P3, N=150, Recruiting, Xijing Hospital of Digestive Diseases

This study presents novel findings elucidating the beneficial effect of REM in ALI. This effect can be attributed to REM's ability to inhibit apoptosis by activating of the PI3K/AKT pathway in endothelial and epithelial cells. Additionally, REM targeted TSPO to regulate this pathway in endothelial cells. These results suggested a potential protective role for REM in ALI/ARDS management.

A high degree of synergism was also observed in patient-derived OAC organoids indicating the potential clinical relevance of the combination. This study demonstrates the role for dual AKT/IAP inhibition in OAC and provides a strong rationale for the further investigation of this highly efficacious combination strategy.

P2/3, N=104, Recruiting, Xijing Hospital of Digestive Diseases | Trial primary completion date: Dec 2024 --> Dec 2025

P3, N=150, Recruiting, Xijing Hospital of Digestive Diseases | Trial primary completion date: Dec 2024 --> Dec 2025

We further demonstrated that dasatinib and MYF-03-176 notably enhance the efficacy of KRAS inhibitors by reducing SRC kinase activity and TEAD activity. Overall, targeting the Hippo-YAP/TAZ pathway has the potential to overcome resistance to KRAS inhibitors.

P2/3, N=110, Active, not recruiting, Amylyx Pharmaceuticals Inc. | Recruiting --> Active, not recruiting

No long-term adverse effects on hematological or biochemical parameters or tissue levels were observed in the mice. Given these findings, this compound demonstrates significant cytotoxic effects and has the potential to serve as a promising chemotherapeutic agent, warranting further investigation at more advanced stages.

In conclusion, UDCA treatment efficiently normalizes the above-mentioned pathological abnormalities and avoids the development of IRR-associated neurological dysfunction by upregulating the beneficial axis of RAS in the brain. Hence, ursodeoxycholic acid presents a novel option for patient care during radiotherapy.

MNP@CD26@17D-mediated ferroptosis might be executed by ferritinophagy as judged by elevated levels of the ferritinophagy marker NCOA4 and a decreased pool of ferritin. As 24 h treatment with MNP@CD26@17D did not induce hemolysis in human erythrocytes in vitro, this newly designed nanoplatform could be considered as an optimal multifunctional tool to target and eliminate senescent cells of skin origin, overcoming their apoptosis resistance.

Berberine hydrochloride and ursodeoxycholic acid were combined to form a double salt (BeU), enhancing solubility and encapsulation. Remarkably, the mean colon length in the FU-PA/BeU NPs@MS group was 1.2 times longer than that in the sulfasalazine group. These dual-targeted FU-PA/BeU NPs@MS show great potential for UC treatment.

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

This review emphasizes how specific gut microbiota and gut microbiota metabolites, including butyrate, propionate, and ursodeoxycholic acid, interact with oncogenic pathways to modulate anti-tumor effects...Furthermore, modulation of the gut microbiota influences glucose and lipid metabolism, thereby enhancing the response to anti-KRAS agents and addressing diarrhea induced by tyrosine kinase inhibitors. By elucidating the connection between gut microbiota and the EGFR/VEGF/KRAS pathways, this review provides valuable insights for advancing targeted cancer therapy and optimizing treatment outcomes in clinical settings.

Compound 16c boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound 16c against VEGFR-2. Compound 16c is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.

In conclusion, this research elucidates that Tan IIA improves cerebral edema and neural function by elevating intracellular expression of SIRT1 and FOXO3α proteins, modulating OSM and inflammatory factors. These findings yielded robust experimental support for the potential use of Tan IIA as a therapeutic agent for CI.

Amidst this context, the present investigation delineates the synergistic potentiation of doxorubicin (DOX)-a canonical chemotherapeutic-by Ursodeoxycholic acid (UDCA), a compound with a historical pedigree in hepatobiliary medicine, now repositioned within oncological pharmacotherapy due to its dichotomous cellular modulation-affording cytoprotection to non-malignant epithelia whilst eliciting apoptotic cascades in neoplastic counterparts. The implications of this research are twofold: firstly, it offers a compelling evidence base for the clinical reevaluation of UDCA in combinatory chemotherapeutic regimens; secondly, it posits a novel mechanistic insight into the modulation of chemotherapeutic efficacy and resistance. Collectively, these insights advocate for the expedited clinical translation of UDCA-DOX synergy, potentially heralding a paradigm shift in the management of NSCLC, thereby addressing a critical lacuna in contemporary oncological therapy.

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