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1.
Recent insights into oxidative metabolism of quercetin: catabolic profiles, degradation pathways, catalyzing metalloenzymes and molecular mechanisms.
Guo, B, Chou, F, Huang, L, Yin, F, Fang, J, Wang, JB, Jia, Z
Critical reviews in food science and nutrition. 2024;(5):1312-1339
Abstract
Quercetin is the most abundant polyphenolic flavonoid (flavonol subclass) in vegetal foods and medicinal plants. This dietary chemopreventive agent has drawn significant interest for its multiple beneficial health effects ("polypharmacology") largely associated with the well-documented antioxidant properties. However, controversies exist in the literature due to its dual anti-/pro-oxidant character, poor stability/bioavailability but multifaceted bioactivities, leaving much confusion as to its exact roles in vivo. Increasing evidence indicates that a prior oxidation of quercetin to generate an array of chemical diverse products with redox-active/electrophilic moieties is emerging as a new linkage to its versatile actions. The present review aims to provide a comprehensive overview of the oxidative conversion of quercetin by systematically analyzing the current quercetin-related knowledge, with a particular focus on the complete spectrum of metabolite products, the enzymes involved in the catabolism and the underlying molecular mechanisms. Herein we review and compare the oxidation pathways, protein structures and catalytic patterns of the related metalloenzymes (phenol oxidases, heme enzymes and specially quercetinases), aiming for a deeper mechanistic understanding of the unusual biotransformation behaviors of quercetin and its seemingly controversial biological functions.
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2.
Tetraarsenic tetrasulfide triggers ROS-induced apoptosis and ferroptosis in B-cell acute lymphoblastic leukaemia by targeting HK2.
Bai, W, Liu, D, Cheng, Q, Yang, X, Zhu, L, Qin, L, Fang, J
Translational oncology. 2024;:101850
Abstract
PURPOSE Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children. Despite cure rates of higher than 85 %, refractory or relapsed ALL still exhibits a bleak prognosis indicative of the dearth of treatment modalities specific for relapsed or refractory ALL. Prior research has implicated metabolic alterations in leukemia pathogenesis, and literature on the therapeutic efficacy of arsenic compounds targeting metabolic pathways in B-cell acute lymphoblastic leukemia (B-ALL) cells is scarce. METHODS A compound extracted from realgar, tetraarsenic tetrasulfide (As4S4), and its antitumor effects on B-ALL were experimentally examined in vitro and in vivo. RESULTS As4S4 apparently targets B-ALL cells by inducing specific cellular responses, including apoptosis, G2/M arrest, and ferroptosis. Interestingly, these effects are attributed to reactive oxygen species (ROS) accumulation, and increased ROS levels have been linked to both the mitochondria-dependent caspase cascade and the activation of p53 signaling. The ROS scavenger N-acetylcysteine (NAC) can counteract the effects of As4S4 treatment on Nalm-6 and RS4;11 cells. Specifically, by targeting Hexokinase-2 (HK2), As4S4 induces alterations in mitochondrial membrane potential and disrupts glucose metabolism, leading to ROS accumulation, and was shown to inhibit B-ALL cell proliferation in vitro and in vivo. Intriguingly, overexpression of HK2 can partially desensitize B-ALL cells to As4S4 treatment. CONCLUSION Tetraarsenic tetrasulfide can regulate the Warburg effect by controlling HK2 expression, a finding that provides both new mechanistic insight into metabolic alterations and pharmacological evidence for the clinical treatment of B-ALL.
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3.
Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-small-cell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial.
Wang, M, Fan, Y, Sun, M, Wang, Y, Zhao, Y, Jin, B, Hu, Y, Han, Z, Song, X, Liu, A, et al
The Lancet. Respiratory medicine. 2024;(3):217-224
Abstract
BACKGROUND Sunvozertinib is an oral, irreversible, and selective tyrosine kinase inhibitor that has a favourable safety profile and encouraging antitumour activity, as shown in phase 1 studies of patients with heavily pretreated non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation (exon20ins). We aimed to assess the antitumour efficacy of sunvozertinib in patients with platinum-pretreated locally advanced or metastatic NSCLC with EGFR exon20ins. METHODS WU-KONG6 is a single-group, open-label, multicentre phase 2 trial of sunvozertinib monotherapy, conducted across 37 medical centres in China. We enrolled adult patients with pathologically or cytologically confirmed locally advanced or metastatic NSCLC whose tumour tissue carried an EGFR exon20ins mutation. All patients had received at least one line of previous systemic therapy, with at least one line containing platinum-based chemotherapy. The primary endpoint was objective response rate (ORR), as assessed by the independent review committee. The ORR was defined as the percentage of patients who achieved complete or partial response, confirmed by two separate assessments with at least 4-week time interval, until disease progression or initiation of any new anti-cancer therapy. Enrolled patients received sunvozertinib 300 mg once daily until meeting discontinuation criteria per the protocol. Patients who received at least one dose of treatment and were evaluable for efficacy analysis were included in the primary analysis, and all patients who received at least one dose of treatment were included in the safety analysis. This study is registered with ChinaDrugTrials.org, CTR20211009, and ClinicalTrials.gov, NCT05712902, and efficacy and safety follow-up are ongoing. FINDINGS Between July 19, 2021, and May 6, 2022, 104 patients were enrolled. At data cutoff (Oct 17, 2022), the last enrolled patient had been followed up for about 6 months. Among 97 patients evaluable for efficacy analysis, 59 (61%) patients achieved tumour response, with a confirmed ORR of 61% (95% CI 50-71). All tumour responses were partial responses. Tumour responses were observed irrespective of age, sex, smoking history, EGFR exon20ins subtypes, brain metastasis at baseline, previous lines of therapy, and history of onco-immunotherapy. In total, 19 death events occurred over a median follow-up period of 7·6 months (IQR 6·1-9·4). Sunvozertinib was well tolerated at 300 mg once daily. The most common grade 3 or worse treatment-related adverse events were blood creatine phosphokinase increased (18 [17%] of 104), diarrhoea (eight [8%]), and anaemia (six [6%]). The most common serious treatment-related adverse events were interstitial lung disease (five [5%] of 104), anaemia (three [3%]), vomiting (two [2%]), nausea (two [2%]) and pneumonia (two [2%]). INTERPRETATION In this phase 2 study, sunvozertinib demonstrated antitumour efficacy in patients with platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins, with a manageable safety profile. A multinational randomised, phase 3 study of sunvozertinib versus platinum-doublet chemotherapy in EGFR exon20ins NSCLC is ongoing (NCT05668988). FUNDING Dizal Pharmaceutical.
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4.
Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons.
Wang, X, Fang, J, Yang, L
Open life sciences. 2024;(1):20220773
Abstract
The purpose of this study was to explore the related research progress of ocular complications (OCs) caused by type 2 diabetes mellitus (T2DM), tear and tarsal function, and the application of deep learning (DL) in the diagnosis of diabetes and OCs caused by it, to provide reference for the prevention and control of OCs in T2DM patients. This study reviewed the pathogenesis and treatment of diabetes retinopathy, keratopathy, dry eye disease, glaucoma, and cataract, analyzed the relationship between OCs and tear function and tarsal function, and discussed the application value of DL in the diagnosis of diabetes and OCs. Diabetes retinopathy is related to hyperglycemia, angiogenic factors, oxidative stress, hypertension, hyperlipidemia, and other factors. The increase in water content in the corneal stroma leads to corneal relaxation, loss of transparency, and elasticity, and can lead to the occurrence of corneal lesions. Dry eye syndrome is related to abnormal stability of the tear film and imbalance in neural and immune regulation. Elevated intraocular pressure, inflammatory reactions, atrophy of the optic nerve head, and damage to optic nerve fibers are the causes of glaucoma. Cataract is a common eye disease in the elderly, which is a visual disorder caused by lens opacity. Oxidative stress is an important factor in the occurrence of cataracts. In clinical practice, blood sugar control, laser therapy, and drug therapy are used to control the above eye complications. The function of tear and tarsal plate will be affected by eye diseases. Retinopathy and dry eye disease caused by diabetes will cause dysfunction of tear and tarsal plate, which will affect the eye function of patients. Furthermore, DL can automatically diagnose and classify eye diseases, automatically analyze fundus images, and accurately diagnose diabetes retinopathy, macular degeneration, and other diseases by analyzing and processing eye images and data. The treatment of T2DM is difficult and prone to OCs, which seriously threatens the normal life of patients. The occurrence of OCs is closely related to abnormal tear and tarsal function. Based on DL, clinical diagnosis and treatment of diabetes and its OCs can be carried out, which has positive application value.
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5.
Research on Coix seed as a food and medicinal resource, it's chemical components and their pharmacological activities: A review.
Li, H, Peng, L, Yin, F, Fang, J, Cai, L, Zhang, C, Xiang, Z, Zhao, Y, Zhang, S, Sheng, H, et al
Journal of ethnopharmacology. 2024;(Pt 3):117309
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Coix lacryma-jobi var. ma-yuen (Romanet du Caillaud) Stapf is a plant of the genus Coix in the Gramineae family. Coix seed is cultivated in various regions throughout China. In recent years, with the research on the medicinal value of Coix seed, it has received more and more widespread attention from people. Numerous pharmacological effects of Coix seed have been demonstrated through modern pharmacological studies, such as hypoglycemia, improving liver function, anti-tumor, regulating intestinal microbiota, improving spleen function, and anti-inflammatory effects. AIMS OF THE STUDY This article is a literature review. In recent years, despite the extensive research on Coix seed, there has yet to be a comprehensive review of its traditional usage, medicinal resources, chemical components, and pharmacological effects is still lacking. To fill this gap, the paper provides an overview of the latest research progress on Coix seed, aiming to offer guidance and references for its further development and comprehensive utilization. MATERIAL AND METHODS To gather information on the traditional usage, phytochemical ingredients, and pharmacological properties of Coix seed, we conducted a literature search using both Chinese and English languages in five databases: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Springer. RESULTS This article is a literature review. The chemical constituents of Coix seed include various fatty acids, esters, polysaccharides, sterols, alkaloids, triterpenes, tocopherols, lactams, lignans, phenols, flavonoids and other constituents. Modern pharmacological research has indeed shown that Coix seed has many pharmacological effects and is a natural anti-tumor drug. In addition to its anti-tumor effect, it also has pharmacological effects such as hypoglycemia, improving liver function, regulating intestinal microbiota, improving spleen function, and anti-inflammatory effects. CONCLUSIONS This article provides a brief overview of the traditional uses, biotechnological applications, chemical components, and pharmacological effects of Coix seed. It highlights the importance of establishing quality standards, discovering new active ingredients, and exploring pharmacological mechanisms in Coix seed research. The article also emphasizes the significance of clinical trials, toxicology studies, pharmacokinetics data, and multidisciplinary collaboration for further advancements in this field. Overall, it aims to enhance understanding of Coix seed and its potential in pharmaceutical development and wellness products.
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6.
Tryptophan sulfonate: A new chemical marker for accurate and efficient inspection of sulfur-treated food products.
Chan, KC, Zhang, WH, Chan, YM, Li, HL, Fang, J, Luo, HY, Xu, J
Food chemistry. 2024;:137360
Abstract
Sulfur treatment for the pesticidal and antibacterial processing of food products has been criticized since it impairs the quality of treated products. The inspection of sulfur-treated products is thus required to achieve the regulation of sulfur treatment. Sulfite assay is currently available for the inspection, but it bears the disadvantages of inaccurate results and complex experimental procedures. Here we report a new chemical marker, namely tryptophan sulfonate, that can be used for the accurate and efficient inspection of sulfur-treated foods. First, the marker was discovered in sulfur-fumigated ginger, yam, and ginseng by untargeted metabolomics. The marker identity was then elucidated using chromatographic separation, nuclear magnetic resonance analysis and chemical synthesis. Finally, to demonstrate its applicability in the inspection, a tryptophan sulfonate assay was developed to test 50 commercial food samples, and the results indicated that it performed better than the sulfite assay in terms of both accuracy and efficiency.
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7.
Bulk RNA-sequencing, single-cell RNA-sequencing analysis, and experimental validation reveal iron metabolism-related genes CISD2 and CYP17A1 are potential diagnostic markers for recurrent pregnancy loss.
He, YB, Han, L, Wang, C, Fang, J, Shang, Y, Cai, HL, Zhou, Q, Zhang, ZZ, Chen, SL, Li, JY, et al
Gene. 2024;:148168
Abstract
BACKGROUND Recurrent pregnancy loss (RPL) is associated with variable causes. Its etiology remains unexplained in about half of the cases, with no effective treatment available. Individuals with RPL have an irregular iron metabolism. In the present study, we identified key genes impacting iron metabolism that could be used for diagnosing and treating RPL. METHODS We obtained gene expression profiles from the Gene Expression Omnibus (GEO) database. The Molecular Signatures Database was used to identify 14 gene sets related to iron metabolism, comprising 520 iron metabolism genes. Differential analysis and a weighted gene co-expression network analysis (WGCNA) of gene expression revealed two iron metabolism-related hub genes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used on clinical samples to confirm our results. The receiver operating characteristic (ROC) analysis and immune infiltration analysis were conducted. In addition, we analyzed the distribution of genes and performed CellChat analysis by single-cell RNA sequencing. RESULTS The expression of two hub genes, namely, CDGSH iron sulfur domain 2 (CISD2)and Cytochrome P450 family 17 subfamily A member 1 (CYP17A1), were reduced in RPL, as verified by both qPCR and immunohistochemistry. The Gene Ontology (GO) analysis revealed the genes predominantly engaged in autophagy and iron metabolism. The area under the curve (AUC) demonstrated better diagnostic performance for RPL using CISD2 and CYP17A1. The single-cell transcriptomic analysis of RPL demonstrated that CISD2 is expressed in the majority of cell subpopulations, whereas CYP17A1 is not. The cell cycle analysis revealed highly active natural killer (NK) cells that displayed the highest communications with other cells, including the strongest interaction with macrophages through the migratory inhibitory factor (MIF) pathway. CONCLUSIONS Our study suggested that CISD2 and CYP17A1 genes are involved in abnormal iron metabolism, thereby contributing to RPL. These genes could be used as potential diagnostic and therapeutic markers for RPL.
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8.
Polyphenols as potential preventers of osteoporosis: A comprehensive review on antioxidant and anti-inflammatory effects, molecular mechanisms, and signal pathways in bone metabolism.
Su, Z, Yao, B, Liu, G, Fang, J
The Journal of nutritional biochemistry. 2024;:109488
Abstract
Osteoporosis (OP) is a skeletal disorder characterized by decreased bone density, alterations in bone microstructure, and increased damage to the bones. As the population ages and life expectancy increases, OP has become a global epidemic, drawing attention from scientists and doctors. Because of polyphenols have favorable antioxidant and anti-allergy effects, which are regarded as potential methods to prevent angiocardipathy and OP. Polyphenols offer a promising approach to preventing and treating OP by affecting bone metabolism, reducing bone resolution, maintaining bone density, and lowering the differentiation level of osteoclasts (OC). There are multiple ways in which polyphenols affect bone metabolism. This article provides an overview of how polyphenols inhibit oxidative stress, exert antibacterial effects, and prevent the occurrence of OP. Furthermore, we will explore the regulatory mechanisms and signaling pathways implicated in this process.
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9.
Glutamine addiction in tumor cell: oncogene regulation and clinical treatment.
Li, X, Peng, X, Li, Y, Wei, S, He, G, Liu, J, Li, X, Yang, S, Li, D, Lin, W, et al
Cell communication and signaling : CCS. 2024;(1):12
Abstract
After undergoing metabolic reprogramming, tumor cells consume additional glutamine to produce amino acids, nucleotides, fatty acids, and other substances to facilitate their unlimited proliferation. As such, the metabolism of glutamine is intricately linked to the survival and progression of cancer cells. Consequently, targeting the glutamine metabolism presents a promising strategy to inhibit growth of tumor cell and cancer development. This review describes glutamine uptake, metabolism, and transport in tumor cells and its pivotal role in biosynthesis of amino acids, fatty acids, nucleotides, and more. Furthermore, we have also summarized the impact of oncogenes like C-MYC, KRAS, HIF, and p53 on the regulation of glutamine metabolism and the mechanisms through which glutamine triggers mTORC1 activation. In addition, role of different anti-cancer agents in targeting glutamine metabolism has been described and their prospective applications are assessed.
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10.
Effects of postoperative antioxidants on the salivary glands in patients with thyroid cancer undergoing radioactive iodine-131 treatment.
Tong, H, Yue, R, Fang, J, Li, X, Yang, S, Hou, Y, Wang, R, Zhang, B, Liu, H, Wu, Z, et al
Nuclear medicine communications. 2024;(4):312-320
Abstract
OBJECTIVE This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 ( 131 I). METHODS A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131 I treatment. RESULTS Comparison of salivary gland function parameters before and after 131 I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P < 0.05). CONCLUSION During high-dose 131 I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect.