Given that CSD proteins YB-1 and DbpA fulfill the criteria of alarmins, we propose that their release signals an inherent danger to the host. Some data hint at an extracellular complex formation at a ratio of 10:1 (DbpA:YB-1) of both proteins.

SEZ6 may serve as a novel biomarker for MTCs. Although SEZ6 lacks any prognostic values in MTC, its positivity in 91% to 93% of MTCs, including MTCs without RET and RAS mutations, renders SEZ6-targetted antibody-drug conjugate therapy a promising targeted therapy for MTCs.

ABBV-011 1.0 mg/kg Q3W monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.

These results underscore the potential of P. edulis (Tainung No. 1) rind as a promising candidate for anti-skin aging, antibacterial, and anticancer applications, meriting further therapeutic investigation.

In this review, we discuss the emerging roles of common RDBPs from the heterogeneous nuclear ribonucleoprotein (hnRNP) family, such as TAR DNA binding protein-43 (TDP43) and fused in sarcoma (FUS) in controlling DNA damage response (DDR). We also explore the implications of RDBP pathology in aging and neurodegenerative diseases and provide a prospective on the therapeutic potential of targeting RDBP pathology mediated DDR defects for motor neuron diseases and aging.

Elevated serum TDP-43 level was associated with and could be used together with Witnessed CA, IL-6, and NSE to predict poor 28-day neurologic outcome in patients after ROSC following cardiac arrest.

The altered expression of some CHD members was significantly related to clinical cancer outcomes, and CHD1/2/8/9 could serve as potential prognostic biomarkers to improve the survival of BrCa patients. However, to evaluate the studied CHD members in detail are needed further investigations including experimental validation.

In response to damaged mitochondrial DNA, ZBP1 can interact with cyclic GMP-AMP synthase to augment IFN-I responses but inhibits toll like receptor 9-mediated inflammatory responses. This review summarizes the structure and expression pattern of ZBP1, discusses its roles in human diseases through immune-dependent (e.g., the production of IFN-I and pro-inflammatory cytokines) and -independent (e.g., the activation of cell death) functions, and highlights the attractive prospect of manipulating ZBP1 as a promising therapeutic target in diseases.

This research proves that downregulation of ZBP1 can inhibit the progression of ESCA. This finding indicates that ZBP1 may be a novel biomarker to improve the diagnosis and treatment of ESCA.

We find that ZNF827 accumulates at stalled forks and DNA damage sites, where it activates ATR and promotes the engagement of homologous recombination-mediated DNA repair. Additionally, we demonstrate that ZNF827 depletion inhibits replication initiation and sensitizes cancer cells to the topoisomerase inhibitor topotecan, revealing ZNF827 as a therapeutic target within the DNA damage response pathway.

P=N/A, N=60, Not yet recruiting, University Hospital, Tours

P1, N=132, Completed, AbbVie | Active, not recruiting --> Completed

Significance Statement Several in vitro and in vivo stability studies of ABBV-011, a calicheamicin-based ADC, identified circulating metabolites and catabolites and suggested that disulfide cleavage may be a key liability for the conjugated linker-payload. These observations may be relevant to other disulfide-linked ADCs, such as Mylotarg and Besponsa, both of which have reported similar half-lives that possibly indicate instability.

These data suggest that small molecules can disrupt the interaction between hSSB1 and ssDNA, and may also affect the ability of cells to repair DNA damage. This test study of small molecules holds the potential to provide insights into fundamental biochemical questions regarding the OB-fold.

P1, N=45, Completed, Guangzhou JOYO Pharma Co., Ltd

P2/3, N=210, Recruiting, Guangzhou JOYO Pharma Co., Ltd

Additionally, the inhibitor of WDHD1 has been found to enhance radiation sensitivity, improve drug resistance, and significantly decrease tumor cell proliferation. This comprehensive review aims to provide an overview of the molecular structure, biological functions, and regulatory mechanisms of WDHD1 in tumors, thereby establishing a foundation for future investigations and potential clinical applications of WDHD1.

Tamoxifen-inducible Ess2-knockout mice showed delayed prostate development with hypoplasia and disruption of luminal cells in the ventral prostate. Overall, these findings identified ESS2 acts as a transcriptional coregulator in prostate cancer and ESS2 can be novel epigenetic therapeutic target for CRPC.

SSBP2 evaluation using IHC can be helpful in the differential diagnosis of SCC and BCC. SSBP2 expression was associated with tumor invasiveness in SCC.

The binding capacity of these compounds was in the order sitosterol > hexadecanoic acid > oleic acid > plumbagin > 2-ethyl-3-methylnaphtho[2,3-b]thiophene-4,9-dione > methyl α-d-galactopyranoside > 3-methoxycatechol > catechol > pyrogallol > hydroxyhydroquinone; thus, sitosterol might exhibit the greatest inhibitory capacity against KpSSB among the selected compounds. Overall, these results may indicate the pharmacological potential of N. miranda for further therapeutic applications.

The RRM and RG2 region appear to bind nucleic acids promiscuously while the ZnF displayed more selectivity for single-stranded structures. With these results, the structural underpinnings of EWS recognition and binding of R-loops and other nucleic acid structures is better understood.

P1, N=132, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | N=233 --> 132

Positive damage modulation at some ETS transcription factor binding sites coincided at base level with melanoma somatic mutation hotspots. Our work provides proof of concept for the study of protein-DNA interactions at individual loci using light and sequencing, and reveals widespread and potent modulation of UV damage in regulatory regions.

Our results revealed that DDB1 expression is heterogeneous in ovarian cancer, suggesting its use as a potential biomarker for poor survival in ovarian cancer.

Mechanistically, rescue assays showed that ATF4 regulated gastric cancer cells' proliferation and invasive ability through SHH. Similarly, ATF4 enhanced the tumor formation of GC cells in a xenograft model.

The identification and validation of miRNAs are important to understand the physiological gene regulation in the CNS, and the pathological implications in ALS, leading to a new avenue for early diagnosis and gene therapies. Here, we offer a recent overview regarding the mechanism underlying the functions of multiple miRNAs across TDP-43, FUS, and SOD1 with the context of cell biology, and challenging for clinical applications in ALS.

This review summarizes our current knowledge of the role of NEAT1 in neurodegenerative diseases and its association with the characteristic aggregation of misfolded proteins: amyloid-β and tau in AD, α-synuclein in PD, mutant huntingtin in HD, and TAR DNA-binding protein-43 fused in sarcoma/translocated in liposarcoma in ALS. The aim of this review is to stimulate further research on more precise and effective treatments for neurodegenerative diseases.

Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

In addition, we discovered that HNRNPK promoted SPIN1 exon 4 inclusion by interacting with an intronic splicing enhancer in intron 4. Collectively, our study suggests a novel epigenetic regulatory pathway of HNRNPK in OSCC, mediated by controlling the transcription activity and alternative splicing of SPIN1 gene.

The decrease in networked mitochondria at the synapse is reversed upon downregulation of the pro-fission factor Drp1. Furthermore, altered expression of specific OXPHOS subunits reverses ALS-associated defects in mitochondrial morphology and function.

HSPB8_fs mutants aggregation alters the differentiation capacity of muscle cells and impairs sarcomere organization. Collectively, these results shed light on a potential pathogenic mechanism shared by the HSPB8_fs mutants described in neuromuscular diseases.Abbreviations : ACD: α-crystallin domain; ACTN: actinin alpha; BAG3: BAG cochaperone 3; C: carboxy; CASA: chaperone-assisted selective autophagy; CE: carboxy-terminal extension; CLEM: correlative light and electron microscopy; CMT2L: Charcot-Marie-Tooth type 2L; CTR: carboxy-terminal region; dHMNII: distal hereditary motor neuropathy type II; EV: empty vector; FRA: filter retardation assay; fs: frameshift; HSPA/HSP70: heat shock protein family A (Hsp70); HSPB1/Hsp27: heat shock protein family B (small) member 1; HSPB8/Hsp22: heat shock protein family B (small) member 8; HTT: huntingtin; KO: knockout; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MD: molecular dynamics; MTOC: microtubule organizing center; MYH: myosin heavy chain; MYOG: myogenin; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; NSC34: Neuroblastoma X Spinal Cord 34; OPTN: optineurin; polyQ: polyglutamine; SQSTM1/p62: sequestosome 1; STUB1/CHIP: STIP1 homology and U-box containing protein 1; TARDBP/TDP-43: TAR DNA binding protein; TAX1BP1: Tax1 binding protein 1; TUBA: tubulin alpha; WT: wild-type.

The present study identified a change in the localization of Kaiso in OC. The significance of this in relation to OC and tumor prognosis needs to be investigated with further studies using larger sample sizes and more sensitive molecular tools.

In addition, to assess the difference in levels depending on a number of clinicopathological factors, the impact on patient survival and interactions with tumor-infiltrating immune cells. This article may help to identify the target for further original research that may contribute to the discovery of new diagnostic biomarkers and define the molecular differences between LUAD and LUSC, which may affect the therapy effectiveness improvement and longer survival.

In addition to the inclusion body formation, sequestration of essential proteins into the LLPS droplets or changes in the LLPS status can directly impair neural functions and cause diseases. In this review, we will discuss the relationship between the LLPS observed in ALS causative proteins and the pathogenesis of the disease and outline potential therapeutic approaches.

Thus, PIN1 and PIN4 inhibition or knockdown might be novel therapeutic targets to suppress HBV infection. targets to suppress HBV infection.

In patients affected by FTD, particularly the youngest, with rapidly progressive decline and early motor affection, fusopathy must be suspected. These cases can include motor signs described in the FTD spectrum. Lower motor neuron affection in EMG could be detected late.

Collectively, our results uncovered an oncogenic function of CHD4 in ovarian cancer and provide a rationale for clinical trials of romidepsin in ovarian cancer patients.

Our findings illustrated that miRNA125a-5p and miRNA125b-1-5p could reduce the expression of DDB2 by binding to the 3'UTR region, and then regulate the expression levels of EMT markers, leading to the enhanced invasion and metastasis of colorectal cancer cells. Thus, miRNA125a-5p and miRNA125b-1-5p might be novel markers of colorectal cancer migration and potential therapeutic targets to treat metastatic colorectal cancer patients.

Therefore, CHD4 may provide a promising therapeutic target for the future treatment of GC. We identified an important hsa_circ_0007396-miR-767-3p-CHD4 axis, which is associated with GC proliferation and carcinogenesis, and may represent a promising therapeutic target for the future cure of GC.

Thus, the interplay between CK2 and PP1 signaling pathways have opposing effects on the phosphorylation status of their mutual substrate - IKAROS. This review summarizes the effects of CK2 and PP1 on IKAROS role in regulation of gene expression and its function as a tumor suppressor in leukemia.

This study identifies CHD4 dominated multi-drug efflux as a promising therapeutic target for overcoming acquired chemoresistance in GC.

Our cell-based reporter assay enables the discovery of HBV cccDNA host factors including YBX1 and is suitable for the characterisation of cccDNA-related host factors, antiviral targets and compounds.