Oxepine-containing pyrazinopyrimidine alkaloids and quinolinone derivatives produced by Aspergillus versicolor AS-212, a deep-sea-derived endozoic fungus.

Four new oxepine-containing pyrazinopyrimidine alkaloids, versicoxepines A - D (1-4), two quinolinone alkaloid analogs including 3-hydroxy-6-methoxy-4-phenylquinolin-2(1H)-one (5) and 3-methoxy-6-hydroxy-4-phenylquinolin-2(1H)-one (6) which were new naturally occurring compounds, together with two known compounds (7 and 8) were isolated from Aspergillus versicolor AS-212, an endozoic fungus isolated from the deep-sea coral Hemicorallium cf. imperiale, which was collected from the Magellan Seamounts in the Western Pacific Ocean. Their structures were determined by extensive analysis of the spectroscopic and X-ray crystallographic data as well as by chiral HPLC analysis, ECD calculation, and DP4+ probability prediction. Structurally, versicoxepines B and C (2 and 3) represent the first example of a new oxepine-containing pyrazinopyrimidine alkaloid whose cyclic dipeptide moiety is composed of the same type of amino acid (Val or Ile). Compound 5 displayed antibacterial activity against aquatic pathogens, Vibrio harveyi and V. alginolyticus, with MICs of 8 µg/mL.

Thermographic evaluation of acupoints in lower limb region of individuals with osteoarthritis: A cross-sectional case-control study protocol.

PURPOSE: Acupuncture has been widely used in the treatment of knee osteoarthritis (KOA), but the selection of acupoints is indeterminate and lacks biological basis. The skin temperature of acupoints can reflect the state of local tissue and may be a potential factor for guiding acupoint selection. This study aims to compare the skin temperature of acupoints between KOA patients and the healthy population. STUDY DESIGN AND METHODS: This is a protocol for a cross-sectional case-control study with 170 KOA patients and 170 age- and gender-matched healthy individuals. Diagnosed patients aged 45 to 70 will be recruited in the KOA group. Participants in the healthy group will be matched with the KOA group based on mean age and gender distribution. Skin temperature of 11 acupoints (ST35, EX-LE5, GB33, GB34, EX-LE2, ST34, ST36, GB39, BL40, SP9, SP10) will be extracted from infrared thermography (IRT) images of the lower limbs. Other measurements will include demographic data (gender, age, ethnicity, education, height, weight, BMI) and disease-related data (numerical rating scale, pain sites, duration of pain, pain descriptors, pain activities). DISCUSSION: The results of this study will provide biological evidence for acupoint selection. This study is a precondition for follow-up studies, in which the value of optimized acupoint selection will be verified. TRIAL REGISTRATION: ChiCTR2200058867.

Acupuncture for cancer-related conditions: An overview of systematic reviews.

BACKGROUND: Acupuncture is commonly used for cancer-related conditions worldwide, and evidence is increasing year on year. There is a need to summarize the evidence of acupuncture for cancer-related conditions comprehensively and critically. OBJECTIVE: To evaluate and summarize the systematic reviews (SRs) that assess the effects and safety of acupuncture for cancer-related conditions, and to inform clinical practice and future studies. METHODS: A comprehensive search was conducted on Pubmed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, Sinomed, and Wanfang from their inception to October 16, 2021. SRs of randomized controlled trials (RCTs) on acupuncture for cancer-related conditions were to be included. Two reviewers screened the eligible articles, and four reviewers in pair extracted data and assessed the methodological quality/risk of bias of all included reviews by AMSTAR 2 and ROBIS tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a summary of meta-analysis or narrative description. RESULTS: Fifty-one SRs of RCTs on acupuncture for cancer-related conditions were included and synthesized. The methodological quality of SRs included 1 "high", 5 "low" and 45 "very low" by AMSTAR 2. Sixteen SRs assessed as low risk of bias (31.37%), and 35 SRs had high risk of bias (68.63%) by ROBIS. Acupuncture showed effective on systemic conditions in relation to different cancers, including cancer-related pain (17 SRs, 80 RCTs), fatigue (7 SRs, 18 RCTs), insomnia (4 SRs, 10 RCTs), quality of life (2 SRs, 15 RCTs); conditions in relation to chemo-radiotherapy, including nausea and vomiting (3 SRs, 36 RCTs) and bone marrow suppression (2 SRs, 21 RCTs); and conditions in relation to specific cancers, including breast cancer-related menopause (3 SRs, 6 RCTs), hot flashes (12 SRs, 13 RCTs), arthralgia (5 SRs, 10 RCTs), and nasopharyngeal cancer-related dysphagia (1 SRs, 7 RCTs). Acupuncture appeared to have benefit for patients with lymphoedema (3 SRs, 3 RCTs), gastrointestinal function (5 SRs, 27 RCTs), and xerostomia (4 SRs, 7 RCTs). Limited evidence showed inconsistent results on acupuncture for chemotherapy-induced peripheral neuropathy (3 SRs, 6 RCTs), depression and anxiety (3 SRs, 9 RCTs). Acupuncture was regarded as a safe therapy for cancer patients as no severe adverse events related were reported. CONCLUSION: Evidence from SRs showed that acupuncture is beneficial to cancer survivors with cancer-related pain, fatigue, insomnia, improved quality of life, nausea and vomiting, bone marrow suppression, menopausal symptoms, arthralgia, and dysphagia, and may also be potential for lymphoedema, gastrointestinal function, and xerostomia. For neuropathy, depression and anxiety, acupuncture should be used as an option based on individual conditions. Acupuncture is relatively safe without serious adverse events. More well-designed clinical trials of acupuncture are recommended on cancer-related depression and anxiety, arthralgia, xerostomia, gastrointestinal dysfunction and dysphagia.

Measurement of pharmacokinetics and tissue distribution of three bioactive constituents from Zanthoxylum armatum DC in rat plasma and tissues through UFLC-MS/MS.

The compounds of N-Methylanhydrotetrahydroberberrubine A, dictamnine and eudesmin were the primary bioactive components in the roots of Zanthoxylum armatum DC (Z. armatum). To clarify the pharmacokinetics and distribution of these three compounds, an ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was employed to determine the contents of these three compounds in rat plasma and seven tissues. The separation was achieved on a Kinetex XB-C18 100A column (2.1 × 50 mm, 2.6 µm, Phenomenex). The optimized mobile phase system was set with 0.1‰ formic acid aqueous solution (A) and acetonitrile (containing 0.1‰ formic acid) (B) with a programmed elution of 0.00 to 0.50 min, 2% B; 0.51-4.00 min, 30%-60% B; and 4.01-5.00 min, 2% B. All analytes were measured with optimized multiple reaction monitoring (MRM) in the positive ion ESI mode. Berberine hydrochloride was selected as the internal standard (IS). The MS/MS transitions of N-Methylanhydrotetrahydroberberrubine A, dictamnine, eudesmin and IS were 339.9135.1, 200.1 → 129.1, 387.4 → 369.0 and 337.1 → 321.1, respectively. The lower limits quantification (LLOQ) of the three analytes was 0.5-20 ng/ml. The linear ranges were 0.5-400 ng/ml for N-Methylanhydrotetrahydroberberrubine A and dictamnine and 20-4000 ng/ml for eudesmin. The present analysis showed that the two alkaloids were quickly absorbed, with Tmax in 0.167-0.292 h, and eudesmin was absorbed in 2.5 h. Moreover, all compounds were found at high concentrations in the gastrointestinal track. These results are helpful for further investigation of the clinical application of Z. armatum.

Barbaloin loaded polydopamine-polylactide-TPGS (PLA-TPGS) nanoparticles against gastric cancer as a targeted drug delivery system: Studies in vitro and in vivo.

Gastric cancer is the third leading cause of cancer-associated death worldwide. Although a decrease in its incidence is observed, gastric cancer still poses a major clinical challenge due to poor prognosis and limited treatments. Barbaloin (BBL) is a main medicinal composition of the Chinese traditional medicine aloe vera. BBL has various bioactivities, including anti-oxidant, anti-inflammatory and anti-tumor properties. Polydopamine (pD)-based surface modification is easy to functionalize polymeric nanoparticles (NPs) surfaces with ligands and/or additional polymeric layers. In the present study, BBL-loaded formulations was developed with pD-modified NPs, which was synthesized by polylactide-TPGS (PLA-TPGS) (pD-PLA-TPGS/NPs). And galactosamine (Gal) was conjugated on the prepared NPs (Gal-pD-PLA-TPGS/NPs) for targeting the gastric cancer cells. Here, we found that BBL-loaded Gal-pD-PLA-TPGS/NPs showed the highest cellular uptake efficacy in gastric cancer cells. Gal-pD-PLA-TPGS/NPs more significantly reduced the gastric cancer cell viability. Further, greater apoptosis, autophagy and ROS generation was induced by Gal-pD-PLA-TPGS/NPs in gastric cancer cells. Additionally, compared to the other two NPs, Gal-pD-PLA-TPGS/NPs most markedly decreased ATP levels in gastric cancer cells. In vivo, Gal-pD-PLA-TPGS/NPs were specifically targeted to tumor site. Moreover, Gal-pD-PLA-TPGS/NPs exhibited the most anti-tumor effects, as evidenced by the lowest tumor volume and tumor weight. Of note, there was no significant difference was observed in body and liver weight, as well as the histological changes in major organs isolated from each group of mice. Together, the findings indicated that BBL-loaded Gal-pD-PLA-TPGS/NPs could be targeted to gastric cancer cells to suppress tumor progression without toxicity.