Human pluripotent stem cell-derived kidney organoids: Current progress and challenges.

Human pluripotent stem cell (hPSC)-derived kidney organoids share similarities with the fetal kidney. However, the current hPSC-derived kidney organoids have some limitations, including the inability to perform nephrogenesis and lack of a corticomedullary definition, uniform vascular system, and coordinated exit pathway for urinary filtrate. Therefore, further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development, regeneration, disease modeling, and drug screening. In this review, we discussed recent advances in the generation of hPSC-derived kidney organoids, how these organoids contribute to the understanding of human kidney development and research in disease modeling. Additionally, the limitations, future research focus, and applications of hPSC-derived kidney organoids were highlighted.

Highly Fluorescent and Photostable Polymeric Nanofibers as Scaffolds for Cell Interfacing and Long-Term Tracking.

Highly fluorescent polymeric nanofibers fabricated via electrospinning of PCL-DPP-PCL (photostable polycaprolactones-di(thiophene-2-yl)-diketopyrrolopyrrole-photostable polycaprolactones) and commercial PCL mixture show superior photostability and cytocompatibility for long-term tracking of cell-substrate interaction. As a proof of concept, these PCL-DPP-PCL nanofibers enable clear visualization of intricate cell-substrate interactions such as oligodendrocyte myelination.

[Effects of Jing'an Oral Liquid on the central neurotransmitter of multiple tics children].

OBJECTIVE: To study the effects of Jing'an Oral Liquid (JOL) on the central neurotransmitters of multiple tics (MT) children. METHODS: Sixty MT children patients were randomly assigned to the treatment group and the control group, 30 cases in each group. Another 30 healthy children were recruited as the health group. JOL and Tiapride Tablet (TT) was respectively given to patients in the treatment group and the control group. The treatment course was 2 months. The levels of central neurotransmitters [dopamine (DA), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), norepinephrine (NE), glutamic acid (GLU), aspartate (ASP), gamma-aminobutyric acid (GABA)] were measured using high performance liquid chromatography (HPLC) before and after treatment, and compared with the health group. RESULTS: Compared with the health group, the levels of 5-HT, HVA, GLU, and ASP significantly increased in the treatment group and the control group before treatment (P < 0.05), GABA significantly decreased (P < 0.05). Compared with before treatment in the same group, the levels 5-HT, HVA, and GLU significantly decreased in the treatment group (P < 0.05), while the levels of NE and GABA significantly increased (P < 0.05). The levels of DA, 5-HT, GLU, and ASP significantly decreased, while the levels of NE ang GABA significantly increased in the control group, showing statistical difference (P < 0.05). There was no statistical difference in each index between the treatment group and the control group before and after treatment (P > 0.05). CONCLUSIONS: (1) The imbalance of a variety of monoamines and amino acid neurotransmitters can lead to MT, especially in the changes of 5-HT, HVA, GLU, ASP, and GABA. (2) JOL can significantly reduce the levels of 5-HT, HVA, and GLU, and significantly increase the levels of NE and GABA, which might be its pharmacodynamic mechanisms for treating MT.

Single-step assembly of cationic lipid-polymer hybrid nanoparticles for systemic delivery of siRNA.

The clinical success of therapeutics of small interfering RNA (siRNA) is still hindered by its delivery systems. Cationic polymer or lipid-based vehicles as the major delivery systems of siRNA cannot sufficiently satisfy siRNA therapeutic applications. It is hypothesized that cationic lipid-polymer hybrid nanoparticles may take advantage of both polymeric and lipid-based nanoparticles for siRNA delivery, while diminishing the shortcomings of both. In this study, cationic lipid-polymer hybrid nanoparticles were prepared by a single-step nanoprecipitation of a cationic lipid (N,N-bis(2-hydroxyethyl)-N-methyl-N-(2-cholesteryloxycarbonyl aminoethyl) ammonium bromide, BHEM-Chol) and amphiphilic polymers for systemic delivery of siRNA. The formed hybrid nanoparticles comprised a hydrophobic polylactide core, a hydrophilic poly(ethylene glycol) shell, and a cationic lipid monolayer at the interface of the core and the shell. Such hybrid nanoparticles exhibited excellent stability in serum and showed significantly improved biocompatibility compared to that of pure BHEM-Chol particles. The hybrid nanoparticles were capable of delivering siRNA into BT474 cells and facilitated the escape of loaded siRNA from the endosome into the cytoplasm. The hybrid nanoparticles carrying polo-like kinase 1 (Plk1)-specific siRNA (siPlk1) remarkably and specifically downregulated expression of the oncogene Plk1 and induced cancer cell apoptosis both in vitro and in vivo and significantly suppressed tumor growth following systemic administration. We demonstrate that this system is stable, nontoxic, highly efficient, and easy to scale up, bringing the clinical application of siRNA therapy one important step closer to reality.

Micelle-to-vesicle morphological transition via light-induced rapid hydrophilic arm detachment from a star polymer.

Micelle-to-vesicle morphological transition has been achieved by light-induced rapid hydrophilic arm detachment from a star polymer. This provides a remote and clean method to control morphology transition of polymeric assemblies.

Sheddable ternary nanoparticles for tumor acidity-targeted siRNA delivery.

Drug delivery systems for cancer therapy usually need to be sterically stabilized by a poly(ethylene glycol) (PEG) layer during blood circulation to minimize nonspecific interactions with serum components. However, PEGylation significantly reduces cellular uptake of the delivery systems after they accumulate at the tumor site, which markedly impairs the in vivo antitumor efficiency. Here, we develop a ternary small interfering RNA (siRNA) delivery system with tumor acidity-activated sheddable PEG layer to overcome the challenge. The sheddable nanoparticle is fabricated by introducing a tumor acidity-responsive PEGylated anionic polymer to the surface of positively charged polycation/siRNA complexes via electrostatic interaction. We show clear evidence that introducing the PEGylated anionic polymer to the surface of a nanoparticle markedly reduces its nonspecific interactions with protein. We further demonstrate that the nanoparticle is capable of deshielding the PEG layer at the slightly acidic tumor extracellular microenvironment to facilitate the delivery of siRNA to the tumor cells after accumulation at the tumor site. Accordingly, this promotes the RNA-interfering efficiencies and enhances the inhibition of tumor growth. Such delivery system with the ability to deshield the PEG layer at the target tissues has remarkable potential in cancer therapy.