Blog of Signaling Pathways

Sperm-carried IGF2 downregulated the expression of mitogens produced by Sertoli cells: A paracrine mechanism for regulating spermatogenesis?

20 views | Dec 14 2023

The presence of IGF2 protein in human spermatozoa influences the expression of mitogens and reproductive hormones in Sertoli cells, indicating a paracrine regulatory mechanism that impacts gonocyte proliferation and spermatogonial fate during spermatogenesis. [Read the Full Post]

Sperm-carried IGF2 downregulated the expression of mitogens produced by Sertoli cells: A paracrine mechanism for regulating spermatogenesis?

0 views | Dec 14 2023

The presence of IGF2 protein in human spermatozoa influences the expression of mitogens and reproductive hormones in Sertoli cells, indicating a paracrine regulatory mechanism that impacts gonocyte proliferation and spermatogonial fate during spermatogenesis. [Read the Full Post]

Sperm-carried IGF2 downregulated the expression of mitogens produced by Sertoli cells: A paracrine mechanism for regulating spermatogenesis?

0 views | Dec 14 2023

The presence of IGF2 protein in human spermatozoa influences the expression of mitogens and reproductive hormones in Sertoli cells, indicating a paracrine regulatory mechanism that impacts gonocyte proliferation and spermatogonial fate during spermatogenesis. [Read the Full Post]

Molecular Profiling and Targeted Therapies in Gliomas

25 views | Dec 14 2023

This review explores the pivotal role of molecular profiling in the diagnosis, classification, and targeted treatment of gliomas, highlighting recent advances, challenges including the blood-brain barrier and tumor heterogeneity, and the pressing need for ongoing research to fully unlock the potential of personalized therapies for glioma patients. [Read the Full Post]

Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3RT618I-driven cells

54 views | Dec 14 2023

The study demonstrates that aurora kinase inhibitors, particularly reversine, exert significant antineoplastic effects in Ba/F3 cells expressing the CSF3RT618I mutation, reducing cell viability, clonogenicity, and proliferative capacity, while modulating key molecular pathways associated with cell cycle and apoptosis in the context of chronic neutrophilic leukemia (CNL). [Read the Full Post]

Cardiac RGS7 and RGS11 drive TGFβ1-dependent liver damage following chemotherapy exposure

15 views | Dec 14 2023

The research findings reveal that RGS7 controls the release of TGFβ1 from the heart, influencing the multiorgan damage caused by chemotherapy and emphasizing the importance of cardiokine signaling in this process. [Read the Full Post]

Lack of pharmacokinetic interaction between derazantinib and naringin in rats

29 views | Dec 14 2023

The study validated a sensitive UPLC-MS/MS method for measuring derazantinib concentration in rat plasma, revealing that co-administration of derazantinib with naringin did not significantly alter its pharmacokinetic parameters, suggesting a safe concomitant use without requiring dose adjustment. [Read the Full Post]

Structure-Based Lead Optimization of Enterovirus D68 2A Protease Inhibitors

36 views | Dec 13 2023

In this study, researchers elucidated the X-ray crystal structures of EV-D68 2Apro and its C107A mutant, utilized molecular dynamics simulations to predict the binding pose of telaprevir, and optimized its structure, leading to the discovery of potent 2Apro inhibitors with improved antiviral activity against Enterovirus D68. [Read the Full Post]

GPER1 contributes to T3-induced osteogenesis by mediating glycolysis in osteoblast precursors

37 views | Dec 13 2023

T3 promotes osteogenesis in MC3T3-E1 cells by enhancing GPER1-mediated glycolysis, as evidenced by increased osteogenic activities, which are reversed by GPER1 inhibition and glycolysis blockade. [Read the Full Post]

Glucose metabolic upregulation via phosphorylation of S6 ribosomal protein affects tumor progression in distal cholangiocarcinoma

69 views | Dec 13 2023

In summary, the study reveals that inhibiting phosphorylated S6 ribosomal protein, a marker of mTORC1 activity, suppresses glucose metabolism pathways and reduces cell proliferation, suggesting mTORC1 as a potential therapeutic target in distal cholangiocarcinoma. [Read the Full Post]

Pharmacological effects of mTORC1/C2 inhibitor in a preclinical model of NASH progression

21 views | Dec 13 2023

The study demonstrates that the mTORC1/C2 inhibitor Ku-0063794 (KU) effectively alleviates NASH-related hepatotoxicity, reduces oxidative stress, modulates gene expression, and decreases inflammation in a mouse model, highlighting its potential as a therapeutic candidate for non-alcoholic steatohepatitis. [Read the Full Post]

Phase 1b safety and pharmacokinetics of intravenous and oral fosmanogepix in patients with acute myeloid leukaemia and neutropenia

26 views | Dec 13 2023

**In this Phase 1b study, fosmanogepix, administered intravenously and orally to acute myeloid leukemia patients with neutropenia undergoing chemotherapy, demonstrated excellent tolerability, with no serious adverse events, and exhibited consistent pharmacokinetic profiles, supporting its potential as a safe and effective antifungal treatment option.** [Read the Full Post]

Indoximod-based chemo-immunotherapy for pediatric brain tumors: a first-in-children phase 1 trial

30 views | Dec 12 2023

The Phase 1 trial of indoximod, an IDO-pathway inhibitor, in combination with chemotherapy and radiation, demonstrated favorable tolerability, significant objective responses, and encouraging immune responses in children with recurrent brain tumors, providing a basis for advancing to Phase 2/3 trials for pediatric brain tumors. [Read the Full Post]

Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor

30 views | Dec 12 2023

In this study, a series of EPHA2 kinase inhibitors, including derivatives of NVP-BHG712 and triazine-based compounds, were synthesized and evaluated, revealing eight inhibitors with low-nanomolar affinities (KD <10 nM) that demonstrated promising effects in controlling human colon carcinoma, highlighting their potential as therapeutic tools in cancer research. [Read the Full Post]

RAGE inhibitor TTP488 (Azeliragon) suppresses metastasis in triple-negative breast cancer

16 views | Dec 12 2023

The study demonstrates that the RAGE inhibitor TTP488 (Azeliragon) significantly impairs metastasis of triple-negative breast cancer by disrupting key metastatic pathways, suggesting its potential as a targeted therapy in clinical trials. [Read the Full Post]

Regulatory mechanism of NOV/CCN3 in the inflammation and apoptosis of lung epithelial alveolar cells upon lipopolysaccharide stimulation

17 views | Dec 12 2023

In the LPS-induced acute lung injury model, CCN3 knockdown significantly attenuated inflammatory cytokine expression, reduced apoptosis in alveolar epithelial cells, and inhibited NF-κB activation, indicating its pivotal role in regulating lung inflammation and apoptosis via the TGF-β/p-Smad or NF-κB pathway. [Read the Full Post]

Chaperone-mediated autophagy protects against hyperglycemic stress

31 views | Dec 12 2023

The study demonstrates the existence of chaperone-mediated autophagy (CMA) in rainbow trout, revealing its activation under high-glucose conditions, mediated by the KFERQ motif, Lamp2A, mitochondrial reactive oxygen species, and the Nfe2l2/Nrf2 pathway, highlighting its crucial role in protecting against glucose-induced stress. [Read the Full Post]

Inhibition of DNA methylation attenuates lung ischemia-reperfusion injury after lung transplantation

34 views | Dec 11 2023

"Inhibition of DNA methylation, particularly through azathioprine treatment, attenuates lung ischemia-reperfusion injury by suppressing inflammation, oxidative stress, and endothelial dysfunction, highlighting its therapeutic potential for improving outcomes in lung transplantation." [Read the Full Post]

Pediatric glioblastoma cells are sensitive to drugs that inhibit eIF2α dephosphorylation and its phosphomimetic S51D variant

19 views | Dec 11 2023

The study demonstrates that combinations of histone deacetylase inhibitors and PARP-1 inhibitors, along with drugs increasing P-eIF2α or modulating its downstream effects, could be a promising and novel approach for treating pediatric glioblastoma (PED-GBM), particularly in cases with specific mutations. [Read the Full Post]

Exosomal EIF5A derived from Lewis lung carcinoma induced adipocyte wasting in cancer cachexia

62 views | Dec 11 2023

The study reveals that exosomal EIF5A derived from Lewis lung carcinoma cells induces adipocyte lipolysis in cancer cachexia by binding with GPBAR1 mRNA, activating the CREB signaling pathway, implicating EIF5A as a potential therapeutic target. [Read the Full Post]