Exploring the role of ubiquitin regulatory X domain family proteins in cancers: bioinformatics insights, mechanisms, and implications for therapy.

UBXD family (UBXDF), a group of proteins containing ubiquitin regulatory X (UBX) domains, play a crucial role in the imbalance of proliferation and apoptotic in cancer. In this study, we summarised bioinformatics proof on multi-omics databases and literature on UBXDF's effects on cancer. Bioinformatics analysis revealed that Fas-associated factor 1 (FAF1) has the largest number of gene alterations in the UBXD family and has been linked to survival and cancer progression in many cancers. UBXDF may affect tumour microenvironment (TME) and drugtherapy and should be investigated in the future. We also summarised the experimental evidence of the mechanism of UBXDF in cancer, both in vitro and in vivo, as well as its application in clinical and targeted drugs. We compared bioinformatics and literature to provide a multi-omics insight into UBXDF in cancers, review proof and mechanism of UBXDF effects on cancers, and prospect future research directions in-depth. We hope that this paper will be helpful for direct cancer-related UBXDF studies.

Triptolide protects against white matter injury induced by chronic cerebral hypoperfusion in mice.

White matter injury is the major pathological alteration of subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion. It is characterized by progressive demyelination, apoptosis of oligodendrocytes and microglial activation, which leads to impairment of cognitive function. Triptolide exhibits a variety of pharmacological activities including anti-inflammation, immunosuppression and antitumor, etc. In this study, we investigated the effects of triptolide on white matter injury and cognitive impairments in mice with chronic cerebral hypoperfusion induced by the right unilateral common carotid artery occlusion (rUCCAO). We showed that triptolide administration alleviated the demyelination, axonal injury, and oligodendrocyte loss in the mice. Triptolide also improved cognitive function in novel object recognition test and Morris water maze test. In primary oligodendrocytes following oxygen-glucose deprivation (OGD), application of triptolide (0.001-0.1 nM) exerted concentration-dependent protection. We revealed that the protective effect of triptolide resulted from its inhibition of oligodendrocyte apoptosis via increasing the phosphorylation of the Src/Akt/GSK3ß pathway. Moreover, triptolide suppressed microglial activation and proinflammatory cytokines expression after chronic cerebral hypoperfusion in mice and in BV2 microglial cells following OGD, which also contributing to its alleviation of white matter injury. Importantly, mice received triptolide at the dose of 20 µg·kg-1·d-1 did not show hepatotoxicity and nephrotoxicity even after chronic treatment. Thus, our results highlight that triptolide alleviates whiter matter injury induced by chronic cerebral hypoperfusion through direct protection against oligodendrocyte apoptosis and indirect protection by inhibition of microglial inflammation. Triptolide may have novel indication in clinic such as the treatment of chronic cerebral hypoperfusion-induced SIVD.

Detection of uric acid depositing in tophaceous gout using a new dual energy spectral CT technology.

OBJECTIVE: To assess the feasibility and diagnostic value of detecting uric acid depositing among patients with tophaceous gout using a dual energy CT based Gemstone spectral imaging (GSI) technology for qualitative analysis of uric acid. METHODS: Thirty one patients with clinically detectable tophaceous gout and 10 healthy volunteers underwent Discovery CT 750 HD scan with GSI mode. We selected four case groups of tophi, muscles, cortical bone, and cancellous bone. Each has a region of interest (ROI) of 10 mm diameter. We then analyzed and compared the difference of CT imaging spectroscopy quantitative parameters including concentration of uric acid, calcium, and water levels. The univariate analysis of variance and independent samples t-test were applied in data analyses. RESULTS: In case group of tophi base substance, the concentration levels were 1268.8 ± 32.2 mg/cm3 for uric acid (Ca), 19.4 ± 9.5 mg/cm3 for calcium (uric acid), 10.8 ± 9.5 mg/cm3 for calcium (water), and 1171.0 ± 26.8 mg/cm3 for water (calcium), respectively. In cortical bone case group, the four base substance concentration levels changed to 1333.6 ± 83.8 mg/cm3, 271.1 ± 85.0 mg/cm3, 262.6 ± 85.4 mg/cm3, and 1230.8 ± 77.0 mg/cm3. In muscles case group, the four base substance concentration levels were 1143.5 ± 15.7 mg/cm3,12.3 ± 5.0 mg/cm3, 4.4 ± 1.9 mg/cm3, and 1054.1 ± 14.6 mg/cm3. Finally, in cancellous bone case group, the corresponding base substance concentration became 1070.9 ± 26.4 mg/cm3, 85.1 ± 46.9 mg/cm3, 77.4 ± 46.7 mg/cm3, and 988.0 ± 23.4 mg/cm3. Except tophi and muscle differences between Calcium (uric acid) concentration and differences in Calcium (water) concentration, which were not significantly different (p> 0.29), the remaining group pairwise comparisons of the parameters were significantly different (p < 0.05). CONCLUSION: Dual-energy spectral CT can detect gout tophi within the peripheral joints of the patients. The quantitative measurement of the tophi concentration provides a new imaging method for quantitatively monitoring clinical outcomes of tophi.

The Emerging Roles of circRNAs in Papillary Thyroid Carcinoma: Molecular Mechanisms and Biomarker Potential.

Papillary thyroid carcinoma (PTC) is a common endocrine malignant tumor. The incidence of PTC has increased in the past decades and presents a younger trend. Accumulating evidence indicates that circular RNAs (circRNAs), featured with non-linear, closed-loop structures, play pivotal roles in tumorigenesis and regulate cell biological processes, such as proliferation, migration, and invasion, by acting as microRNA (miRNA) sponges. Additionally, due to their unique stability, circRNAs hold promising potential as diagnostic biomarkers and effective therapeutic targets for PTC treatment. In this review, we systematically arrange the expression level of circRNAs, related clinical characteristics, circRNA-miRNA-mRNA regulatory network, and molecular mechanisms. Furthermore, related signaling pathways and their potential ability of diagnostic biomarkers and therapeutic targets are discussed, which might provide a new strategy for PTC diagnosis, monitoring, and prognosis.

Machine learning modeling and prognostic value analysis of invasion-related genes in cutaneous melanoma.

In this study, we aimed to develop an invasion-related risk signature and prognostic model for personalized treatment and prognosis prediction in skin cutaneous melanoma (SKCM), as invasion plays a crucial role in this disease. We identified 124 differentially expressed invasion-associated genes (DE-IAGs) and selected 20 prognostic genes (TTYH3, NME1, ORC1, PLK1, MYO10, SPINT1, NUPR1, SERPINE2, HLA-DQB2, METTL7B, TIMP1, NOX4, DBI, ARL15, APOBEC3G, ARRB2, DRAM1, RNF213, C14orf28, and CPEB3) using Cox and LASSO regression to establish a risk score. Gene expression was validated through single-cell sequencing, protein expression, and transcriptome analysis. Negative correlations were discovered between risk score, immune score, and stromal score using ESTIMATE and CIBERSORT algorithms. High- and low-risk groups exhibited significant differences in immune cell infiltration and checkpoint molecule expression. The 20 prognostic genes effectively differentiated between SKCM and normal samples (AUCs >0.7). We identified 234 drugs targeting 6 genes from the DGIdb database. Our study provides potential biomarkers and a risk signature for personalized treatment and prognosis prediction in SKCM patients. We developed a nomogram and machine-learning prognostic model to predict 1-, 3-, and 5-year overall survival (OS) using risk signature and clinical factors. The best model, Extra Trees Classifier (AUC = 0.88), was derived from pycaret's comparison of 15 classifiers. The pipeline and app are accessible at https://github.com/EnyuY/IAGs-in-SKCM.

Biomarker of Pulmonary Inflammatory Response in LUAD: miR-584-5p Targets RAB23 to Suppress Inflammation Induced by LPS in A549 Cells.

BACKGROUND: Pulmonary inflammatory response (PIR) is one of the prognostic risk factors of lung adenocarcinoma (LUAD), with a high mortality rate. OBJECTIVES: This study aims to investigate prognostic microRNA (miRNA) to improve clinical prognosis prediction and postoperative inflammation treatment in LUAD patients. METHODS: About 201 differentially expressed microRNAs (DE-miRNAs) in LUAD were mined by differential analysis. Univariate/multivariate Cox analyses established and validated prognostic risk miRNAs in TCGA-LUAD. KEGG and GO were used to link risk signatures and biological functions. After 48 hours of exposure to 50 ng/mL LPS, the miR-584-5p/RAB23 regulatory network was verified in qRT-PCR, Western Blotting, and the Luciferase Reporter Assay in A549 cells. RESULTS: MiR-584-5p and miR-101-3p were validated as riskscore correlated with LUAD patients' 1-year survival (p < 0.001) and participate in multiple inflammation-related pathways. RAB23, a RAS oncogene, is involved in inflammatory MAPK signaling. Evidence suggests that miR-584-5p regulates inflammation in LUAD by targeting RAB23. A549 cells were transfected with the mimic and inhibitor of miR-584-5p, confirming the negative regulatory relationship between miR-584-5p and RAB23. In the A549 induced by LPS, either over-expression of miR-584-5p or knock-down of RAB23 expression decreased the expression of inflammatory factors and increased cell viability. CONCLUSION: Prognostic-related risk miR-584-5p can regulate the expression of RAB23 at both the mRNA and protein levels, thereby influencing the development of a PIR in LUAD. This will have significant implications for the clinical prognosis prediction and therapy decision-making of LUAD patients with PIR.

Consumers' knowledge, attitude, and behavior towards antimicrobial resistance and antimicrobial use in food production in China.

Background: Antimicrobial resistance (AMR) can be induced by overuse or misuse of antimicrobials. Few researches were involved in consumers' knowledge and attitude toward antimicrobial use (AMU) in food production. This study was designed to investigate the knowledge and awareness, perception, and attitude of Chinese consumers toward AMU in food production. Their behavior, purchase intention of antimicrobial-free food products, and confidence in information sources were also investigated. Methods: As a descriptive cross-sectional study, an online electronic survey questionnaire was conducted between February 25 and March 8, 2022, involving 1,065 consumers in China. Factor analysis was conducted to identify underlying patterns of the attitudes and information sources. Spearman correlations were employed to determine the relationship between knowledge, attitudes and the intention to pay extra. The differences in knowledge and attitudes were performed by independent t-test and one-way analysis of variance (ANOVA) test, and the difference in intention was performed by Chi-square test, when compared with demographic factors. Results: The findings showed that even though 75.0% of them heard of AMR, and 48.2% knew the definition of AMR, the level of consumers' knowledge of AMU in farming production and food regulations in China was not high (48.9% of participants replied correctly). About half viewed AMU and AMR as a potential risk to their health. Of these participants, 61.3% claimed that they were more likely looking for specific information about AMU on food packaging, and 58.3% changed their eating or cooking habits due to the concern. In addition, 79.8% were willing to pay extra for antimicrobial-free food products. Information sources from professionals and authorities were considered more accurate than those from media, the internet, word of mouth, and others. Conclusions: Chinese consumers had insufficient knowledge and neutral attitudes about AMU in farming production and food regulations in China. A large proportion of the participants were willing to purchase antimicrobial-free food products. Most of them obtained related information from the media. This study highlighted the importance of updated education and effective communication with consumers in China. It helps to develop the reliable foodborne AMR surveillance system along food chain and improve government communication and consumer awareness.

NAD+ Modulates the Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells via Akt Signaling Pathway.

Nicotinamide adenine dinucleotide hydrate (NAD+) acts as the essential component of the tricarboxylic citric acid (TCA) cycle and has important functions in diverse biological processes. However, the roles of NAD+ in regulating adult neural stem/progenitor cells (aNSPCs) remain largely unknown. Here, we show that NAD+ exposure leads to the reduced proliferation and neuronal differentiation of aNSPCs and induces the apoptosis of aNSPCs. In addition, NAD+ exposure inhibits the morphological development of neurons. Mechanistically, RNA sequencing revealed that the transcriptome of aNSPCs is altered by NAD+ exposure. NAD+ exposure significantly decreases the expression of multiple genes related to ATP metabolism and the PI3k-Akt signaling pathway. Collectively, our findings provide some insights into the roles and mechanisms in which NAD+ regulates aNSPCs and neuronal development.