Blog of Signaling Pathways

Necrostatin-1 attenuates delayed paraplegia after transient spinal cord ischemia in rabbits by inhibiting the upregulation of receptor-interacting protein kinase 1 and 3

105 views | Aug 17 2023

Nec-1, a necroptosis inhibitor, effectively reduces delayed motor neuron death and mitigates delayed paraplegia following transient spinal cord ischemia in rabbits, primarily by selectively inhibiting necroptosis while minimally affecting apoptosis. [Read the Full Post]

Preclinical investigations of the efficacy of the glutaminase inhibitor CB-839 alone and in combinations in chronic lymphocytic leukemia

47 views | Aug 17 2023

The study findings indicate that CB-839, a GLS-1 inhibitor, has limited efficacy as a standalone treatment for CLL and shows limited synergy when combined with commonly used CLL drugs. [Read the Full Post]

Development of a colloidal gold immunochromatographic strip with enhanced signal for the detection of bovine parvovirus

53 views | Aug 17 2023

The study successfully developed a signal-enhanced GICG strip with high sensitivity and specificity for detecting Bovine Parvovirus (BPV), making it a promising rapid and convenient diagnostic tool for BPV infection in the field. [Read the Full Post]

The Host Protein CAD Regulates the Replication of FMDV through the Function of Pyrimidines' De Novo Synthesis

81 views | Aug 17 2023

This study elucidates the role of HDAC1 and the AKT-mTOR signaling pathway in promoting FMDV replication, while also highlighting the importance of the CAD ACTase domain and de novo pyrimidine synthesis, providing potential targets for the development of drugs against Foot-and-mouth disease virus. [Read the Full Post]

Nicotinamide ameliorates mitochondria-related neuronal apoptosis and cognitive impairment via the NAD+/SIRT3 pathway

57 views | Aug 16 2023

Nicotinamide (NAM) can alleviate neuronal apoptosis and microglial over-activation in a rat model of schizophrenia by modulating the NAD+-SIRT3-SOD2 signaling pathway, indicating its potential as a novel treatment approach for the disorder. [Read the Full Post]

Switch type I to type II TRK inhibitors for combating clinical resistance induced by xDFG mutation for cancer therapy

73 views | Aug 16 2023

Compound 12d demonstrated potent inhibitory activity against various TRK fusion proteins, including those associated with acquired resistance to first-generation inhibitors, suggesting its potential as a lead compound for the treatment of TRK-driven cancers. [Read the Full Post]

BDNF and its signaling in cancer

0 views | Aug 16 2023

BDNF signaling plays a significant role in cancer progression, and targeted therapies aimed at inhibiting BDNF and its associated pathways hold promise as potential therapeutic approaches. [Read the Full Post]

Involvement of a flavoprotein, acetohydroxyacid synthase, in growth and riboflavin production in riboflavin-overproducing Ashbya gossypii mutant

82 views | Aug 16 2023

This study demonstrates that branched-chain amino acids, particularly through the regulation of acetohydroxyacid synthase, play a crucial role in enhancing riboflavin production in the Ashbya gossypii mutant strain, offering a novel approach for optimizing riboflavin production in this organism. [Read the Full Post]

Reparixin improves survival in critically ill and transplant patients: A meta-analysis

45 views | Aug 16 2023

Reparixin, an anti-inflammatory drug inhibiting interleukin 8 (IL-8) activity, was found to improve survival in critically ill or transplant patients, including both COVID-19 and non-COVID-19 patients, without increasing the risk of infection, according to a meta-analysis of nine randomized controlled trials. [Read the Full Post]

Dichloroacetic acid and rapamycin synergistically inhibit tumor progression

113 views | Aug 15 2023

Rapamycin treatment leads to the inactivation of the pyruvate dehydrogenase complex (PDHc) through mTOR signaling inhibition, reducing cancer cells' response to rapamycin, while reactivating PDHc with dichloroacetic acid (DCA) enhances their susceptibility to rapamycin treatment. [Read the Full Post]

Recombinant Treponema pallidum Protein Tp47 Promoted the Phagocytosis of Macrophages by Activating NLRP3 Inflammasome Induced by PKM2-Dependent Glycolysis

24 views | Aug 15 2023

Tp47-induced activation of glycolysis and the NLRP3 inflammasome in macrophages promotes phagocytosis, with the upregulation of the M2 isoform of pyruvate kinase (PKM2) playing a crucial role in glycolysis-dependent NLRP3 activation. [Read the Full Post]

Hybrid Analogues of Hydrazone and Phthalimide: Design, Synthesis, In vivo, In vitro, and In silico Evaluation as Analgesic Agents

91 views | Aug 15 2023

A new series of hybrid hydrazone and phthalimide compounds were synthesized and evaluated, showing significant analgesic activity, selective COX-2 inhibition, and favorable cytostatic properties with a high therapeutic index. [Read the Full Post]

Pharmacological inhibition of serine synthesis enhances temozolomide efficacy by decreasing O6-methylguanine DNA methyltransferase (MGMT) expression and reactive oxygen species (ROS)-mediated DNA damage in glioblastoma

14 views | Aug 15 2023

The study found that the selective inhibitor NCT503, when combined with temozolomide (TMZ), demonstrated synergistic effects in inhibiting glioblastoma cell growth and inducing apoptosis, potentially offering a promising treatment strategy for MGMT-high glioblastoma patients. [Read the Full Post]

JNJ-64619178 radiosensitizes and suppresses fractionated ionizing radiation-induced neuroendocrine differentiation (NED) in prostate cancer

60 views | Aug 15 2023

The study demonstrates that JNJ-64619178 inhibits DNA damage repair, radiosensitizes prostate cancer cells, and suppresses FIR-induced neuroendocrine differentiation, suggesting its potential as a therapeutic agent for enhancing the effectiveness of radiation therapy in prostate cancer treatment. [Read the Full Post]

Development of an autophagy activator from Class III PI3K complexes, Tat-BECN1 peptide: Mechanisms and applications

49 views | Aug 14 2023

Tat-BECN1 peptide, derived from Beclin 1 subunit of Class III PI3K complexes, shows promise as a specific autophagy activator and has demonstrated potential therapeutic applications in various physiological and pathological models, although further research is required for clinical translation. [Read the Full Post]

Pharmacological Inventions for Alzheimer Treatment in the United States of America: A Revision Patent from 2010 - 2020

28 views | Aug 14 2023

The study analyzed pharmacological treatments for Alzheimer's disease protected in the US Patent Office, revealing a focus on targeting Aβ accumulation and the need for further research to establish the efficacy of the patented molecules. [Read the Full Post]

In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part III

99 views | Aug 14 2023

The study utilized PBPK/PD modeling and virtual clinical trial simulations to evaluate the potential efficacy of the siremadlin and trametinib combination as a therapy for melanoma, based on in vitro studies and in vivo extrapolation. [Read the Full Post]

Co-Targeting of MDM2 and CDK4/6 with Siremadlin and Ribociclib for the Treatment of Patients with Well-Differentiated or Dedifferentiated Liposarcoma: Results from a Proof-of-Concept, Phase Ib Study

85 views | Aug 14 2023

The combination of siremadlin and ribociclib showed manageable toxicity and early signs of antitumor activity in patients with advanced well-differentiated or dedifferentiated liposarcoma. [Read the Full Post]

Microneedle-assisted vaccination combined with autophagy regulation for antitumor immunotherapy

67 views | Aug 14 2023

The whole cell-encapsulated antitumor vaccine microneedle patch (TCV-DMNs) combined with transdermal co-delivery of GM-CSF and Tat-beclin 1 promotes effective antigen delivery, enhances dendritic cell activation and antigen presentation through autophagy regulation, resulting in a robust antitumor immune response and extended survival. [Read the Full Post]

ACSS2-mediated NF-κB activation promotes alkaliptosis in human pancreatic cancer cells

81 views | Aug 13 2023

ACSS2, an enzyme involved in acetyl-coenzyme A production and histone acetylation, has been identified as a positive regulator of alkaliptosis in human pancreatic ductal adenocarcinoma cells, potentially offering new therapeutic strategies for PDAC treatment. [Read the Full Post]