The chemical constituents from Cephalotaxus lanceolata were isolated and purified by using multiple chromatographic techniques, including octadecylsilane(ODS), silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). A total of 17 compounds obtained were identified by using spectroscopic methods such as nuclear magnetic resonance(NMR), mass spectrometry(MS), and ultraviolet(UV) combined with literature data. Compound 1 was a new alkaloid dimer, named cephalancetine E. The known compounds were determined as cephalancetine A(2), 11-hydroxycephalotaxine(3), 4-hydroxycephalotaxine(4), cephalotaxine(5), epicephalotaxine(6), cephalotaxine β-N-oxide(7), acetylcephalotaxine(8), cephalotine A(9), cephalotine B(10), 11-hydroxycephalotaxine hemiketal(11), 3-deoxy-3,11-epoxy-cephalotaxine(12), cephalotaxinone(13), isocephalotaxinone(14), 2,11-epoxy-1,2-dihydro-8-oxo-cephalotaxine(15), cephalotaxamide(16), and drupacine(17), respectively. Compounds 11, 12, and 15 were isolated from the Cephalotaxus genus for the first time. The biological activity was tested for compounds 1-17. The results reveal that compound 17 displays potent inhibitory activities against three human cancer cell lines(HepG-2, MCF-7, and SH-SY5Y).
Cephalotaxus/chemistry* ; Humans ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Harringtonines/pharmacology* ; Molecular Structure ; Dimerization ; Alkaloids/isolation & purification* ; Magnetic Resonance Spectroscopy

Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

The present study aimed to explore the chemical constituents from the stems and leaves of Cephalotaxus fortunei. Seven lignans were isolated from the 75% ethanol extract of C. fortunei by various chromatographic methods, including silica gel, ODS column chromatography, and HPLC. The structures of the isolated compounds were elucidated according to physicochemical properties and spectral data. Compound 1 is a new lignan named cephalignan A. The known compounds were identified as 8-hydroxy-conidendrine(2), isolariciresinol(3), leptolepisol D(4), diarctigenin(5), dihydrodehydrodiconiferyl alcohol 9'-O-β-D-glucopyranoside(6), and dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside(7). Compounds 2 and 5 were isolated from the Cephalotaxus plant for the first time.
Cephalotaxus ; Lignans/analysis* ; Plant Leaves/chemistry* ; Ethanol ; Chromatography, High Pressure Liquid

Antibodies, Monoclonal, Humanized ; Humans ; Myocarditis ; Taxus

Objective: To investigate the sensitization characteristics of Juniperus chinensis pollen in patients with allergic rhinitis and/or allergic asthma in Beijing area, and to explore the characteristics of Juniper chinensis pollen sensitized population. Methods: Patients with suspected allergic rhinitis and/or asthma from January 2017 to December 2019 in the outpatient department of Allergy Department of Beijing Shijitan Hospital were selected in this study. Skin prick test (SPT) was performed with Juniper chinensis pollen allergen reagent to compare different age and disease allergen distribution, and to observe the sensitization characteristics of its population. All of the analyses were performed using SAS software version 9.4. Results: A total of 8 380 patients were enrolled in the end. The total positive rate of Juniper chinensis pollen SPT reached 49.92% (4 183/8 380). The positive rate of Juniper chinensis pollen SPT was highest in the 10-14 age group, reaching 60.99% (283/464). Compared with other age groups, there was a statistical difference (χ²=266.77, P<0.01). The SPT positive rate of patients aged less than 10 years increased with the increase of age, while the SPT positive rate of patients aged over 40 years decreased with the increase of age. Single Juniper chinensis pollen was less allergenic, accounting for about 25.05% (1 048/4 183), and the patients' age was (35.21±12.39) years. Regardless of single Juniper chinensis pollen or other pollen allergies, allergic rhinitis was the main disease. Among the patients with SPT positive Juniper chinensis pollen combined with other inhaled pollen allergens, willow pollen accounted for the first (74.99%). The positive rate of Juniper chinensis pollen was the highest in patients with single allergic rhinitis, accounting for 52.05% (3 797/7 295), and the rate in patients with single allergic asthma was the lowest, accounting for 17.49% (53/303), with statistically difference (χ²=138.99, P<0.01). Conclusions: Juniper chinensis pollen is highly sensitized in patients with allergic rhinitis and/or allergic asthma in Beijing . The positive rate of SPT is highest among 10-14 age group, most of which showed strong positive reaction, and allergic rhinitis is more common in Juniper chinensis pollen sensitization diseases.
Adolescent ; Adult ; Allergens ; Asthma ; Child ; Humans ; Juniperus ; Pollen ; Rhinitis, Allergic ; Skin Tests

OBJECTIVE: "Multi-targeting" drugs can prove fruitful to combat drug-resistance of multifactorial disease-cervical cancer. This study envisioned to reveal if Thuja homeopathic mother tincture (MT) and its bioactive component could combat human papillomavirus (HPV)-16-infected SiHa cervical cancer cells since it is globally acclaimed for HPV-mediated warts. METHODS: Thuja MT was studied for its antiproliferative and antimigratory properties in SiHa cells followed by microscopic determination of reactive oxygen species (ROS) generation by 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) staining and loss in mitochondrial membrane potential (MtMP) by rhodamine 123 (Rh123) staining. Apoptosis and autophagy inductions were studied by acridine orange/ethidium bromide (AO/EB) staining and immunoblot analyses of marker proteins. The bioactive component of Thuja MT detected by gas chromatography-mass spectrometry was studied for antiproliferative and antimigratory properties along with in silico prediction of its cellular targets by molecular docking and oral drug forming competency. RESULTS: Thuja MT showed significant antiproliferative and antimigratory potential in SiHa cells at a 50% inhibitory concentration (IC₅₀) of 17.3 µL/mL. An increase in DCFDA fluorescence and loss in Rh123 fluorescence prove that Thuja MT acted through the burst of ROS and loss in MtMP respectively. AO/EB-stained cells under the microscope and immunoblot analyses supported Thuja-induced cellular demise via dual pathways-apoptosis and autophagy. Immunoblots showed cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) along with upregulation of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, and p62 proteins. Hence, the apoptotic cascade followed a caspase-3-dependent pathway supported by PARP-1 cleavage, while autophagic death was Beclin-1-dependent and mediated by accumulation of LC3BII and p62 proteins. Thujone, detected as the bioactive principle of Thuja MT, showed greater anti-proliferative and anti-migratory potential at an IC₅₀ of 77 µg/mL, along with excellent oral drug competency with the ability for gastrointestinal absorption and blood-brain-barrier permeation with nil toxicity. Molecular docking depicted thujone with the strongest affinity for mammalian target of rapamycin, phosphoinositide 3-kinase, and protein kinase B followed by B-cell lymphoma 2, murine double minute 2 and adenosine monophosphate-activated protein kinase, which might act as upstream triggers of apoptotic-autophagic crosstalk. CONCLUSION Robust "multi-targeting" anticancer potential of Thuja drug and thujone for HPV-infected cervical cancer ascertained its therapeutic efficacy for HPV infections.
Animals ; Apoptosis ; Autophagy ; Beclin-1/pharmacology* ; Bicyclic Monoterpenes ; Caspase 3 ; Cell Line, Tumor ; Female ; Humans ; Mammals/metabolism* ; Mice ; Molecular Docking Simulation ; Papillomavirus Infections/drug therapy* ; Phosphatidylinositol 3-Kinases ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Reactive Oxygen Species/metabolism* ; Thuja/metabolism* ; Uterine Cervical Neoplasms/pathology*

BACKGROUND AND OBJECTIVES: The impact of SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery score (SS) and SS II in patients who receive percutaneous coronary intervention with second-generation everolimus-eluting stents (EES) has not been fully validated.METHODS: The SS, SS II were calculated in 1,248 patients with left main and/or 3-vessel disease treated with EES. Patient-oriented composite endpoint (POCE; all-cause death, any myocardial infarction (MI), any revascularization) and target lesion failure (TLF: cardiac death, target-vessel MI, target lesion revascularization) were analyzed.RESULTS: The mean SS was 21.1±9.6. Three-year POCE increased according to the SS group (15.2% vs. 19.9% vs. 27.4% for low (≤22), intermediate (≥23, ≤32), high (≥33) SS groups, p<0.001). By multivariate Cox proportional hazard analysis, SS group was an independent predictor of 3-year POCE (hazard ratio, 1.324; 95% confidence interval, 1.095–1.601; p=0.004). The receiver operating characteristic curves revealed that the SS II was superior to the SS for 3-year POCE prediction (area under the curve [AUC]: 0.611 vs. 0.669 for SS vs. SS II, p=0.019), but not for 3-year TLF (AUC: 0.631 vs. 0.660 for SS vs. SS II, p=0.996). In subgroup analysis, SS II was superior to SS in patients with cardiovascular clinical risk factors, and in those presenting as stable angina.CONCLUSIONS: The usefulness of SS and SS II was still valid in patients with left main and/or 3-vessel disease. SS II was superior to SS for the prediction of patient-oriented outcomes, but not for lesion-oriented outcomes.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00698607ClinicalTrials.gov Identifier: NCT01605721
Angina, Stable ; Death ; Drug-Eluting Stents ; Humans ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Risk Factors ; ROC Curve ; Stents ; Taxus ; Thoracic Surgery

A pollen/food-associated syndrome (PFAS) has been described between peach and cypress pollen. Cross-reactive allergens were characterized which belong to the Gibberellin-regulated protein (GRP) family, BP14 in cypress pollen and Pru p 7 in peach. GRP are small cationic protein with anti-microbial properties. A patient suffering from a peach/cypress syndrome was explored clinically and biologically using 2 types of immunoglobulin E (IgE) multiarray microchip, immunoblots and a basophil activation test to assess the clinical relevance of various extracts and purified allergens from fruits or cypress pollen. In addition to PR10 sensitization, the patient showed specific IgE to Pru p 7, BP14 and allergen from pomegranate. These last 3 allergens and allergenic sources are able to induce ex vivo basophil activation characterized by the monitoring of the expression of CD63 and CD203c, both cell surface markers correlated with a basophil mediator release. Up to 100% of cells expressed CD203c at 50 ng/mL of BP14 protein. In contrast, snakin-1, a GRP from potato sharing 82% sequence identity with Pru p 7 did not activate patient's basophils. These results strongly suggest that, like Pru p 7, BP14 is a clinically relevant allergenic GRP from pollen. Allergen members of this newly described protein family are good candidates for PFAS where no cross-reactive allergens have been characterized.
Allergens ; Basophils ; Cupressus* ; Fruit ; Humans ; Immunoglobulin E ; Immunoglobulins ; Pollen* ; Prunus persica ; Punicaceae ; Solanum tuberosum

The discovery of hydroxylases in the anticancer drug taxol biosynthesis pathway is a hotspot and difficulty in current research. In this study, a new hydroxylase gene TcCYP725A22 (GenBank accession number: MF448646.1) was used to construct a sub-cellular localization vector pCAMIBA1303-TcCYP725A22-EGFP to get the transient expression in onion epidermal cells. Laser confocal microscopy revealed that the protein encoded by this gene was localized in the cell membrane. Furthermore, the recombinant plant expression plasmid pBI121-TcCYP725A22 was constructed. After transient transformation to the Taxus chinensis mediated by Agrobacterium tumefaciens LBA4404, qRT-PCR and LC-MS were utilized to analyze the effects of TcCYP725A22 overexpression on the synthesis of taxol. The results showed that, in the TcCYP725A22 overexpressed cell line, expression levels of most defined hydroxylase genes for taxol biosynthesis were increased, and the yield of taxanes were also increased. It was concluded that the hydroxylase gene TcCYP725A22 is likely involved in the biosynthetic pathway of taxol.
Biosynthetic Pathways ; Mixed Function Oxygenases ; Paclitaxel ; Taxoids ; Taxus

OBJECTIVES: Tree pollen causes allergic rhinitis and asthma. We investigated children who diagnosed as rhinitis or asthma, living in Busan, for tree allergen sensitization, component allergen, oral allergy syndrome, and the relationship between pollen counts and allergen sensitization.METHODS: Pollen were collected in Busan, from January 1 to December 31, 2017, using a Rotorod sampler and enumerated using a microscope. We conducted a study of children with rhinitis or asthma at Busan St. Mary's Hospital in 2017, administered an ISAAC questionnaire, and an oral allergy syndrome survey. Serum specific Ig E tests were performed.RESULTS: Among the 57 patients, the mean age was 9.3 years. The pollen counts in decreasing order were as follows: pine, alder, oak, juniper, beech, ginkgo, and birch. For sensitization, birch and alder 35.1%, Japanese cedar 19.3%, juniper 17.5%, pine 10.5%, and Japanese cypress 8.2%. The component Ig E was tested in 27 patients. Bet v 1 had a high correlation with birch, alder, and peach. Bet v 2 showed a statistically significant correlation with all tree pollen except cypress. Bet v 4 did not have any apparent correlation. Bet v 6 had the same pattern as Bet v 2, but correlation coefficient was higher than that of Bet v 2. Oral allergy syndrome was noted in 7 patients, including peach, peanut, apple, tomato, kiwi, and sesame.CONCLUSIONS: Alder and juniper are clinically important tree pollens in Busan. These pollens cause sensitization to birch and Japanese cedar by cross-reaction.
Alnus ; Arachis ; Asian Continental Ancestry Group ; Asthma ; Betula ; Busan ; Child ; Cryptomeria ; Cupressus ; Fagus ; Ginkgo biloba ; Humans ; Hypersensitivity ; Juniperus ; Lycopersicon esculentum ; Pollen ; Prunus persica ; Rhinitis ; Rhinitis, Allergic ; Sesamum ; Trees