Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy.

Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy. One-third of patients have drug-refractory seizures and are left with suboptimal therapeutic options such as brain tissue-destructive surgery. Here, we report the development and characterization of a cell therapy alternative for drug-resistant MTLE, which is derived from a human embryonic stem cell line and comprises cryopreserved, post-mitotic, medial ganglionic eminence (MGE) pallial-type GABAergic interneurons.

Old drugs, new tricks: leveraging known compounds to disrupt coronavirus-induced cytokine storm.

A major complication in COVID-19 infection consists in the onset of acute respiratory distress fueled by a dysregulation of the host immune network that leads to a run-away cytokine storm. Here, we present an in silico approach that captures the host immune system's complex regulatory dynamics, allowing us to identify and rank candidate drugs and drug pairs that engage with minimal subsets of immune mediators such that their downstream interactions effectively disrupt the signaling cascades driving cytokine storm. Drug-target regulatory interactions are extracted from peer-reviewed literature using automated text-mining for over 5000 compounds associated with COVID-induced cytokine storm and elements of the underlying biology.

COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources.

Analysis of Signaling Activity in Psoriasis.

In our previous work, we built the model of dependent pathways involved in the development of the psoriatic lesions. Peroxisome proliferator-activated receptor gamma () is a nuclear receptor and transcription factor which regulates the expression of many proinflammatory genes. We tested the hypothesis that low levels of expression promote the development of psoriatic lesions triggering the -related signaling cascade.

The Model of -Downregulated Signaling in Psoriasis.

Interactions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma () is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of expression promote the development of psoriatic lesions.

Apatinib Mesylate in the treatment of advanced progressed lung adenocarcinoma patients with EGFR-TKI resistance -A Multicenter Randomized Trial.

Few pieces of evidence have been published on the use of Apatinib Mesylate (AM) against EGFR-TKI resistance in lung adenocarcinoma (LA) patients. Here, we investigate the clinical efficacy and safety of AM in the treatment of advanced progressed epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) resistant LA patients. We conducted a double-blind, randomized controlled trial in 68 patients admitted to 18 hospitals of Anhui province in China.

Empowerment of 15-Lipoxygenase Catalytic Competence in Selective Oxidation of Membrane ETE-PE to Ferroptotic Death Signals, HpETE-PE.

sn2-15-Hydroperoxy-eicasotetraenoyl-phosphatidylethanolamines ( sn2-15-HpETE-PE) generated by mammalian 15-lipoxygenase/phosphatidylethanolamine binding protein-1 (15-LO/PEBP1) complex is a death signal in a recently identified type of programmed cell demise, ferroptosis. How the enzymatic complex selects sn2-ETE-PE as the substrate among 1 of ∼100 total oxidizable membrane PUFA phospholipids is a central, yet unresolved question. To unearth the highly selective and specific mechanisms of catalytic competence, we used a combination of redox lipidomics, mutational and computational structural analysis to show they stem from (i) reactivity toward readily accessible hexagonally organized membrane sn2-ETE-PEs, (ii) relative preponderance of sn2-ETE-PE species vs other sn2-ETE-PLs, and (iii) allosteric modification of the enzyme in the complex with PEBP1.

Hair follicle morphogenesis and epidermal homeostasis in we/we wal/wal mice with postnatal alopecia.

Mice with skin and hair follicle (HF) defects are common models of human skin disorders. A mutant strain with the we/we wal/wal genotype develops alopecia. We found the hair shaft structure in the pelage of mutant mice to have significant defects.