Hovendulcisic acid A-D: four novel ceanothane-type triterpenoids from Hovenia dulcis stems with anticancer properties.

Sixteen ceanothane-type triterpenoids, including four new compounds-hovendulcisic acids A-D (1-4) -were purified from the stems of Hovenia dulcis Thunb. The structures of 1-4 were confirmed by comprehensive means including ECD and quantum chemical calculations. Putative biosynthetic pathways of 1-16 were proposed, and 3, 5, and 15 exhibited antitumor activity on A549 and MDA-MB-231 cells.

The Effect of Chinese Medicine Compound in the Treatment of Rheumatoid Arthritis on the Level of Rheumatoid Factor and Anti-Cyclic Citrullinated Peptide Antibodies: A Systematic Review and Meta-Analysis.

Objectives: To evaluate the current evidence whether Chinese medicine compound (CMC) can reduce the serum levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP). Methods: We comprehensively searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), the Database for Chinese Technical Periodicals (VIP), and Wanfang data. We then performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) assessing the CMC therapy methods. This study is registered with PROSPERO, number CRD42020216284. Results: In total, 65 studies were eligible for inclusion, including 6099 patients. The result of the meta-analysis showed that compared with common Western medicine therapy, CMC monotherapy or combined with Western medicine was able to reduce serum RF (SMD= -0.85, 95%CI -1.04 to -0.67) and anti-CCP (SMD= -0.56, 95%CI -0.79 to -0.32) levels to some extent. In the efficacy meta-analysis, a greater number of CMC-treated patients achieved the efficacy criteria after a period of treatment, where the relative risk (RR) was 1.20 [1.08, 1.33] for achieving ACR20, 1.57 [1.38, 1.78] for ACR50, and 2.21 [1.72, 2.84] for ACR70. At the same time, there was a statistically significant difference in the effective rate of the patient's TCM symptoms (RR = 1.22, 95%CI 1.19-1.26). Conclusions: Through this meta-analysis and systematic review, we found that CMC for the treatment of RA is effective in reducing RF and anti-CCP levels and might have better clinical efficacy than Western medicine monotherapy. Some active components are responsible for this efficacy and worth further exploring.

Keap1 Cystenine 151 as a Potential Target for Artemisitene-Induced Nrf2 Activation.

Artemisitene (ATT) activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) by increasing its stabilization and reducing ubiquitination. The cysteine (Cys) residues of the cytosolic Nrf2 repressor Kelch-like ECH-associated protein-1 (Keap1) function as redox sensors and may be crucial in activating Nrf2. To determine whether ATT-induced Nrf2 activation is dependent on the modification of Keap1 and to elucidate the underlying mechanism, we transfected cell lines with six different Keap1 mutant constructs, each with a Cys (-77, -151, -257, -273, -288, and -297) to Ser substitution. Only the Cys151Ser mutant prevented ATT-mediated activation of Nrf2, indicating that the Cys151 residue of Keap1 likely interacts with ATT and is essential for Nrf2 stabilization and transcription of downstream genes. Our finding provides a pharmacological basis for using artemisitene against oxidative stress-related diseases.

Tanshinol suppresses cardiac allograft rejection in a murine model.

BACKGROUND: Achieving long-term cardiac allograft survival without continuous immunosuppression is highly desired in organ transplantation. Studies have shown that Salvia miltiorrhiza, an herb also known as danshen, improves microcirculation and is highly effective in treating coronary heart disease. Our objective is to determine whether tanshinol, an ingredient of danshen, improves cardiac allograft survival. METHODS: Fully vascularized heterotopic heart transplantation was performed using BALB/c mice as donors and C57BL/6 mice as recipients, which were then treated with tanshinol and rapamycin. CD4+FoxP3+ regulatory T cells (Tregs) were quantified by flow analyses, whereas CCL22 was measured by real-time polymerase chain reaction and Western blotting. RESULTS: We found that tanshinol significantly delayed cardiac allograft rejection. It promoted long-term allograft survival induced by rapamycin, a mammalian target-of-rapamycin (mTOR) inhibitor. Tanshinol increased CD4+FoxP3+ Treg numbers in cardiac allografts, but not spleens and lymph nodes, of recipient mice by enhancing chemokine CCL22 expression in cardiac allografts, especially cardiac dendritic cells. In contrast, rapamycin increased Treg numbers in both lymphoid organs and allografts, suggesting that it generally expands Tregs. Moreover, Tregs induced by rapamycin plus tanshinol were more potent in suppressing T-cell proliferation in vitro than those from untreated recipients. Neutralizing CCL22 hindered CD4+FoxP3+ Treg migration to cardiac allografts and reversed long-term allograft survival induced by tanshinol plus rapamycin. CONCLUSIONS: Tanshinol suppresses cardiac allograft rejection by recruiting CD4+FoxP3+ Tregs to the graft, whereas rapamycin does so via expanding the Tregs. Thus, tanshinol cooperates with rapamycin to further extend cardiac allograft survival.

Artemisitene activates the Nrf2-dependent antioxidant response and protects against bleomycin-induced lung injury.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant response and xenobiotic metabolism. Activation of the Nrf2 signaling pathway has been demonstrated to confer protection against environmental insults and prevent disease or inhibit the progression of diseases related to oxidative stress. In an attempt to identify novel improved Nrf2 inducers for systemic protection against tissue damage by environmental insults, we identified artemisitene as a novel Nrf2 activator using antioxidant responsive element luciferase assay in MDA-MB-231 cells. Further studies suggest that artemisitene activates Nrf2 by decreasing Nrf2 ubiquitination and increasing its stability. In Nrf2 wild-type mice, systemic administration of artemisitene strongly inhibits bleomycin-induced lung damage. Artemisitene represents a novel class of Nrf2 inducer, and artemisitene-based therapeutic approach targeting Nrf2 may also provide antioxidant protection for humans against tissue damage by toxic chemicals.-Chen, W., Li, S., Li, J., Zhou, W., Wu, S., Xu, S., Cui, K., Zhang, D. D., Liu, B. Artemisitene activates the Nrf2-dependent antioxidant response and protects against bleomycin-induced lung injury.

Giant abdominal leiomyoma of male: a case report and literature reviews.

Abdominal leiomyomas are extremely rare intraabdominal tumors, especially in male patient. Here, we report a case of a 22 years-old male with a huge abdominal leiomyoma. The patient presented with a chief complaint of abdominal distension for three months, no others significant symptom were found. CT-scan showed a cystic-solid huge mass in the middle and lower abdominal peritoneal cavity with uneven density. An exploratory laparotomy was performed and the tumor was completely resected. Microscopically, Tumor cells have a spindled shape, eosinophilic cytoplasm, and cigar-like nuclei, arranged in bundles or intersecting fascicles. Immunohistochemistry, the tumor cells were SMA, desmin diffuse positive and CD117, S-100 negative, interestingly, ER, PR were positive. The characteristics of a few of the male abdominal leiomyoma reported in the literature were generalized.

Dendritic fibromyxolipoma in the latissimus dorsi: a case report and review of the literature.

Dendritic fibromyxolipoma is an uncommon benign soft tissue tumor. Here, we report a case in a 53-year-old man presenting a painless mass located deep in the latissimus dorsi of the right back. Microscopically, the tumor was mainly consisted of small spindle and stellate cells, abundant myxoid stroma, collagen bundles and mature adipose tissue. Immunohistochemical study showed the spindle and stellate cells were positive for CD34, Bcl-2 and Vimentim, but not for Keratin, EMA, SMA and Desmin. To date, one year after operation, the patient is well without evidence of recurrence or metastasis. The implication of this report is to provide insights into further understanding of this rare tumor with review of the literature.

Phenylaminopropyl-functionalized stationary phase for open-tubular capillary electrochromatography of alkaloids and aromatic acids.

A multi-functional open-tubular (OT) column covalently modified with [3-(phenylamino)propyl]trimethoxysilane (PPTMS) via a single-step silanization reaction has been developed, and employed for alkaloids and aromatic acids analytes by CEC. Both anodic and cathodic EOF could be gained in the PPTMS-bonded column, and anodic EOF was exhibited when the pH of running buffer was less than 8.0. Using thiourea as the EOF marker, a satisfactory column stability was denoted, and the RSD values for migration time and peak area were gained at 0.5 and 3.7% (intra-day, n=5), 1.7 and 5.6% (inter-day, n=3), 3.9 and 5.8% (column-to- column, n=16 in four batches). With anodic EOF mode (pH=2.0 of 10 mmol/L phosphate buffer), favorable separations of cationic alkaloids (viz. uridine, adenosine, cytidine, adenine, cytosine) were successfully achieved with column efficiencies ranging from 95,000 to 187,000 plates/m, and the undesired adsorption on the inter-wall of capillary column could be avoided. Besides, six anionic aromatic acids could be also separated efficiently in the co-electroosmotic mode with anodic EOF. And high efficiencies ranged from 176,000 to 235,000 plates/m were gained with a good repeatability. PPTMS-bonded capillary column might be used as an alternative functional medium to physical coating capillary column for the analyses of aromatic organic acids and bases.

Successful photodynamic therapy with topical 5-aminolevulinic acid for five cases of cervical intraepithelial neoplasia.

OBJECTIVES: Photodynamic therapy (PDT) is a minimally invasive treatment for cervical intraepithelial neoplasia. The purpose of this study was to assess the feasibility and effectiveness of PDT in patients with CIN and high-risk HPV infection. METHODS: Five patients diagnosed CIN 2 or CIN 3 with human papillomavirus (HPV) infection were included. Each patient had gynecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy. Two grams of 5-aminolevulinic acid (ALA) gel (118 mg/g) was topically applied to the cervix and covered with a special plastic cap for 3-4 h, followed by 20 min illumination of both ecto- and endo-cervical canal with red coherent light (wavelength 633 nm) using a PDT laser and a special light catheter. The PDT therapy was repeated with an interval of 1 week. Follow-up examination including biopsy and histology, colposcopy, HPV DNA testing were carried out after 3, 6 and 9 months. RESULTS: Treatment could be accomplished in all cases and no severe side effect was encountered. All the CIN2 patients had a complete response for 9 months and one CIN3 HPV remained positive for 6 months after three or four treatments. CONCLUSION: PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects and can be easily performed on outpatient basis.