Water-Degradable Oxygen-Rich Polymers with AB/ABB Units from Fast and Selective Copolymerization.

Researchers have been chasing plastics that can automatically and fully degrade into valuable products under natural conditions. Here, we develop a series of water-degradable polymers from the first reported fast and selective cationic copolymerization of formaldehyde (B) with cyclic anhydrides (A). In addition to readily accessible monomers, the method is performed at industrially relevant temperatures (~100 °C), takes tens or even minutes, and uses common acid as the catalyst. Interestingly, such polymers possess tunable AB/ABB-type repeating units, which are considered to be thermodynamic and kinetic products, respectively, resulting in low carbon content ([O] : [C] up to 1 : 1). Notably, the polymers can completely degrade to valuable diacids within 150 days in water at ambient temperature owing to the incorporation of carboxyl terminals and acid-responsive acetal units. By washing with aqueous sodium carbonate, the polymers are relatively stable over several months.

Modular Alcohol Click Chemistry Enables Facile Synthesis of Recyclable Polymers with Tunable Structure.

The facile synthesis of chemically recyclable polymers derived from sustainable feedstocks presents enormous challenges. Here, we develop a novel, modular, and efficient click reaction for connecting primary, secondary, or tertiary alcohols with activated alkenes via a bridge molecule of carbonyl sulfide (COS). The click reaction is successfully applied to synthesize a series of recyclable polymers by the step polyaddition of diols, diacrylates, and COS. Diols and diacrylates are common chemicals and can be produced from biorenewable sources, and COS is released as the industrial waste. In addition to sustainable monomers, the approach is atom-economical, wide in scope, metal-free, and performed under mild conditions, affording unprecedented polymers with nearly quantitative yields. The produced polymers also possess predesigned and widely tunable structure owing to the versatility of our method and the broad variety of monomers. The in-chain thiocarbonate and ester polar groups can play as breakpoints, allowing these polymers to be easily recycled. Overall, the polymers have broad prospects for green materials given their facile synthesis, readily available feedstocks, desirable performance, and chemical recyclability.

Chemically Recyclable Polyethylene-like Sulfur-Containing Plastics from Sustainable Feedstocks.

The green revolution in plastics should be accelerated due to growing sustainability concerns. Here, we develop a series of chemically recyclable polymers from the first reported cascade polymerization of H2 O, COS, and diacrylates. In addition to abundant feedstocks, the method is efficient and air-tolerant, uses common organic bases as catalysts, and yields polymers with high molecular weights under mild conditions. Such polymers, structurally like polyethylene with low-density in-chain polar groups, manifest impressive toughness and ductility comparable to high-density polyethylene. The in-chain ester group acts as a breaking point, enabling these polymers to undergo chemical recycling through two loops. The structures and properties of these polymers also have an immeasurably expanded range owing to the versatility of our method. The readily available raw materials, facile synthesis, and high performance make these polymers promising prospects as sustainable materials in practice.

Hypoxia-Inducible Factor-1α Protects Against Intervertebral Disc Degeneration Through Antagonizing Mitochondrial Oxidative Stress.

Intervertebral disc degeneration (IVDD) demonstrates a gradually increased incidence and has developed into a major health problem worldwide. The nucleus pulposus is characterized by the hypoxic and avascular environment, in which hypoxia-inducible factor-1α (HIF-1α) has an important role through its participation in extracellular matrix synthesis, energy metabolism, cellular adaptation to stresses and genesis. In this study, the effects of HIF-1α on mouse primary nucleus pulposus cells (MNPCs) exposed to TNF-α were observed, the potential mechanism was explored and a rabbit IVDD model was established to verify the protective role of HIF-1α on IVDD. In vitro results demonstrated that HIF-1α could attenuate the inflammation, apoptosis and mitochondrial dysfunction induced by TNF-α in MNPCs; promote cellular anabolism; and inhibit cellular catabolism. In vivo results demonstrated that after establishment of IVDD model in rabbit, disc height and IVD extracellular matrix were decreased in a time-dependent manner, MRI analysis showed a tendency for decreased T2 values in a time-dependent manner and supplementation of HIF-1α improved histological and imaginative IVDD while downregulation of HIF-1α exacerbated this degeneration. In summary, HIF-1α protected against IVDD, possibly through reducing ROS production in the mitochondria and consequent inhibition of inflammation, metabolism disorders and apoptosis of MNPCs, which provided a potential therapeutic instrument for the treatment of IVDD diseases.

Scutellarin Protects Against Mitochondrial Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation to Attenuate Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a predominant cause of disc herniation and is widespread worldwide. Inflammatory responses, mitochondrial dysfunction, and extracellular matrix degradation are known to be involved in IVDD. Scutellarin, an active ingredient extracted from Erigeron breviscapus (Vaniot) Ha, Hand-Mazz, is reported to exhibit therapeutic potential in several degenerative diseases by suppressing inflammation and regulating metabolism. However, whether scutellarin can improve IVDD remains unknown. Human primary nucleus pulposus cells (HNPCs) were cultured and stimulated with TNF-α in the presence or absence of scutellarin. Furthermore, a rat needle puncture model was established, and scutellarin was injected into the IVD to verify its protective function against IVDD. Scutellarin attenuated the inflammatory reaction and retained the production of major IVD components both in vitro and in vivo. Mechanistically, scutellarin reduced the amount of reactive oxygen species (ROS), alleviated mitochondrial damage, and decreased the expression levels of apoptosis-related biomarkers upon stimulation with TNF-α. In addition, scutellarin antagonized the activation of the nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway and suppressed the activity of the NLRP3 inflammasome mediated by TNF-α. This study reveals that scutellarin protects against degeneration of nucleus pulposus cells, which might shed light on treatment of IVDD in the future.

In situ Co-Delivery of Doxorubicin and Cisplatin by Injectable Thermosensitive Hydrogels for Enhanced Osteosarcoma Treatment.

Purpose: Osteosarcoma is considered as the most common primary malignant bone tumor in children and adolescents, and the treatments including chemotherapy and surgery were far from satisfactory. Localized tumor treatments by hydrogels incorporating combined chemotherapeutic drugs have recently emerged as superior approaches for enhanced anti-tumor effects and reduced systemic toxicity. Methods: A novel injectable thermosensitive poly (lactide-co- glycolide)-poly (ethylene glycol)-poly(lactide-co-glycolide) triblock copolymer hydrogel containing doxorubicin and cisplatin for the localized chemotherapy of osteosarcoma were synthesized and characterized. The in vitro drug release properties of the drugs-loaded hydrogels were investigated. To study the anti-tumor efficacy of hydrogels depots in vitro, the cytotoxicity and apoptosis rate against Saos-2 and MG-63 cells were evaluated by MTT, Annexin V and PCR methods. The in vivo synergistic anti-tumor efficacy of the multi-drugs co-loaded hydrogels was investigated by human osteosarcoma xenografts. Additionally, the systemic toxic side effects were evaluated by ex vivo histological analysis of the major organs of the mice. Results: The PLGA-PEG-PLGA copolymer solution underwent a sol-gel transition at appropriate temperature and degraded in the PBS, presenting a friendly biocompatibility in vitro. The in vitro cell viability tests demonstrated that DOX and CDDP co-loaded hydrogels exhibited synergistic anti-proliferation effect, due to the sustained release of drugs from the drugs-loaded hydrogel. The treatment with DOX and CDDP co-loaded hydrogel led to the highest efficiency in inhibiting the tumor growth, enhanced tumor necrosis rate and increased regulation of the apoptosis-related gene expressions, indicating a synergistic anti-tumor efficacy in vivo. Additionally, ex vivo histological analysis of the nude mice exhibited low systemic toxicity. Conclusion: The combination treatment of osteosarcoma by localized, sustained co-delivery of DOX and CDDP by PLGA-PEG-PLGA hydrogel may serve as a promising strategy for efficient clinical treatment of osteosarcoma.

LncRNA MEG3 targeting miR-424-5p via MAPK signaling pathway mediates neuronal apoptosis in ischemic stroke.

Emerging evidence suggests that long non-coding RNAs (lncRNAs) are significant regulators in the pathological process of ischemic stroke (IS). However, little is known about lncRNAs and their roles in IS. In this study, we aimed to screen out differentially expressed lncRNAs and revealed the underlying mechanisms in IS. The results of bioinformatic analysis showed that lncRNA MEG3 and Sema3A were over-expressed in IS samples, while miR-424-5p was lower-expressed. Correlation between MEG3/miR-424-5p, and miR-424-5p/Sema3A were predicted with miRanda and TargetScan, and verified by dual luciferase assay. Inhibition of MEG3 remarkably increased the expression of miR-424-5p and decreased the expression of Sema3A, which also led to in an increased cell viability and decreased cellular apoptosis in oxygen-glucose deprivation and reoxygenation (OGD/R) model, as well as an activated MAPK signaling pathways. Consistently, MEG3 was upregulated in MCAO mice, knockdown of MEG3 reduced the infarct volume and improved neurobehavioral outcomes in rats following MCAO. In conclusion, it was demonstrated that MEG3 accelerated the process of IS by suppressing miR-424-5p, which targeted Sema3A and the activated MAPK pathway. These results might provide useful information for exploring the potential therapeutic targets in IS.

Correction to: Hepatic metastatic paraganglioma 12 years after retroperitoneal paraganglioma resection: a case report.

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Hepatic metastatic paraganglioma 12 years after retroperitoneal paraganglioma resection: a case report.

BACKGROUND: Paragangliomas, also known as chemodectomas, are rare tumors arise from chemoreceptor tissue, and most commonly locate at the bifurcation of the common carotid, the jugular foramen, aortic arch, and retroperitoneum. Paragangliomas generally are considered to be benign tumors, and rarely produce local or distant metastases. Metastasis to liver is extremely rare. CASE PRESENTATION: We report the case of a 39-year-old woman, who had undergone resection of a retroperitoneal paraganglioma at her local hospital for 12 years. She was referred to our hospital for further evaluation of a hepatic mass, which was misdignosed as hepatocellular carcinoma (HCC) and was treated by transarterial chemoembolization (TACE) in the local hospital 6 years ago. At admission, CT scan revealed a huge hypervascular mass with many feeding arteries, almost the same size as 5 years ago. Ultrasound-guided biopsy of the liver tumor was performed and immunohistochemical examination confirmed the diagnosis of hepatic metastatic paraganglioma. Though liver metastasis failed to achieve complete response or partial response to TACE treatment, it remained stable without progression during the 7-year follow-up. CONCLUSION: Paragangliomas are slow growing tumors and metastasis may develop decades after resection of the primary lesion. Long-term follow-up is necessary, and curative or palliative treatment should be considered to control symptoms, improve life quality, reduce complications and prolong survival.