Integrated Osteoinductive Factors─Exosome@MicroRNA-26a Hydrogel Enhances Bone Regeneration.

MicroRNAs (miRNAs) are a new therapeutic tool that can target multiple genes by inducing translation repression and target mRNA degradation. Although miRNAs have gained significant attention in oncology and in work on genetic disorders and autoimmune diseases, their application in tissue regeneration remains hindered by several challenges, such as miRNA degradation. Here, we reported Exosome@MicroRNA-26a (Exo@miR-26a), an osteoinductive factor that can be substituted for routinely used growth factors, which was constructed using bone marrow stem cell (BMSC)-derived exosomes and microRNA-26a (miR-26a). Exo@miR-26a-integrated hydrogels significantly promoted bone regeneration when implanted into defect sites; as the exosome stimulated angiogenesis, miR-26a promoted osteogenesis while the hydrogel enabled a site-directed release. Moreover, BMSC-derived exosomes further facilitated healthy bone regeneration by repressing osteoclast differentiation-related genes rather than damaging osteoclasts. Taken together, our findings demonstrate the promising potential of Exo@miR-26a for bone regeneration and provide a new strategy for the application of miRNA therapy in tissue engineering.

Traditional Chinese Medicine Containing Arsenic Treated MDS Patients Effectively through Regulating Aberrant Hypomethylation.

Aberrant hypermethylation and hypomethylation both play important roles in myelodysplastic syndrome (MDS). Hypomethylating agents targeting hypermethylation have been employed for the MDS treatment, but the treatment effect is limited. Novel drugs for DNA hypomethylation-targeted therapy may be needed to improve clinic efficacy for the treatment of MDS. Chinese medicine (CM) herbs have been used to treat MDS for many years in our hospital. However, the long-term treatment effect and mechanism remain unclear. In this study, all 135 patients received CM treatment for at least 36 months. The response rates for CM treatment were 81.53% (106/130) for hematological improvement in 130 MDS-RCMD patients and 80% (4/5) for bone marrow CR in 5 MDS-RAEB patients, respectively. The Human Methylation 850K BeadChip showed that 115 genes (50.88%) were aberrantly hypomethylated in 5 MDS patients compared with 3 healthy individuals. GO-analysis showed that these hypomethylated genes participated in many cancer-related biological functions and pathways. Furthermore, 60 genes were hypermethylated and the protein expression level of DNMT1 was significantly increased in the 5 MDS patients after 6 months of CM treatment. Our study suggests that CM can improve aberrant hypomethylation by increasing DNMT1 expression in MDS. The data support the clinical application of CM herbs containing arsenic as an innovative hypermethylation-inducing regimen for the treatment of MDS.

Relation of Blood Arsenic Concentration with Effect and Safety of Arsenic-Containing Qinghuang Powder () in Patients with Myelodysplastic Syndrome.

OBJECTIVE: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS). METHODS: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. RESULTS: After 2 courses of treatment, the total effective rate was 89.6% (146/163), with 31.3% (51/163) of hematological improvement and 58.3% (95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P<0.05), the absolute neutrophil count increased from 0.81 ± 0.48 × 109/L to 1.08 ± 0.62 × 109/L (P<0.05), and no significant changes were observed in platelet counts (P>0.05). Among 46 patients previously depended on blood transfusion, 28.3% (13/46) completely got rid of blood transfusion and 21.7% (10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 µ g/L (P<0.05), 3 months with 33.56 ± 15.28 µ g/L (P<0.05), and 6 months with 36.78 ± 11.92 µ g/L (P<0.05), respectively, as compared with those before treatment (4.08 ± 2.11 µ g/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months (P>0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ± 10.38 vs. 37.89 ± 11.84, µ g/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03, µ g/L, P<0.05). CONCLUSION: QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.

Study on the Clinical Safe and Effective Methods of Arsenic-Containing Compound-Qinghuang Powder in the Treatment of Myelodysplastic Syndrome.

OBJECTIVE: To establish the clinical safe and effective methods of arsenic-containing compound-Qinghuang Powder (compound-QHP) in the treatment of myelodysplastic syndrome (MDS). METHODS: 200 patients with MDS were treated with compound-QHP (daily dose of 0.1 g realgar). The blood arsenic concentrations (BACs) were detected by atomic fluorescence spectrophotometry (HF-AFS). After treatment for 1 month, the patients were randomly divided into group A and group B when the BACs were less than 20 µg/L. Daily dose of realgar was maintained in group A and it was increased to that when the BACs were more than 20 µg/L in group B. The BAC and clinical efficacy and safety in two groups were compared at the end of the treatment with compound-QHP. RESULTS: The average BAC of group B was significantly higher than that of group A (P < 0.01). The rates of hematology improvement and reduced transfusion were significantly higher in group B than in group A (P < 0.05). The HGB, ANC, and PLT significantly increased in group B after treatment (P > 0.05). CONCLUSIONS: Monitoring the BAC and adjusting the daily dose of realgar to increase the effective BAC and then improving efficacy without increasing the clinical toxicity are the clinical safe and effective methods in the treatment of MDS.