Blog of Signaling Pathways

Radiation induces IRAK1 expression to promote radioresistance by suppressing autophagic cell death via decreasing the ubiquitination of PRDX1 in glioma cells

96 views | Jun 06 2023

The study found that overexpression of IRAK1 in glioma patients is associated with a poor prognosis, and that IRAK1 knockdown inhibits malignancy and enhances radiosensitivity by targeting the IRAK1-PRDX1 axis. [Read the Full Post]

Characterization of a Novel Milk-Clotting Aspartic Protease from Penicillium sp. and Structural Explanation for its High Milk-Clotting Index

82 views | Jun 06 2023

PsMCE is a novel milk-clotting enzyme with specific hydrolysis activity on κ-casein proteins and potential applications in cheese making due to its thermolability and high milk-clotting index value. [Read the Full Post]

Potential drug discovery for COVID-19 treatment targeting Cathepsin L using a deep learning-based strategy

16 views | Jun 06 2023

The study suggests that CTSL could be a promising therapeutic target for COVID-19, and the researchers used Chemprop to identify small molecules and FDA-approved drugs that can block CTSL activity, finding five molecules and drugs that can inhibit the activity of CTSL and inhibit the infection of both pseudotype and live SARS-CoV-2, including daptomycin. [Read the Full Post]

Protective Effect of Calpain Inhibition During Cold Ischemia on Ischemia-reperfusion Injury After Lung Transplantation

28 views | Jun 06 2023

The study showed that the administration of ALLN during cold ischemia improves IR lung injury in a lung transplant animal model by suppressing necroptosis. [Read the Full Post]

Canine distemper virus N protein induces autophagy to facilitate viral replication

63 views | Jun 06 2023

This study revealed that CDV N protein induces complete autophagy to facilitate viral replication, providing new insights into the interaction between CDV and the host autophagy machinery. [Read the Full Post]

Vascular lipid droplets formed in response to TNF, hypoxia, or OA: biochemical composition and prostacyclin generation

95 views | Jun 05 2023

The study investigates the role of lipid droplets (LDs) and adipose triglyceride lipase (ATGL)-dependent prostacyclin (PGI2) generation in the response of endothelial cells to proinflammatory stimuli, demonstrating that LDs formation and ATGL-mediated PGI2 generation represent a universal response to vascular proinflammatory insult. [Read the Full Post]

AdipoRon Engages Microglia to Antinociception through the AdipoR1/AMPK Pathway in SNI Mice

103 views | Jun 05 2023

AdipoRon may alleviate neuropathic pain by inhibiting microglia-derived TNF-α expression through the AdipoR1/AMPK pathway. [Read the Full Post]

Alpha-tocopherol enhances spermatogonial stem cell proliferation and restores mouse spermatogenesis by up-regulating BMI1

68 views | Jun 05 2023

This study investigates the role of BMI1 in spermatogonial stem cell proliferation and male reproduction, and demonstrates the potential modulatory effect of alpha-tocopherol on BMI1 both in vitro and in vivo. [Read the Full Post]

Identification of Embryonic Chicken Proteases Activating Newcastle Disease Virus and Their Roles in the Pathogenicity of Virus Used as In Ovo Vaccine

28 views | Jun 05 2023

The study identified five trypsin-like proteases that activate NDV in chicken embryos and found that the F protein with a 3B-FCS was crucial for the attenuation of NDV, providing a potential target for the rational design of safe in ovo ND vaccines. [Read the Full Post]

Phytochemical characterization, antioxidant activity and antihypertensive evaluation of Ocimum basilicum L. in l-NAME induced hypertensive rats and its correlation analysis

95 views | Jun 05 2023

The study found that Ocimum basilicum Linn. leaves extracts have potential as antihypertensive drugs due to their bioactive metabolites, with phenolic compounds playing a role in inhibiting l-Name induced hypertension and flavonoids contributing to antioxidant activities. [Read the Full Post]

The Class IIA Histone Deacetylase (HDAC) Inhibitor TMP269 Downregulates Ribosomal Proteins and Has Anti-Proliferative and Pro-Apoptotic Effects on AML Cells

40 views | Jun 04 2023

The study found that HDAC genes are overexpressed in AML patients and cell lines, and that TMP269, a class IIA HDAC inhibitor, has anti-leukemic activity when combined with venetoclax and may be a potential therapeutic drug for AML. [Read the Full Post]

A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy

91 views | Jun 04 2023

The study demonstrates that covalent drugs that alkylate mutated residues on oncoproteins can generate unique MHC-I-restricted neoantigens, which can be targeted with a bispecific T cell engager construct to elicit a cytotoxic T cell response against cancer cells, including those resistant to direct inhibition. [Read the Full Post]

Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization

35 views | Jun 04 2023

The study suggests that targeting the EGFR T790M-cis-L792F/STAT3 Tyr705/IL-4 pathway could be a potential strategy to suppress osimertinib resistance in NSCLC. [Read the Full Post]

From PROTAC to inhibitor: Structure-guided discovery of potent and orally bioavailable BET inhibitors

110 views | Jun 04 2023

The passage describes the discovery of a potent BET inhibitor called 1q (SJ1461) through a CLICK chemistry-based approach, which shows improved profiles compared to existing BET inhibitors and has promising potential for further development as a cancer therapy. [Read the Full Post]

Inhibitor of Apoptosis Proteins Antagonist Induces T-cell Proliferation after Cross-Presentation by Dendritic Cells

42 views | Jun 04 2023

Researchers have identified AZD5582 as a compound that enhances dendritic cell cross-presentation of tumor antigens, leading to an increased frequency of systemic tumor antigen-specific CD8+ T cells, which could improve the clinical benefit of immune checkpoint blockade in patients who are unlikely to respond. [Read the Full Post]

Jmjd4 Facilitates Pkm2 Degradation in Cardiomyocytes and Is Protective Against Dilated Cardiomyopathy

64 views | Jun 03 2023

The study found that Jmjd4 plays a critical role in maintaining metabolic homeostasis in adult cardiomyocytes by degrading Pkm2 and its deficiency may lead to DCM, which suggests that targeting Jmjd4 and Pkm2 may be a potential therapeutic strategy for DCM and other cardiac diseases with metabolic dysfunction. [Read the Full Post]

PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism

34 views | Jun 03 2023

The authors proposed a "two-step approach" to target both PKM2 and PDK1 simultaneously, and designed a novel PKM2/PDK1 dual-target agent E5, which showed promising anti-tumor activity and restored the sensitivity of EGFR-TKIs resistant NSCLC cells to gefitinib. [Read the Full Post]

KDELC2 Upregulates Glioblastoma Angiogenesis via Reactive Oxygen Species Activation and Tumor-Associated Macrophage Proliferation

78 views | Jun 03 2023

This study demonstrates that KDELC2 promotes glioblastoma angiogenesis via the activation of multiple pathways, including NLRP3 inflammasome, autophagy, ER stress, and TAM polarization. [Read the Full Post]

NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors

124 views | Jun 03 2023

This study highlights the need for cautious evaluation and dosage optimization of inhibitors targeting respiratory complex I in cancer treatment. [Read the Full Post]

Smad7 Is Highly Expressed in Human Degenerative Discs and Participates in IL-1 β-Induced Apoptosis of Rat AF Cells via the Mitochondria Pathway

44 views | Jun 03 2023

Smad7 participates in IL-1β-induced apoptosis of rat annulus fibrosus cells via the mitochondria pathway and may be a potential target for the prevention and treatment of degenerative disc disease. [Read the Full Post]