This study indicated that cordycepin exerted antidepressant effect by modulating GSK3β/β-catenin pathway, suggesting its potential as a candidate agent for depression.

We revealed that the HIF1A inhibitors echinomycin (EC) and YC-1 upregulated CXCL10/11 genes induced by IFN-γ in tumor cells in vitro...Combination therapy enhanced tumor infiltration of CD8 T cells and suppressed tumor angiogenesis. The present study suggests that HIF1A signaling in tumor cells dominates ICI resistance via the downregulation of tumor-derived CXCL10/11.

The combination of TURBT with pirarubicin and BCG intravesical instillation significantly lowers the recurrence rate in HRNMIBC patients and enhances both quality of life and immune function recovery. Independent factors affecting HRNMIBC recurrence include tumor number, stage, grade, and primary tumor status.

In conclusion, HO has an inhibitory effect on NASH fibrosis. This effect is mediated by targeting upregulation of hepatocyte FXR, which in turn attenuates hepatocyte apoptosis and thus indirectly inhibits the activation of HSCs.

P1, N=1134, Not yet recruiting, NICHD Global Network for Women's and Children's Health

Overall, our investigation demonstrated that nigericin and dactinomycin play therapeutic roles in tumours by promoting RMS cell pyroptosis. Interference with GEFT and drug combination can exert a great inhibitory effect on tumours.

Results demonstrated that CMSSF has the potential to be used as a natural growth promoter to enhance immunity, antioxidation, as well as overall health and growth performance of grower pigs.

Actinomycin D assay was performed to investigate the effect of PCBP2 depletion on TROAP mRNA stabilization...Our study demonstrated that PCBP2 stabilized TROAP to promote the malignant progression of gastric cancer. Targeting PCBP2 and its downstream target TROAP may provide a novel therapeutic strategy for the treatment of gastric cancer.

Additionally, administration of DAAA improved cardiac function following coronary artery ligation in mice. DAAA could be considered a promising adjunctive therapy to prevent post-MI heart failure through promoting angiogenesis.

P4, N=100, Recruiting, Radboud University Medical Center | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2027

RNA pull-down, RNA immunoprecipitation (RIP), and actinomycin D experiments were performed to investigate the relationships between SRSF9 and USP22...SRSF9 enhanced the malignant characteristics of OC through a positive feedback loop of SRSF9/USP22/ZEB1. This functional circuit may help in the development of novel therapeutic approaches for treating OC.

TRAF6 mRNA stability was tested using actinomycin D treatment...Meanwhile, ELAVL1 knockdown relieved caerulein-induced AR42J cell injury and macrophage M1 polarization, while these effects were abolished by TRAF6 overexpression. TRAF6, stabilized by ELAVL1, promoted caerulein-induced AR42J cell injury and macrophage M1 polarization, suggesting that it might accelerate AP9 progression.

Our findings demonstrate that the combination of anti-PD-L1 and cordycepin effectively suppressed tumor growth by regulating the proportion of T cells and reprograming type-II macrophages.

Actinomycin D treatment and RT‒qPCR assays were performed to determine the mRNA stability of AXIN1...Our study provides a new method for the treatment of asthma. This work not only deepens our understanding of the molecular underpinnings of asthma but also identifies potential therapeutic targets for the development of novel treatments aimed at inhibiting ASMC proliferation and alleviating asthma symptoms.

Furthermore, the interaction between MOV10 and integrin α3 (ITGA3) was verified by RNA immunoprecipitation assay, and the actinomycin D assay was used to detect ITGA3 mRNA stability...Furthermore, it was demonstrated that S100A16 regulated the stability of ITGA3 mRNA via MOV10 to mediate ECM‑receptor interactions. In conclusion, S100A16 may bind to MOV10 to stabilize ITGA3 mRNA and regulate ECM‑receptor interactions, hence contributing to the malignant progression of LUAD.

USP1 mRNA stability was determined after actinomycin D treatment...HOXA10 downregulation inhibited in vivo NPC proliferation through the PTPRG-AS1/USP1 axis. In conclusion, HOXA10 facilitates NPC cell proliferation in vitro and in vivo through the PTPRG-AS1/USP1 axis.

The mRNA stability was analyzed using actinomycin D (ActD)... Our findings indicated that LINC01134 functioned as an oncogene in CRC by binding directly to SLC1A5 mRNA and increasing its stability. Therefore, targeting LINC01134 could be a potential therapeutic target for treating CRC.

RIP, dual luciferase reporter gene and actinomycin D assay were conducted to verify the interactions between RBM15 and its targeted gene, and the presence of m6A modification site of its targeted mRNA, respectively...RBM15 regulated E2F2 in an m6A modification-dependent manner thereby boosting malignant cellular processes in CRC. The RBM15/E2F2 axis may be a novel target for CRC therapy.

m6A-modified circXPO1 by ALKBH5/IGF2BP2 axis destabilized WWC2 via interaction with FMRP to activate Hippo-YAP pathway, thereby facilitating CRC growth and metastasis. Targeting circXPO1 might be a potential therapeutic strategy for CRC.

The stability of PCNA mRNA was assessed after treatment with actinomycin D. An in vivo nude mouse xenograft model was created to validate the role of RBM15B...Furthermore, PCNA overexpression mitigated the effects of RBM15B knockdown on PC cell proliferation. In conclusion, RBM15B promotes PC cell proliferation by enhancing the stability of PCNA mRNA through YTHDF1-mediated m6A modification.

For patients with pCR, the differences in EFS (log-rank p = 0.47) and OS (log-rank p = 0.38) were not statistically significant among the three groups, and the EFS (log-rank p = 0.59) and OS (log-rank p = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups. PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.

KDM4A silences BMP9 expression by removing histone methyl groups from the BMP9 gene region, leading to further enhancement of glutamine metabolism, which contributes to malignant tumor progression. In addition, using JIB-04 in combination with exogenous BMP9 could inhibit the malignant progression of breast cancer cells and the growth of tumors more significantly.

Cordycepin, pentostatin and adenosine were identified in Cm-EE. Co-culturing cancer cells with effector immune cells during cordycepin or Cm-EE incubation resulted in elevated cancer cell death. These findings highlight the potential of cordycepin and Cm-EE in improving the efficacy of cancer immunotherapy for BC and HCC.

P=N/A, N=20, Recruiting, Duke University | Not yet recruiting --> Recruiting

P=N/A, N=20, Not yet recruiting, Shanghai Sixth People's Hospital; Shanghai Sixth People's Hospital

CDK1 mRNA stability was detected through actinomycin D assay...Furthermore, HAND2-AS1 impeded HB cell proliferation and cycle progression while inducing cell apoptosis by downregulating CDK1. Our research highlights that HAND2-AS1 can exert a tumor-suppressive effect on HB through the negative regulation of CDK1, and the HAND2-AS1/CDK1 is expected to be a diagnostic molecular marker and therapeutic target for HB in clinical practice.

P4, N=100, Not yet recruiting, Boston Children's Hospital | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2028 --> Dec 2028

Actinomycin D was used to evaluate mRNA stability...Furthermore, Lico A could affect the MDM2/p53 pathway by downregulating IGF2BP3 expression. Lico A exerts the anti-proliferative and pro-ferroptosis activity in AML cells by affecting the IGF2BP3/MDM2/p53 pathway, providing new evidence for Lico A as a promising agent for the treatment of AML.

Moreover, prolonged half-life time, slower metabolism and higher exposure of COR were observed in diabetes-induced liver injury animal model via pharmacokinetics studies. Altogether, COR holds potential as a therapeutic agent for ameliorating hepatic injury and fibrosis in diabetes by suppressing the activation of the SOX9-mediated Wnt/β-catenin pathway.

The properties of circRNA were verified by RNase R, actinomycin D, and fluorescence in situ hybridization (FISH)...Knockdown of its expression inhibits cell proliferation, invasion, EMT and autophagy and promotes apoptosis. CircBIRC6/miRNA-574-5p/DNAJB1 is a molecular axis that regulates prostate cancer cells.

Thus, our study successfully evaluated ENG/CD105 expression, DNA methylation, immune response, and CD regulation, which act as a novel diagnostic, prognostic, and therapeutic biomarker for BRCA. This research also fills critical knowledge gaps in this ENG/cancer field and highlights ENG's potential importance for the diagnosis, prognosis, and treatment of BRCA.

Our results provide new ideas for the combination strategy of THP with TLR agonists which improves prognosis of breast cancer.

P=N/A, N=22857, Recruiting, The University of Newcastle | Not yet recruiting --> Recruiting

ADAM10 is also negatively associated with tumor immunosuppression and interrelated with the immune infiltration of tumors. Overall, the present study determined ADAM10 expression by AD, CD and m6 2A, and in AD or CD/ADAM10/LAG3 signaling in cancers, and suggested a potential method for immunotherapy of cancers by targeting ADAM10 using the small molecules AD, CD and m6 2A.

METTL14/IGF2BP2-mediated m6A modification of STEAP1 aggravated ALI induced by sepsis. These findings suggest potential therapeutic targets for the treatment of this disease.

CircRNA ATF6 suppresses BCa cell growth, migration and invasion through the miR-146a-5p/FLNA axis.

METTL3 and IGF2BP1-mediated m6A modification of ZHX2 promoted RCC progression. The finding suggests that ZHX2 may serve as a potential therapeutic target in RCC, providing valuable insights for future clinical interventions.

The stability of circ_0023179 was verified using ribonuclease R enzyme, actinomycin D and agarose gel electrophoresis...The downregulation of miR-615-5p and the upregulation of CDH3 mitigated the inhibitory effect of silencing circ_0023179 on NSCLC cell proliferation. In conclusion, silencing circ_0023179 inhibited NSCLC cell proliferation by targeting the miR-615-5p/CDH3 axis involved in NSCLC progression.

In addition, our results demonstrate that COR downregulates StAR expression by reducing the expression of the SP1 transcription factor. These results provide a better understanding of the biological function of COR on StAR expression in the ovary, which may lead to the development of alternative therapeutic approaches for female reproductive disorders.

Messenger RNA stability was evaluated by qRT-PCR after treatment with actinomycin D. The methylated RNA immunoprecipitation (MeRIP) qPCR, dual-luciferase reporter analyses and m6A dot blotting were carried out to measure the m6A modification...Mechanistically, the downregulation of ASNS by STM2457 may be due to the decrease of m6A modification level in ASNS mRNA mediated by METTL3. Our findings suggest that STM2457 may serve as a potential therapeutic agent and ASNS may be a new promising therapeutic target for CRC.

P4, N=0, Withdrawn, Boston Children's Hospital | N=50 --> 0 | Trial completion date: Jul 2028 --> Dec 2028 | Not yet recruiting --> Withdrawn | Trial primary completion date: May 2028 --> Sep 2028

Targeting GSDME with CD implies therapeutic significance and a mechanism for antitumor roles in some types of cancers via increasing the sensitivity of chemotherapy. Altogether, our study may provide a strategy and biomarker for clinical diagnosis, prognostics, and treatment of cancers by targeting GSDME.