Expression and Clinical Significance of NUDCD1, PI3K/AKT/mTOR Signaling Pathway-Related Molecules and Immune Infiltration in Breast Cancer.

BACKGROUND: NUDCD1 (NudC Domain Containing 1) performs an essential function in biological processes such as cell progression, migration, cell cycle, and intracellular material transport. Many solid tumors express it highly, which is a prospective biomarker and therapeutic approach. However, the expression and clinical importance of NUDCD1 across breast cancer is unclear. METHODS: The expressions of NUDCD1 in breast cancers and normal breast tissues were studied utilizing the TIMER database and immunohistochemical analysis. Subsequently, we validate the association between the expression of NUDCD1 and clinicopathologic features and prognosis of breast cancer. The immunohistochemical experiments of pathway-related molecules were done on 214 breast cancer tissue microarrays. The investigation of correlation between NUDCD1 expression and tumor immune infiltration was subsequently conducted. RESULTS: Through the utilization of bioinformatics analysis and immunohistochemical experiments, it was determined that NUDCD1 exhibited upregulation within breast cancer. Furthermore, it was discovered that an elevated expression of NUDCD1 may potentially be linked to a worse prognosis in breast cancer. Our study reveals that the PI3K/AKT/mTOR signaling pathway may perform a function in NUDCD1 regulating breast cancer progression via enrichment analysis. Furthermore, the expression of NUDCD1 may be associated with the degree of immunological infiltration. CONCLUSION: The expression of NUDCD1 was explored to be elevated in breast cancer and was observed to be correlated with a poorer prognosis. p-AKT, PI3K, AKT, mTOR, and p-mTOR expression levels underwent significant elevation in breast cancer. The function of NUDCD1 within breast cancer might be associated with the PI3K/AKT/mTOR signaling pathway.

Causal associations between human gut microbiota and hemorrhoidal disease: A two-sample Mendelian randomization study.

Hemorrhoidal disease (HEM) is a common condition affecting a significant proportion of the population. However, the causal relationship between the gut microbiota and hemorrhoids remains unclear. In this study, we employed a Mendelian randomization (MR) approach to investigate the potential associations between them. In this study, the exposure factor was determined by selecting summary statistics data from a large-scale gut microbiome whole-genome association study conducted by the MiBioGen Consortium, which involved a sample size of 18,340 individuals. The disease outcome data consisted of 218,920 cases of HEM and 725,213 controls of European ancestry obtained from the European Bioinformatics Institute dataset. Two-sample MR analyses were performed to assess the causalities between gut microbiota and hemorrhoids using various methods, including inverse-variance weighting, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), simple mode, and weighted median. Reverse MR analyses were performed to examine reverse causal association. Our findings suggest phylum Cyanobacteria (OR = 0.947, 95% CI: 0.915-0.980, P = 2.10 × 10 - 3), genus Phascolarctobacterium (OR = 0.960, 95% CI: 0.924-0.997, P = .034) and family FamilyXI (OR = 0.974, 95% CI: 0.952-0.997, P = .027) have potentially protective causal effects on the risk of HEM, while genus Ruminococcaceae_UCG_002 (OR = 1.036, 95% CI: 1.001-1.071, P = .042), family Peptostreptococcaceae (OR = 1.042, 95% CI: 1.004-1.082, P = .029), genus Oscillospira (OR = 1.048, 95% CI: 1.005-1.091, P = .026), family Alcaligenaceae (OR = 1.048, 95% CI: 1.005-1.091, P = .036) and order Burkholderiales (OR = 1.074, 95% CI: 1.020-1.130, P = 6.50 × 10-3) have opposite effect. However, there was a reverse causal relationship between HEM and genus Oscillospira (OR = 1.140, 95% CI: 1.002-1.295, P = .046) This is the first MR study to explore the causalities between specific gut microbiota taxa and hemorrhoidal disease, which may offer valuable insights for future clinical interventions for hemorrhoidal disease.

Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer.

AIMS: This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of breast cancer. METHODS: Single-cell RNA transcriptomic analysis and bioinformatic analysis are used to screen relevant genes in breast cancer metastatic hepatic specimens. MeRIP, dual-luciferase analysis and bioinformation were used to detect m6A modulation. Mass spectrometry (MS), co-inmunoprecipitation (co-IP) and immunofluorescence colocalization were executed to explore the mechanism of GPRC5A in breast cancer cells. RESULT: GPRC5A was upregulated in triple-negative breast cancer (TNBC) and was associated with a poor prognosis. In vitro and in vivo experiments demonstrated that knockdown of GPRC5A alleviated metastasis and resistance to docetaxel in TNBC. Overexpression of GPRC5A had the opposite effects. The m6A methylation of GPRC5A mRNA was modulated by METTL3 and YTHDF1, which facilitates its translation. GPRC5A inhibited the ubiquitination-dependent degradation of LAMTOR1, resulting in the recruitment of mTORC1 to lysosomes and activating the mTORC1/p70s6k signaling pathway. CONCLUSION: METTL3/YTHDF1 axis up-regulates GPRC5A expression by m6A methylation. GPRC5A activates mTORC1/p70s6k signaling pathway by recruiting mTORC1 to lysosomes, consequently promotes docetaxel-resistance and liver metastasis.

Utility of GATA-3 immunocytochemistry for the assessment of fine-needle aspiration in breast cancer patients with suspicious axillary lymph nodes at ultrasound.

BACKGROUND: Ultrasound-guided fine-needle aspiration cytology (FNAC) is a routine preoperative method for evaluating suspicious axillary lymph nodes (ALNs) in patients with breast cancer. However, a range of reasons such as morphological pitfalls, technical artifacts, and sampling errors restrict the sensitivity and accuracy of FNAC. This retrospective study investigated the diagnostic value of GATA-binding protein 3 (GATA-3) immunocytochemistry for FNAC. METHODS: Breast cancer patients who underwent preoperative FNAC for suspicious ALNs, relevant GATA-3 immunocytochemistry, and postoperative status of ALNs were reviewed from the period of March 2020 to February 2022. Altogether, 102 patients were included in the study. FNAC material smears stained with hematoxylin and eosin was initially assessed by two cytopathologists and categorized into five groups: nondiagnostic, negative, atypical, suspicious, and positive for malignancy. Only group of cells positive for malignancy was considered positive. For each case, two selected slides were digitized (whole slide imaged) at ×40 magnification and decolored for GATA-3 immunocytochemistry. The expression of GATA-3 was scored ranging from 0 to 9 (Score ≥3: Positive, Score ≤2: Negative). If either FNAC or GATA-3 immunocytochemistry was positive or the combined test positive, then the case was considered positive. The sensitivity, specificity, and accuracy of FNAC, GATA-3 immunocytochemistry, and combined FNAC/GATA-3 immunocytochemistry were analyzed by χ2 and Fisher's tests. RESULTS: The mean age of the study participants was 50.62 (ranging: 30-73 years). Invasive breast carcinoma (not otherwise specified) accounted for most histological subtypes, and grade 2 was the leading Nottingham grade. Sixteen cases directly underwent mastectomy while the other 86 patients had neoadjuvant therapy. A more serious diagnosis was made based on GATA-3 detection in 22.5% (n = 23) of 102 cases. Of the 23 cases, metastasis was confirmed by GATA-3 detection in 21 cases, and an uncertain diagnosis was ascertained based on GATA-3 immunocytochemistry in 2 with nondiagnostic FNAC results. The sensitivity (77/87, 88.5%) of GATA-3 detection for distinguishing malignancies from benign lesions was higher than that of FNAC alone (62/87, 71.3%) (p < .05). CONCLUSIONS: GATA-3 immunocytochemistry exhibited high diagnostic efficacy in distinguishing malignant breast cancer cells. Moreover, combined FNAC and GATA-3 immunocytochemistry achieved optimal results in terms of reducing the false-negative rate and promoting accuracy.

Analysis of risk factors for post-operative recurrence after percutaneous endoscopic lumbar discectomy in patients with lumbar disc herniation: a meta-analysis.

BACKGROUND: This study aimed to systematically evaluate risk factors for post-operative recurrence after percutaneous endoscopic lumbar discectomy (PELD) in patients with lumbar disc herniation (LDH). METHODS: The eligible studies were retrieved from PubMed, Embase, and Web of Science databases. Quality assessment was performed. The effects of binary variables (sex, Modic change (MC), type 2 diabetes (T2DM), and smoking) on post-operative recurrence were evaluated as odds ratio (OR) and 95% confidence interval (CI). The effects of continuous variables (sagittal range of motion (SROM), body mass index (BMI), and age) were assessed as weighted mean difference (WMD) and 95% CI. Sensitivity analysis and publication bias were conducted to evaluate the reliability of pooled results. RESULTS: Eight studies were included, and their methodological quality was medium. MC (OR (95% CI) = 3.88 (2.24-6.74), P < 0.001), smoking (OR (95% CI) = 1.87 (1.45, 2.42), P < 0.001), T2DM (OR (95% CI) = 1.61 (1.12, 2.31), P = 0.010), SROM (WMD (95% CI) = 2.33 (0.95, 3.70), P = 0.001), BMI (WMD (95% CI) = 1.68 (1.37, 1.99) kg/m2, P < 0.001), and age (WMD (95% CI) = 9.95 (5.05, 14.86) years, P < 0.001) were significantly related to post-operative recurrence in patients with LDH after PELD. Significant publication bias was not observed among studies in all outcome indicators. CONCLUSION: Our findings reveal that high levels of age, BMI, and SROM, history of T2DM or smoking, or more MC may be correlated with post-operative recurrence after PELD.

Adipocyte-derived exosomes promote the progression of triple-negative breast cancer through circCRIM1-dependent OGA activation.

Triple-negative breast cancer (TNBC) has an escalating morbidity and a dismal prognosis. Obesity has been reported to be strongly linked to adverse TNBC outcomes. Exosomes (Exos) transport RNA and proteins between cells and serve as intermediaries for cell-to-cell communication. Accumulated evidence suggests that adipose-secreted circular RNAs (circRNAs) can modulate protein glycosylation in TNBC to facilitate tumor cell outgrowth. Herein, exo-circCRIM1 expression was found to be elevated in TNBC patients with a high body fat percentage. Functional experiments demonstrated that by inhibiting miR-503-5p, exo-circCRIM1 enhanced TNBC evolution and metastasis while activating glycosylation hydrolase OGA. Furthermore, OGA negatively regulates FBP1 by decreasing its protein stability. Moreover, the levels of OGA and FBP1 were positively related to the infiltration level of some immune cells in TNBC. These findings indicate that exo-cirCRIM1 secreted by adipocytes contributes to TNBC progression by inhibiting miR-503-5p and activating the OGA/FBP1 signaling pathway. The findings reveal a novel intercellular signaling pathway mediated by adipose-derived exosomes and suggest that treatment targeting the secreted exosome-circCRIM1 may reverse TNBC progression.

Diagnostic Value and Challenges of BRAF V600E Molecular Testing and Thyroid Fine-Needle Aspiration Cytology: A Retrospective Study from a Tertiary Institution in Southern Hunan Province, China.

INTRODUCTION: Combined thyroid fine-needle aspiration (FNA) cytology and valine-to-glutamate substitution at codon 600 of B-Raf proto-oncogene, serine/threonine kinase (BRAF V600E) mutation detection are procedures used for diagnosing thyroid nodules in many Chinese tertiary institutions. This retrospective study at our institution aimed to explore the effectiveness and challenges of the combined approach in diagnosing thyroid nodules and the correlation between BRAF V600E mutation status and behavior of papillary thyroid carcinoma. METHODS: Thyroid FNA cytology and BRAF V600E mutation detection results were reviewed between November 2020 and July 2022. A total of 623 patients, each of whom underwent thyroidectomy and final pathological examination after FNA cytology diagnosis, were included in the study. The relationship between the BRAF V600E mutational status and pathological parameters was analyzed using the χ2 test. The effectiveness and challenges of FNA cytology alone and the combined procedure were also evaluated based on the final pathology. RESULTS: Of 623 patients, 591 were diagnosed with papillary thyroid carcinoma (PTC), of which 456 were positive for the BRAF V600E mutation. It demonstrated near-perfect specificity for identifying PTC, and its incidence rate showed an age-specific curve with an inverted U-shaped distribution. The final pathological examination showed that the combined procedure had a higher sensitivity (83.91%) than FNA cytology alone (63.45%) for distinguishing PTC from other lesions (p < 0.001). Mutational status was associated with a larger maximum tumor diameter (p = 0.003) and a tendency of capsular invasion (p = 0.0542) but possibly unrelated to central lymph node metastasis (p = 0.1846). Nodular goiters accounted for most benign entities initially designated as Bethesda categories III-V. CONCLUSION: BRAF V600E mutational analysis complements cytopathology and improves the PTC detection rate in FNA cytology samples due to the high prevalence of the mutation in China. BRAF V600E mutation does not show a statistical correlation with tumor aggressiveness. Morphological pitfalls such as histocyte aggregation, cystic-lining cells in nodular goiters, and oncocytes in Hashimoto's thyroiditis, were overwhelmingly found in BRAF V600E-negative specimens.

Electroconvulsive Therapy Reduces Protein Expression Level of EP300 and Improves Psychiatric Symptoms and Disturbance of Thought in Patients with Schizophrenia.

Objective: Although electroconvulsive therapy (ECT) has been employed as an effective treatment strategy and to improve mental symptoms in schizophrenia (SCZ), its action mechanisms remain unclear. Our previous study found that some genes and biological pathways were closely related to ECT through genetic technology analysis, such as LTP pathway and EP300. This study combined with healthy controls and symptomatology analysis to further explore the changes of expression of EP300 protein in treatment and related symptoms of SCZ. Methods: One hundred and one patients with SCZ and 45 healthy controls (HCs) were enrolled in this study. Patients with SCZ received acute courses of 6 times bilateral ECT. The peripheral blood of patients with SCZ (BECT: before ECT; AECT: after ECT) and the HCs was collected to calculate the changes of expression level of EP300 protein by enzyme-linked immunosorbent assay. The Positive and Negative Symptoms Scale (PANSS) was used to evaluate the severity of symptoms of SCZ patients and the efficiency of the ECT. Results: There was a statistical difference of EP300 protein expression in patients with SCZ (BECT and AECT) (F = 114.5, p < 0.05). ECT reduced plasma expression level of EP300 protein in patients with SCZ, which was not statistically different from that in HCs (t = 4.47, p = 0.20). The change of the expression level of EP300 protein in patients with SCZ (BECT and AECT) has a positive correlation with reduction rate of positive symptoms (r = 0.228, p < 0.05) and disturbance of thought (r = 0.219, p < 0.05). Conclusion: Our study suggests that the expression level of EP300 protein has a significant change in patients with SCZ treating with ECT, and EP300 may have some connections with positive symptoms and disturbance thought of patients with SCZ.

COVID-19 vaccine booster dose hesitancy among key groups: A cross-sectional study.

Vaccination is an important tool for controlling the spread of coronavirus disease. Notably, it is important to achieve higher vaccine booster coverage across key groups - including front-line workers who could be exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and those who live and work in crowded places - to prevent or reduce the risk of severe infection and poor disease outcomes. The purpose of the study was to understand the COVID-19 vaccine booster hesitancy among key groups in Luzhou, China, to analyze its influencing factors, and to provide scientific basis and theoretical guidance for the implementation of targeted intervention. Guided by the "3Cs" model, a self-designed questionnaire was prepared through a literature search using the Delphi method. All questionnaires were completed online through a QR code. Among the 548 participants, 173 had vaccine hesitation, accounting for 31.6%. Indeed, the scores for perceived safety, expected vaccine effectiveness, and trust in the vaccine delivery system were all lower in the hesitance group than in the non-hesitance group. However, the scores for low necessity were higher in the hesitance group. The factors influencing booster hesitancy were examined, and the probability of hesitancy decreased by 72.2% and 62.5% for every 1-point increase in the confidence and safety scores, respectively. Meanwhile, the probability of hesitancy increased by 25.8% for every 1-point increase in the low necessity score. Although the COVID-19 vaccine booster hesitancy reported in the study was relatively low, a large gap remains in the willingness to receive COVID-19 vaccination in China. Therefore, the state and relevant departments should take targeted measures to help reduce vaccine hesitancy among the public and enable smooth progress in the large-scale COVID-19 vaccine booster campaign in the future.

Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis.

Currently, there is no consensus on whether maintenance dialysis increases cancer risk in patients with end-stage renal disease (ESRD). Therefore, this study was to systematically evaluate the risk of cancer among ESRD patients undergoing maintenance dialysis. Related studies on the impact of maintenance dialysis on cancer risk were retrieved from PubMed, Embase, Cochrane Library, and other databases from their respective inceptions to 19 February 2021. ESRD patients receiving maintenance dialysis were classified into cancer including non-melanoma skin cancer (NMSC) and cancer excluding NMSC. Standardized incidence ratio (SIR) with its 95% confidence interval (95% CI) was calculated to assess cancer risk. Fourteen studies were included in the meta-analysis. The risk of cancer in patients undergoing maintenance dialysis (with or without NMSC) was significantly higher than controls both in cancer including NMSC (SIR = 1.38, 95% CI: 1.27-1.49, P < 0.001) and cancer excluding NMSC (SIR = 1.34, 95% CI: 1.23-1.47, P < 0.001). Subgroup results identified the higher risk of cancer incidence in both men and women receiving maintenance dialysis. Meanwhile, elevated excess risks were observed among patients with younger age and shorter follow-up time (P < 0.001). Meanwhile, the combined SIR of bladder, cervix, colorectum, kidney, liver, thyroid, tongue, and other cancers were all increased (P < 0.05). ESRD patients undergoing dialysis has higher risk of cancer.

Efficacy of Melatonin for Insomnia in Children with Autism Spectrum Disorder: A Meta-analysis.

AIM: This study aimed to evaluate the effectiveness of melatonin in treating insomnia in children with autism spectrum disorder (ASD). METHODS: Comprehensive searches were conducted in the PubMed, EMBASE, and Web of Science databases from their inception to April 20, 2022. Data were extracted and assessed for quality by two researchers. Statistical analysis was performed using the Stata 15.0 software. RESULTS: Four studies including 238 patients were included. The results showed that compared with the control group, melatonin could shorten the sleep-onset latency (standardized mean difference [SMD] = - 1.34, 95% CI: -2.19 to -0.48), reduce the number of awakenings (SMD = -2.35, 95% CI: -4.62 to -0.08), and prolong the total sleep time (SMD = 1.42, 95% CI: 0.5-2.33) in children with ASD. CONCLUSION: Melatonin has a certain effect on relieving sleep disturbances in children with ASD, which can shorten sleep latency, reduce the number of awakenings, and prolong total sleep time. Larger studies are required to verify this hypothesis.

Transbronchial brushing cytology and paired biopsy in endobronchial tuberculosis: A report of 72 cases focusing on the morphological features.

Objectives: The objectives of this study were to review the transbronchial brushing cytology and histological specimens of endobronchial tuberculosis (EBTB) and to explore the morphological features, diagnostic pitfalls, and dilemmas. Material and Methods: Transbronchial brushing cytology and concurrent biopsy specimens obtained between July 2017 and June 2020 were reviewed. EBTB was confirmed based on the clinical response to the anti-TB treatment in addition to the positive findings of at least one of the following methods: Acid-fast bacilli stain (AFB), auramine-rhodamine stain (A-R), detection of TB bacterial DNA (TB-DNA) by polymerase chain reaction, T-cell spot test (T-spot), and typical pathologic changes of TB on cytology or bronchoscopy biopsy. A total of 72 confirmed cases were studied. Results: Of the 72 patients, 42/72 (58.3%) and 30/72 (41.7%) were female and male patients, respectively. Bronchoscopic findings revealed five subtypes of EBTB, including inflammation infiltration, ulceration necrosis, granulation hyperplasia, cicatrices stricture, and tracheobronchial malacia. AFB, A-R, TB-DNA, and T-spot were positive in 39, 26, 33, and 46 cases, respectively. The detection rate of necrosis in the cytological specimens (90.3%) was significantly higher than that in the biopsy specimens (77.8%; P < 0.01). The percentage of Langhans giant cells detected by cytology (13.9%) was significantly lower than that detected by the pathological examinations of the tissues (38.9%) (P < 0.01). The detection rates of metaplastic squamous cells and epithelioid cells showed no significant difference with respect to the cytology and biopsy findings. In addition to the two patients who had concurrent carcinomas, atypical cells were reported in nine patients through cytopathological diagnosis, among them two were suspected to have carcinomas, two were with the impression that spindle cell neoplasms could not be excluded, and the other five were considered as reactive atypia. Moreover, one biopsy could not rule out the well-differentiated squamous cell carcinoma. Conclusion: Some morphological variations may cause challenges in cytological evaluation. Moreover, diagnostic dilemmas can occur even in the assessments of tissue pathology.

Inducing ferroptosis has the potential to overcome therapy resistance in breast cancer.

Breast cancer is the most common type of malignancy among women. Due to the iron-dependent character of breast cancer cells, they are more sensitive to ferroptosis compared to normal cells. It is possible to reverse tumor resistance by inducing ferroptosis in breast cancer cells, thereby improving tumor treatment outcomes. Ferroptosis is highly dependent on the balance of oxidative and antioxidant status. When ferroptosis occurs, intracellular iron levels are significantly increased, leading to increased membrane lipid peroxidation and ultimately triggering ferroptosis. Ferroptotic death is a form of autophagy-associated cell death. Synergistic use of nanoparticle-loaded ferroptosis-inducer with radiotherapy and chemotherapy achieves more significant tumor suppression and inhibits the growth of breast cancer by targeting cancer tissues, enhancing the sensitivity of cells to drugs, reducing the drug resistance of cancer cells and the toxicity of drugs. In this review, we present the current status of breast cancer and the mechanisms of ferroptosis. It is hopeful for us to realize effective treatment of breast cancer through targeted ferroptosis.

Prognosis stratification in breast cancer and characterization of immunosuppressive microenvironment through a pyrimidine metabolism-related signature.

Pyrimidine metabolism is a hallmark of cancer and will soon become an essential part of cancer therapy. In the tumor microenvironment, cells reprogram pyrimidine metabolism intrinsically and extracellularly, thereby promoting tumorigenesis. Metabolites in pyrimidine metabolism have a significant impact on promoting cancer advancement and modulating immune system responses. In preclinical studies and practical clinical applications, critical targets in pyrimidine metabolism are acted upon by drugs to exert promising therapeutic effects on tumors. However, the pyrimidine metabolism in breast cancer (BC) is still largely underexplored. In this study, 163 credible pyrimidine metabolism-related genes (PMGs) were retrieved, and their somatic mutations and expression levels were determined. In addition, by using The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, 12 PMGs related to the overall survival (OS) were determined using the univariate Cox regression analysis. Subsequently, by performing the LASSO Cox hazards regression analysis in the 12 PMGs in TCGA-BRCA dataset, we developed a prognosis nomogram using eight OS-related PMGs and then verified the same in the METABRIC, GSE96058, GSE20685, GSE42568 and GSE86166 data. Moreover, we validated relationships between the pyrimidine metabolism index (PMI) and the survival probability of patients, essential clinical parameters, including the TNM stage and the PAM50 subtypes. Next, we verified the predictive capability of the optimum model, including the signature, the PAM50 subtype, and age, using ROC analysis and calibration curve, and compared it with other single clinical factors for the predictive power of benefit using decision curve analysis. Finally, we investigated the potential effects of pyrimidine metabolism on immune checkpoints, tumor-infiltrating immune cells, and cytokine levels and determined the potential implications of pyrimidine metabolism in BC immunotherapy. In conclusion, our findings suggest that pyrimidine metabolism has underlying prognostic significance in BC and can facilitate a new management approach for patients with different prognoses and more precise immunotherapy.

Database Mining Detected a Cuproptosis-Related Prognostic Signature and a Related Regulatory Axis in Breast Cancer.

Background: Breast cancer is the frequent cause of disease burden related to cancer among women. It affects one in 20 women globally and up to one in eight women in high-income countries. Cuproptosis is a copper-induced modality of mitochondrial cell death that is involved in tumor proliferation and metastasis. Methods: To construct a prognostic cuproptosis-related signature, LASSO Cox regression analysis was employed. Additionally, ceRNA was developed with an aim of exploring the possible lncRNA-miRNA-mRNA regulatory axis in breast cancer. Results: The expression of FDX1, DLD, DLAT, LIAS, LIPT1, GLS MTF1, and PDHA1 was downregulated, while CDKN2A expression level was elevated in breast cancer in contrast with normal tissue. We furthermore reviewed the genetic mutation landscape of genes linked to cuproptosis in breast cancer. Prognosis analysis revealed poor OS and RFS rates in breast cancer patients with elevated levels of CDKN2A and PDHA1 and low levels of MTF1, DLD, LIPT1, and FDX1. We then constructed a cuproptosis-related signature with six genes (DKN2A, MTF1, PDHA1, DLD, LIPT1, and FDX1) for breast cancer, which predicted the OS rate with an accuracy that ranged from medium to high. Further analysis demonstrated a significant correlation between the cuproptosis-related prognostic signature and pTNM stage, MSI score, drug sensitivity, TMB score, and immune cell infiltration. Moreover, we identified the lncRNA XIST/miR-92b-3p/MTF1 regulatory axis for breast cancer. Conclusion: Multiomics approaches were used to create a cuproptosis-related signature with six genes (DKN2A, MTF1, PDHA1, DLD, LIPT1, and FDX1) for breast cancer. We discovered the lncRNA XIST/miR-92b-3p/MTF1 regulatory axis for breast cancer, which has not yet been investigated previously.

CircKIF4A Is a Prognostic Factor and Modulator of Natural Killer/T-Cell Lymphoma Progression.

Background: Natural killer/T-cell lymphoma (NKTL) is difficult to treat. Circular RNAs (circ RNAs) have been implicated in tumorigenesis. However, the function of circKIF4A in NKTL has not been investigated. Methods: QPCR analysis was used to compare circKIF4A levels in NKTL cell lines versus normal cell lines. Kaplan-Meier survival analysis was used to assess the effect of circKIF4A on the prognosis of NKTL. The correlation between clinicopathological features and circKIF4A expression was examined using cox regression analysis. Luciferase reporter, RNA immunoprecipitation and immunohistochemistry assays were also used to investigate the mechanisms of circKIF4A in NKTL. Results: Our analyses revealed that circKIF4A is significantly upregulated in NKTL cell lines and that its upregulation correlates with the poor prognosis of NKTL. The silencing of circKIF4A significantly suppressed glucose uptake and lactate production in NKTL cells. Moreover, we showed that circKIF4A, PDK1, and BCL11A bind miR-1231 and that circKIF4A regulates PDK1 and BCL11A expressions by sponging miR-1231. Conclusions: During NKTL progression, circKIF4A regulated PDK1 and BCL11A levels by sponging miR-1231. Our data indicated that circKIF4A is oncogenic in NKTL and that it is a predictor of poor prognosis of NKTL.

LINC01234 Accelerates the Progression of Breast Cancer via the miR-525-5p/Cold Shock Domain-Containing E1 Axis.

Backgrounds: Long noncoding RNAs (lncRNAs) are strongly associated with the development of breast cancer (BC). As yet, the function of LINC01234 in BC remains unknown. Methods: Using biological information, the potential lncRNA, miRNA, and target gene were predicted. LINC01234 and miR-525-5p expression in BC tissues was detected using quantitative real-time reverse transcription polymerase chain reaction. Fluorescence in situ hybridization was used to determine the distribution of LINC01234. Cell proliferation was analyzed using CCK-8 assay, colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and apoptosis evaluated using flow cytometry. Western blotting was used to evaluate protein expression. Dual-luciferase® reporter, RNA pull-down, and RNA immunoprecipitation assays were performed to analyze the binding relationships among LINC01234, miR-525-5p, and cold shock domain-containing E1 (CSDE1). Results: We screened out LINC01234, found to be significantly increased in BC tissues, associated with a poor prognosis, and positively correlated with tumor size of BC. Knockdown of LINC01234 suppressed BC cell growth and facilitated apoptosis. Dual-luciferase reporter®, RNA pull-down, and RNA immunoprecipitation assays confirmed that LINC01234 and CSDE1 directly interacted with miR-525-5p. Upregulation of miR-525-5p and suppression of CSDE1 inhibited BC cell growth and induced cell apoptosis. Conclusion: Upregulation of LINC01234 contributes to the development of BC through the miR-525-5p/CSDE1 axis. LINC01234 may be one of the potential diagnostic and treatment targets for BC.

Altered spontaneous brain activity in major depressive disorder: An activation likelihood estimation meta-analysis.

BACKGROUND: Wide application of resting-state functional magnetic resonance imaging (fMRI) in psychiatric research has revealed that major depressive disorder (MDD) manifest abnormal neural activities in several brain regions involving key resting state networks. However, inconsistent results have hampered our understanding of the exact neuropathology associated with MDD. Therefore, our aim was to conduct a meta-analysis to identify the consistent vulnerable brain regions of MDD in resting state, and to reveal the potential pathogenesis of MDD. METHODS: A systematic review analysis was conducted on studies involving brain resting-state changes in MDD using low-frequency amplitude (ALFF), fractional low-frequency amplitude (fALFF) and regional homogeneity (ReHo) analysis. The meta-analysis was based on the activation likelihood estimation method, using the software of Ginger ALE 2.3. RESULTS: 25 studies (892 MDD and 799 healthy controls) were included. Based on the meta-analysis results of ReHo, we found robust reduction of resting-state spontaneous brain activity in MDD, including the left cuneus and right middle occipital gyrus (cluster size = 216, 256 mm3, uncorrected P < 0.0001), while no increased spontaneous activation in any of the brain regions. We also found reduced ALFF in the left middle occipital gyrus (cluster size = 224 mm3, uncorrected P < 0.0001), and no increased spontaneous brain activation in any regions. CONCLUSION: Our meta-analysis study using the activation likelihood estimation method demonstrated that MDD showed significant abnormalities in spontaneous neural activity, compared with healthy controls, mainly in areas associated with visual processing, such as the cuneus and the middle occipital gyrus. Dysfunction of these brain regions may be one of the pathogenesis of MDD.

Comprehensive analysis of a pyroptosis-related gene signature of clinical and biological value in acute myeloid leukaemia.

Acutemyeloidleukaemia(AML) is an illness of varied origin and unpredictable prognosis. Pyroptosis, a novel class of gasdermin-mediated programmed cell death (PCD), serves a critical function in anti-leukemia. But, the correlation between pyroptosis-related genes (PRGs) and AML prognosis is undetermined. Here, we obtained the RNA profile and matched clinical information of AML patients from the TCGA and GEO databases. 6 PRGs were identified to be strongly related to AML prognosis via univariate COX analysis. Next, the LASSO regression analysis was used to develop a PRG signature for AML prognosis, which was then employed for the stratification of patients into a low- (LR) or high-risk (HR) group. Kaplan-Meier analysis revealed that the HR group, but not the LR group, had worse prognosis. In addition, ROC curve analysis revealed that our prognotic model had good predictive value. Functional enrichment analysis indicated that the immune status was remarkably different between the two risk groups. In vitro experiments demonstrated that pyroptosis serves an essential function in anti-leukemia treatment. In summary, our newly developed model has good predictive value and can offer guidance into the precise estimation of AML prognosis and targeting pyroptosis is a potential therapeutic alternative for AML.

Low CRIM1 Levels Predict Poor Prognosis in Breast Cancer Patients.

Background: CRIM1 is involved in the development and preservation of the nervous system, capillary development, and vascular maintenance. Although CRIM1 was reported to involve in multiple cancers, its role in breast cancer is unclear. Methods: We investigated CRIM1 expression levels using Oncomine, HPA, and immunohistochemistry analyses. BC-GenExMiner was employed to evaluate the relationship of CRIM1 expression with the clinicopathological characteristics of breast cancer. Its association with breast cancer prognosis was assessed by Kaplan-Meier analysis and PrognoScan. The correlation of the expression of CRIM1 with tumor immune infiltration was explored via TIMER. Gene set enrichment analysis (GSEA) was utilized to determine the cascades that are linked to CRIM1 in breast cancer. Finally, we explored CRIM1 and its co-expressed genes using R (3.6.3). Results: Here, we find that CRIM1 expression was downregulated in various subtypes of breast cancer, and it was lowest in triple-negative breast cancers. ER and PR status were positively correlated with CRIM1 expression, while HER-2 expression was negatively correlated with CRIM1 expression. But in our immunohistochemical results in breast cancer specimens collected from our laboratory, HER-2 expression was positively correlated with CRIM1 expression. The expression of CRIM1 was correlated with menopause status, T stage, pathologic stage, histological type, and P53 status but not with age, N-stage, M-stage, Radiation therapy, and BRCA1/2 status. Survival analysis found that low CRIM1 expression was correlated with poorer DMFS, RFS and OS. Notably, CRIM1 expression was positively linked to the level of infiltration by CD8+ T-cells, endothelial cells, and neutrophils, and negatively linked to NK, B-cells, CD4+ T-cells, tumor purity, macrophage M1, and Tregs. Besides, DIXDC1 and PFDN6 were correlated to CRIM1 possibly. Conclusion: Our findings demonstrated that low CRIM1 expression predict poor prognosis of breast cancer and CRIM1 might be used as a possible treatment target or prognostic marker in breast cancer. More researches are needed to better understand the prognostic value of CRIM1 in breast cancer.