expression, thus affecting X:AA ratios. It could be concluded that the dynamics of X:AA ratios were attributed to the different gene contents and expression preferences of the X chromosome, rather than the stable dosage compensation.

Dynamic Chromatin States Coupling with Key Transcription Factors in Colitis-Associated Colorectal Cancer.

Inflammation is one of the critical risk factors for colorectal cancer (CRC). However, the mechanisms for transition from colitis to CRC remain elusive. Recently, epigenetic changes have emerged as important regulatory factors for colitis-associated cancer. Here, a systematic epigenomic study of histone modifications is performed, including H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K9me3, in an AOM-DSS-induced CRC mouse model. In combination with transcriptomic data, the authors generate a dataset of 105 deep sequencing files and illustrate the dynamic landscape of chromatin states at five time points during inflammation-cancer transition. Functional gene clusters are identified based on dynamic transcriptomic and epigenomic information, and key signaling pathways in the process are illustrated. This study's results reveal that enhancer state regions play important roles during inflammation-cancer transition. It predicts novel transcription factors based on enhancer information, and experimentally proves OTX2 as a critical tumor suppressive transcription factor. Taken together, this study provides comprehensive epigenomic data and reveals novel molecular mechanisms for colitis-associated cancer.