Stimuli-Responsive Delivery Systems for Intervertebral Disc Degeneration.

As a major cause of low back pain, intervertebral disc degeneration is an increasingly prevalent chronic disease worldwide that leads to huge annual financial losses. The intervertebral disc consists of the inner nucleus pulposus, outer annulus fibrosus, and sandwiched cartilage endplates. All these factors collectively participate in maintaining the structure and physiological functions of the disc. During the unavoidable degeneration stage, the degenerated discs are surrounded by a harsh microenvironment characterized by acidic, oxidative, inflammatory, and chaotic cytokine expression. Loss of stem cell markers, imbalance of the extracellular matrix, increase in inflammation, sensory hyperinnervation, and vascularization have been considered as the reasons for the progression of intervertebral disc degeneration. The current treatment approaches include conservative therapy and surgery, both of which have drawbacks. Novel stimuli-responsive delivery systems are more promising future therapeutic options than traditional treatments. By combining bioactive agents with specially designed hydrogels, scaffolds, microspheres, and nanoparticles, novel stimuli-responsive delivery systems can realize the targeted and sustained release of drugs, which can both reduce systematic adverse effects and maximize therapeutic efficacy. Trigger factors are categorized into internal (pH, reactive oxygen species, enzymes, etc.) and external stimuli (photo, ultrasound, magnetic, etc.) based on their intrinsic properties. This review systematically summarizes novel stimuli-responsive delivery systems for intervertebral disc degeneration, shedding new light on intervertebral disc therapy.

Complete Plastid Genomes of Nine Species of Ranunculeae (Ranunculaceae) and Their Phylogenetic Inferences.

The tribe Ranunculeae, Ranunculaceae, comprising 19 genera widely distributed all over the world. Although a large number of Sanger sequencing-based molecular phylogenetic studies have been published, very few studies have been performed on using genomic data to infer phylogenetic relationships within Ranunculeae. In this study, the complete plastid genomes of nine species (eleven samples) from Ceratocephala, Halerpestes, and Ranunculus were de novo assembled using a next-generation sequencing method. Previously published plastomes of Oxygraphis and other related genera of the family were downloaded from GenBank for comparative analysis. The complete plastome of each Ranunculeae species has 112 genes in total, including 78 protein-coding genes, 30 transfer RNA genes, and four ribosomal RNA genes. The plastome structure of Ranunculeae samples is conserved in gene order and arrangement. There are no inverted repeat (IR) region expansions and only one IR contraction was found in the tested samples. This study also compared plastome sequences across all the samples in gene collinearity, codon usage, RNA editing sites, nucleotide variability, simple sequence repeats, and positive selection sites. Phylogeny of the available Ranunculeae species was inferred by the plastome data using maximum-likelihood and Bayesian inference methods, and data partitioning strategies were tested. The phylogenetic relationships were better resolved compared to previous studies based on Sanger sequencing methods, showing the potential value of the plastome data in inferring the phylogeny of the tribe.