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1.
Mol Cancer ; 23(1): 19, 2024 01 20.
Article in English | MEDLINE | ID: mdl-38243263

ABSTRACT

Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.


Subject(s)
Neoplasms , Humans , CD8-Positive T-Lymphocytes , Cell Cycle , Cell Membrane , Neoplasms/drug therapy , Neoplasms/genetics , Prognosis
2.
J Transl Med ; 22(1): 142, 2024 02 09.
Article in English | MEDLINE | ID: mdl-38331839

ABSTRACT

BACKGROUND: Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status. METHOD: A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5-23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora. RESULT: There was no significant difference in α diversity and ß diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated. CONCLUSIONS: The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.


Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Humans , Gastrointestinal Microbiome/genetics , Body Mass Index , RNA, Ribosomal, 16S/genetics , Overweight/complications , Overweight/genetics , Colorectal Neoplasms/complications , Colorectal Neoplasms/genetics , Tumor Microenvironment
3.
J Transl Med ; 21(1): 373, 2023 06 08.
Article in English | MEDLINE | ID: mdl-37291572

ABSTRACT

OBJECTIVE: The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC. METHOD: The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing. RESULT: The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O - glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV. CONCLUSIONS: The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O - glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.


Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Humans , Gastrointestinal Microbiome/genetics , Interleukin-6 , Colorectal Neoplasms/pathology , Bacteroidetes/genetics , Feces/microbiology , RNA, Ribosomal, 16S/genetics , Tumor Microenvironment
4.
Eur Radiol ; 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37930411

ABSTRACT

OBJECTIVES: To investigate a comprehensive segmentation of chest X-ray (CXR) in promoting deep learning-based World Health Organization's (WHO) radiologically confirmed pneumonia diagnosis in children. METHODS: A total of 4400 participants between January 2016 and June 2021were identified for a cross-sectional study and divided into primary endpoint pneumonia (PEP), other infiltrates, and normal groups according to WHO's diagnostic criteria. The CXR was divided into six segments of left lung, right lung, mediastinum, diaphragm, ext-left lung, and ext-right lung by adopting the RA-UNet. To demonstrate the benefits of lung field segmentation in pneumonia diagnosis, the segmented images and images that were not segmented, which constituted seven segmentation combinations, were fed into the CBAM-ResNet under a three-category classification comparison. The interpretability of the CBAM-ResNet for pneumonia diagnosis was also performed by adopting a Grad-CAM module. RESULTS: The RA-UNet achieved a high spatial overlap between manual and automatic segmentation (averaged DSC = 0.9639). The CBAM-ResNet when fed with the six segments achieved superior three-category diagnosis performance (accuracy = 0.8243) over other segmentation combinations and deep learning models under comparison, which was increased by around 6% in accuracy, precision, specificity, sensitivity, F1-score, and around 3% in AUC. The Grad-CAM could capture the pneumonia lesions more accurately, generating a more interpretable visualization and enhancing the superiority and reliability of our study in assisting pediatric pneumonia diagnosis. CONCLUSIONS: The comprehensive segmentation of CXR could improve deep learning-based pneumonia diagnosis in childhood with a more reasonable WHO's radiological standardized pneumonia classification instead of conventional dichotomous bacterial pneumonia and viral pneumonia. CLINICAL RELEVANCE STATEMENT: The comprehensive segmentation of chest X-ray improves deep learning-based WHO confirmed pneumonia diagnosis in children, laying a strong foundation for the potential inclusion of computer-aided pediatric CXR readings in precise classification of pneumonia and PCV vaccine trials efficacy in children. KEY POINTS: • The chest X-ray was comprehensively segmented into six anatomical structures of left lung, right lung, mediastinum, diaphragm, ext-left lung, and ext-right lung. • The comprehensive segmentation improved the three-category classification of primary endpoint pneumonia, other infiltrates, and normal with an increase by around 6% in accuracy, precision, specificity, sensitivity, F1-score, and around 3% in AUC. • The comprehensive segmentation gave rise to a more accurate and interpretable visualization results in capturing the pneumonia lesions.

5.
BMC Surg ; 23(1): 236, 2023 Aug 12.
Article in English | MEDLINE | ID: mdl-37573297

ABSTRACT

BACKGROUND: Total intersphincteric resection (ISR) is the ultimate anus-preserving surgery for patients with ultra-low rectal cancer (ULRC), which can result in various degrees of anorectal dysfunction. Known as low anterior resection syndrome (LARS), it seriously affects the postoperative quality of life of patients. The aim of this study was to discuss the value of mesorectal reconstruction with pedicled greater omental transplantation (PGOT) to relieve LARS following total ISR in patients with ULRC, hoping to provide new ideas and strategies for the prevention and improvement of LARS. METHODS: We retrospectively analyzed hospitalization data and postoperative anorectal function of 26 ULRC patients, who were met inclusion and exclusion criteria in our center from January 2015 to February 2022. And combined with the results of anorectal manometry and rectal magnetic resonance imaging (MRI) defecography of some patients, we assessed comprehensively anorectal physiological and morphological changes of the patients after surgery, and their correlation with LARS. RESULTS: In this study, 26 patients with ULRC were enrolled and divided into observation group (n = 15) and control group (n = 11) according to whether PGOT was performed. There were no significant differences in surgical results such as operative time, intraoperative blood loss and postoperative complications between the two groups (P > 0.05). Postoperative follow-up showed that patients in both groups showed severe LARS within 3 months after surgery, but from the 3rd month after surgery, LARS in both groups gradually began to decrease, especially in the observation group, which showed faster recovery and better recovery, with statistically significant difference (P < 0.001). Through anorectal manometry, the mean rectal resting pressure in the observation group was significantly lower than that in the control group (P = 0.010). In addition, the postoperative thickness of the posterior rectal mesenterium in the observation group was significantly higher than that in the control group (P = 0.001), and also higher than the preoperative level (P = 0.018). Moreover, rectal MRI defecography showed that the neo-rectum had good compliance under the matting of greater omentum, and its intestinal peristalsis was coordinated. CONCLUSIONS: ULRC patients, with the help of greater omentum, coordinated their neo-rectum peristalsis after total ISR and recovery of LARS was faster and better. PGOT is expected to be an effective strategy for LARS prevention and treatment of ULRC patients after surgery and is worthy of clinical promotion.


Subject(s)
Rectal Neoplasms , Humans , Rectal Neoplasms/surgery , Low Anterior Resection Syndrome , Postoperative Complications , Retrospective Studies , Omentum/surgery , Quality of Life , Rectum/surgery
6.
World J Surg Oncol ; 20(1): 20, 2022 Jan 22.
Article in English | MEDLINE | ID: mdl-35065641

ABSTRACT

PURPOSE: To achieve excellent postoperative bowel function in familial adenomatous polyposis (FAP) patients, it is important to reconstruct the digestive tract. The aim of this study is to preliminarily discuss the advantages of total proctocolectomy with straight ileoanal anastomosis (TPC-SIAA) plus pedicled omental transposition for FAP. METHODS: A retrospective study was carried out in two hospitals analysing data for FAP patients who underwent surgical treatments between 2015 and 2021. Perioperative outcomes and early and mid-term anal functions were analysed. RESULTS: After excluding 4 patients who underwent total proctocolectomy with permanent ileostomy, 10 patients were enrolled in the study. Among the 10 patients, 3 received TPC-SIAA plus pedicled omental transposition, 3 received total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA), and 4 received total colectomy with ileal pouch-rectal anastomosis (TC-IPRA). Except for one case conversion to laparotomy, laparoscopic surgery was performed for the other cases. The incidence of early postoperative complications was apparently higher with pouch anastomosis (57.1%) than straight anastomosis (0%). Frequencies of bowel movement and low anterior resection syndrome (LARS) score were higher for TPC-SIAA than the other two surgical procedures in the early term; over time, however, the frequencies of bowel movement and LARS score both showed a decreasing trend. In addition, combined with anorectal pressure detection and magnetic resonance imaging defecography at the 3rd month after TPC-SIAA plus pedicled omental transposition, defecation coordination was good. The dynamics and receptivity of the new rectum tended to be as expected. CONCLUSION: Although the three surgical procedures are safe and feasible surgical options for FAP, TPC-SIAA plus pedicled omental transposition is more consistent with intestinal physiology, with good intestinal compliance, and anal function tended to be as expected over time. Nevertheless, more extensive studies are needed to confirm these benefits.


Subject(s)
Adenomatous Polyposis Coli , Proctocolectomy, Restorative , Rectal Neoplasms , Adenomatous Polyposis Coli/surgery , Anastomosis, Surgical , Humans , Postoperative Complications , Retrospective Studies , Syndrome , Treatment Outcome
7.
J Transl Med ; 19(1): 27, 2021 01 07.
Article in English | MEDLINE | ID: mdl-33413474

ABSTRACT

BACKGROUND: KRAS gene is the most common type of mutation reported in colorectal cancer (CRC). KRAS mutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated. METHODS: 535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment between KRAS-mutant and KRAS wild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence of KRAS mutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction in KRAS-mutant CRC patients was established and validated. RESULTS: NF-κB and T-cell receptor signaling pathways were significantly inhibited in KRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased in KRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased in KRAS-mutant compared to KRAS wild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes. CONCLUSIONS: KRAS mutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments in KRAS-mutant CRC patients.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Relaxin , Antigens, Neoplasm , Colonic Neoplasms/genetics , Colorectal Neoplasms/genetics , Genes, ras , Humans , Mutation/genetics , Prognosis , Proto-Oncogene Proteins p21(ras)/genetics , Tumor Microenvironment
8.
Childs Nerv Syst ; 36(5): 1079-1081, 2020 05.
Article in English | MEDLINE | ID: mdl-31970474

ABSTRACT

A fractured catheter in the posterior auricular vein is exceedingly rare. Imaging revealed that it was migrating freely and currently overlapped the temporal bone. With multidisciplinary cooperation, general anesthesia, and three-dimensional computed tomography (3D-CT) for guidance, the catheter was removed uneventfully.


Subject(s)
Device Removal , Jugular Veins , Catheters , Humans , Tomography, X-Ray Computed
9.
Med Sci Monit ; 25: 1709-1717, 2019 Mar 06.
Article in English | MEDLINE | ID: mdl-30837449

ABSTRACT

BACKGROUND In colorectal cancer (CRC), perineural invasion (PNI) is usually identified histologically in biopsy or resection specimens and is considered a high-risk feature for recurrence of CRC and is an indicator for adjuvant therapy. Preoperative identification of PNI could help determine the need for adjuvant therapy and the approach to surgical resection. This study aimed to develop and validate a nomogram for the preoperative prediction of PNI in patients with CRC. MATERIAL AND METHODS A total of 664 patients with CRC from a single center were classified into a training dataset (n=468) and a validation dataset (n=196). The least absolute shrinkage and selection operator (LASSO) regression model was used to select potentially relevant features. Multivariate logistic regression analysis was used to develop the nomogram. The performance of the nomogram was assessed based on its calibration, discrimination, and clinical utility. RESULTS The nomogram consisted of five clinical features and provided good calibration and discrimination in the training dataset, with an area under the curve (AUC) of 0.704 (95% CI, 0.657-0.751). Application of the nomogram in the validation cohort showed acceptable discrimination, with the AUC of 0.692 (95% CI, 0.617-0.766) and good calibration. Decision curve analysis (DCA) showed that the nomogram was clinically useful. CONCLUSIONS The nomogram developed in this study might allow clinicians to predict the risk of PNI in patients with CRC preoperatively. The nomogram showed favorable discrimination and calibration values, which may help optimize preoperative treatment decision-making for patients with CRC.


Subject(s)
Decision Support Techniques , Neoplasm Invasiveness/diagnosis , Nomograms , Aged , Area Under Curve , Biomarkers, Tumor , China , Colorectal Neoplasms/complications , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/surgery , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Peripheral Nerves/physiopathology , Reproducibility of Results , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed/methods
11.
Tumour Biol ; 37(4): 4597-602, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26508023

ABSTRACT

Gastric cancer is one of the death-related malignant tumors worldwide. It remains a challenge for the diagnosis and treatment of gastric cancer. Special AT-rich sequence-binding protein 2 (SATB2) is a new tumor suppressive gene and plays important roles in many cancers. However, the role of SATB2 in gastric cancer is still unknown. In the present study, we demonstrated that downregulation of SATB2 was associated with shortened survival in patients with gastric cancer. Ectopic expression of SATB2 inhibited gastric cancer cell proliferation, colony formation, and migration. Overexpression of SATB2 repressed the expression of extracellular signal-regulated kinase 5 (ERK5), and activation of ERK5 restored the SATB2-induced inhibition of proliferation and migration in gastric cancer. This study provided evidence that SATB2 acted as a tumor suppressive gene gastric cancer, serving as a potential therapeutic target.


Subject(s)
Cell Movement , Cell Proliferation , Matrix Attachment Region Binding Proteins/physiology , Stomach Neoplasms/metabolism , Transcription Factors/physiology , Cell Line, Tumor , Down-Regulation , Enzyme Repression , Gene Expression Regulation, Neoplastic , Humans , Mitogen-Activated Protein Kinase 7/genetics , Mitogen-Activated Protein Kinase 7/metabolism , Proportional Hazards Models , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology
12.
Gene ; 934: 149021, 2024 Oct 19.
Article in English | MEDLINE | ID: mdl-39427827

ABSTRACT

Lung cancer is a major cause of cancer-related deaths worldwide, and it poses a significant threat to global health due to its high incidence and mortality rates. There is an urgent need for better prevention, early detection, and effective treatments for this disease. The treatment options for lung cancer depend on various factors such as the stage of the disease, the type of cancer, and the patient's overall health. Currently, the primary treatment strategies include surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, and combination therapies. Berberine, a natural alkaloid found in medicinal plants, has demonstrated potential as an effective anti-cancer agent against lung cancer. The present study aims to summarize the evidence supporting Berberine's ability to inhibit the growth of lung cancer cells, induce apoptosis, and slow down tumor growth in both laboratory and animal studies. The study also shed light on the complex molecular mechanisms involved in its anti-tumor effects, including its impact on signaling pathways, DNA repair systems, and interaction with non-coding RNAs, all of which contribute to tumor suppression. Additionally, the synergistic effects of Berberine with other natural compounds and chemotherapy drugs are discussed. Overall, its multifaceted approach and proven effectiveness justify further research to develop Berberine into a viable treatment option for lung cancer patients. Abbreviations: BBR, Berberine; EMT, epithelial-mesenchymal transition; NSCLC, non-small cell lung cancer; ROS, reactive oxygen species; ASK1, Apoptosis Signal-regulating Kinase 1; JNK, c-Jun N-terminal kinase; BHC, Berberine Hydrochloride; DSB, double-strand breaks; CSN, COP9 signalosome; NIR, near-infrared; LLC, Lewis lung carcinoma; RTK, receptor tyrosine kinase; B-Phyt-LCNs, Berberine-Phytantriol liquid crystalline nanoparticles; ER, endoplasmic reticulum; Ber-LCNs, Berberine-loaded liquid crystalline nanoparticles; BNS, Berberine nanostructure; BER-CS-NPs, Berberine-loaded chitosan nanoparticles; B-Phyt-LCNs, Berberine-Phytantriol liquid crystalline nanoparticles; B-Phyt-LCNs, Berberine-loaded liquid crystalline nanoparticles; Ber-LCNs, Berberine-loaded liquid crystalline nanoparticles; B-ZnO NPs, Berberine-loaded zinc oxide nanoparticles; B-C60, Berberine-C60 complex; LTP, Low-Temperature Plasma.

13.
Rev Esc Enferm USP ; 58: e20230183, 2024.
Article in English | MEDLINE | ID: mdl-38985820

ABSTRACT

OBJECTIVE: To observe the therapeutic effect of gentiopicroside, as the main component of Gentianaceae, on wounds in pressure injury (PI) model rats and explore its mechanism. METHOD: Male Sprague Dawley rats were randomly divided into control group, model group and gentiopicroside groups (50, 100 and 200 mg·kg-1·d-1 for 9 consecutive days). The mice's skeletal muscle fibroblast line NOR-10 cells were collected after being treated with gentiopicroside (0.2~5.0 M) and basic fibroblast growth factor receptor 1 (bFGFR1) inhibitor (5.0 M SU5402) for 7 days. RESULTS: Compared to the model group, the gentiopicroside groups showed significantly increased wound healing rates, reduced inflammatory cells in the wound tissues, and significantly increased expression levels of proliferating cell nuclear antigen (PCNA) and bFGFR1, accompanied by increased proliferation of new myofibroblasts. Gentiopicroside upregulated the mRNA expression of bFGFR1 and PCNA in NOR-10 cells in a dose-dependent manner; however, SU5402 reversed the effect of gentiopicroside. CONCLUSION: Gentiopicroside may promote myofibroblast proliferation by upregulating the expression of bFGFR1 and PCNA and ultimately accelerating the healing of PI wounds.


Subject(s)
Iridoid Glucosides , Pressure Ulcer , Rats, Sprague-Dawley , Up-Regulation , Wound Healing , Animals , Iridoid Glucosides/pharmacology , Iridoid Glucosides/administration & dosage , Wound Healing/drug effects , Male , Rats , Pressure Ulcer/drug therapy , Mice , Disease Models, Animal , Dose-Response Relationship, Drug , Proliferating Cell Nuclear Antigen/metabolism , Random Allocation , Cell Proliferation/drug effects
14.
Transl Res ; 270: 52-65, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38552953

ABSTRACT

The transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins. We screened T-UCRs that may be related to colorectal cancer (CRC) by performing a whole-genome T-UCR gene microarray and further studied the functional mechanism of T-UCR uc.285+ in the development of CRC. Modulation of uc.285+ affected the proliferation of CRC cell lines and influenced the expression of the CDC42 gene. We also found that uc.285+ promoted the proliferation of CRC cells by directly binding to CDC42 mRNA and enhancing its stability while directly binding to CDC42 protein and affecting its stability. In short, our research on the characteristics of cell proliferation found that uc.285+ has a biological function in promoting CRC proliferation. uc.285+ may have considerable potential as a new diagnostic biomarker for CRC.


Subject(s)
Cell Proliferation , Colorectal Neoplasms , RNA, Messenger , cdc42 GTP-Binding Protein , Humans , cdc42 GTP-Binding Protein/metabolism , cdc42 GTP-Binding Protein/genetics , Cell Line, Tumor , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Protein Binding , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Untranslated/genetics , RNA, Untranslated/metabolism
15.
Microbiol Spectr ; 12(5): e0272023, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38572984

ABSTRACT

Gut microbiota has demonstrated an increasingly important role in the onset and development of colorectal cancer (CRC). Nonetheless, the association between gut microbiota and KRAS mutation in CRC remains enigmatic. We conducted 16S rRNA sequencing on stool samples from 94 CRC patients and employed the linear discriminant analysis effect size algorithm to identify distinct gut microbiota between KRAS mutant and KRAS wild-type CRC patients. Transcriptome sequencing data from nine CRC patients were transformed into a matrix of immune infiltrating cells, which was then utilized to explore KRAS mutation-associated biological functions, including Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways. Subsequently, we analyzed the correlations among these KRAS mutation-associated gut microbiota, host immunity, and KRAS mutation-associated biological functions. At last, we developed a predictive random forest (RF) machine learning model to predict the KRAS mutation status in CRC patients, based on the gut microbiota associated with KRAS mutation. We identified a total of 26 differential gut microbiota between both groups. Intriguingly, a significant positive correlation was observed between Bifidobacterium spp. and mast cells, as well as between Bifidobacterium longum and chemokine receptor CX3CR1. Additionally, we also observed a notable negative correlation between Bifidobacterium and GOMF:proteasome binding. The RF model constructed using the KRAS mutation-associated gut microbiota demonstrated qualified efficacy in predicting the KRAS phenotype in CRC. Our study ascertained the presence of 26 KRAS mutation-associated gut microbiota in CRC and speculated that Bifidobacterium may exert an essential role in preventing CRC progression, which appeared to correlate with the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:proteasome binding. Furthermore, the RF model constructed on the basis of KRAS mutation-associated gut microbiota exhibited substantial potential in predicting KRAS mutation status in CRC patients.IMPORTANCEGut microbiota has emerged as an essential player in the onset and development of colorectal cancer (CRC). However, the relationship between gut microbiota and KRAS mutation in CRC remains elusive. Our study not only identified a total of 26 gut microbiota associated with KRAS mutation in CRC but also unveiled their significant correlations with tumor-infiltrating immune cells, immune-related genes, and biological pathways (Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways). We speculated that Bifidobacterium may play a crucial role in impeding CRC progression, potentially linked to the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:Proteasome binding. Furthermore, based on the KRAS mutation-associated gut microbiota, the RF model exhibited promising potential in the prediction of KRAS mutation status for CRC patients. Overall, the findings of our study offered fresh insights into microbiological research and clinical prediction of KRAS mutation status for CRC patients.


Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Machine Learning , Mutation , Proto-Oncogene Proteins p21(ras) , Humans , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gastrointestinal Microbiome/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Male , Female , RNA, Ribosomal, 16S/genetics , Middle Aged , Aged , Feces/microbiology , Bifidobacterium/genetics , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , CX3C Chemokine Receptor 1/genetics , CX3C Chemokine Receptor 1/metabolism
16.
Front Pediatr ; 11: 1141397, 2023.
Article in English | MEDLINE | ID: mdl-37215600

ABSTRACT

Intracranial germ cell tumors (iGCTs) are uncommon brain tumors that mainly occur in children. Differing in histology, location, and gender of the patients, iGCTs are often divided into germinomas and non-germinomatous germ cell tumors (NGGCTs). Early diagnosis and timely treatment are crucial to iGCTs, the subtypes of which have substantial variations. This review summarized the clinical and radiological features of iGCTs at different sites, and reviewed the recent advances in neuroimaging of iGCTs, which can help predict tumor subtypes early and guide clinical decision-making.

17.
Quant Imaging Med Surg ; 13(2): 852-864, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36819275

ABSTRACT

Background: Deep learning (DL) has been suggested for the automated measurement of leg length discrepancy (LLD) on radiographs, which could free up time for pediatric radiologists to focus on value-adding duties. The purpose of our study was to develop a unified solution using DL for both automated LLD measurements and comprehensive assessments in a large and comprehensive radiographic dataset covering children at all stages, from infancy to adolescence, and with a wide range of diagnoses. Methods: The bilateral femurs and tibias were segmented by a cascaded convolutional neural network (CNN), referred to as LLDNet. Each LLDNet was conducted through use of residual blocks to learn more abundant features, a residual convolutional block attention module (Res-CBAM) to integrate both spatial and channel attention mechanisms, and an attention gate structure to alleviate the semantic gap. The leg length was calculated by localizing anatomical landmarks and computing the distances between them. A comprehensive assessment based on 9 indices (5 similarity indices and 4 stability indices) and the paired Wilcoxon signed-rank test was undertaken to demonstrate the superiority of the cascaded LLDNet for segmenting pediatric legs through comparison with alternative DL models, including ResUNet, TransUNet, and the single LLDNet. Furthermore, the consistency between the ground truth and the DL-calculated measurements of leg length was also comprehensively evaluated, based on 5 indices and a Bland-Altman analysis. The sensitivity and specificity of LLD >5 mm were also calculated. Results: A total of 976 children were identified (0-19 years old; male/female 522/454; 520 children between 0 and 2 years, 456 children older than 2 years, 4 children excluded). Experiments demonstrated that the proposed cascaded LLDNet achieved the best pediatric leg segmentation in both similarity indices (0.5-1% increase; P<0.05) and stability indices (13-47% percentage decrease; P<0.05) compared with the alternative DL methods. A high consistency of LLD measurements between DL and the ground truth was also observed using Bland-Altman analysis [Pearson correlation coefficient (PCC) =0.94; mean bias =0.003 cm]. The sensitivity and specificity established for LLD >5 mm were 0.792 and 0.962, respectively, while those for LLD >10 mm were 0.938 and 0.992, respectively. Conclusions: The cascaded LLDNet was able to achieve promising pediatric leg segmentation and LLD measurement on radiography. A comprehensive assessment in terms of similarity, stability, and measurement consistency is essential in computer-aided LLD measurement of pediatric patients.

18.
Sci Rep ; 13(1): 19003, 2023 11 03.
Article in English | MEDLINE | ID: mdl-37923781

ABSTRACT

Exploring and analyzing the effectiveness of an intelligent pacifying strategy information system based on assisted decision-making in reducing the sedation rate of children in short-duration magnetic resonance scans. A total of 125 children aged 3-5 years who underwent MRI scans at a children's hospital from July to December 2021 participated in this study, during which 62 children were assigned to a control group from July to September, and 63 children were assigned to an intervention group from October to December. In the intervention group, the pacifier used the intelligent pacifying strategy information system based on assisted decision-making to assess children's temperament, and utilization of a system-generated pacification plan according to assessment results. In the control group, the pacification plan was formulated by the pacifier based on their own experience and discussion with families of the participating children. The success rate of pacification, duration of pacification, and image quality of the two groups were compare. Compared with the control group, the intervention group had a higher success rate of pacification and lower duration of pacification, with statistically significant differences (P < 0.05). There was no difference in image quality between the two groups (P > 0.05). The intelligent pacifying strategy information system can help reduce the use of the sedative drugs in children aged 3-5 years who underwent a short-duration MRI scan.


Subject(s)
Magnetic Resonance Imaging , Temperament , Humans , Child , Magnetic Resonance Imaging/methods , Time Factors , Outcome Assessment, Health Care
19.
Pathol Oncol Res ; 29: 1611082, 2023.
Article in English | MEDLINE | ID: mdl-37123533

ABSTRACT

Background: Colon cancer (CC) is the fifth most prevalent cancer around the globe and poses a major risk to human health. Even though Kremen2 serves as a prognostic indicator in individuals with malignant tumours, its role in evaluating the prognosis of individuals with colon cancer has not been confirmed. Methods: Here, we examined the protein expression of Kremen2 in CC tissues and paired adjacent normal tissues by immunohistochemistry (IHC), then analyzed the clinical and RNA-seq data presented in The Cancer Genome Atlas (TCGA) database to confirm the relationship between Kremen2 levels and CC. In addition, the associations between Kremen2 mRNA expression and infiltrating immune cells were examined. Results: The study showed that the mRNA expression and protein level of Kremen2 were increased in CC tissues compared with adjacent normal tissues. According to Kaplan-Meier analysis, high Kremen2 expression in CC was linked to poor overall survival and progression-free survival. Clinical correlation analysis highlighted that a high level of Kremen2 expression was strongly linked with tumour progression, particularly lymph node metastasis. Cox regression analysis highlighted that Kremen2 was an independent prognostic indicator for CC. Bioinformatic studies highlighted that Kremen2 might be associated with the immune status in CC. Conclusion: Increased Kremen2 could serve as a potential prognostic CC biomarker.


Subject(s)
Biomarkers, Tumor , Colonic Neoplasms , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Colonic Neoplasms/pathology , Lymphatic Metastasis , RNA, Messenger
20.
Medicine (Baltimore) ; 102(18): e33390, 2023 May 05.
Article in English | MEDLINE | ID: mdl-37144998

ABSTRACT

Left-sided colon cancer (LC) and right-sided colon cancer (RC) are 2 essentially different diseases, and the potential mechanisms regulating them remain unidentified. In this study, we applied weighted gene co-expression network analysis (WGCNA) to confirm a yellow module, mainly enriched in metabolism-related signaling pathways related to LC and RC. Based on the RNA-seq data of colon cancer in The Cancer Genome Atlas (TCGA) and GSE41258 dataset with their corresponding clinical information, a training set (TCGA: LC: n = 171; RC: n = 260) and a validation set (GSE41258: LC: n = 94; RC: n = 77) were divided. Least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis identified 20 prognosis-related genes (PRGs) and helped constructed 2 risk (LC-R and RC-R) models in LC and RC, respectively. The model-based risk scores accurately performed in risk stratification for colon cancer patients. The high-risk group of the LC-R model showed associations with ECM-receptor interaction, focal adhesion, and PI3K-AKT signaling pathway. Interestingly, the low-risk group of the LC-R model showed associations with immune-related signaling pathways like antigen processing and presentation. On the other hand, the high-risk group of the RC-R model showed enrichment for cell adhesion molecules and axon guidance signaling pathways. Furthermore, we identified 20 differentially expressed PRGs between LC and RC. Our findings provide new insights into the difference between LC and RC, and uncover the potential biomarkers for the treatment of LC and RC.


Subject(s)
Colonic Neoplasms , Phosphatidylinositol 3-Kinases , Humans , Phosphatidylinositol 3-Kinases/genetics , Prognosis , Colonic Neoplasms/genetics , Gene Expression Profiling
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