Berberine, a traditional Chinese herbal compound, is known for its broad range of biological activities, including anticancer and phototoxic effects. However, the precise mechanisms underlying its phototoxicity in liver cancer cells remain unclear. In this study, we investigated the potential of berberine as a photosensitizer for photodynamic therapy (PDT) by examining its phototoxic effects under blue light irradiation (488nm). The results showed that berberine rapidly translocated from the mitochondria to the nucleus upon light exposure, ultimately inducing cell death in SNU449 and Huh7 cells. Additionally, we observed a significant increase in reactive oxygen species, linking the phototoxic effects to oxidative stress. EdU/DAPI staining further revealed a marked reduction in DNA replication, with a complete absence of SNU449 cells in the S phase, indicating cell cycle arrest following treatment with berberine and PDT. Transcriptomic analysis also showed extensive gene expression changes, with GO enrichment indicating altered chromatin accessibility and cellular stress response following berberine and PDT combination therapy. qPCR and Western blotting confirmed that ER stress was significantly induced, triggering the activation of the pro-apoptotic protein DDIT3, which contributes to berberine-PDT-induced cell death. These findings underscore the potential of berberine as a photosensitizer and provide a promising approach for enhancing liver cancer treatment using PDT.

The DNA damage response (DDR) network comprises a range of protein factors and post-translational modifications (PTMs) that cooperate to maintain genomic stability following DNA damage. Lysine crotonylation (Kcr) is an emerging PTM, though its role in the DDR has not been thoroughly explored. We used quantitative proteomics to identify global Kcr substrates and assess their changes in response to DNA damage. Our results revealed 593 Kcr sites on 360 proteins that increased by more than 1.5-fold, while 331 Kcr sites on 233 proteins decreased by more than 0.67-fold following etoposide-induced DNA damage. Alterations in Kcr levels particularly in RNA splicing factors were most markedly pronounced before and after DNA damage. This study presents the first Kcr proteome regulated during the DDR and highlights the potential critical role of RNA-related factors in this process.

Cancer cells often remodel their catabolic processes to support proliferation, growth, survival, and progression. This study investigated the transcriptional dysregulation of choline catabolism genes in pan-cancer, using TCGA and mRNA expression profiles from liver cancer cohorts. The studies revealed that choline catabolic genes, including choline kinase A, choline kinase B, choline dehydrogenase, and choline phosphotransferase, were prominently activated in stage-specific hepatocellular carcinoma (HCC) liver tumors with significant p-values (p<0.0001). Additionally, these genes were further analyzed for their ontological functionality, showing that they play a crucial role in the biosynthesis of phosphatidylcholine, essential for membrane synthesis during cell proliferation and survival. Furthermore, ROC curve analysis demonstrated greater specificity and sensitivity for these genes in stage-specific HCC tumors with significant area under the curve values. Overall survival studies also confirmed that these genes were associated with poor survival in HCC patients with significant p-values (p<0.05). Gene effect score analysis revealed higher negative scores for choline catabolic genes in liver tumor cell lines. Moreover, integrative genomic drug sensitivity studies identified a negative correlation with this catabolism, highlighting potential therapeutic targets such as Bryostatin1, Amuvatinib, FH535, Linsitinib, and DMOG. These findings could pave the way for the use of targeted therapies that focus on choline catabolic dysregulation in HCC treatment.

NINJ1 (Ninjurin 1) mediates plasma membrane rupture (PMR) during the lytic phase in response to inducers of various programmed cell death mechanisms, such as pyroptosis, leading to the release of inflammatory molecules like HMGB1 and LDH. NINJ1, however, has not been previously studied in the context of breast cancer. Here, I found that NINJ1 transcript levels are higher in breast tumors than in non-malignant breast tissue. Estrogen receptor (ER)-positive or progesterone receptor (PR)-positive breast tumors exhibited higher NINJ1 expression compared to ER-negative or PR-negative tumors, respectively, independent of menopausal status. By contrast, NINJ1 expression did not vary with HER2 status, another molecular marker defining breast cancer subtypes. The lowest NINJ1 expression was observed in triple-negative breast cancer (TNBC), the subtype with the highest recurrence and mortality rates. Tumor stage and patient race also seemed to influence NINJ1 mRNA expression levels. More importantly, breast cancer patients with high NINJ1 expression had a more favorable prognosis than those with low expression across multiple survival parameters. In summary, higher NINJ1 levels in ER-positive and PR-positive breast cancer may contribute to the improved survival rates observed in this patient group. Future work now remains to identify the mechanistic basis of NINJ1-mediated antitumor immunity in breast cancer.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by extracellular senile plaques. The pathogenesis of AD remains unclear. This study aims to explore the molecular mechanism of AD through bioinformatics and next generation sequencing (NGS) data analysis. NGS dataset GSE125583 was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the “limma” R bioconductor package. Gene Ontology (GO) and REACTOME enrichment analysis were conducted. Analysis and visualization of protein–protein interaction network (PPI) and modules were carried out with HIPPIE and Cytoscape. Subsequently, miRNA-hub gene regulatory network and TF-hub gene regulatory network were built to predict the underlying microRNAs (miRNAs) and transcription factors (TFs) associated with hub genes. Finally, receiver operating characteristic (ROC) curve to assess the diagnostic efficacy of hub genes, which have been validated with training and validation datasets. Totally 956 DEGs (479 up regulated DEGs and 477 down regulated DEGs) were identified from GSE125583. GO and REACTOME pathway enrichment analysis indicated that DEGS were mainly enriched in regulation of biological quality, cell junction, channel activity, cell communication, plasma membrane, signaling receptor activity, neuronal system and GPCR ligand binding. 10 hub genes were selected, including PAK1, ELAVL2, NSF, HTR2C, TERT, UBD, MKI67, HSPB1, PYHIN1 and TES. MiRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed and analyzed successfully. Hsa-mir-4517, hsa-mir-3652, EGR1 and ZNF354C were predicted as possible key miRNAs and TFs for progression of AD. In conclusion, the results in this study provided reliable key genes and signaling pathways for AD, which will be useful for AD molecular mechanisms, diagnosis, prognosis and candidate targeted treatment.

The article titled “The Complete telomere-to-telomere Sequence of a Mouse Genome” provides a significant advancement in the field of genomics by completing the telomere-to-telomere (T2T) sequencing of the mouse genome, a task that had previously been hindered by gaps, particularly in regions rich in repetitive sequences. Their work addresses long-standing limitations in the current mouse genome assembly, GRCm39, which, despite being the most widely used reference, left over about 8% of the genome unsequenced. These previously inaccessible regions include crucial areas such as ribosomal DNA arrays, pericentromeric regions, and subtelomeric regions, as well as additional protein-coding genes.