Ce6-modified Fe ions-doped carbon dots as multifunctional nanoplatform for ferroptosis and photodynamic synergistic therapy of melanoma.

BACKGROUND: Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. RESULTS: Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T2-weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. CONCLUSIONS: Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma.

Molecular Etiology in Thumb Polydactyly in Mutated GLI3 Mouse Gene.

Sporadic thumb polydactyly with nonfamily inheritance is the most common in clinical work. This study focused on characterization of GLI3 gene function. We constructed the plasmid with p.m948i point mutation of GLI3 and transfected it into mouse embryonic fibroblasts (MEFs) to study the effects and potential mechanism of the mutant gene. The RNA of GLI3 mutant cells was extracted and analyzed by transcriptome sequencing and bioinformatics. Finally, we constructed cbx3 overexpression plasmid, designed siRNA for gene silencing, and transfected it into the MEFs. Cell proliferation and invasion ability of the MEFs were examined. The results showed that there were 2,452 differential expression genes in the MEFs transfected with GLI3 mutant plasmid compared with wild-type MEFs. The results of differential expression analysis showed that the cbx3 gene was significantly up-regulated. Overexpression of cbx3 in MEFs promoted cell proliferation and invasion, while siRNA knockdown of cbx3 expression reduced proliferation and invasion. GLI3 gene mutation in MEFs resulted in cbx3 up-regulation and promoted MEF proliferation and invasion. This study further clarified the potential function of GLI3 in limb development, established a new relationship between gene mutation and polydactyly, and preliminarily clarified the possible signal pathway, all of which have laid a foundation for further study on the etiology of polydactyl.

Loading and Releasing Behavior of Selenium and Doxorubicin Hydrochloride in Hydroxyapatite with Different Morphologies.

Doxorubicin (Dox)-loaded or selenium-substituted hydroxyapatite (HA) has been developed to achieve anti-osteosarcoma or bone regeneration in a number of studies. However, currently, there is a lack of studies on the combination of Dox and selenium loading in/on HA and comparative research studies on which form and size of HA are more suitable for drug loading and release in the treatment osteogenesis after osteosarcoma resection. Herein, selenium-doped rod-shaped nano-HA (n-HA) and spherical mesoporous HA (m-HA) were successfully prepared. The doping efficiency of selenium and the Dox loading capacity of selenium-doped HA with different morphologies were studied. The release kinetics of Dox and the selenium element in phosphate-buffered saline with different pH values was also comparatively investigated. The drug loading results showed that n-HA exhibited 3 times higher selenium doping amount than m-HA, and the Dox entrapment efficiency of selenium-doped n-HA (0.1Se-n-HA) presented 20% higher than that of selenium-doped m-HA (0.1Se-m-HA). The Dox release behaviors of HA in two different morphologies showed similar release kinetics, with almost the same Dox releasing ratio but slightly more Dox releasing amount in selenium-doped HA than in HA without selenium. The selenium release from selenium-doped n-HA-D (0.1Se-n-HA-D) particles was 2 times as much as that of selenium-doped m-HA-D (0.1Se-m-HA) particles. Our study indicated that n-HA loaded with Dox and selenium may be a promising drug delivery strategy for inhibition of osteosarcoma recurrence and promoting osteogenesis simultaneously.

Efficacy of Platelet-rich Plasma for Low Back Pain: A Systematic Review and Meta-analysis.

BACKGROUND: Platelet-rich plasma (PRP) may be beneficial for patients with low back pain. However, the results remain controversial. We conducted a systematic review and meta-analysis to explore the efficacy of PRP for low back pain. METHODS: PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases were searched systematically. Randomized controlled trials (RCTs) assessing the effect of PRP on low back pain were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcome was pain scores within 8 weeks. Meta-analysis was performed using the random-effects model. RESULTS: Three RCTs involving 131 patients were included in the meta-analysis. Overall, compared with control intervention for low back pain, PRP injection was found to reduce pain scores significantly (mean difference: - 1.47; 95% confidence interval [CI], - 2.12 to - 0.81; p < 0.0001), improve the number of patients with > 50% pain relief at 3 months (risk ratio [RR]: 4.14; 95% CI, 2.22-7.74; p < 0.00001), and offer relatively good patient satisfaction (RR: 1.91; 95% CI, 1.04-3.53; p = 0.04). No increase in adverse events was reported after PRP injection (RR: 1.92; 95% CI, 0.94-3.91; p = 0.07). CONCLUSIONS: Compared with control intervention for low back pain, PRP injection was found to improve pain relief and patient satisfaction significantly with no increase in adverse events.

Identification of novel mutations in preaxial polydactyly patients through whole-exome sequencing.

BACKGROUND: Polydactyly is one of the most common hereditary limb malformation characterized by additional digits in hands and/or feet. With extra fingers/toes, which could be very problematic, polydactyly patients are usually treated in early childhood by removing of extra digits with surgery. Genetically, polydactyly is caused by mutations of genes that involve in digit formation. METHODS: In the current report, we performed genetic analysis for polydactyly using DNA samples from a cohort of 20 Chinese patients. All patients show preaxial polydactyly in one of their hands. RESULTS: With whole-exome sequencing (WES), we have identified two novel heterozygous mutations c.G2844A in GLI3 gene (OMIM 165240) and c.1409_1410del in EVC gene (OMIM 604831). Compound heterozygous mutations that affect KIAA0586 gene (OMIM 610178) are also detected. Proteins encoded by the genes have important roles in primary cilia and regulate sonic hedgehog signaling pathway. CONCLUSION: Our study highlights the important roles of primary cilia in limb development, and helps to further understand the molecular mechanisms for polydactyly formation.