Gut microbiota dysbiosis-mediated ceramides elevation contributes to corticosterone-induced depression by impairing mitochondrial function.

The role of gut microbiota (GM) dysbiosis in the pathogenesis of depression has received widespread attention, but the mechanism remains elusive. Corticosterone (CORT)-treated mice showed depression-like behaviors, reduced hippocampal neurogenesis, and altered composition of the GM. Fecal microbial transplantation from CORT-treated mice transferred depression-like phenotypes and their dominant GM to the recipients.

Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system.

Background: The detailed transcriptomic profiles during human serotonin neuron (SN) differentiation remain elusive. The establishment of a reporter system based on SN terminal selector holds promise to produce highly-purified cells with an early serotonergic fate and help elucidate the molecular events during human SN development process.

Methods: A fifth Ewing variant (FEV)-EGFP reporter system was established by CRISPR/Cas9 technology to indicate SN since postmitotic stage.

Corticosterone Impairs Hippocampal Neurogenesis and Behaviors through -Mediated ROS Accumulation.

Stress is known to induce a reduction in adult hippocampal neurogenesis (AHN) and anxiety-like behaviors. Glucocorticoids (GCs) are secreted in response to stress, and the hippocampus possesses the greatest levels of GC receptors, highlighting the potential of GCs in mediating stress-induced hippocampal alterations and behavior deficits. Herein, RNA-sequencing (RNA-seq) analysis of the hippocampus following corticosterone (CORT) exposure revealed the central regulatory role of the gene, which exhibited interactions with oxidative stress-related differentially expressed genes (DEGs), suggesting a potential link between and oxidative stress-related pathways.

A Novel Dextran-Based Dual Drug Conjugate Targeted Tumors with High Biodistribution Ratio of Tumors to Normal Tissues.

Purpose: Most chemotherapeutic agents possess poor water solubility and show more significant accumulations in normal tissues than in tumor tissues, resulting in serious side effects. To this end, a novel dextran-based dual drug delivery system with high biodistribution ratio of tumors to normal tissues was developed.

Methods: A bi-functionalized dextran was developed, and several negatively charged dextran-based dual conjugates containing two different types of drugs, docetaxel and docosahexaenoic acid (DTX and DHA, respectively) were synthesized.

The enhanced antitumor activity of the polymeric conjugate covalently coupled with docetaxel and docosahexaenoic acid.

Docetaxel (DTX) has been widely used for the treatment of many types of cancer. However, DTX is poorly water-soluble and commercial DTX is formulated in non-ionic surfactant polysorbate 80 and ethanol, thereby leading to hypersensitivity and serious side effects. Herein, a polymer dual drug conjugate was synthesized by coupling DTX and docosahexaenoic acid (DHA) with bifunctionalized dextran.

Cisplatin enhances protein ‑GlcNAcylation by altering the activity of OGT, OGA and AMPK in human non‑small cell lung cancer cells.

‑GlcNAcylation is a dynamic and reversible post‑translational modification of proteins that is modulated by ‑GlcNAc transferase (OGT) and ‑GlcNAcase (OGA). Alterations in the protein expression of ‑linked β‑‑acetylglucosamine (‑GlcNAc) can be induced by multiple factors. However, little is known of the effects of chemotherapeutic agents on ‑GlcNAcylation and the relevant molecular mechanisms in cancer cells.