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1.
Nat Prod Res ; : 1-9, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39229856

ABSTRACT

A phytochemical study on the stems and leaves of Cratoxylum cochinchinense (Lour.) Blume resulted in the isolation and characterisation of a new polyprenylated xanthone, cratocochinone (1), as well as seven known analogues, fuscaxanthone K (2), pruniflorone Q (3), 1,3,5,8-tetrahy-droxy- 2-(3-methybut-2-enyl)-4-(3,7-dimethylocta-2,6-dienyl) xanthone (4), cochinensoxanthone (5), cratoxylum-xanthone B (6), cochinchinone I (7) and cochinchinone K (8). The chemical structure of 1 was determined by comprehensive spectral analyses. The known compounds 2 - 8 were identified by comparing their experimental spectroscopic data with those reported data in the literature. The anti-inflammatory and anti-HIV effects of all isolates 1-8 were evaluated. As a result, compounds 1-8 showed remarkable inhibitory effects against nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells showing IC50 values ranging from 0.68 ± 0.06 to 10.27 ± 0.18 µM. Meanwhile, compounds 1-8 displayed notable anti-HIV-1 reverse transcriptase (RT) effects with EC50 values ranging from 0.19 to 10.72 µM.

2.
Nat Prod Res ; : 1-8, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39267311

ABSTRACT

Phytochemical study on the stems and leaves of Artocarpus tonkinensis led to the isolation of a new 2-arylbenzofuran, artocartone (1), as well as seven known 2-arylbenzofurans (2-8). The chemical structure of 1 was established by means of comprehensive spectroscopic analyses and the known compounds were determined by comparing their MS and NMR data with those reported data in literature. The antiproliferative activities of all isolates 1-8 against five human cancer cell lines: HL-60, SMMC-7721, A-375, MCF-7 and SW480 in vitro were evaluated. As a result, compounds 1- 8 displayed notable antiproliferative activities against various human cancer cell lines with IC50 values in the range of 0.28 ± 0.05-26.89 ± 0.18 µM.

3.
Int J Colorectal Dis ; 39(1): 142, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39289219

ABSTRACT

OBJECTIVE: The aim of this study is to evaluate the significance of combined detection of Septin9 and syndecan-2 (SDC2) methylation markers and serum tumor markers for the early diagnosis of colorectal cancer. METHODS: A total of 116 patients diagnosed with colorectal cancer between December 2022 and February 2024 were designated as the colorectal cancer group. Additionally, 31 patients with colorectal adenoma were assigned to the adenoma group, while 44 individuals undergoing routine physical examinations were included in the control group. Concentrations of Septin9, SDC2, fecal occult blood (FOB), and four tumor markers-carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 724 (CA724)-were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves for Septin9, SDC2, the four tumor markers, FOB, the combination of Septin9 and SDC2, and the combined use of all seven indicators (CEA, CA19-9, CA125, CA72-4, FOB, Septin9, and SDC2). RESULTS: The colorectal cancer group exhibited the highest positive rates for Septin9, SDC2, the four tumor markers, the combined detection of Septin9 and SDC2, and the combined detection of all seven indicators, compared to both the adenoma and control groups (P < 0.05). The adenoma group also showed higher positive rates than the control group (P < 0.05). For patients with stage I-III colorectal cancer, the positive rates for the combined detection of Septin9 and SDC2 were 81.3%, 78.9%, and 90.2%, respectively, surpassing those for the combined detection of the four tumor markers (43.8%, 55.3%, and 61.0%). Additionally, the positive rates for the two-gene combination in stage III colorectal cancer were higher than those for FOB (P < 0.05). The sensitivity and area under the curve (AUC) for SDC2 were 73.3% and 0.855, respectively, exceeding the sensitivity and AUC for the combined four tumor markers, which were 60.3% and 0.734 (P < 0.05). The combined detection of the two methylated genes demonstrated a sensitivity of 86.2% and an AUC of 0.908, outperforming both FOB and the combined detection of the four tumor markers (P < 0.05). CONCLUSION: The detection of SDC2 exhibits high sensitivity for colorectal cancer, and when combined with Septin9, it significantly enhances the diagnostic accuracy for early-stage colorectal cancer, offering substantial clinical value.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms , Early Detection of Cancer , Septins , Syndecan-2 , Humans , Septins/blood , Septins/genetics , Syndecan-2/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/diagnosis , Biomarkers, Tumor/blood , Female , Male , Middle Aged , Early Detection of Cancer/methods , Aged , ROC Curve , Adult , Occult Blood
4.
CNS Neurosci Ther ; 30(8): e14902, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39138637

ABSTRACT

AIMS: Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD. METHODS: The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression. RESULTS: Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3. CONCLUSIONS: CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p.


Subject(s)
Delirium , MicroRNAs , Neurons , Postoperative Complications , RNA, Circular , Sirtuin 3 , Animals , Sirtuin 3/metabolism , Sirtuin 3/genetics , Delirium/metabolism , Mice , MicroRNAs/metabolism , MicroRNAs/genetics , RNA, Circular/metabolism , Neurons/metabolism , Neurons/drug effects , Male , Postoperative Complications/metabolism , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/drug effects , Mice, Inbred C57BL , Tibial Fractures/surgery , Membrane Potential, Mitochondrial/drug effects , Membrane Potential, Mitochondrial/physiology
5.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3540-3547, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-39041125

ABSTRACT

The chemical constituents from the stems and leaves of Artocarpus tonkinensis in Artocarpus of Moraceae were systematically studied by means of silica gel, octadecylsilyl(ODS), and Sephadex LH-20 gel column chromatographies, as well as preparative high-performance liquid chromatography(Pre-HPLC) and a variety of chromatographic separation techniques. The spectral data and physicochemical properties of the compounds were obtained from separation and compared with those of the compounds reported in the literature. As a result, 11 compounds isolated from the 90% ethanol extract of the stems and leaves of A. tonkinensis were identified as artocatonkine(1), 5,6,7,4'-tetramethoxyflavone(2), apigenin-4'-O-ß-D-glucoside(3), rayalinol(4), psorachalcone A(5), 4-ketopinoresinol(6), ficusesquilignan B(7), pinnatifidanin AI(8), pinnatifidanin A(9), O-methylmellein(10), and trans-4-hydroxymellein(11). Among these compounds, compound 1 was a new prenylated flavone, and compounds 2-11 were isolated from the plants belonging to the genus Artocarpus for the first time. Furthermore, all compounds 1-11 were evaluated for their anti-rheumatoid arthritis activities, and the MTS method was used to measure their inhibitory effects on the proliferation of synovioblasts in vitro. The results of activity evaluation showed that flavonoid compounds 1-3, 5, and lignan compounds 8 and 9 displayed significant anti-rheumatoid arthritis activities, showing the IC_(50) values in inhibiting the proliferation of synovioblasts MH7A from(6.38±0.06) µmol·L~(-1) to(168.58±0.28)µmol·L~(-1).


Subject(s)
Artocarpus , Cell Proliferation , Plant Leaves , Plant Stems , Artocarpus/chemistry , Plant Leaves/chemistry , Plant Stems/chemistry , Cell Proliferation/drug effects , Humans , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Cell Line , Molecular Structure , Chromatography, High Pressure Liquid
6.
Nat Prod Res ; : 1-12, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693725

ABSTRACT

The genus Liparis, a group of perennial ornamental herbs in the family Orchidaceae, is widely distributed in tropical and subtropical regions. Many species of the genus Liparis have been commonly used as traditional herbal medicines for the treatment of menorrhagia, haemoptysis, traumatic bleeding, snake bites, and pneumonia. This review describes the ornamental value of plants of the genus Liparis and summarises the chemical constituents and pharmacological activities reported during the last decade. The main chemical constituents of this genus are phenolic acids, alkaloids, flavonoids, etc. Most phenolic acids and alkaloids have a nervogenic acid skeleton, and most alkaloids also have a pyrrolizidine skeleton. Extracts from the genus Liparis plants showed significant haemostatic, antitumor, anti-inflammatory, hypolipidemic, antioxidant, and antibacterial activities. This paper proposed ideas and research directions for the future study of plants in the genus Liparis, providing valuable information for the development of new drugs and promoting their utilisation.

7.
J Pain Res ; 17: 1055-1065, 2024.
Article in English | MEDLINE | ID: mdl-38505503

ABSTRACT

A negative correlation exists between attention and pain. The cognitive impairments linked to pain can significantly impede a patient's healing process and everyday tasks, particularly for individuals experiencing persistent pain. Furthermore, it has been demonstrated that diversion can effectively decrease pain levels in individuals. The focus of this review is to analyze clinical trials and fundamental investigations regarding alterations in focus and persistent discomfort. Moreover, we investigated the common neuroanatomy associated with attention and pain. Furthermore, we examined the impact of various neuromodulators on the transmission of pain and processes related to attention, while also considering the potential neural mechanisms that contribute to the co-occurrence of pain and attention deficits. Further investigation in this field will enhance our comprehension of patient symptoms and the underlying pathophysiology, ultimately resulting in more objective approaches to treatment.

8.
Mol Neurobiol ; 61(8): 5459-5480, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38200350

ABSTRACT

The mechanism of ketamine-induced neurotoxicity development remains elusive. Mitochondrial fusion/fission dynamics play a critical role in regulating neurogenesis. Therefore, this study was aimed to evaluate whether mitochondrial dynamics were involved in ketamine-induced impairment of neurogenesis in neonatal rats and long-term synaptic plasticity dysfunction. In the in vivo study, postnatal day 7 (PND-7) rats received intraperitoneal (i.p.) injection of 40 mg/kg ketamine for four consecutive times at 1 h intervals. The present findings revealed that ketamine induced mitochondrial fusion dysfunction in hippocampal neural stem cells (NSCs) by downregulating Mitofusin 2 (Mfn2) expression. In the in vitro study, ketamine treatment at 100 µM for 6 h significantly decreased the Mfn2 expression, and increased ROS generation, decreased mitochondrial membrane potential and ATP levels in cultured hippocampal NSCs. For the interventional study, lentivirus (LV) overexpressing Mfn2 (LV-Mfn2) or control LV vehicle was microinjected into the hippocampal dentate gyrus (DG) 4 days before ketamine administration. Targeted Mfn2 overexpression in the DG region could restore mitochondrial fusion in NSCs and reverse the inhibitory effect of ketamine on NSC proliferation and its faciliatory effect on neuronal differentiation. In addition, synaptic plasticity was evaluated by transmission electron microscopy, Golgi-Cox staining and long-term potentiation (LTP) recordings at 24 h after the end of the behavioral test. Preconditioning with LV-Mfn2 improved long-term cognitive dysfunction after repeated neonatal ketamine exposure by reversing the inhibitory effect of ketamine on synaptic plasticity in the hippocampal DG. The present findings demonstrated that Mfn2-mediated mitochondrial fusion dysfunction plays a critical role in the impairment of long-term neurocognitive function and synaptic plasticity caused by repeated neonatal ketamine exposure by interfering with hippocampal neurogenesis. Thus, Mfn2 might be a novel therapeutic target for the prevention of the developmental neurotoxicity of ketamine.


Subject(s)
Animals, Newborn , Cognition , GTP Phosphohydrolases , Hippocampus , Ketamine , Mitochondrial Dynamics , Neural Stem Cells , Neurogenesis , Rats, Sprague-Dawley , Animals , Male , Rats , Anesthesia/adverse effects , Cognition/drug effects , GTP Phosphohydrolases/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Ketamine/administration & dosage , Ketamine/adverse effects , Ketamine/toxicity , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondrial Dynamics/drug effects , Mitochondrial Proteins , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , Neurogenesis/drug effects , Neuronal Plasticity/drug effects
9.
Oral Oncol ; 148: 106657, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38101313

ABSTRACT

OBJECTIVES: To develop consensus on patient characteristics and disease-related factors considered in deciding treatment approaches for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) based on real-world treatment patterns in 4 territories in Asia-Pacific. METHODS: A three-round modified Delphi involving a multidisciplinary panel of HN surgeons, medical oncologists, and radiation oncologists was used. Of 41 panelists recruited, responses of 26 from Australia, Japan, Singapore, and Taiwan were analyzed. All panelists had ≥five years' experience managing LA-HNSCC patients and treated ≥15 patients with LA-HNSCC annually. RESULTS: All statements on definitions of LA-HNSCC, treatment intolerance and cisplatin dosing reached consensus. 4 of 7 statements on unresectability, 2 of 4 on adjuvant chemoradiotherapy, 7 of 13 on induction chemotherapy, 1 of 8 on absolute contraindications and 7 of 11 on relative contraindications to high-dose cisplatin did not reach consensus. In all territories except Taiwan, high-dose cisplatin was preferred in definitive and adjuvant settings for patients with no contraindications to cisplatin; weekly cisplatin (40 mg/m2) preferred for patients with relative contraindications to high-dose cisplatin. For Taiwan, the main treatment option was weekly cisplatin. For patients with absolute contraindications to cisplatin, carboplatin ± 5-fluorouracil or radiotherapy alone were preferred alternatives in both definitive and adjuvant settings. CONCLUSION: This multidisciplinary consensus provides insights into management of LA-HNSCC in Asia-Pacific based on patient- and disease-related factors that guide selection of treatment modality and systemic treatment. Despite strong consensus on use of cisplatin-based regimens, areas of non-consensus showed that variability in practice exists where there is limited evidence.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Cisplatin/therapeutic use , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/drug therapy , Consensus , Chemoradiotherapy/adverse effects , Carboplatin , Asia , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
10.
Cancer Imaging ; 23(1): 112, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37978567

ABSTRACT

BACKGROUND: To predict the microvascular invasion (MVI) in patients with cHCC-ICC. METHODS: A retrospective analysis was conducted on 119 patients who underwent CT enhancement scanning (from September 2006 to August 2022). They were divided into MVI-positive and MVI-negative groups. RESULTS: The proportion of patients with CEA elevation was higher in the MVI-positive group than in the MVI-negative group, with a statistically significant difference (P = 0.02). The MVI-positive group had a higher rate of peritumoral enhancement in the arterial phase (P = 0.01) whereas the MVI-negative group had more oval and lobulated masses (P = 0.04). According to the multivariate analysis, the increase in CEA (OR = 10.15, 95% CI: 1.11, 92.48, p = 0.04), hepatic capsular withdrawal (OR = 4.55, 95% CI: 1.44, 14.34, p = 0.01) and peritumoral enhancement (OR = 6.34, 95% CI: 2.18, 18.40, p < 0.01) are independent risk factors for predicting MVI. When these three imaging signs are combined, the specificity of MVI prediction was 70.59% (series connection), and the sensitivity was 100% (parallel connection). CONCLUSIONS: Our multivariate analysis found that CEA elevation, liver capsule depression, and arterial phase peritumoral enhancement were independent risk factors for predicting MVI in cHCC-ICC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/blood supply , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/blood supply , Retrospective Studies , Microvessels/diagnostic imaging , Neoplasm Invasiveness , Tomography, X-Ray Computed
11.
Zhongguo Zhong Yao Za Zhi ; 48(18): 5014-5023, 2023 Sep.
Article in Chinese | MEDLINE | ID: mdl-37802843

ABSTRACT

The chemical constituents from the stems and leaves of Cratoxylum cochinchinense were isolated and purified using silica gel, ODS gel, and Sephadex LH-20 gel column chromatography, as well as preparative HPLC. The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, and the comparison of their physicochemical and spectroscopic data with the reported data in literature. As a result, 21 compounds were isolated from the 90% ethanol extract of the stems and leaves of C. cochinchinense, which were identified as cratocochine(1), 1-hydroxy-3,7-dimethoxyxanthone(2), 1-hydroxy-5,6,7-trimethoxyxanthone(3), ferrxanthone(4), 3,6-dihydroxy-1,5-dimethoxyxanthone(5), 3,6-dihydroxy-1,7-dimethoxyxanthone(6), 1,2,5-trihydroxy-6,8-dimethoxyxanthone(7), securixanthone G(8), gentisein(9), 3,7-dihydroxy-1-methoxyxanthone(10), pancixanthone B(11), garcimangosxanthone A(12), pruniflorone L(13), 9-hydroxy alabaxanthone(14), cochinchinone A(15), luteolin(16), 3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol(17), N-benzyl-9-oxo-10E,12E-octadecadienamide(18), 15-hydroxy-7,13E-labdadiene(19), stigmasta-4,22-dien-3-one(20), and stigmast-5-en-3ß-ol(21). Among these isolates, compound 1 was a new xanthone, compounds 2-5, 7, 8, 12, and 16-21 were isolated from the Cratoxylum plant for the first time, and compounds 11 and 13 were obtained from C. cochinchinense for the first time. Furthermore, all isolated compounds 1-21 were appraised for their anti-rheumatoid arthritis activities by MTS method through measuring their anti-proliferative effect on synoviocytes in vitro. As a result, xanthones 1-15 displayed notable anti-rheumatoid arthritis activities, which showed inhibitory effects on the proliferation of MH7A synoviocytes with the IC_(50) values ranging from(8.98±0.12) to(228.68±0.32) µmol·L~(-1).


Subject(s)
Arthritis , Clusiaceae , Synoviocytes , Xanthones , Clusiaceae/chemistry , Xanthones/pharmacology , Xanthones/analysis , Plant Leaves/chemistry , Cell Proliferation
12.
Int J Biol Macromol ; 253(Pt 2): 126770, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37683741

ABSTRACT

Translesion synthesis (TLS) is a kind of DNA repair that maintains the stability of the genome and ensures the normal growth of life in cells under emergencies. Y-family DNA polymerases, as a kind of error-prone DNA polymerase, mainly perform TLS. Previous studies have suggested that the occurrence of tumors is associated with the overexpression of human DNA polymerase of the Y family. And the combination of Y-family DNA polymerase inhibitors is promising for cancer therapy. Here we report the functional and structural characterization of a member of the Y-family DNA polymerases, TTEDbh. We determine TTEDbh is an extreme TLS polymerase that can cross oxidative damage sites, and further identify the amino acids and novel structures that are critical for DNA binding, synthesis, fidelity, and oxidative damage bypass. Moreover, previously unnoticed structural elements with important functions have been discovered and analyzed. These studies provide a more experimental basis for further elucidating the molecular mechanisms of DNA polymerase in the Y family. It could also shed light on the design of drugs to target tumors.


Subject(s)
DNA Damage , Neoplasms , Humans , DNA-Directed DNA Polymerase/chemistry , DNA Repair , DNA Replication
13.
Molecules ; 28(16)2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37630303

ABSTRACT

Four new xanthones, cratocochinones A-D (1-4), together with eight known analogues (5-12), were isolated from the stems and leaves of Cratoxylum cochinchinense. The chemical structures of cratocochinones A-D (1-4) were elucidated by comprehensive spectroscopic analyses and the known compounds were identified by comparisons with the spectral data reported in the literature. All isolated compounds 1-12 were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1-12 showed remarkable inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro, with IC50 values in the range of 0.86 ± 0.05 to 18.36 ± 0.21 µM. Meanwhile, compounds 1-12 exhibited significant anti-HIV-1 activities with EC50 which ranged from 0.22 to 11.23 µM. These findings indicate that the discoveries of these xanthones, isolated from the stems and leaves of C. cochinchinense, showing significant anti-inflammatory and anti-HIV-1 effects could be of great importance to the research and development of new natural anti-inflammatory and anti-HIV agents.


Subject(s)
Anti-HIV Agents , Clusiaceae , HIV-1 , Xanthones , Animals , Mice , Plant Leaves , Anti-HIV Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Xanthones/pharmacology
14.
Biomolecules ; 13(4)2023 04 04.
Article in English | MEDLINE | ID: mdl-37189394

ABSTRACT

The scaffolding protein Axin is an important regulator of the Wnt signaling pathway, and its dysfunction is closely related to carcinogenesis. Axin could affect the assembly and dissociation of the ß-catenin destruction complex. It can be regulated by phosphorylation, poly-ADP-ribosylation, and ubiquitination. The E3 ubiquitin ligase SIAH1 participates in the Wnt pathway by targeting various components for degradation. SIAH1 is also implicated in the regulation of Axin2 degradation, but the specific mechanism remains unclear. Here, we verified that the Axin2-GSK3 binding domain (GBD) was sufficient for SIAH1 binding by the GST pull-down assay. Our crystal structure of the Axin2/SIAH1 complex at 2.53 Å resolution reveals that one Axin2 molecule binds to one SIAH1 molecule via its GBD. These interactions critically depend on a highly conserved peptide 361EMTPVEPA368 within the Axin2-GBD, which forms a loop and binds to a deep groove formed by ß1, ß2, and ß3 of SIAH1 by the N-terminal hydrophilic amino acids Arg361 and Thr363 and the C-terminal VxP motif. The novel binding mode indicates a promising drug-binding site for regulating Wnt/ß-catenin signaling.


Subject(s)
Glycogen Synthase Kinase 3 , Wnt Signaling Pathway , Humans , Axin Protein/genetics , Axin Protein/metabolism , Glycogen Synthase Kinase 3/metabolism , beta Catenin/metabolism , Ubiquitination
15.
Drugs R D ; 23(2): 121-127, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37012461

ABSTRACT

BACKGROUND AND OBJECTIVE: Abiraterone acetate tablet is an inhibitor of androgen synthesis, primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the bioequivalence and pharmacokinetics of the reference and test formulations of abiraterone acetate tablets in healthy Chinese volunteers. METHODS: A single-center, open, single-dose, randomized, three-period, three-sequence, semi-repeat (only repeated reference formulations), and reference formulation-corrected fasting reference-scaled average bioequivalence test was conducted in 36 healthy volunteers included in this study. Volunteers were randomly assigned to one of three groups in a 1:1:1 ratio. There was a minimum 7-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of abiraterone acetate tablets was determined by liquid chromatography-tandem mass spectrometry, and adverse events were recorded. RESULTS: Under fasting conditions, the maximum plasma concentration (Cmax) was 27.02 ± 14.21 ng/mL, area under the concentration-time curve from time zero to time t (AUCt) was 125.30 ± 82.41 h·ng/mL, and AUC from time zero to infinity (AUC∞) was 133.70 ± 83.99 h·ng/mL. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of AUCt and AUC∞ were in the range of 0.8000-1.2500, and the coefficient of variation (CVWR) of Cmax was more than 30%. The Critbound result was - 0.0522, and the GMR was between 0.8000 and 1.2500. CONCLUSION: Both test and reference formulations of abiraterone acetate tablets were bioequivalent in healthy Chinese subjects under fasting conditions. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04863105, registered 26 April 2021-retrospectively registered ( https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000ARAA&selectaction=Edit&uid=U00050YQ&ts=2&cx=-vbtjri.


Subject(s)
Abiraterone Acetate , East Asian People , Male , Humans , Therapeutic Equivalency , Abiraterone Acetate/pharmacokinetics , Cross-Over Studies , Area Under Curve , Fasting , Tablets , Healthy Volunteers
16.
J Phys Chem Lett ; 14(12): 3047-3056, 2023 Mar 30.
Article in English | MEDLINE | ID: mdl-36946651

ABSTRACT

Organic charge transfer (CT) cocrystals open a new door for the exploitation of low-dimensional near-infrared (NIR) emitters by a convenient self-assembly approach. However, research about the fabrication of sheet-like NIR-emitting microstructures that are significant for structural construction and integrated application is limited by the unidirectional molecular packing mode. Herein, via regulation of the biaxial intermolecular CT interaction, single-crystalline microsheets with remarkable NIR emission from 720 to 960 nm were synthesized via the solution self-assembly process of dithieno[3,2-b:2',3'-d]thiophene and 7,7,8,8-tetracyanoquinodimethane. The expected sheet-like structure is conducive to achieving a two-dimensional (2D) optical waveguide with an ultralow optical loss rate of 0.250 dB/µm at 860 nm. More significantly, these as-prepared organic microsheets with tunable thicknesses (h) from 100 to 1100 nm exhibit thickness-dependent NIR optical transportation performance. These findings could pave the way to a new class of low-dimensional NIR emitters for 2D photonics at telecom wavelengths.

17.
Zhongguo Zhong Yao Za Zhi ; 48(1): 105-113, 2023 Jan.
Article in Chinese | MEDLINE | ID: mdl-36725263

ABSTRACT

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2'-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3'-bisdemethyl pinoresinol(8), 3, 3'-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-ß-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-ß-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) µmol·L~(-1).


Subject(s)
Arthritis , Morinda , Synoviocytes , Fruit/chemistry , Morinda/chemistry , Cell Proliferation
18.
Nat Prod Res ; 37(9): 1456-1462, 2023 May.
Article in English | MEDLINE | ID: mdl-34894893

ABSTRACT

The phytochemical investigation on the fruits of Morinda citrifolia led to the isolation and characterization of a new anthraquinone, moricitrifone (1), along with seven known anthraquinones (2-8). The chemical structure of 1 was elucidated by extensive spectral analyses. The known compounds (2-8) were identified by comparing their spectral data with those reported in the literature. The antiproliferative activities of all isolated anthraquinones (1-8) against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 were evaluated in vitro. Compounds 1-8 exhibited remarkable antiproliferative activities with IC50 values ranging from 0.26 ± 0.05 to 16.58 ± 0.18 µM, which were comparable to those of doxorubicin.


Subject(s)
Morinda , Humans , Morinda/chemistry , Molecular Structure , Fruit/chemistry , Plant Extracts/chemistry , Anthraquinones/chemistry
19.
Nat Prod Res ; 37(12): 1961-1968, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35975763

ABSTRACT

The phytochemical study on the stems and leaves of Morinda citrifolia L. resulted in the isolation of a new naturally occurring bisabolane-type sesquiterpenoid, morincitrinoid A (1), together with five known analogues (2-6). The chemical structure of 1 was elucidated by comprehensive spectral analyses. The known compounds 2-6 were identified by comparing their spectral data with those reported in the literature, which were isolated from M. citrifolia for the first time. In addition, the anti-inflammatory and anti-HIV activities of compounds 1-6 were evaluated in vitro. Compounds 1-6 displayed significant inhibitory activities on NO (nitric oxide) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells with IC50 values ranging from 0.98 ± 0.07 to 6.32 ± 0.11 µM, which was comparable to hydrocortisone. Meanwhile, compounds 1-6 showed remarkable anti-HIV-1 reverse transcriptase (RT) effects with the EC50 values ranging from 0.16 to 6.29 µM.


Subject(s)
Monocyclic Sesquiterpenes , Animals , Mice , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Nitric Oxide/chemistry , Morinda/chemistry , Monocyclic Sesquiterpenes/chemistry , Monocyclic Sesquiterpenes/pharmacology , Molecular Structure
20.
Front Endocrinol (Lausanne) ; 13: 1050305, 2022.
Article in English | MEDLINE | ID: mdl-36465610

ABSTRACT

Objectives: Pseudohypoparathyroidism (PHP) is a rare disease, especially when combined with pregnancy. We aimed to explore the changes in serum calcium/parathyroid hormone (PTH) level and medical treatment in a case series of PHP during pregnancy and the postpartum period. Methods: A total of five PHP patients with six pregnancies were enrolled. The classification of PHP was based on (epi)genetic analysis. Clinical characteristics, biochemical indices, and treatment strategies before, during, and after pregnancy were retrospectively collected. Results: All patients received calcium and vitamin D agents with nearly normal serum calcium before pregnancy except patient 2 who was found hypocalcemic during gestation. All patients chose Cesarean section, and one suffered preterm delivery due to oligoamnios. The neonatal birth weight ranged from 2,250 to 4,300 g, and all neonates were free of hypocalcemia-related symptoms. The change in calcium metabolism was inconsistent including stable, improved, or worsened during pregnancy. Serum PTH level remained low in the first two trimesters in patients with stable and improved conditions while increased in the last two trimesters in patients with a worsened condition. Serum calcium changed inconsistently while PTH increased consistently during lactation. For patients who did not breastfeed, calcium homeostasis improved after delivery. Conclusion: Calcium homeostasis and medicine dosage changed differently in PHP patients during pregnancy and lactation. However, most patients had good pregnancy outcomes. Serum PTH levels might predict changes in calcium metabolism during pregnancy.


Subject(s)
Bone Density Conservation Agents , Pseudohypoparathyroidism , Pregnancy , Infant, Newborn , Humans , Female , Calcium , Cesarean Section , Retrospective Studies , Pseudohypoparathyroidism/complications , Pseudohypoparathyroidism/drug therapy , Postpartum Period
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