Aberrant expression of lysine-specific demethylase 1 (LSD1) has been consistently implicated in a broad spectrum of malignancies, underscoring its relevance as a therapeutic target. Despite growing interest, the development of LSD1 inhibitors continues to face significant challenges, in part due to the enzyme's dual role in catalysis and as a scaffolding protein within chromatin-remodeling complexes. Recent insights into the non-enzymatic functions of LSD1 have shifted the focus toward disrupting its protein-protein interactions, particularly with chromatin-modifying enzymes, as a complementary or alternative therapeutic strategy. In light of the limited systematic evaluation of available technologies, this work provides a critical overview and comparative analysis of current screening platforms and binding affinity assays, with particular attention to approaches capable of identifying LSD1 scaffold inhibitors. These efforts aim to accelerate the discovery of next-generation LSD1-targeted therapies with improved translational potential in oncology.

Cryoanalgesia is a technique for reducing postoperative pain that involves freezing peripheral nerves while preserving their ability to regain function over time. The technique has been used for decades, and randomized trials have shown a reduction in pain and opioid use in some patients undergoing thoracotomy and pectus excavatum repair. In these trials, outcomes were highly dependent on the control groups. Randomized studies of patients undergoing minimally invasive thoracic surgery have failed to show the same results. Furthermore, several studies have reported chronic pain and neuropathic-type pain in patients treated with cryoanalgesia. In this review, we discuss the electrophysiologic and histopathologic basis of cryoanalgesia, highlight randomized trials of cryoanalgesia in thoracic surgery, and outline potential pitfalls, such as chronic pain, to offer insight into which patients may benefit most from cryoanalgesia and potential future directions of study.

Esophageal squamous cell carcinoma (ESCC) is characterized by intrinsic radioresistance, primarily mediated by hyperactivation of DNA damage response (DDR) pathways. This repair capacity significantly diminishes radiotherapy efficacy, contributing to poor patient outcomes. Targeting DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a master regulator of non-homologous end joining (NHEJ), represents a promising strategy to overcome radioresistance. Immunohistochemistry (IHC) was performed on paired biopsy specimens from esophageal squamous cell carcinoma (ESCC) patients (n = 20) collected before neoadjuvant radiotherapy and after surgical resection. In vitro, ESCC cell lines (TE13 and Eca9706) were co-treated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitors (AZD7648 or NU7741) or PRKDC-targeting siRNA plus irradiation. Subsequent functional assays were conducted to assess cell viability, apoptosis, cell cycle distribution, and underlying molecular mechanisms. In vivo, the combined efficacy of AZD7648 and irradiation was evaluated in xenograft tumor models. Phosphorylated DNA-PKcs (Ser2056) in ESCC tissues was significantly elevated following irradiation. Inhibition of DNA-PKcs markedly enhanced radiosensitivity in both ESCC cell lines and xenograft models, correlating with prolonged G2/M arrest and increased apoptosis. Mechanistically, the combined therapy activated the ATM (Ser1981)-Chk2 (Thr68) axis and concurrently enhanced phosphorylation of Chk1 at Ser345, reinforcing G2/M arrest through Wee1 kinase-mediated inhibitory phosphorylation of CDC2 at Tyr15. Consequently, irreparable DNA double-strand breaks (DSBs) accumulated, triggering Caspase-3-dependent cleavage of PARP and execution of the intrinsic apoptosis pathway. Our study reveals a novel mechanism by which DNA-PKcs inhibition augments radiosensitivity in ESCC. Targeting DNA-PKcs could represent a promising strategy to improve the efficacy of radiotherapy in ESCC, offering a potential therapeutic approach to overcome radioresistance.

Objective: To investigate the impact of different low density lipoprotein-cholesterol (LDL-C) levels on the risk of gastrointestinal cancer. Methods: A prospective cohort study was used to observe 126 050 in service and retired employees of Kailuan Group who participated in the physical examination for the first time in 2006 or 2008. A total of 122 734 people were finally included in the statistical analysis. The subjects were divided into five groups according to the baseline quintile of low-density lipoprotein cholesterol, namely Q1 group, Q2 group, Q3 group, Q4 group and Q5 group. The impact of different LDL-C groups on the incidence of gastrointestinal tumors was analyzed by Cox proportional hazard model. Results: During follow-up of (12.83±2.43) years, 1 460 cases of gastrointestinal tumors occurred, including 225 cases of esophageal cancer, 431 cases of gastric cancer and 804 cases of colorectal cancer. Cox proportional hazard model analysis found that after adjusting for age, sex, body mass index, high-sensitivity C-reactive protein, education, smoking, alcohol consumption, diabetes, hypertension, physical exercise, excessive salt intake, family history of cancer and taking lipid-lowering drugs, compared with Q5 group, the hazard ratio (HR) values of gastrointestinal tumors in Q1, Q2, Q3 and Q4 groups were 1.28 (95% CI: 1.08, 1.50), 1.07 (95% CI: 0.90, 1.26), 1.31 (95% CI: 1.11, 1.54) and 1.12 (95% CI: 0.94, 1.33), respectively. The HR values of esophageal cancer were 1.21 (95% CI: 0.80, 1.82), 0.82 (95% CI: 0.52, 1.30), 1.47 (95% CI: 1.00, 2.17) and 0.84 (95% CI: 0.54, 1.31), respectively. The HR values of gastric cancer were 1.05 (95% CI: 0.78, 1.41), 0.84 (95% CI: 0.61, 1.16), 1.21 (95% CI: 0.91, 1.63) and 1.04 (95% CI: 0.77, 1.41), respectively. The HR values of colorectal cancer were 1.44 (95% CI: 1.15, 1.80), 1.28 (95% CI: 1.02, 1.62), 1.31 (95% CI: 1.04, 1.65) and 1.26 (95% CI: 1.00, 1.59), respectively. Conclusions: The decrease of baseline LDL-C level may be a risk factor for gastrointestinal malignant tumors, but low LDL-C increases the risk of malignant tumors in a location dependent manner. Although low LDL-C level increases the risk of colorectal cancer, it has no significant correlation with esophageal cancer and gastric cancer.

Esophageal cancer (ESCA) ranks among the most lethal malignancies worldwide, with late-stage diagnosis, poor prognosis, and limited treatment options contributing to its high mortality. MicroRNAs (miRNAs), short non-coding RNAs with gene-silencing functions, have emerged as crucial regulators in cancer biology and hold promise as diagnostic and therapeutic tools. This study investigates miRNA-mRNA interactions in ESCA using a comprehensive in silico approach to uncover potential regulatory nodes that may underlie tumor progression. Fourteen overexpressed genes in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) were selected. TargetScanHuman and miRDB were used to detect miRNAs with high-confidence 8mer seed matches (score ≥90). The majority of genes exhibited multi-miRNA targeting with clustered or overlapping seed regions, indicative of cooperative or redundant repression mechanisms. Several miRNAs demonstrated highly stable interactions, with favorable MFE and ΔG values, reinforcing their silencing potential. GC/GC3 enrichment further supported duplex stability. GO analysis revealed that the target genes are predominantly involved in transcriptional regulation, apoptosis inhibition, immune response modulation, and cell signaling-pathways central to cancer pathogenesis. TCGA-based validation showed that only a subset of predicted interactions is functionally relevant, with hsa-miR-30d-5p exhibiting a significant inverse correlation with CHST2. These findings highlight the importance of integrating predictive and expression data to identify biologically meaningful miRNA-mRNA interactions in esophageal cancer.