KDM4B: A promising oncology therapeutic target.

Epigenetic modifications are significant in tumor pathogenesis, wherein the process of histone demethylation is indispensable for regulating gene transcription, apoptosis, DNA replication, and repair of damaged DNA. The lysine demethylases (KDMs) serve an essential role in the aforementioned processes, with particular emphasis on the KDM4 family, also referred to as JMJD2. Multiple studies have underscored the significance of the KDM4 family in the regulation of various biological processes including, but not limited to, the cell cycle, DNA repair mechanisms, signaling pathways, and the progression of tumor formation. Nevertheless, it is imperative to elucidate the underlying mechanism of KDM4B, which belongs to the KDM4 gene family. This review presents a comprehensive examination of the structure, mechanism, and function of KDM4B, as well as a critical analysis of the current body of research pertaining to its involvement in tumorigenesis and development. Furthermore, this review explores the potential therapeutic strategies that specifically target KDM4B.

USP31 serves as a potential biomarker for predicting prognosis and immune responses for clear cell renal cell carcinoma via single-cell and bulk RNA-sequencing.

BACKGROUND: Currently, there is no research available on the prognosis, potential effect and therapeutic value of USP31 in clear cell renal cell carcinoma (ccRCC). To address this gap, the present study aimed to shed light on its potential roles and possible mechanisms in ccRCC. METHODS: R software was utilized to conduct bioinformatics analyses with the data derived from The Cancer Genome Atlas (i.e. KIRC) and Gene Expression Omnibus datasets. The expression of USP31 in ccRCC was validated by a PCR. The independent prognostic ability of USP31 was evaluated by Cox regression analysis. We conducted gene set enrichment analysis (GSEA) to explore the potential USP31-related pathways. We also discussed the relationships between USP31 and immunity, by predicting its possible upstream transcription factors (TFs) by ChEA3. RESULTS: In ccRCC, USP31 demonstrated a high level of expression and this increased expression was correlated with a poor prognosis (p < 0.05). Through univariate and multivariate Cox regression analysis, USP31 was identified as an independent prognostic factor for ccRCC (p < 0.05). Furthermore, eight USP31-related pathways were identified by GSEA (p < 0.05). Moreover, USP31 was found to be associated with microsatellite instability, tumor microenvironment, a variety of immune cells and immune checkpoints and immune infiltration (p < 0.05). Additionally, Patients with high USP31 expression in ccRCC were shown to have better curative effects after immunotherapy (p < 0.05). Finally, we found that AR, USF1, MXI1 and CLOCK could be the potential upstream TFs of USP31. CONCLUSIONS: USP31 could serve as a potential biomarker for predicting both prognosis and immune responses, revealing its potential mechanisms of TF-USP31 mRNA networks in ccRCC.

A machine learning model based on MRI for the preoperative prediction of bladder cancer invasion depth.

OBJECTIVES: To construct and validate a prediction model based on full-sequence MRI for preoperatively evaluating the invasion depth of bladder cancer. METHODS: A total of 445 patients with bladder cancer were divided into a seven-to-three training set and test set for each group. The radiomic features of lesions were extracted automatically from the preoperative MRI images. Two feature selection methods were performed and compared, the key of which are the Least Absolute Shrinkage and Selection Operator (LASSO) and the Max Relevance Min Redundancy (mRMR). The classifier of the prediction model was selected from six advanced machine-learning techniques. The receiver operating characteristic (ROC) curves and the area under the curve (AUC) were applied to assess the efficiency of the models. RESULTS: The models with the best performance for pathological invasion prediction and muscular invasion prediction consisted of LASSO as the feature selection method and random forest as the classifier. In the training set, the AUC of the pathological invasion model and muscular invasion model were 0.808 and 0.828. Furthermore, with the mRMR as the feature selection method, the external invasion model based on random forest achieved excellent discrimination (AUC, 0.857). CONCLUSIONS: The full-sequence models demonstrated excellent accuracy for preoperatively predicting the bladder cancer invasion status. CLINICAL RELEVANCE STATEMENT: This study introduces a full-sequence MRI model for preoperative prediction of the depth of bladder cancer infiltration, which could help clinicians to recognise pathological features associated with tumour infiltration prior to invasive procedures. KEY POINTS: • Full-sequence MRI prediction model performed better than Vesicle Imaging-Reporting and Data System (VI-RADS) for preoperatively evaluating the invasion status of bladder cancer. • Machine learning methods can extract information from T1-weighted image (T1WI) sequences and benefit bladder cancer invasion prediction.

The ferric iron chelator 2,2'-dipyridyl attenuates basilar artery vasospasm and improves neurological function after subarachnoid hemorrhage in rabbits.

We investigated the efficacy of the ferrous iron (Fe(2+)) chelator 2,2'-dipyridyl (DP) to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH). Thirty-six New Zealand white rabbits were randomly assigned to four groups: untreated control, SAH, SAH + dimethyl sulfoxide (DMSO) vehicle, and SAH + DP. SAH was induced by injection of autologous blood into the cisterna magna and then DP or vehicle was infused into the cistern magna for 5 days (20 mg/kg/day or an equal volume of DMSO). Neurological deficit score (NDS) was used to assess neurological function and cerebral angiography to measure basilar artery (BA) diameter following SAH. TUNEL staining was used to detect BA endothelial cell apoptosis, and immunohistochemistry and Western blotting to assess changes in caspase-3 protein levels 5 days post-SAH. The SAH + DP group had a significantly larger mean BA diameter and lower mean NDS post-SAH compared to the SAH + DMSO and SAH groups (p < 0.05). TUNEL-positive cell numbers and caspase-3 levels were significantly reduced in BA endothelial cells of the SAH + DP group as compared to the SAH and SAH + DMSO groups (p < 0.05). The iron chelator DP reduced vasospasm and neurological sequelae in rabbits, likely by chelating the Fe(2+) in oxyhemoglobin and reducing oxidative stress-induced endothelial cell apoptosis.

Intraarterial thrombolysis and stent placement for acute basilar artery occlusion.

PURPOSE: To study retrospectively the prognostic factors for acute basilar artery occlusion treated with intraarterial thrombolysis and stent placement. MATERIALS AND METHODS: Within 3-48 hours of disease onset, 52 patients with basilar artery occlusion were treated with emergency intraarterial thrombolysis with recombinant tissue plasminogen activator (rtPA) or urokinase (UK) or intraarterial thrombolysis combined with stent placement. Sixteen patients simultaneously received stent placement for the partial recanalization of basilar artery occlusion after intraarterial thrombolysis. The National Institutes of Health Stroke Scale (NIHSS) scores and the modified Rankin Scale (mRS) scores of the patients were estimated. RESULTS: A favorable clinical outcome occurred in 22 patients (42.3%), and 20 patients (38.5%) died. The survival rate was 61.5% (32 patients). Successful recanalization of basilar artery occlusion was achieved in 24 patients (46.2%), and partial recanalization was achieved in 16 patients (30.7%). The rate of recanalization was 76.9%. NIHSS scores less than 14, treatment time window less than 24 hours, and a good recanalization were markedly correlated with good clinical prognosis. NIHSS scores less than 14 and treatment time window less than 24 hours were significantly correlated with recanalization. NIHSS scores less than 14 and good recanalization could act as independent predictors for clinical prognosis. CONCLUSIONS: NIHSS scores less than 14 on admission and successful recanalization can predict favorable outcome for patients with basilar artery occlusion. This study shows that intraarterial thrombolysis and stent placement may be a useful treatment for acute basilar artery occlusion.

Protective Effects of Astragaloside IV on Delayed Cerebral Vasospasm in an Experimental Rat Model of Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral vasospasm is an important cause of morbidity and mortality in patients with subarachnoid hemorrhage (SAH). This study aimed to assess the effects of Astragaloside IV (AS-IV) on delayed cerebral vasospasm after SAH. METHODS: A rat model of SAH was established by puncturing one side of the internal carotid artery. Then, rats received daily intraperitoneal injections of AS-IV (20 mg/kg; SAH-AS-IV group), 0.1% dimethyl sulfoxide (DMSO) (SAH-DMSO group), or saline (SAH group) for 5 days; an additional control group consisted of rats receiving sham surgery and saline injections. Morphologic characteristics of the basilar artery (BA) were measured from histologic sections stained with hematoxylin and eosin and used as indicators of cerebral vasospasm. Immunohistochemistry was used to detect Toll-like receptor-4 (TLR4) and nuclear factor kappa B (NF-κB) p65 protein levels in the BA. Enzyme-linked immunosorbent assay was used to measure the plasma concentrations of tumor necrosis factor-alpha and interleukin-6. RESULTS: Compared with controls, the SAH-DMSO and SAH groups showed increased wall thickness and reduced luminal cross-sectional area (indicative of vasospasm) and increased TLR4 expression and enhanced NF-κB activation in the BA, as well as elevated plasma levels of tumor necrosis factor-alpha and interleukin-6. Administration of AS-IV was associated with significant attenuation of all the aforementioned changes induced by SAH (P < 0.05). CONCLUSIONS: AS-IV may attenuate delayed cerebral vasospasm after SAH through inhibition of TLR4/NF-κB-mediated inflammatory signaling pathways.

The protective effect of cardamonin on the factors involved in delayed cerebral vasospasm in a rat model of subarachnoid hemorrhage.

Delayed cerebral vasospasms (DCVS) may affect the prognosis of patients after subarachnoid hemorrhage (SAH), but available preventive approaches are inefficient. The objective of this study was to explore the effects of cardamonin treatment on factors associated with the occurrence of DCVS after SAH. Rat models of SAH were created using the internal carotid artery puncture method. Rats were randomized into four groups: SAH (n = 10), SAH + vehicle (saline solution) group (n = 10), SAH + cardamonin group (n = 10), and a control (sham operation) group (n = 6). H&E staining was used to determine the wall thickness of the basilar artery. Immunohistochemistry was used to detect p-AKT and alpha smooth muscle actin (α-SMA). Immunofluorescence was used to detect the changes in C-myc expression. The TUNEL assay was used to detect apoptosis. Basilar artery wall thickness in the SAH + cardamonin and control groups were significantly lower than in the SAH group and SAH + vehicle groups (all P < 0.01). Apoptosis and the expression of p-AKT and C-myc in the SAH + cardamonin group were significantly lower than in the SAH and SAH + vehicle groups (P < 0.05), while α-SMA expression was higher than in the SAH and SAH + vehicle groups (P < 0.01). Cardamonin seems to alleviate cerebral vasospasms after SAH. These effects may involve the inhibition of p-AKT, C-myc expression and apoptosis, and the increase of α-SMA expression.