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Fulltext Mycomedicine: A Unique Class of Natural Products with Potent Anti-tumour Bioactivities

Dai R, Liu M, Nik Nabil WN, Xi Z, Xu H

Molecules, 2021 Feb 19;26(4).
PMID: 33669877 DOI: 10.3390/molecules26041113

Mycomedicine is a unique class of natural medicine that has been widely used in Asian countries for thousands of years. Modern mycomedicine consists of fruiting bodies, spores, or other tissues of medicinal fungi, as well as bioactive components extracted from them, including polysaccharides and, triterpenoids, etc. Since the discovery of the famous fungal extract, penicillin, by Alexander Fleming in the late 19th century, researchers have realised the significant antibiotic and other medicinal values of fungal extracts. As medicinal fungi and fungal metabolites can induce apoptosis or autophagy, enhance the immune response, and reduce metastatic potential, several types of mushrooms, such as Ganoderma lucidum and Grifola frondosa, have been extensively investigated, and anti-cancer drugs have been developed from their extracts. Although some studies have highlighted the anti-cancer properties of a single, specific mushroom, only limited reviews have summarised diverse medicinal fungi as mycomedicine. In this review, we not only list the structures and functions of pharmaceutically active components isolated from mycomedicine, but also summarise the mechanisms underlying the potent bioactivities of several representative mushrooms in the Kingdom Fungi against various types of tumour.
Repurposing cardiac glycosides for anticancer treatment: a review of clinical studies

Nik Nabil WN, Dai R, Liu M, Xi Z, Xu H

Drug Discov Today, 2024 Aug 03;29(10):104129.
PMID: 39098384 DOI: 10.1016/j.drudis.2024.104129

Cardiac glycosides (CGs), which are traditionally used for heart disease, show promise for cancer therapy. However, there is a lack of a comprehensive review of clinical studies in this area, and so far, CGs have not been widely integrated into clinical cancer treatment. This review covers clinical studies from the past five years, highlighting the potential of CGs to reduce cancer risk, enhance chemotherapy effectiveness, mitigate chemotherapy-induced side effects and improve quality of life. Future clinical trials should personalize the dosage of CGs, integrate molecular testing and investigate immunogenic cell death induction and the potential of CGs for treating bone cancer and metastasis. Optimizing the repurposing of CGs for anticancer treatment requires consideration of specific CGs, cancer types and concurrent medications.
Fulltext Recent advances of γ-aminobutyric acid: Physiological and immunity function, enrichment, and metabolic pathway

Heli Z, Hongyu C, Dapeng B, Yee Shin T, Yejun Z, Xi Z, et al.

Front Nutr, 2022;9:1076223.
PMID: 36618705 DOI: 10.3389/fnut.2022.1076223

γ-aminobutyric acid (GABA) is a non-protein amino acid which naturally and widely occurs in animals, plants, and microorganisms. As the chief inhibitory neurotransmitter in the central nervous system of mammals, it has become a popular dietary supplement and has promising application in food industry. The current article reviews the most recent literature regarding the physiological functions, preparation methods, enrichment methods, metabolic pathways, and applications of GABA. This review sheds light on developing GABA-enriched plant varieties and food products, and provides insights for efficient production of GABA through synthetic biology approaches.
Fulltext Unveiling the dual role of autophagy in vascular remodelling and its related diseases

Ren H, Dai R, Nik Nabil WN, Xi Z, Wang F, Xu H

Biomed Pharmacother, 2023 Dec;168:115643.
PMID: 37839111 DOI: 10.1016/j.biopha.2023.115643

Vascular remodelling is an adaptive response to physiological and pathological stimuli that leads to structural and functional changes in the vascular intima, media, and adventitia. Pathological vascular remodelling is a hallmark feature of numerous vascular diseases, including atherosclerosis, hypertension, abdominal aortic aneurysm, pulmonary hypertension and preeclampsia. Autophagy is critical in maintaining cellular homeostasis, and its dysregulation has been implicated in the pathogenesis of various diseases, including vascular diseases. However, despite emerging evidence, the role of autophagy and its dual effects on vascular remodelling has garnered limited attention. Autophagy can exert protective and detrimental effects on the vascular intima, media and adventitia, thereby substantially influencing the course of vascular remodelling and its related vascular diseases. Currently, there has not been a review that thoroughly describes the regulation of autophagy in vascular remodelling and its impact on related diseases. Therefore, this review aimed to bridge this gap by focusing on the regulatory roles of autophagy in diseases related to vascular remodelling. This review also summarizes recent advancements in therapeutic agents targeting autophagy to regulate vascular remodelling. Additionally, this review offers an overview of recent breakthroughs in therapeutic agents targeting autophagy to regulate vascular remodelling. A deeper understanding of how autophagy orchestrates vascular remodelling can drive the development of targeted therapies for vascular diseases.
Unpacking the environmental quality through the effects of natural resources, renewable energy consumption, banking development and industrial value addition: An empirical evidence from BRICS countries

Bashir MA, Qing L, Dewil R, Xi Z, Razi U, Jingting L

J Environ Manage, 2024 Sep;367:122058.
PMID: 39106799 DOI: 10.1016/j.jenvman.2024.122058

This study explores the association between natural resources rent, industrial value addition, banking development, renewable energy consumption, total reserves and environmental quality in the dynamic context of BRICS nations from 1995 to 2019. BRICS economies are responsible for global greenhouse gas emissions and confront pressing environmental challenges, including biodiversity loss and pollution. For the dependent variable, the environmental quality, the study constructed a composite index using PCA for all environmental indicators where interdependencies among variables are prevalent. Besides this, the study incorporates two interaction terms to determine the indirect influence of natural resource rent and banking development on environmental quality through the mediating role of industrial value addition. By applying the CS-ARDL technique, the outcomes of the study reveal that natural resources rent, industrial value addition, and total reserves positively influence ENQ, indicating the adverse consequences of industrial sectors on environmental quality and continued environmental degradation due to resource-intensive industrial production, underscoring the urgency of sustainable resource management. In contrast, banking development and renewable energy consumption negatively influence ENQ, signifying the positive role of developed banking sectors in supporting eco-friendly projects and enhancing environmental quality. This study offers valuable insights for policy interventions to foster a more sustainable future.
Corrigendum to 'Unpacking the environmental quality through the effects of natural resources, renewable energy consumption, banking development and industrial value addition: An empirical evidence from BRICS countries' [J. Environ. Manage. 367, September 2024, 122058]

Adnan Bashir M, Qing L, Dewil R, Xi Z, Razi U, Jingting L

J Environ Manage, 2024 Aug 16.
PMID: 39153948 DOI: 10.1016/j.jenvman.2024.122221
Prediction models for intradialytic hypotension in hemodialysis patients: A protocol for systematic review and critical appraisal

Li Z, Yang L, Xi Z, Yi W, Zeng X, Ma D, et al.

PLoS One, 2024;19(9):e0310191.
PMID: 39250467 DOI: 10.1371/journal.pone.0310191

Intradialytic hypotension (IDH) is common in hemodialysis patients and can lead to several complications. Risk factors for IDH include demographic characteristics, comorbidities, dialysis procedure factors, and so on. Clinical studies on predictive models for dialysis-induced hypotension have shown inconsistent results. This systematic review aims to evaluate published prediction models for IDH, analyzing their characteristics, predictors, efficacy, and the methodological quality and applicability. The protocol has been prepared using the Preferred Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines. The systematic review protocol for IDH prediction in hemodialysis patients has been registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY2023110081, DOI: 10.37766/inplasy2023.11.0081). A comprehensive search across five major databases (PubMed, Web of Science, Cochrane Library, CNKI, and Wanfang) will be conducted for studies on prediction models of IDH among hemodialysis patients. Two researchers will independently screen literature, extract data, and evaluate the bias risk and applicability of included studies using prediction modelling study tools. This systematic review will provide critical insights into the efficacy and quality of reporting of the IDH model in hemodialysis patients. This will guide clinical staff in selecting the most appropriate IDH prediction model and inform future research endeavors in IDH prediction.
Fulltext Widespread ancient whole-genome duplications in Malpighiales coincide with Eocene global climatic upheaval

Cai L, Xi Z, Amorim AM, Sugumaran M, Rest JS, Liu L, et al.

New Phytol, 2019 Jan;221(1):565-576.
PMID: 30030969 DOI: 10.1111/nph.15357

Whole-genome duplications (WGDs) are widespread and prevalent in vascular plants and frequently coincide with major episodes of global and climatic upheaval, including the mass extinction at the Cretaceous-Tertiary boundary (c. 65 Ma) and during more recent periods of global aridification in the Miocene (c. 10-5 Ma). Here, we explore WGDs in the diverse flowering plant clade Malpighiales. Using transcriptomes and complete genomes from 42 species, we applied a multipronged phylogenomic pipeline to identify, locate, and determine the age of WGDs in Malpighiales using three means of inference: distributions of synonymous substitutions per synonymous site (Ks ) among paralogs, phylogenomic (gene tree) reconciliation, and a likelihood-based gene-count method. We conservatively identify 22 ancient WGDs, widely distributed across Malpighiales subclades. Importantly, these events are clustered around the Eocene-Paleocene transition (c. 54 Ma), during which time the planet was warmer and wetter than any period in the Cenozoic. These results establish that the Eocene Climatic Optimum likely represents a previously unrecognized period of prolific WGDs in plants, and lends further support to the hypothesis that polyploidization promotes adaptation and enhances plant survival during episodes of global change, especially for tropical organisms like Malpighiales, which have tight thermal tolerances.
Fulltext Towards a Framework for Better Understanding of Quiescent Cancer Cells

Nik Nabil WN, Xi Z, Song Z, Jin L, Zhang XD, Zhou H, et al.

Cells, 2021 03 05;10(3).
PMID: 33807533 DOI: 10.3390/cells10030562

Quiescent cancer cells (QCCs) are cancer cells that are reversibly suspended in G0 phase with the ability to re-enter the cell cycle and initiate tumor growth, and, ultimately, cancer recurrence and metastasis. QCCs are also therapeutically challenging due to their resistance to most conventional cancer treatments that selectively act on proliferating cells. Considering the significant impact of QCCs on cancer progression and treatment, better understanding of appropriate experimental models, and the evaluation of QCCs are key questions in the field that have direct influence on potential pharmacological interventions. Here, this review focuses on existing and emerging preclinical models and detection methods for QCCs and discusses their respective features and scope for application. By providing a framework for selecting appropriate experimental models and investigative methods, the identification of the key players that regulate the survival and activation of QCCs and the development of more effective QCC-targeting therapeutic agents may mitigate the consequences of QCCs.
Fulltext Saikosaponin A enhances Docetaxel efficacy by selectively inducing death of dormant prostate cancer cells through excessive autophagy

Feng J, Xi Z, Jiang X, Li Y, Nik Nabil WN, Liu M, et al.

Cancer Lett, 2023 Feb 01;554:216011.
PMID: 36442771 DOI: 10.1016/j.canlet.2022.216011

Quiescent cancer cells (QCCs), also known as dormant cancer cells, resist and survive chemo- and radiotherapy, resulting in treatment failure and later cancer recurrence when QCCs resume cell cycle progression. However, drugs selectively targeting QCCs are lacking. Saikosaponin A (SSA) derived from Bupleurum DC., is highly potent in eradicating multidrug-resistant prostate QCCs compared with proliferative prostate cancer cells. By further exacerbating the already increased autophagy through inactivation of Akt-mTOR signaling, SSA triggered cell death in QCCs. Contrarily, inhibition of autophagy or activation of Akt signaling pathway prevented SSA-induced cell death. The multicycle of Docetaxel treatments increased the proportion of QCCs, whereas administering SSA at intervals of Docetaxel treatments aggravated cell death in vitro and led to tumor growth arrest and cell death in vivo. In conclusion, SSA is posed as a novel QCCs-eradicating agent by aggravating autophagy in QCCs. In combination with the current therapy, SSA has potential to improve treatment effectiveness and to prevent cancer recurrence.
Deeply Altered Genome Architecture in the Endoparasitic Flowering Plant Sapria himalayana Griff. (Rafflesiaceae)

Cai L, Arnold BJ, Xi Z, Khost DE, Patel N, Hartmann CB, et al.

Curr Biol, 2021 03 08;31(5):1002-1011.e9.
PMID: 33485466 DOI: 10.1016/j.cub.2020.12.045

Despite more than 2,000-fold variation in genome size, key features of genome architecture are largely conserved across angiosperms. Parasitic plants have elucidated the many ways in which genomes can be modified, yet we still lack comprehensive genome data for species that represent the most extreme form of parasitism. Here, we present the highly modified genome of the iconic endophytic parasite Sapria himalayana Griff. (Rafflesiaceae), which lacks a typical plant body. First, 44% of the genes conserved in eurosids are lost in Sapria, dwarfing previously reported levels of gene loss in vascular plants. These losses demonstrate remarkable functional convergence with other parasitic plants, suggesting a common genetic roadmap underlying the evolution of plant parasitism. Second, we identified extreme disparity in intron size among retained genes. This includes a category of genes with introns longer than any so far observed in angiosperms, nearing 100 kb in some cases, and a second category of genes with exceptionally short or absent introns. Finally, at least 1.2% of the Sapria genome, including both genic and intergenic content, is inferred to be derived from host-to-parasite horizontal gene transfers (HGTs) and includes genes potentially adaptive for parasitism. Focused phylogenomic reconstruction of HGTs reveals a hidden history of former host-parasite associations involving close relatives of Sapria's modern hosts in the grapevine family. Our findings offer a unique perspective into how deeply angiosperm genomes can be altered to fit an extreme form of plant parasitism and demonstrate the value of HGTs as DNA fossils to investigate extinct symbioses.
Pulsatilla Decoction and its bioactive component β-peltatin induce G2/M cell cycle arrest and apoptosis in pancreatic cancer

Wu R, Xi Z, Liu M, Ren H, Dai R, Jiang X, et al.

Chin Med, 2023 May 28;18(1):61.
PMID: 37246229 DOI: 10.1186/s13020-023-00774-0

BACKGROUND: Pancreatic cancer (PAC), a malignancy that is fatal and commonly diagnosed at a late stage. Despite considerable advancements in cancer treatment, the survival rate of PAC remains largely consistent for the past 60 years. The traditional Chinese medicine formula Pulsatilla Decoction (PD) has been clinically used to treat inflammatory diseases for millennia and recently as a supplementary anti-cancer treatment in China. However, the bioactive ingredients and mechanisms underlying its anti-cancer effect remains unclear.
METHODS: The composition and quality control of PD were verified through analysis by high performance liquid chromatography. Cell viability was determined using Cell Counting Kit-8 assay. The cell cycle distribution was analyzed through PI staining and flow cytometry analysis, while apoptotic cells were measured by double staining with Annexin V-FITC and PI. We used immunoblotting to examine protein expressions. The in vivo effects of β-peltatin and podophyllotoxin were evaluated on a subcutaneously-xenografted BxPC-3 cell nude mice model.
RESULTS: The current study demonstrated that PD markedly inhibited PAC cell proliferation and triggered their apoptosis. Four herbal PD formula was then disassembled into 15 combinations of herbal ingredients and a cytotoxicity assay showed that the Pulsatillae chinensis exerted the predominant anti-PAC effect. Further investigation indicated that β-peltatin was potently cytotoxic with IC50 of ~ 2 nM. β-peltatin initially arrested PAC cells at G2/M phase, followed by apoptosis induction. Animal study confirmed that β-peltatin significantly suppressed the growth of subcutaneously-implanted BxPC-3 cell xenografts. Importantly, compared to podophyllotoxin that is the parental isomer of β-peltatin but clinically obsoleted due to its severe toxicity, β-peltatin exhibited stronger anti-PAC effect and lower toxicity in mice.
CONCLUSIONS: Our results demonstrate that Pulsatillae chinensis and particularly its bioactive ingredient β-peltatin suppress PAC by triggering cell cycle arrest at G2/M phase and apoptosis.

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