P=N/A, N=128, Not yet recruiting, First Affiliated Hospital Xi'an Jiaotong University

The data from the present study support an inhibitory effect of miR-24s on XIAP expression. However, this inhibitory potency depends on the rs28382740 SNP genotype and may alleviate CRC progression by regulating the expression of XIAP.

Here, we determined the effects of gut microbiome-derived metabolites l-tryptophan, butyrate, trimethylamine (TMA), 3-methyl-4-(trimethylammonio)butanoate (3,4-TMAB), 4-(trimethylammonio)pentanoate (4-TMAP), ursodeoxycholic acid (UDCA), glycocholic acid (GCA) and benzoate on the first line of defence in the gut...These findings reiterate the complexity of understanding microbiome effects on host physiology and underline that microbiome metabolites are crucial mediators of barrier function and the innate response to infection. Understanding these metabolites at the cellular level will allow us to move towards a better mechanistic understanding of microbiome influence over host physiology, a crucial step in advancing microbiome research.

Collectively, ABRACL transcriptionally upregulated by CBX4 promoted the malignant progression of GC.

In the present review, the expression, function and participation of the STAT3-survivin axis in the progression of CRC were investigated. In addition, an update on the pre-clinical and clinical trials evaluating potential treatments targeting the STAT3-survivin axis is presented.

P2, N=54, Recruiting, Swiss Group for Clinical Cancer Research | Not yet recruiting --> Recruiting

EZH2 mutation is associated with VM development in breast cancer patients. The EZH2K515R mutation leads to VM and a poor prognosis by enhancing proliferation and invasion and inhibiting apoptosis in breast cancer cells.

It displayed superior pharmacokinetic properties compared to cisplatin. The inflammatory and hypoxic TME was suppressed by downregulating COX-2, MMP9, and HIF-1α, which resulted in inhibited angiogenesis in tumors by inhibiting the HIF-1α/VEGFA axis. Additionally, the immunosuppressive TME was reversed by blocking the immune checkpoint PD-L1, further improving the density of CD3+ and CD8+ tumor-infiltrating lymphocytes, and promoting macrophage polarization from M2- to M1-type.

P=N/A, N=170, Recruiting, Department of Gynecology and Obstetrics Hospital Affiliated to Zhejiang University Medical College; Women's Hospital, Medical School of Zhejiang Unive

HA, a novel natural small molecule, demonstrated promising therapeutic efficacy against ICC through its multi-target inhibitory effects on the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. Moreover, it exhibited notable therapeutic benefits in a primary ICC model (KRAS/P19/SB), positioning it as a novel therapeutic agent for ICC.

In summary, NG alleviates GEF-induced hepatotoxicity by anti-oxidation, inhibiting cell apoptosis, and autophagy. Therefore, this study suggests the use of NG to mitigate GEF's toxicity to the liver.

The pancreas of homozygous mutant mice displays reduced chymotrypsin activity and total protein synthesis...Administration of TUDCA or sulindac partially alleviates the phenotype...- Truncated CTRB1 misfolds and accumulates in the ER; yet, mutant mice display a histologically normal pancreas at 3 months age.- CTRB1 and associated chaperones colocalize in the ER, the cytoplasm, and the nucleus of acinar cells.- Transcriptomics analysis reveals reduced activity of the acinar program and increased activity of pathways involved in ER stress, unfolded protein response, and inflammation.- Mutant mice are sensitized to pancreatic damage and do not recover properly from a mild caerulein-induced pancreatitis.- TUDCA administration partially relieves the ER stress in mutant mice.How might it impact on clinical practice in the foreseeable future?: - The new mouse model provides a tool to identify the mechanisms leading to increased pancreatic cancer risk in CTRB2 exon 6 carriers. - The findings suggest that drugs that cause ER stress relief and/or reduce inflammation might provide preventive opportunities.

P=N/A, N=20, Recruiting, General University Hospital, Prague | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

The levels of four differential bile acids (glycocholic acid, taurolithocholic acid, tauroursodeoxycholic acid, and glycolithocholic acid) significantly increased in the high-salt group. Further correlation analysis indicated that the levels of ET-1 and TNF-α were positively correlated with these differential bile acid levels. This study provides new evidence for salt-sensitive cardiovascular diseases and metabolic changes caused by a high-salt diet in rats.

Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and quantitative analysis also revealed that FMGs regulated taurine and hypotaurine metabolism and bile acid metabolism. These findings provide a valuable understanding of the role of FMGs in liver fibrosis management.

On the other hand, the GSH-Px activity and SOD level were decreased along with a decreased neural reflex score. Our investigation concluded that Rh2 treatment significantly alleviated SAE damage and inhibited LPS-induced response via up-regulation of the Nrf2/HO-1 pathway to promote anti-oxidative stress capacity and inhibit neural cell apoptosis.

They both promoted cell proliferation and inhibited apoptosis in the effects of HQ on BMSCs by downregulating the expression of Cyt-C, Bax, Caspase 3, and Caspase 9 and upregulating the expression of Bcl-xl. Therefore, we concluded that Suv39h1 and the Wnt/β-catenin signaling pathway may mutually regulate each other in the effects of HQ on BMSCs in order to ameliorate the altered function of BMSCs.

Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H. pylori-infected GES-1 cells, thereby exerting a protective effect on gastric mucosal epithelial cells.

P2/3, N=110, Recruiting, Amylyx Pharmaceuticals Inc. | Phase classification: P3 --> P2/3 | N=600 --> 110 | Trial completion date: May 2027 --> Nov 2029

P3, N=664, Active, not recruiting, Amylyx Pharmaceuticals Inc. | Trial completion date: Mar 2024 --> Jan 2026

P2, N=54, Not yet recruiting, Swiss Group for Clinical Cancer Research | Initiation date: Jun 2024 --> Oct 2024

Mechanistically, corylin can interact with Raf-1 and promote the formation of the Raf-1/ASK1 complex, thus inhibiting cardiomyocyte apoptosis. In conclusion, our results demonstrate that corylin ameliorated cardiac dysfunction after MIR injury by reducing myocardial apoptosis.

These results supported that RNF135 contributes to human OS development through PI3K/AKT-dependent mechanisms. Targeting RNF135 may provide a new therapeutic approach for treating this human malignancy.

Furthermore, PKM2 upregulates heterogeneous nuclear ribonucleoprotein K (hnRNPK) expression and increases CRC cell proliferation and migration/invasion via regulating hnRNPK ubiquitination. These findings provide evidence that SHP2D61Y and SHP2E76K regulate CDDP-induced apoptosis, glucose metabolism, and CRC migration/invasion through PKM2 nuclear translocation and PKM2/hnRNPK signaling.

In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.

P3, N=120, Not yet recruiting, Hopital Foch | Initiation date: Apr 2024 --> Jul 2024

P4, N=80, Not yet recruiting, Amira Adel Fouly

The ability of colony formation and migration of T-HaCaT cells decreased. In conclusion, arsenite activated NRF2 in the later stages, decreasing apoptosis characterized by inhibiting endoplasmic reticulum stress-depended and mitochondria-depended apoptosis pathway, and further promoting NaAsO2-induced HaCaT cellular malignant transformation.

P4, N=22, Completed, The First Affiliated Hospital of Fujian Medical University; The First Affiliated Hospital of Fujian Medical University | Recruiting --> Completed

Finally, docking studies were conducted to assess the binding patterns of these active derivatives. The results showed that the binding patterns inside the active sites of both the VEGFR-2 and AKT-1 (allosteric pocket) crystal structures were identical to the reference ligands.

In summary, SETD8 inhibits the apoptosis and ferroptosis of ES cells through the YBX1/RAC3 axis, which provides new insights into the mechanism of tumorigenesis of ES. SETD8 may be a potential target for clinical intervention in ES patients.

P4, N=16, Active, not recruiting, Universitaire Ziekenhuizen KU Leuven | Unknown status --> Active, not recruiting | Trial completion date: Nov 2017 --> Nov 2025 | Trial primary completion date: Nov 2017 --> Nov 2025

Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.

P4, N=431, Completed, Daewoong Pharmaceutical Co. LTD. | Recruiting --> Completed

We show for the first time, that miR-20a modulation affects both these key functions of cytochrome c during HCC development. Our study thus demonstrates the promising 'two birds with one stone' approach of therapeutic in vivo targeting of an oncogenic miRNA, whereby more than one key deregulated cellular process is affected, and unequivocally leads to more effective attenuation of HCC progression and significantly longer overall survival.

(4) This study demonstrates UDCA's potent anti-inflammatory effects on NF-κB and FXR signaling pathways, and thus its potential to modulate hepatic inflammation and carcinogenesis through interactions with NF-κB and FXR. The decrease in micro-RNA 21 expression further underscores its therapeutic potential.

These challenges include: The impact of chemotherapy-induced genome chaos (e.g., multinucleation) on resistance and relapse, oncogenic function of caspase 3, cancer cell anastasis (recovery from late stages of apoptosis), and pitfalls of ubiquitously used preclinical chemosensitivity assays (e.g., cell "viability" and tumor growth delay studies in live animals) that score such pro-survival responses as "lethal" events. The studies outlined herein underscore the need for new directions in the management of solid tumors.

The cytotoxic activity of all the synthesized hybrids was investigated against the breast MCF-7 cancerous cell line using doxorubicin (Dox) as a positive control...Furthermore, the effects of hybrid 6b on the expression levels of pro-apoptotic Bax and pro-survival Bcl2 were assessed. The results showed that this compound upregulated the level of Bax expression as well as declined the expression value of Bcl-2 with regard to the untreated control.

Bmi-1 served as a potential therapeutic target for improving the efficacy of clinical treatment in retinoblastoma. All the findings revealed the functions of Bmi-1/RKIP axis in retinoblastoma tumorigenesis.

P3, N=333, Recruiting, Intensity Therapeutics, Inc. | Not yet recruiting --> Recruiting

Here, we investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic Navitoclax in oral cancer cells treated with the selective KSP inhibitor, Ispinesib, or AurB inhibitor, Barasertib, aiming to potentiate cell death. A mechanistic analysis underlying this synergistic activity, undertaken by live-cell imaging, is presented. Our data underscore the importance of combining BH3-mimetics with antimitotics in clinical trials to maximize their effectiveness.

Overexpression of USP36 disrupts the formation of the XIAP-Smac complex and promotes RIPK1 ubiquitination, validating USP36 as an inhibitor to intrinsic and extrinsic apoptosis through deubiquitinating survivin and cIAP1. Therefore, our results suggest that USP36 is involved in colorectal cancer progression and is a potential therapeutic target.