ABSTRACT
Background: Traditional Chinese medicine (TCM) had been extensively used in China for wound management and had shown great potential in wound treatment while its mechanism is still needed to be addressed. Objective: The present study sought to investigate the therapuetic effect of the TCM ARCC on acute and chronic wounds. Methods: Here, using the ultra-low temperature preparation method, the mixed ultramicro powder prepared with Angelica (A), Angelica (R), Calcined Gypsum (C) and Caleramide (C) named as ARCC. The effects of ARCC on wound healing in adult and aged mice were comparatively evaluated through a full-thickness skin defect model. In addition, we randomly selected 10 patients aged 55 to 70 years from a cohort of 500 patients with diabetic feet to assess their prognosis. Results: As the results showed that the healing rate had delayed in aged mice compared to adult mice, while ARCC prominently augmented the healing process in aged mice. Moreover, ARCC treatment wounds in aged mice showed accelerated re-epithelization, enhanced granulation tissue formation, and increased vascularization, which was similar to that of adult mice. Furthermore, ARCC also achieved therapeutic effects in diabetic foot patients, accelerating wound healing. The results found that foot ulcers improved significantly 7 days after the ARCC administration, and 80% of patients were healed within 1 month. Discussion: In the present study, ARCC was found to have therapeutic effects on both acute and chronic wounds in animal models. ARCC also demonstrated therapeutic effects in diabetic feet, which promoted wound healing, prevented wound infection, and avoided the risk of further surgery or amputation. All these evidences suggested ARCC was a promising approach for wound treatment. Conclusions: ARCC might be recommended as a promising therapeutic medication in diabetic and chronic refractory wounds.
ABSTRACT
Glioma is the most common primary intracranial tumor, in which glioblastoma (GBM) is the most malignant and lethal. However, the current chemotherapy drugs are still unsatisfactory for GBM therapy. As the natural products mainly extracted from Eucalyptus species, phloroglucinol-terpene adducts have the potential to be anti-cancer lead compounds that attracted increasing attention. In order to discover the new lead compounds with the anti-GBM ability, we isolated Eucalyptal A with a phloroglucinol-terpene skeleton from the fruit of E. globulus and investigated its anti-GBM activity in vitro and in vivo. Functionally, we verified that Eucalyptal A could inhibit the proliferation, growth and invasiveness of GBM cells in vitro. Moreover, Eucalyptal A had the same anti-GBM activity in tumor-bearing mice as in vitro and prolonged the overall survival time by maintaining mice body weight. Further mechanism research revealed that Eucalyptal A downregulated SRSF1 expression and rectified SRSF1-guided abnormal alternative splicing of MYO1B mRNA, which led to anti-GBM activity through the PDK1/AKT/c-Myc and PAK/Cofilin axes. Taken together, we identified Eucalyptal A as an important anti-GBM lead compound, which represents a novel direction for glioma therapy.
Subject(s)
Brain Neoplasms/metabolism , Carcinogenesis/drug effects , Eucalyptol/therapeutic use , Glioma/metabolism , Myosin Type I/metabolism , Protein Splicing/drug effects , Serine-Arginine Splicing Factors/biosynthesis , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/therapeutic use , Brain Neoplasms/genetics , Brain Neoplasms/prevention & control , Carcinogenesis/metabolism , Carcinogenesis/pathology , Cell Line, Tumor , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Eucalyptol/isolation & purification , Eucalyptol/pharmacology , Gene Expression Regulation, Neoplastic , Glioma/genetics , Glioma/prevention & control , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Myosin Type I/genetics , Protein Splicing/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Serine-Arginine Splicing Factors/antagonists & inhibitors , Serine-Arginine Splicing Factors/genetics , Xenograft Model Antitumor Assays/methodsABSTRACT
Metallothionein (MT) is a low-molecular-weight protein with a high metal binding capacity and plays a key role in organism adaptation to heavy metals. In this study, a metallothionein gene was successfully cloned and sequenced from Antarctic sea-ice yeast Rhodotorula mucilaginosa AN5. Nucleotide sequencing and analysis revealed that the gene had four exons interrupted by three introns. MTs complementary DNA (named as RmMT) had an open reading frame of 321 bp encoding a 106 amino acid protein with a predicted molecular weight of 10.3 kDa and pI of 8.49. The number of amino acids and distribution of cysteine residues indicated that RmMT was a novel family of fungal MTs. Quantitative real-time polymerase chain reaction analysis showed that RmMT expression was elevated under copper-induced stress. The RmMT gene was transferred into E. coli and the RmMT expressing bacteria showed improved tolerance to copper ion and increased accumulation of heavy metals, such as Cu2+ , Pb2+ , Zn2+ , Cd2+ , and Ag+ . Moreover, in vitro studies, purified recombinant RmMT demonstrated that it could be used as a good scavenger of superoxide anion, hydroxyl, and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals. In summary, these results demonstrate that RmMT plays a key role in the tolerance and bioaccumulation of heavy metals.