Correction to 1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549).

[This corrects the article DOI: 10.1021/acsomega.2c03325.].

Abnormalities in the migration of neural precursor cells in familial bipolar disorder.

Cellular migration is a ubiquitous feature that brings brain cells into appropriate spatial relationships over time; and it helps in the formation of a functional brain. We studied the migration patterns of induced pluripotent stem cell-derived neural precursor cells (NPCs) from individuals with familial bipolar disorder (BD) in comparison with healthy controls. The BD patients also had morphological brain abnormalities evident on magnetic resonance imaging. Time-lapse analysis of migrating cells was performed, through which we were able to identify several parameters that were abnormal in cellular migration, including the speed and directionality of NPCs. We also performed transcriptomic analysis to probe the mechanisms behind the aberrant cellular phenotype identified. Our analysis showed the downregulation of a network of genes, centering on EGF/ERBB proteins. The present findings indicate that collective, systemic dysregulation may produce the aberrant cellular phenotype, which could contribute to the functional and structural changes in the brain reported for bipolar disorder. This article has an associated First Person interview with the first author of the paper.

1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549).

A series of novel 1,2,3-triazole derivatives of capsaicin and its structural isomer (new natural product hybrid capsaicinoid) were synthesized by exploiting one-/two-point modification of capsaicin without altering the amide linkage (neck). The newly synthesized compounds were screened for their antiproliferative activity against an NCI panel of 60 cancer cell lines at a single dose of 10 µM. Most of the compounds have demonstrated reduced growth between 55 and 95%, whereas capsaicin (10) has shown reduced growth between 0 and 24%. Compounds showing more than 50% growth inhibition were further evaluated for the IC50 value. Among the cell lines tested, lung cancer cell lines (A549, NCI-H460) were found to be more susceptible toward most of the synthesized compounds. Compounds 14g and 14j demonstrated good antiproliferative activity in NCI-H460 with IC50 values of 6.65 and 5.55 µM, respectively, while compounds 18b, 18c, 18f, and 18m demonstrated potential antiproliferative activity in A549 cell lines with IC50 values ranging between 2.9 and 10.5 µM. Among the compounds, compound 18f was found to demonstrate the best activity with an IC50 value of 2.91 µM against A549. Furthermore, 18f induces cell cycle arrest at the S-phase and disrupts the mitochondrial membrane potential, reducing cell migration potential by inducing cellular apoptosis and higher ROS generation along with a decrease in mitochondrial membrane potential in addition to surface and nuclear morphological alterations such as a reduction in the number and shrinkage of cells coupled with nuclear blabbing indicating the sign of apoptosis of A549 non-small cell lung cancer cell lines. Compound 18f has emerged as a lead molecule and may serve as a template for further discovery of capsaicinoid scaffolds.

Role of Platelet Cytokines in Dengue Virus Infection.

Platelets are anucleated blood cells derived from bone marrow megakaryocytes and play a crucial role in hemostasis and thrombosis. Platelets contain specialized storage organelles, called alpha-granules, contents of which are rich in cytokines such as C-X-C Motif Chemokine Ligand (CXCL) 1/4/7, (C-C motif) ligand (CCL) 5/3, CXCL8 (also called as interleukin 8, IL-8), and transforming growth factor ß (TGF-ß). Activation of platelets lead to degranulation and release of contents into the plasma. Platelet activation is a common event in many viral infections including human immunodeficiency virus (HIV), H1N1 influenza, Hepatitis C virus (HCV), Ebola virus (EBV), and Dengue virus (DENV). The cytokines CXCL8, CCL5 (also known as Regulated on Activation, Normal T Expressed and Secreted, RANTES), tumor necrosis factor α (TNF-α), CXCL1/5 and CCL3 released, promote development of a pro-inflammatory state along with the recruitment of other immune cells to the site of infection. Platelets also interact with Monocytes and Neutrophils and facilitate their activation to release different cytokines which further enhances inflammation. Upon activation, platelets also secrete factors such as CXCL4 (also known as platelet factor, PF4), CCL5 and fibrinopeptides which are critical regulators of replication and propagation of several viruses in the host. Studies suggest that CXCL4 can both inhibit as well as enhance HIV1 infection. Data from our lab show that CXCL4 inhibits interferon (IFN) pathway and promotes DENV replication in monocytes in vitro and in patients significantly. Inhibition of CXCL4 mediated signaling results in increased IFN production and suppressed DENV and JEV replication in monocytes. In this review, we discuss the role of platelets in viral disease progression with a focus on dengue infection.