Harnessing the AI/ML in Drug and Biological Products Discovery and Development: The Regulatory Perspective.

Artificial Intelligence (AI) has the disruptive potential to transform patients' lives via innovations in pharmaceutical sciences, drug development, clinical trials, and manufacturing. However, it presents significant challenges, ethical concerns, and risks across sectors and societies. AI's rapid advancement has revealed regulatory gaps as existing public policies struggle to keep pace with the challenges posed by these emerging technologies.

Reprogramming of somatic cells to induced neural stem cells.

Recent investigations have demonstrated that defined sets of exogenous factors (chemical and/or biochemical) can convert human and mouse somatic cells into induced neural stem cells (iNSCs). Considering the self-renewal and multi-potential differentiation capabilities of iNSCs, generation of these cells has considerably enhanced cell therapy for treatment of neurodegenerative disorders. These cells can also serve as models for investigation of the mechanism(s) underlying neurodegenerative diseases and as an asset in drug discovery.

Zika virus directly infects peripheral neurons and induces cell death.

Zika virus (ZIKV) infection is associated with neurological disorders of both the CNS and peripheral nervous systems (PNS), yet few studies have directly examined PNS infection. Here we show that intraperitoneally or intraventricularly injected ZIKV in the mouse can infect and impact peripheral neurons in vivo. Moreover, ZIKV productively infects stem-cell-derived human neural crest cells and peripheral neurons in vitro, leading to increased cell death, transcriptional dysregulation and cell-type-specific molecular pathology.

Induction of Neural Progenitor-Like Cells from Human Fibroblasts via a Genetic Material-Free Approach.

Background: A number of studies generated induced neural progenitor cells (iNPCs) from human fibroblasts by viral delivering defined transcription factors. However, the potential risks associated with gene delivery systems have limited their clinical use. We propose it would be safer to induce neural progenitor-like cells from human adult fibroblasts via a direct non-genetic alternative approach.

Direct conversion of human fibroblasts into dopaminergic neural progenitor-like cells using TAT-mediated protein transduction of recombinant factors.

Recent progress in the generation of induced neural progenitor cells (iNPCs) holds tremendous potential for regenerative medicine. However, a major limitation is the lack of a reliable source for cell replacement therapy in neurological diseases such as Parkinson's disease (PD). Here, we show that the combination of small molecules (SM) and TAT-mediated protein transduction of SOX2 and LMX1a in a 3D sphere culture directly convert human fibroblasts to induced dopaminergic neural progenitor-like cells (iDPCs).

Induced neural lineage cells as repair kits: so close, yet so far away.

Transdifferentiation or direct reprogramming of somatic cells into neural lineage cells has provided an invaluable new tool to advance the regenerative neural medicine. Here, we provide an overview of the various strategies currently available for producing of induced neural lineage cells in vitro as well as the direct reprogramming of neural cells in vivo. We also discussing some of the challenges faced in harnessing the potential of induced neural lineage cells for biomedical applications.

Lithium induces follicular atresia in rat ovary through a GSK-3β/β-catenin dependent mechanism.

Lithium chloride (LiCl) is a drug used to treat bipolar disorder, but has side effects in the female reproductive system. Although lithium is known to decrease folliculogenesis and induce follicular atresia in rodent ovaries, its cellular and molecular effects in the ovary have not yet been addressed. To investigate these effects, 23-day-old immature female rats were injected with 10 IU pregnant mare serum gonadotropin (PMSG), followed by injections of 250 mg/kg LiCl every 12 hr for four doses.