bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cantharidin suppresses hepatocellular carcinoma development by regulating EZH2/H3K27me3-dependent cell cycle progression and antitumour immune response
Authors: Yan Jia , Deng Xiu ling , Ma Shi qi , hui Li Yu , Gao Yu min , Shi Gui tao , Wang Hai sheng 
Published: May 2023

Abstract
Background
Cantharidin (CTD) is a major ingredient of cantharis (Mylabris phalerata Pallas) and has been used extensively in traditional Chinese medicines. It has been shown to exhibit anticancer activity in multiple types of cancer, especially hepatocellular carcinoma (HCC). However, there is no systematic study on the relationships among the regulatory networks of its targets in HCC therapy. We focused on histone epigenetic regulation and the influence of CTD on the immune response in HCC.

Methods
We performed a comprehensive analysis of novel CTD targets in HCC based on network pharmacology and RNA-seq approaches. The mRNA levels of target genes were analyzed by qRT-PCR, and the corresponding protein levels were confirmed using enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining (IHC). ChIP-seq data were visualized by IGV software. The associations of gene transcript levels with the cancer immune score and infiltration level were investigated using TIMER. In vivo, the H22 mouse model of hepatocellular carcinoma was established by treatment with CTD and 5-Fu. The immune cell proportions in the blood were elevated in model mice, as shown by flow cytometry.

Results
We identified 58 targets of CTD, which were involved in various pathways in cancer, including apoptosis, the cell cycle, EMT and immune pathways. Moreover, we found that 100 EMT-related genes were differentially expressed after CTD treatment in HCC cells. Interestingly, our results confirmed that the EZH2/H3K27me3 -related cell cycle pathway is a therapeutic target of CTD in antitumour. In addition, we evaluated the influence of CTD on the immune response. Our data showed that the significantly enriched gene sets were positively correlated with the chemokine biosynthetic and chemokine metabolic modules. The proportions of CD4+/CD8 + T cells and B cells were increased, but the proportion of Tregs was decreased after treatment with CTD in vivo. Moreover, we found that the expression of the inflammatory factor and immune checkpoint genes PD­1/PD-L1 was significantly reduced in the mouse model.

Conclusion
We performed a novel integrated analysis of the potential role of CTD in HCC treatment. Our results provide innovative insight into the mechanism by which cantharidin exerts antitumour effects by regulating target genes expression to mediate apoptosis, EMT, cell cycle progression and the immune response in HCC. Based on the effect of CTD on the immune response, it can be used as a potential effective drug to activate antitumour immunity for the treatment of liver cancer.
Comprehensive chemical profiling of Bassia indica Wight. aerial parts extract using UPLC-ESI–MS/MS, and its antiparasitic activity in Trichinella spiralis infected mice: in silico supported in vivo study
Authors: Mohammed Magdy M. D. , Heikal Elham A. , Ellessy Fatma M. , Aboushousha Tarek , Ghareeb Mosad A. 
Published: May 2023

Abstract
Background
Trichinellosis is a public health threat infected both animals and humans as a result of eating undercooked meat. It caused by Trichinella spiralis that has widespread drug resistance and even developed many sophisticated strategies for their survival, this increases the demand in searching for new anthelmintic drugs from natural source.

Methods
Our objectives were to test the in vitro and in vivo anthelmintic activity of Bassia indica BuOH frac., and to characterize its chemical composition using UPLC-ESI–MS/MS. Besides an in silico molecular docking study with the prediction of the PreADMET properties.

Results
In vitro investigation of B. indica BuOH frac., showed severe destruction of the adult worm and larvae, marked cuticle swelling, areas with vesicles, blebs and loss of annulations. This was assured via in vivo study, which revealed a significant reduction (P < 0.05) in the mean adult worm count with efficacy of 47.8% along with a significant decrease (P < 0.001) in the mean larval count per gram muscle with efficacy 80.7%. Histopathological examinations of the small intestine and muscular sections showed marked improvement. In addition, immunohistochemical findings demonstrated that B. indica BuOH frac. depressed the proinflammatory cytokines expressions of TNF-α, which was obviously upregulated by T. spiralis. Precise chemical investigation of the BuOH frac. using UPLC-ESI–MS/MS resulted in the identification of 13 oleanolic type triterpenoid saponins; oleanolic acid 3-O-6´-O-methyl-β-D-glucurono-pyranoside (1), chikusetsusaponin-IVa (2) and its methyl ester (3), chikusetsusaponin IV (4) and its methyl ester (5), momordin-Ic (6) and its methyl ester (7), betavulgaroside-I (8), -II (9) -IV (10), -X (11), licorice-saponin-C2 (12) and -J2 (13). In addition, 6 more phenolics were identified as syringaresinol (14), 3,4-di-O-caffeoylquinic acid (15), 3-O-caffeoyl-4-O-dihydrocaffeoylquinic acid (16), 3,4-di-O-caffeoylquinic acid butyl ester (17), 3,5-di-O-galloyl-4-O-digalloylquinic acid (18) and quercetin 3-O-(6´´-feruloyl)-sophoroside (19). The auspicious anthelmintic activity was further ascertained using in silico molecular docking approach that targeted certain protein receptors (β-tubulin monomer, tumor necrosis factor alpha (TNF-α), cysteine protease (Ts-CF1), calreticulin protein (Ts-CRT)), all the docked compounds (1–19) fit into the binding site of the active pocket with binding affinities noteworthy than albendazole. In addition, ADMET properties, drug score and drug likeness were predicted for all compounds.
The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank
Authors: Hydes Theresa J. , Kennedy Oliver J. , Buchanan Ryan , Cuthbertson Daniel J. , Parkes Julie , Fraser Simon D. S. , Roderick Paul 
Published: May 2023

Abstract
Background
Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD.

Methods
A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.73 m2 or albuminuria > 3 mg/mmol) were prospectively followed up by electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (HR) associated with having NAFLD (elevated hepatic steatosis index or ICD-code) and NAFLD fibrosis (elevated fibrosis-4 (FIB-4) score or NAFLD fibrosis score (NFS)) on cardiovascular events (CVE), progression to end-stage renal disease (ESRD) and all-cause mortality.

Results
56.2% of individuals with CKD had NAFLD at baseline, and 3.0% and 7.7% had NAFLD fibrosis according to a FIB-4 > 2.67 and NFS ≥ 0.676, respectively. The median follow-up was 13 years. In univariate analysis, NAFLD was associated with an increased risk of CVE (HR 1.49 [1.38–1.60]), all-cause mortality (HR 1.22 [1.14–1.31]) and ESRD (HR 1.26 [1.02–1.54]). Following multivariable adjustment, NAFLD remained an independent risk factor for CVE overall (HR 1.20 [1.11–1.30], p < 0.0001), but not ACM or ESRD. In univariate analysis, elevated NFS and FIB-4 scores were associated with increased risk of CVE (HR 2.42 [2.09–2.80] and 1.64 [1.30–2.08]) and all-cause mortality (HR 2.82 [2.48–3.21] and 1.82 [1.47–2.24]); the NFS score was also associated with ESRD (HR 5.15 [3.52–7.52]). Following full adjustment, the NFS remained associated with an increased incidence of CVE (HR 1.19 [1.01–1.40]) and all-cause mortality (HR 1.31 [1.13–1.52]).

Conclusions
In people with CKD, NAFLD is associated with an increased risk of CVE, and the NAFLD fibrosis score is associated with an elevated risk of CVE and worse survival.
Polyamine metabolism patterns characterized tumor microenvironment, prognosis, and response to immunotherapy in colorectal cancer
Authors: Zhang Enkui , Ding Chengsheng , Li Shuchun , Aikemu Batuer , Zhou Xueliang , Fan Xiaodong , Sun Jing , Yang Xiao , Zheng Minhua 
Published: May 2023

Abstract
Background
Changes in Polyamine metabolism (PAM) have been shown to establish a suppressive tumor microenvironment (TME) and substantially influence the progression of cancer in the recent studies. However, newly emerging data have still been unable to fully illuminate the specific effects of PAM in human cancers. Here, we analyzed the expression profiles and clinical relevance of PAM genes in colorectal cancer (CRC).

Methods
Based on unsupervised consensus clustering and principal component analysis (PCA) algorithm, we designed a scoring model to evaluate the prognosis of CRC patients and characterize the TME immune profiles, with related independent immunohistochemical validation cohort. Through comparative profiling of cell communities defined by single cell sequencing data, we identified the distinct characteristics of polyamine metabolism in the TME of CRC.

Results
Three PAM patterns with distinct prognosis and TME features were recognized from 1224 CRC samples. Moreover, CRC patients could be divided into high- and low-PAMscore subgroups by PCA-based scoring system. High PAMscore subgroup were associated to more advanced stage, higher infiltration level of immunosuppressive cells, and unfavorable prognosis. These results were also validated in CRC samples from other public CRC datasets and our own cohort, which suggested PAM genes were ideal biomarkers for predicting CRC prognosis. Notably, PAMscore also corelated with microsatellite instability-high (MSI-H) status, higher tumor mutational burden (TMB), and increased immune checkpoint gene expression, implying a potential role of PAM genes in regulating response to immunotherapy. To further confirm above results, we demonstrated a high-resolution landscape of TME and cell–cell communication network in different PAM patterns using single cell sequencing data and found that polyamine metabolism affected the communication between cancer cells and several immune cells such as T cells, B cells and myeloid cells.

Conclusion
In total, our findings highlighted the significance of polyamine metabolism in shaping the TME and predicting the prognosis of CRC patients, providing novel strategies for immunotherapy and the targeting polyamine metabolites.
Exploring the role of pyroptosis in shaping the tumor microenvironment of colorectal cancer by bulk and single-cell RNA sequencing
Authors: Ding Chengsheng , Yang Xiao , Li Shuchun , Zhang Enkui , Fan Xiaodong , Huang Ling , He Zirui , Sun Jing , Ma Junjun , Zang Lu , Zheng Minhua 
Published: May 2023

Abstract
Background
Emerging studies have shown that pyroptosis plays a non-negligible role in the development and treatment of tumors. However, the mechanism of pyroptosis in colorectal cancer (CRC) remains still unclear. Therefore, this study investigated the role of pyroptosis in CRC.

Methods
A pyroptosis-related risk model was developed using univariate Cox regression and LASSO Cox regression analyses. Based on this model, pyroptosis-related risk scores (PRS) of CRC samples with OS time > 0 from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database were calculated. The abundance of immune cells in CRC tumor microenvironment (TME) was predicted by single-sample gene-set enrichment analysis (ssGSEA). Then, the responses to chemotherapy and immunotherapy were predicted by pRRophetic algorithm, the tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms, respectively. Moreover, the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset (PRISM) were used to explore novel drug treatment strategies of CRC. Finally, we investigated pyroptosis-related genes in the level of single-cell and validated the expression levels of these genes between normal and CRC cell lines by RT-qPCR.

Results
Survival analysis showed that CRC samples with low PRS had better overall survival (OS) and progression-free survival (PFS). CRC samples with low PRS had higher immune-related gene expression and immune cell infiltration than those with high PRS. Besides, CRC samples with low PRS were more likely to benefit from 5-fluorouracil based chemotherapy and anti-PD-1 immunotherapy. In novel drug prediction, some compounds such as C6-ceramide and noretynodrel, were inferred as potential drugs for CRC with different PRS. Single-cell analysis revealed pyroptosis-related genes were highly expressed in tumor cells. RT-qPCR also demonstrated different expression levels of these genes between normal and CRC cell lines.

Conclusions
Taken together, this study provides a comprehensive investigation of the role of pyroptosis in CRC at the bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) levels, advances our understanding of CRC characteristics, and guides more effective treatment regimens.

Graphical Abstract
Comprehensive analysis of three female patients with different types of X/Y translocations and literature review
Authors: Liu Shanquan , Zheng Jiemei , Liu Xijing , Lai Yi , Zhang Xuan , He Tiantian , Yang Yan , Wang He , Zhang Xuemei 
Published: May 2023

Abstract
Background
X/Y translocations are highly heterogeneity in terms of clinical genetic effects, and most patients lack complete pedigree analysis for clinical and genetic characterization.

Results
This study comprehensively analyzed the clinical and genetic characteristics of three new patients with X/Y translocations. Furthermore, cases with X/Y translocations reported in the literature and studies exploring the clinical genetic effects in patients with X/Y translocations were reviewed. All three female patients were carriers of X/Y translocations with different phenotypes. The karyotype for patient 1 was 46,X,der(X)t(X;Y)(p22.33;q12)mat, patient 2 was 46,X,der(X)t(X;Y)(q21.2;q11.2)dn, and patient 3 was 46,X,der(X)t(X;Y)(q28;q11.223)t(Y;Y)(q12;q11.223)mat. C-banding analysis of all three patients revealed a large heterochromatin region in the terminal region of the X chromosome. All patients underwent chromosomal microarray analysis, which revealed the precise copy number loss or gain. Data on 128 patients with X/Y translocations were retrieved from 81 studies; the phenotype of these patients was related to the breakpoint of the chromosome, size of the deleted region, and their sex. We reclassified the X/Y translocations into new types based on the breakpoints of the X and Y chromosomes.

Conclusion
X/Y translocations have substantial phenotypic diversity, and the genetic classification standards are not unified. With the development of molecular cytogenetics, it is necessary to combine multiple genetic methods to obtain an accurate and reasonable classification. Thus, clarifying their genetic causes and effects promptly will help in genetic counseling, prenatal diagnosis, preimplantation genetic testing, and improvement in clinical treatment strategies.
Dual inhibition of CDK12 and CDK13 uncovers actionable vulnerabilities in patient-derived ovarian cancer organoids
Authors: Cesari Eleonora , Ciucci Alessandra , Pieraccioli Marco , Caggiano Cinzia , Nero Camilla , Bonvissuto Davide , Sillano Francesca , Buttarelli Marianna , Piermattei Alessia , Loverro Matteo , Camarda Floriana , Greco Viviana , De Bonis Maria , Minucci Angelo , Gallo Daniela , Urbani Andrea , Vizzielli Giuseppe , Scambia Giovanni , Sette Claudio 
Published: May 2023

Abstract
Background
High grade serous ovarian cancer (HGSOC) is highly lethal, partly due to chemotherapy resistance and limited availability of targeted approaches. Cyclin dependent kinases 12 and 13 (CDK12/13) are promising therapeutic targets in human cancers, including HGSOC. Nevertheless, the effects of their inhibition in HGSOC and the potential synergy with other drugs are poorly known.

Methods
We analyzed the effects of the CDK12/13 inhibitor THZ531 in HGSOC cells and patient-derived organoids (PDOs). RNA sequencing and quantitative PCR analyses were performed to identify the genome-wide effects of short-term CDK12/13 inhibition on the transcriptome of HGSOC cells. Viability assays with HGSOC cells and PDOs were performed to assess the efficacy of THZ531 as single agent or in combination with clinically relevant drugs.

Results
The CDK12 and CDK13 genes are deregulated in HGSOC and their concomitant up-regulation with the oncogene MYC predicts poor prognosis. HGSOC cells and PDOs display high sensitivity to CDK12/13 inhibition, which synergizes with drugs in clinical use for HGSOC. Transcriptome analyses revealed cancer-relevant genes whose expression is repressed by dual CDK12/13 inhibition through impaired splicing. Combined treatment with THZ531 and inhibitors of pathways regulated by these cancer relevant genes (EGFR, RPTOR, ATRIP) exerted synergic effects on HGSOC PDO viability.

Conclusions
CDK12 and CDK13 represent valuable therapeutic targets for HGSOC. We uncovered a wide spectrum of CDK12/13 targets as potential therapeutic vulnerabilities for HGSOC. Moreover, our study indicates that CDK12/13 inhibition enhances the efficacy of approved drugs that are already in use for HGSOC or other human cancers.
CircZNF215 promotes tumor growth and metastasis through inactivation of the PTEN/AKT pathway in intrahepatic cholangiocarcinoma
Authors: Liao Wenwei , Du Jinpeng , Li Lian , Wu Xianquan , Chen Xing , Feng Qingbo , Xu Lin , Chen Xiangzheng , Liao Mingheng , Huang Jiwei , Yuan Kefei , Zeng Yong 
Published: May 2023

Abstract
Background
Increasing evidence shows that circular RNAs (circRNAs), a novel class of noncoding RNAs, play a crucial role in the development of cancers, including intrahepatic cholangiocarcinoma (iCCA). Nevertheless, their functions and exact mechanisms in iCCA progression and metastasis are still unclear. Ipatasertib is a highly selective inhibitor of AKT that inhibits tumor growth by blocking the PI3K/AKT pathway. In addition, phosphatase and tensin homolog (PTEN) can also inhibit the activation of the PI3K/AKT pathway, but it is not clear whether the cZNF215-PRDX-PTEN axis plays a role in the antitumor activity of ipatasertib.

Methods
We identified a new circRNA (circZNF215, termed cZNF215) through high-throughput circRNA sequencing (circRNA-seq). In addition, RT‒qPCR, immunoblot assay, RNA pull-down assay, RNA immunoprecipitation (RIP) assay, and fluorescence in situ hybridization assay (FISH) were used to investigate the interaction of cZNF215 with peroxiredoxin 1 (PRDX1). Coimmunoprecipitation (Co-IP) assays and duolink in situ proximity ligation assays (PLAs) were conducted to analyze the effects of cZNF215 on the interaction between PRDX1 and PTEN. Finally, we tested the potential effects of cZNF215 on the antitumor activity of ipatasertib with in vivo experiments.

Results
We found that cZNF215 expression was obviously upregulated in iCCA tissues with postoperative metastases and was correlated with iCCA metastasis and poor outcome in patients with iCCA. We further revealed that overexpression of cZNF215 promoted iCCA cell growth and metastasis in vitro and in vivo, while cZNF215 knockdown had the opposite effect. Mechanistic studies suggested that cZNF215 competitively interacted with PRDX1, which blocked the association between PRDX1 and PTEN, subsequently leading to oxidation-induced inactivation of the PTEN/AKT pathway and finally contributing to iCCA progression and metastasis. Additionally, we also revealed that silencing cZNF215 in iCCA cells had the potential to enhance the antitumor effect of ipatasertib.

Conclusions
Our study demonstrates that cZNF215 facilitates iCCA progression and metastasis by regulating the PTEN/AKT pathway and may serve as a novel prognostic predictor in patients with iCCA.
SPUMONI 2: improved classification using a pangenome index of minimizer digests
Authors: Ahmed Omar Y. , Rossi Massimiliano , Gagie Travis , Boucher Christina , Langmead Ben 
Published: May 2023

AbstractGenomics analyses use large reference sequence collections, like pangenomes or taxonomic databases. SPUMONI 2 is an efficient tool for sequence classification of both short and long reads. It performs multi-class classification using a novel sampled document array. By incorporating minimizers, SPUMONI 2’s index is 65 times smaller than minimap2’s for a mock community pangenome. SPUMONI 2 achieves a speed improvement of 3-fold compared to SPUMONI and 15-fold compared to minimap2. We show SPUMONI 2 achieves an advantageous mix of accuracy and efficiency in practical scenarios such as adaptive sampling, contamination detection and multi-class metagenomics classification.
In vitro anti-Toxoplasma gondii activity of Ganoderma lucidum extracts
Authors: ahmadi Mohammad , Salimi Mahboobeh , Saraei Mehrzad , Nezhad Niloofar Salavati , Javadi Amir , Mohammadi Faezeh , Heydarian Peyman , Ali Ehsan , Hajialilo Elham 
Published: May 2023

Abstract
Objective
Ganoderma extracts have the potential to be used as anti-cancer, anti-inflammatory, immunomodulator, and antimicrobial agents, as evaluated in numerous studies. This study was aimed to determine the lethal and inhibitory effects of aqueous, hydroalcoholic, and alcoholic extracts of Ganoderma lucidum on Toxoplasma gondii RH strain tachyzoites, in vitro.

Results
All three types of extracts showed toxoplasmacidal effects. The highest percentage of mortality was related to hydroalcoholic extract. The EC50 of Ganoderma extracts for tachyzoites were 76.32, 3.274, and 40.18 for aqueous, hydroalcoholic and alcoholic extracts, respectively. The selectivity index obtained for hydroalcoholic extract was 71.22, showing the highest activity compared to other extracts. According to our findings, the hydroalcoholic part was the most effective substance among the extracts. This basic study showed obvious anti-toxoplasma effect of Ganoderma lucidum extracts. These extracts can be used as candidates for further in-depth and comprehensive studies especially In vivo experiments to prevent toxoplasmosis.
Automatic and standardized quality assurance of digital mammography and tomosynthesis with deep convolutional neural networks
Authors: Hejduk Patryk , Sexauer Raphael , Ruppert Carlotta , Borkowski Karol , Unkelbach Jan , Schmidt Noemi 
Published: May 2023

AbstractObjectivesThe aim of this study was to develop and validate a commercially available AI platform for the automatic determination of image quality in mammography and tomosynthesis considering a standardized set of features.Materials and methodsIn this retrospective study, 11,733 mammograms and synthetic 2D reconstructions from tomosynthesis of 4200 patients from two institutions were analyzed by assessing the presence of seven features which impact image quality in regard to breast positioning. Deep learning was applied to train five dCNN models on features detecting the presence of anatomical landmarks and three dCNN models for localization features. The validity of models was assessed by the calculation of the mean squared error in a test dataset and was compared to the reading by experienced radiologists.ResultsAccuracies of the dCNN models ranged between 93.0% for the nipple visualization and 98.5% for the depiction of the pectoralis muscle in the CC view. Calculations based on regression models allow for precise measurements of distances and angles of breast positioning on mammograms and synthetic 2D reconstructions from tomosynthesis. All models showed almost perfect agreement compared to human reading with Cohen’s kappa scores above 0.9.ConclusionsAn AI-based quality assessment system using a dCNN allows for precise, consistent and observer-independent rating of digital mammography and synthetic 2D reconstructions from tomosynthesis. Automation and standardization of quality assessment enable real-time feedback to technicians and radiologists that shall reduce a number of inadequate examinations according to PGMI (Perfect, Good, Moderate, Inadequate) criteria, reduce a number of recalls and provide a dependable training platform for inexperienced technicians.