Blog of Signaling Pathways

Health Status, Quality of Life, Psychosocial Well-being, and Wearables Data of Patients With Active Ulcerative Colitis Receiving Filgotinib Therapy (FilgoColitis Study): Protocol for a Real-world Observational Study

68 views | Jun 18 2023

The FilgoColitis study is a prospective observational study evaluating the long-term effectiveness of filgotinib in patients with active ulcerative colitis, focusing on patient-reported outcomes and incorporating the use of innovative wearables to collect physical activity data. [Read the Full Post]

Efficacy and safety of selective JAK 1 inhibitor filgotinib in active rheumatoid arthritis patients with inadequate response to methotrexate: comparative study with filgotinib and tocilizumab examined by clinical index as well as musculoskeletal ultrasound assessment (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial

42 views | Jun 18 2023

This interventional clinical trial aims to compare the effectiveness of filgotinib monotherapy to tocilizumab monotherapy in rheumatoid arthritis patients with an inadequate response to methotrexate, utilizing clinical disease activity indices, musculoskeletal ultrasound, and serum biomarkers as evaluation parameters. [Read the Full Post]

HDAC4 mediated LHPP deacetylation enhances its destabilization and promotes the proliferation and metastasis of nasopharyngeal carcinoma

95 views | Jun 18 2023

The study reveals that the HDAC4/LHPP signaling axis promotes the proliferation and metastasis of nasopharyngeal carcinoma through upregulation of TYK2-STAT1 phosphorylation activation, providing new insights and potential intervention targets for NPC metastasis. [Read the Full Post]

Targeting the undruggable: menin inhibitors ante portas

45 views | Jun 18 2023

The menin-MLL axis inhibitors show promise as targeted therapies for acute myeloid leukemias with MLL rearrangements and NPM1 mutations, with early clinical data demonstrating favorable response rates and potential for improved outcomes. [Read the Full Post]

A Non-Canonical Role for the Glycosyltransferase Enzyme UGT2B17 as a Novel Constituent of the B Cell Receptor Signalosome

48 views | Jun 18 2023

Elevated expression of glycosyltransferase UGT2B17 in chronic lymphocytic leukemia (CLL) is associated with poor survival, enhanced BCR pathway signaling, and increased phosphorylation of Bruton tyrosine kinase (BTK), highlighting its potential as an oncogenic factor and therapeutic target. [Read the Full Post]

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

0 views | Jun 17 2023

This study identified potential lead compounds, including natural-product-derived compounds and approved drugs, that have the potential to be developed as anti-Ebola drugs, pending further experimental testing. [Read the Full Post]

GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer

83 views | Jun 17 2023

The study demonstrates the potential of hyaluronic acid-decorated metal-organic frameworks delivering the JMJD3 demethylase inhibitor GSK-J1 (HA@MOF@GSK-J1) as an effective and targeted strategy for treating carboplatin-resistant ovarian cancer. [Read the Full Post]

Astrocytic c-Jun N-terminal kinase-histone deacetylase-2 cascade contributes to glutamate transporter-1 decrease and mechanical allodynia following peripheral nerve injury in rats

29 views | Jun 17 2023

The decrease of glutamate transporter-1 (GLT-1) and upregulation of histone deacetylase 2 (HDAC2) in spinal astrocytes, mediated by the JNK-HDAC2 cascade and neuroimmune activation, contribute to enhanced excitatory transmission and the development of persistent pain following peripheral nerve injury. [Read the Full Post]

Porcine Deltacoronavirus Infection Cleaves HDAC2 to Attenuate Its Antiviral Activity

56 views | Jun 17 2023

The study revealed that porcine deltacoronavirus (PDCoV) infection inhibits cellular histone deacetylase 2 (HDAC2) activity through cleavage by the viral nonstructural protein 5 (nsp5), highlighting a common strategy employed by mammalian coronaviruses to counteract the antiviral role of HDAC2 and providing potential targets for the development of antiviral drugs. [Read the Full Post]

Abrogation of Cellular Senescence Induced by Temozolomide in Glioblastoma Cells: Search for Senolytics

89 views | Jun 17 2023

Targeting senescent cells with senolytic drugs, such as ABT-737, navitoclax, chloroquine, ATMi, ATRi, BV-6, PX-866, fisetin, and artesunate, may improve the outcome of glioblastoma therapy by preventing recurrences and reducing tumor inflammation. [Read the Full Post]

Inhibition of histone methyltransferase SETD8 represses DNA virus replication

37 views | Jun 16 2023

UNC0379, an inhibitor of histone H4K20 methyltransferase SETD8, shows promise as an effective inhibitor of multiple DNA viruses by enhancing the expression of anti-viral genes and repressing viral replication, potentially offering a new strategy for the treatment of DNA virus-related diseases. [Read the Full Post]

Episodes of Early Pleistocene West Antarctic Ice Sheet Retreat Recorded by Iceberg Alley Sediments

36 views | Jun 16 2023

This study in the Scotia Sea provides evidence of past episodes of West Antarctic Ice Sheet instability and suggests that intense IBRD deposition, likely sourced from the Weddell Sea and/or Amundsen Sea embayment(s), occurred during a warm climate phase approximately 1.2 million years ago. [Read the Full Post]

Comparison of pharmacological inhibitors of lysine-specific demethylase 1 in glioblastoma stem cells reveals inhibitor-specific efficacy profiles

82 views | Jun 16 2023

This study demonstrates the cytotoxic effects of LSD1 inhibitors in patient-derived glioblastoma models and identifies potential resistance-associated genes, providing valuable insights for the development of future combination therapies. [Read the Full Post]

SIRT2 inhibition by AGK2 enhances mycobacteria-specific stem cell memory responses by modulating beta-catenin and glycolysis

55 views | Jun 16 2023

This study demonstrates that inhibiting SIRT2 during BCG vaccination enhances the immune response, particularly the generation of stem cell memory T cells, and suggests SIRT2 inhibitors as potential immunoprophylaxis against tuberculosis. [Read the Full Post]

Wolbachia Ferrochelatase as a potential drug target against filarial infections

99 views | Jun 16 2023

Targeting the ferrochelatase enzyme in Wolbachia's heme biosynthetic pathway presents a potential therapeutic strategy for filarial infections, leading to the discovery of four promising drug candidates that can inhibit the worms' growth and survival. [Read the Full Post]

Erk1/2-Dependent HNSCC Cell Susceptibility to Erastin-Induced Ferroptosis

51 views | Jun 15 2023

The study demonstrated that erastin-induced ferroptosis in HNSCC cells is dependent on the expression of Erk1/2, suggesting that Erk1/2 activation can serve as a predictor for the response of HNSCC cells to erastin treatment, thereby highlighting its potential as a therapeutic strategy for HNSCC. [Read the Full Post]

The HDAC inhibitor domatinostat induces type I interferon α in Merkel cell carcinoma by HES1 repression

112 views | Jun 15 2023

The study revealed that the anti-tumor effect of the HDAC inhibitor domatinostat on Merkel cell carcinoma cells is mediated through the suppression of HES1, allowing for the induction of IFNα and subsequent apoptosis. [Read the Full Post]

Triplet Therapy in Metastatic Castrate Sensitive Prostate Cancer (mCSPC)-A Potential New Standard of Care

26 views | Jun 15 2023

This article reviews the phase-three data on triplet therapy for metastatic castrate-sensitive prostate cancer (mCSPC), addresses knowledge gaps, discusses implementation challenges, and proposes a treatment selection algorithm for clinicians. [Read the Full Post]

Personalizing approaches to the management of metastatic hormone sensitive prostate cancer: role of advanced imaging, genetics and therapeutics

24 views | Jun 15 2023

Advancements in the diagnosis and management of metastatic hormone-sensitive prostate cancer (mHSPC), including improved imaging techniques, germline multigene testing, and the integration of multiple agents, have significantly enhanced patient care and outcomes in the last decade. [Read the Full Post]

A comparative analysis to determine the optimum histone deacetylase inhibitors and administration route for improving survival and organ injury in rats after hemorrhagic shock

58 views | Jun 15 2023

The study found that intravenous administration of nonselective and isoform-specific HDACIs, including MS-275, LMK-235, tubastatin A, and TSA, was superior to intraperitoneal administration in improving survival rates and reducing histopathological scores, apoptosis cell numbers, and inflammatory cytokine levels in rats with hemorrhagic shock. [Read the Full Post]