Blog of Signaling Pathways

Age- and sex-adjusted reference intervals for steroid hormones measured by liquid chromatography‑tandem mass spectrometry (LC-MS/MS) using a widely available kit

37 views | Dec 18 2023

This study established reference intervals for nine endogenous steroids using a commercially available liquid chromatography-tandem-mass-spectrometry (LC MS/MS) kit, revealing age and sex as major determinants of steroid levels while highlighting limitations in sensitivity for certain compounds, thereby providing valuable insights for interpreting steroid profiles in routine laboratory analyses. [Read the Full Post]

Pharmacological Modulation of the Ca2+/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction

47 views | Dec 18 2023

The study demonstrates that blocking L-type Ca2+ channels attenuates cardiac arrhythmias induced by acute myocardial infarction, implicating the Ca2+/cAMP/adenosine signaling pathway as a promising therapeutic target to reduce severe and fatal arrhythmias in humans. [Read the Full Post]

Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion

50 views | Dec 18 2023

Pseudolycorine chloride (PLY), a constituent of Narcissus tazetta L. var. Chinensis Roem, demonstrates immunomodulatory effects by inhibiting myeloid-derived suppressor cells (MDSCs) and Th17 cell-mediated inflammation, making it a promising candidate for the treatment of multiple sclerosis and other autoimmune diseases. [Read the Full Post]

Thioredoxin domain-containing protein 12 (TXNDC12) in red spotted grouper (Epinephelus akaara): Molecular characteristics, disulfide reductase activities, and immune responses

21 views | Dec 18 2023

The study on the thioredoxin domain-containing protein 12 (EaTXNDC12) in red spotted grouper reveals its crucial role in cellular redox homeostasis, immune regulation, and antioxidant activities, providing valuable insights into the molecular mechanisms governing these processes in fish species. [Read the Full Post]

Enhancing reporting quality and impact of early phase dose-finding clinical trials: CONSORT Dose-finding Extension (CONSORT-DEFINE) guidance

41 views | Dec 18 2023

CONSORT-DEFINE provides international, consensus-driven guidelines for reporting early phase dose-finding trials, emphasizing essential items to enhance transparency, completeness, and reproducibility, thereby promoting clear interpretation and informed decision-making in medical research and practice. [Read the Full Post]

GRP78 acts as a cAMP/PKA signaling modulator through the MC4R pathway in porcine embryonic development

63 views | Dec 17 2023

In this study, inhibiting Glucose-regulated protein 78 (GRP78) function using HA15 during porcine embryonic development disrupted the MC4R pathway, downregulated cAMP/PKA signaling, inhibited cell cycle progression, and induced mitochondrial dysfunction, revealing the crucial role of GRP78 in regulating these processes. [Read the Full Post]

miR-6071 inhibits hepatocellular carcinoma progression via targeting PTPN11

34 views | Dec 17 2023

The study reveals that miR-6071 functions as a crucial regulator by targeting PTPN11, inhibiting liver cancer stem cells' self-renewal and tumorigenesis, and sensitizing hepatocellular carcinoma cells to lenvatinib treatment, making it a potential therapeutic target and predictive biomarker for postoperative lenvatinib therapy. [Read the Full Post]

Drug repurposing and structure-based discovery of new PDE4 and PDE5 inhibitors

47 views | Dec 17 2023

The study utilized high-throughput drug repurposing screening and structure-based drug design to identify novel PDE4 inhibitors, leading to the unexpected discovery of a dual PDE4/PDE5 inhibitor (CVT-313) and the subsequent development of a highly selective PDE5 inhibitor (compound 2), exemplifying the efficiency of this integrated approach in drug discovery. [Read the Full Post]

Claudin-3 facilitates the progression and mediates the tumorigenic effects of TGF-β in glioblastoma multiforme

46 views | Dec 17 2023

The study demonstrates that upregulated Claudin-3 in glioblastoma multiforme stimulates tumor cell growth, promotes epithelial-mesenchymal transition, and enhances the tumorigenic effects of transforming growth factor-β, suggesting that specific inhibitors targeting Claudin-3 could represent a promising approach for treating this aggressive brain tumor. [Read the Full Post]

Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function

0 views | Dec 17 2023

The study shows that small molecule tyrosine kinase inhibitors targeting Syk and BTK effectively inhibit essential platelet functions, such as adhesion, secretion, and aggregation, but exhibit differential effects on downstream signaling pathways and protein activities in platelets. [Read the Full Post]

Rac and Cdc42 inhibitors reduce macrophage function in breast cancer preclinical models

22 views | Dec 16 2023

Rac and Cdc42 inhibitors EHop-016 and MBQ-167 demonstrate dual efficacy by simultaneously targeting metastatic cancer cells and immunosuppressive myeloid cells in the tumor microenvironment, creating an anti-tumor environment in breast cancer. [Read the Full Post]

5-HT6 receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines

71 views | Dec 16 2023

The study presents a novel series of 6-piperazinyl-7-azaindoles demonstrating potent 5-HT6 receptor antagonism, with a focus on optimizing the lead structure and exploring structure-activity relationships, highlighting Compound 29 as a promising candidate for further drug development. [Read the Full Post]

Simufilam Reverses Aberrant Receptor Interactions of Filamin A in Alzheimer's Disease

38 views | Dec 16 2023

Simufilam disrupts aberrant FLNA-receptor interactions in Alzheimer's disease, preventing Aβ42 signaling, tau hyperphosphorylation, and inflammatory responses, thereby promoting brain health and potentially offering a promising treatment approach for the condition. [Read the Full Post]

Dual action of serotonin on local excitatory and inhibitory neural circuits regulating the corticotropin-releasing factor neurons in the paraventricular nucleus of the hypothalamus

21 views | Dec 16 2023

Serotonin modulates corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus by upregulating glutamatergic interneurons via 5-HT7 receptors and downregulating GABAergic interneurons via 5-HT2C receptors, as demonstrated in an electrophysiological study using the CRF-modified yellow fluorescent protein (Venus) ΔNeo mouse model. [Read the Full Post]

Prospects of Topoisomerase Inhibitors as Promising Anti-Cancer Agents

52 views | Dec 16 2023

The review underscores the significance of topoisomerase inhibitors, such as irinotecan and etoposide, in cancer treatment by disrupting DNA replication and inducing cell death, emphasizing their potential as crucial anti-cancer medications. [Read the Full Post]

An overview of the past decade of bufalin in the treatment of refractory and drug-resistant cancers: current status, challenges, and future perspectives

34 views | Dec 15 2023

The research on bufalin, a compound found in toad venom, demonstrates significant potential in overcoming drug resistance in cancer cells through its diverse mechanisms of action, chemo-sensitizing properties, derivative development, and proactive consideration of obstacles, emphasizing the need for further in-depth studies and clinical trials. [Read the Full Post]

Combined inhibition of FGFR4 and VEGFR signaling enhances efficacy in FGF19 driven hepatocellular carcinoma

21 views | Dec 15 2023

The combination of Lenvatinib, a multi-kinase inhibitor, and FGFR4 inhibitor H3B-6527 demonstrates enhanced efficacy in treating FGF19-driven hepatocellular carcinoma by leveraging Lenvatinib's cell non-autonomous VEGFR activity, indicating a promising potential for clinical application. [Read the Full Post]

Aberrant PI3Kδ splice isoform as a potential biomarker and novel therapeutic target for endocrine cancers

37 views | Dec 15 2023

**Utilizing PI3Kδ-S as a Prognostic Biomarker and Therapeutic Target Offers a Promising Strategy for Advanced Endocrine Cancers.** [Read the Full Post]

Open-Label, Multicenter, Randomized, Biomarker-Integrated Umbrella Trial for Second-Line Treatment of Advanced Gastric Cancer: K-Umbrella Gastric Cancer Study

26 views | Dec 15 2023

This controlled umbrella trial demonstrated the feasibility of IHC-based screening for druggable targets in HER2-negative advanced gastric cancer, with targeted agents in the biomarker group showing mixed efficacy, indicating the potential for early screening of novel therapies in specific subgroups. [Read the Full Post]

Therapeutical interference with the epigenetic landscape of germ cell tumors: a comparative drug study and new mechanistical insights

49 views | Dec 15 2023

The study identified seven epigenetic inhibitors that efficiently decreased cell viability in cisplatin-resistant Type II germ cell tumors, highlighting their potential as alternative therapeutic options, and provided comprehensive insights into their off-target effects and modes of action. [Read the Full Post]