Biodiversity Medicine: New Horizon and New Opportunity for Cancer.

SUMMARY: Accessibility to standard of care remains a challenge to patients in low- and middle-income countries (LMIC), hampering efforts to alleviate the burden of cancer and to improve overall health outcomes. In response to this pressing global health care issue, we propose here a new strategy to create affordable, easily accessible, and effective therapeutic solutions to address this inequity in cancer treatment: the use of science-based biodiversity medicine as an alternative to modern drug therapy, in which we will leverage and combine high-throughput omics technologies with artificial intelligence, to study local biodiversity, their potential anticancer properties, and short- and long-term clinical response and outcomes.

Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches.

Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.

High-Resolution QTOF-MRM for Highly Accurate Identification and Quantification of Trace Levels of Triterpenoids in Ganoderma lucidum Mycelium.

The accurate quantification of triterpenoids in Ganoderma lucidum mushroom in the mycelium stage is challenging due to their low concentrations, interference from other possible isomers, and the complex matrix. Here, a high-resolution quadrupole-time-of-flight mass spectrometry "multiple reaction monitoring" with target enhancement (HR-QTOF-MRM) method was developed to quantify seven target triterpenoids in G. lucidum. The performance of this method was compared against an optimized QQQ-MRM method. The HR-QTOF-MRM was shown to be capable of distinguishing target triterpenoids from interferent peaks in the presence of matrices. The HR-QTOF-MRM LOD and LLOQ values were found to be one to two times lower than those derived from the QQQ-MRM method. Intraday and interday variabilities of the HR-QTOF-MRM demonstrated better reproducibility than the QQQ-MRM. In addition, excellent recoveries of the analytes ranging from 80 to 117% were achieved. Spiking experiments were carried out to verify and compare the quantitative accuracy of the two methods. The HR-QTOF-MRM method provided better percent accuracy, ranging from 84% to 99% (<3% RSD), compared with the range of 69 to 114% (<4%RSD) given by the QQQ-MRM method. These results demonstrate that the new HR-QTOF-MRM mode is able to improve sensitivity, reproducibility, and accuracy of trace level analysis of triterpenoids in the complex biological samples. The triterpenoid concentrations were in the range of nondetect to 0.06-6.72 mg/g of dried weight in fruiting body and to 0.0009-0.01 mg/g of dried weight in mycelium.

Characterization of Polysaccharides from Wild Edible Mushrooms from Thailand and Their Antioxidant, Antidiabetic, and Antihypertensive Activities.

Bioactive polysaccharides from three wild edible mushrooms (Rugibolutus extremiorientalis, Russula emetica, and Phleobopus portentosus) extracted by conventional refluxing extraction (RFE) and ultrasound-assisted extraction (UAE) were investigated. The result indicated that the PS of R. extremiorientalis extracted by RFE exhibited the greatest antioxidant activities on ABTS cation free radical scavenging (153.0 mg TEAC/g of the extract), DPPH radical scavenging (9.91 mg TEAC/g of the extract), and also reducing power capacity (10.2 mg TEAC/g of the extract). Whereas, those of R. emetica extracted by UAE have the highest antidiabetic and antihypertensive activities (56.3% and 70.5% inhibition, respectively). All crude PS extracts were composed mainly of carbohydrate and protein plus a small proportion of phenolic compounds of which glucose was the prevalent monosaccharide of all polysaccharides. PS of both R. extremiorientalis and R. emetica contained of ß-glycosidic conformation, while those of Ph. portentosus contained both α- and ß-glycosidic conformations.

UPLC-ESI-MRM/MS for Absolute Quantification and MS/MS Structural Elucidation of Six Specialized Pyranonaphthoquinone Metabolites From Ventilago harmandiana.

Pyranonaphthoquinones (PNQs) are important structural scaffolds found in numerous natural products. Research interest in these specialized metabolites lies in their natural occurrence and therapeutic activities. Nonetheless, research progress has thus far been hindered by the lack of analytical standards and analytical methods for both qualitative and quantitative analysis. We report here that various parts of Ventilago harmandiana are rich sources of PNQs. We developed an ultraperformance liquid chromatography-electrospray ionization multiple reaction monitoring/mass spectrometry method to quantitatively determine six PNQs from leaves, root, bark, wood, and heartwood. The addition of standards in combination with a stable isotope of salicylic acid-D6 was used to overcome the matrix effect with average recovery of 82% ± 1% (n = 15). The highest concentration of the total PNQs was found in the root (11,902 µg/g dry weight), whereas the lowest concentration was found in the leaves (28 µg/g dry weight). Except for the root, PNQ-332 was found to be the major compound in all parts of V. harmandiana, accounting for ∼48% of the total PNQs quantified in this study. However, PNQ-318A was the most abundant PNQ in the root sample, accounting for 27% of the total PNQs. Finally, we provide novel MS/MS spectra of the PNQs at different collision induction energies: 10, 20, and 40 eV (POS and NEG). For structural elucidation purposes, we propose complete MS/MS fragmentation pathways of PNQs using MS/MS spectra at collision energies of 20 and 40 eV. The MS/MS spectra along with our discussion on structural elucidation of these PNQs should be very useful to the natural products community to further exploring PNQs in V. harmandiana and various other sources.

Comparative Evaluation of Phytochemicals, and Antidiabetic and Antioxidant Activities of Cuscuta reflexa Grown on Different Hosts in Northern Thailand.

For the first time, total phytochemical profiles of methanol crude extracts of Cuscuta reflexa grown on three different hosts, Coccinia grandis, Ficus racemosa- and Samanea saman, that were cultivated in northern Thailand were examined, along with their antidiabetic and antioxidant activities. The highest level of total flavonoids (114.4 mg QE/ g extract) and total phenolic content (90.8 mg GAE/ g extract) were observed in the extract of Cu. reflexa that was grown on Co. grandis. The GC-MS results showed that various types of phenolic compounds, hydrocarbons, saturated fatty acids and methyl ester of fatty acids, unsaturated fatty acids and methyl ester of fatty acids, vitamin E, terpenes and sterol contained in the extracts of Cu. reflexa were-capable of being grown on three hosts. Moreover, the HPLC results showed the presence of gallic acid, catechin, vanillic acid, rutin and quercetin in all Cu. reflexa samples The extract of Cu. reflexa that was grown on Co. grandis represented the highest antidiabetic activity with a percent inhibition of 51.2. Moreover, the extract also possessed the greatest antioxidant activity (DPPH; IC50 168.6 µg/mL, FRAP; 40.5 mg GAE/ g extract).