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Variations of metabolites and proteome in Lonicera japonica Thunb. buds and flowers under UV radiation

Zhu W, Zheng W, Hu X, Xu X, Zhang L, Tian J

Biochim Biophys Acta Proteins Proteom, 2017 Apr;1865(4):404-413.
PMID: 28087425 DOI: 10.1016/j.bbapap.2017.01.004

Lonicera japonica Thunb., also known as Jin Yin Hua and Japanese honeysuckle, is used as a herbal medicine in Asian countries. Its flowers have been used in folk medicine in the clinic and in making food or healthy beverages for over 1500years in China. To investigate the molecular processes involved in L. japonica development from buds to flowers exposed to UV radiation, a comparative proteomics analysis was performed. Fifty-four proteins were identified as differentially expressed, including 42 that had increased expression and 12 that had decreased expression. The levels of the proteins related to glycolysis, TCA/organic acid transformation, major carbohydrate metabolism, oxidative pentose phosphate, stress, secondary metabolism, hormone, and mitochondrial electron transport were increased during flower opening process after exposure to UV radiation. Six metabolites in L. japonica buds and flowers were identified and relatively quantified using LC-MS/MS. The antioxidant activity was performed using a 1,1-diphenyl-2-picrylhydrazyl assay, which revealed that L. japonica buds had more activity than the UV irradiated flowers. This suggests that UV-B radiation induces production of endogenous ethylene in L. japonica buds, thus facilitating blossoming of the buds and activating the antioxidant system. Additionally, the higher metabolite contents and antioxidant properties of L. japonica buds indicate that the L. japonica bud stage may be a more optimal time to harvest than the flower stage when using for medicinal properties.
TEOA, a triterpenoid from Actinidia eriantha, induces autophagy in SW620 cells via endoplasmic reticulum stress and ROS-dependent mitophagy

Zhang D, Gao C, Li R, Zhang L, Tian J

Arch Pharm Res, 2017 May;40(5):579-591.
PMID: 28211011 DOI: 10.1007/s12272-017-0899-9

2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62. Further analysis illustrated that TEOA promoted the phosphorylation of PERK and elF2α, followed by up-regulation of the downstream protein CHOP, suggesting the involvement of PERK/eIF2α/CHOP pathway and ER stress in TEOA-induced autophagy in SW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin, ubiquitin and p62 activation revealed that TEOA induced specific autophagy-mitophagy in SW620 cells. Additionally, an antioxidant NAC attenuated the TEOA-induced mitophagy, indicating that TEOA triggers mitophagy via a ROS-dependent pathway. Collectively, our findings revealed a novel cellular mechanism of TEOA in the colon cancer cell line SW620, thus providing a molecular basis for developing TEOA into an anti-tumor candidate.
Fulltext What can we learn from the Baduanjin rehabilitation as COVID-19 treatment?: A narrative review

Zhu Z, Pan X, Zhong F, Tian J, Ong MLY

Nurs Open, 2023 May;10(5):2819-2830.
PMID: 36575646 DOI: 10.1002/nop2.1572

AIM: To understand Baduanjin rehabilitation therapy in mild COVID-19 patients.
DESIGN: A narrative review.
METHODS: A literature search for COVID-19 and Baduanjin treatments was conducted on Chinese and English electronic databases: China National Knowledge Infrastructure, Wanfang Data, Embase, PubMed, Scopus, Science Direct, Ebscohost, SPORTDiscus and ProQuest.
RESULTS: Twelve studies on the Baduanjin rehabilitation for COVID-19 patients have been included. We acknowledged the considerable published research and current clinical practice using Baduanjin for COVID-19 treatment in the following areas: anxiety, depression, insomnia, lung function rehabilitation, immunity and activity endurance.
CONCLUSION: The use of Baduanjin as adjuvant therapy for COVID-19 patients' rehabilitation is still limited, therefore, more clinical studies are needed to confirm its efficacy.
Fulltext A meta-analysis of the effect of the Early Start Denver Model in children with autism spectrum disorder

Wang Z, Loh SC, Tian J, Chen QJ

Int J Dev Disabil, 2022;68(5):587-597.
PMID: 36210899 DOI: 10.1080/20473869.2020.1870419

Objectives: To examine and analyse the intervention effects of the Early Start Denver Model (ESDM) on children with autism spectrum disorder (ASD). Methods: This meta-analysis evaluated the effect sizes in four major domains of measurement (autism symptoms, language, cognition, and social communication). A total of 624 participants with ASD were included in 11 high-quality randomized controlled trial studies. Results: The results indicated that the ESDM intervention resulted in significant improvement with moderate effect sizes in the cognition (g = 0.28), autism symptoms (g = 0.27), and language (g = 0.29) domains. The effect sizes of autism symptoms and language were moderated by country (Western versus Asian countries). However, there were no significant effects observed for the social communication domain. Conclusion: The ESDM intervention significantly improved autism symptoms, language, and cognition. The effect sizes of autism symptoms and language were larger in Asian countries than in Western countries.
Fulltext The effect and action mechanism of resveratrol on the vascular endothelial cell by high glucose treatment

Liu X, Tian J, Bai Q, Ashraf MA, Sarfraz M, Zhao B

Saudi J Biol Sci, 2016 Jan;23(1):S16-21.
PMID: 26858561 DOI: 10.1016/j.sjbs.2015.06.021

To investigate the effect and action mechanism of resveratrol on the vascular endothelial cell by high glucose treatment. Primarily cultured human umbilical vein endothelial cells (HUVECs) were pretreated by resveratrol (0.2 μmol/L) and holding for 6 h, and then cultured in Dulbecco Modified Eagle Medium (DMEM) within 0.45 mmol/L of palmimte acid and 32.8 mmol/L of glucose, which is holding for 12 h. The cells were collected to analyze the expression of E-selected element. Supernatant of cultured cells, induced by 100 nmol/L insulin for 30 min, was used to analyze the nitric oxide content. Compared with normal control cells, the secretion of nitric oxide is stimulated by insulin decrease, however, the expression of E-selected element increased in HUVEC. Resveratrol treatment increased the secretion of nitric oxide stimulated by insulin and decreased the expression of E-selected element and partly counteracts the impairment of high glucose and palmitate acid on the function of endothelial cells. Resveratrol can improve and protect the function of high glucose and fatty acid cultured endothelial cell, and therefore may be a promising medicine in the prevention or therapy of diabetic macrovascular diseases.
Changes of alternative splicing in Arabidopsis thaliana grown under different CO2 concentrations

Huang W, Chen X, Guan Q, Zhong Z, Ma J, Yang B, et al.

Gene, 2019 Mar 20;689:43-50.
PMID: 30528270 DOI: 10.1016/j.gene.2018.11.083

Atmospheric CO2 level is one of the most important factors which affect plant growth and crop production. Although many crucial genes and pathways have been identified in response to atmospheric CO2 changes, the integrated and precise mechanisms of plant CO2 response are not well understood. Alternative splicing (AS) is an important gene regulation process that affects many biological processes in plants. However, the AS pattern changes in plants in response to elevated CO2 levels have not yet been investigated. Here, we used RNA-Seq data of Arabidopsis thaliana grown under different CO2 concentration to analyze the global changes in AS. We found that AS increased with the rise in CO2 concentration. Additionally, we identified 345 differentially expressed (DE) genes and 251 differentially alternative splicing (DAS) genes under the elevated CO2 condition. Moreover, the results showed that the expression of most of the DAS genes did not change significantly, indicating that AS can serve as an independent mechanism for gene regulation in response to elevated CO2. Furthermore, our analysis of function categories revealed that the DAS genes were associated mainly with the stimulus response. Overall, this the first study to explore the changes of AS in plants in response to elevated CO2.
Fulltext Organ-Specific Analysis of Morus alba Using a Gel-Free/Label-Free Proteomic Technique

Zhu W, Zhong Z, Liu S, Yang B, Komatsu S, Ge Z, et al.

Int J Mol Sci, 2019 Jan 16;20(2).
PMID: 30654535 DOI: 10.3390/ijms20020365

Morus alba is an important medicinal plant that is used to treat human diseases. The leaf, branch, and root of Morus can be applied as antidiabetic, antioxidant, and anti-inflammatory medicines, respectively. To explore the molecular mechanisms underlying the various pharmacological functions within different parts of Morus, organ-specific proteomics were performed. Protein profiles of the Morus leaf, branch, and root were determined using a gel-free/label-free proteomic technique. In the Morus leaf, branch, and root, a total of 492, 414, and 355 proteins were identified, respectively, including 84 common proteins. In leaf, the main function was related to protein degradation, photosynthesis, and redox ascorbate/glutathione metabolism. In branch, the main function was related to protein synthesis/degradation, stress, and redox ascorbate/glutathione metabolism. In root, the main function was related to protein synthesis/degradation, stress, and cell wall. Additionally, organ-specific metabolites and antioxidant activities were analyzed. These results revealed that flavonoids were highly accumulated in Morus root compared with the branch and leaf. Accordingly, two root-specific proteins named chalcone flavanone isomerase and flavonoid 3,5-hydroxylase were accumulated in the flavonoid pathway. Consistent with this finding, the content of the total flavonoids was higher in root compared to those detected in branch and leaf. These results suggest that the flavonoids in Morus root might be responsible for its biological activity and the root is the main part for flavonoid biosynthesis in Morus.
Phosphoinositide 3-kinase δ inactivation prevents vitreous-induced activation of AKT/MDM2/p53 and migration of retinal pigment epithelial cells

Han H, Chen N, Huang X, Liu B, Tian J, Lei H

J Biol Chem, 2019 10 18;294(42):15408-15417.
PMID: 31467081 DOI: 10.1074/jbc.RA119.010130

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that play a critical role in transmitting signals from cell-surface molecules to intracellular protein effectors. Key PI3Ks include PI3Kα, PI3Kβ, and PI3Kδ, which are regulated by receptors. The signaling pathway comprising the PI3Ks, along with a Ser/Thr kinase (AKT), a proto-oncogene product (mouse double minute (MDM)2), and a tumor suppressor protein (p53), plays an essential role in experimental proliferative vitreoretinopathy (PVR), which is a fibrotic blinding eye disorder. However, which PI3K isoforms are involved in PVR is unknown. A major characteristic of PVR is the formation of epi (or sub)-retinal membranes that consist of extracellular matrix and cells, including retinal pigment epithelium (RPE) cells, glial cells, and macrophages. RPE cells are considered key players in PVR pathogenesis. Using immunoblotting and immunofluorescence analyses, we herein provide the evidence that PI3Kδ is highly expressed in human RPEs when it is primarily expressed in leukocytes. We also found that PI3Kδ inactivation through two approaches, CRISPR/Cas9-mediated depletion and a PI3Kδ-specific inhibitor (idelalisib), not only blocks vitreous-induced activation of AKT and MDM2 but also abrogates a vitreous-stimulated decrease in p53. Furthermore, we demonstrate that PI3Kδ inactivation prevents vitreous-induced proliferation, migration, and contraction of human RPEs. These results suggest that PI3Kδ may represent a potential therapeutic target for RPE-related eye diseases, including PVR.
Fulltext Transcriptional regulation of Lonicera japonica Thunb. during flower development as revealed by comprehensive analysis of transcription factors

Wang T, Yang B, Guan Q, Chen X, Zhong Z, Huang W, et al.

BMC Plant Biol, 2019 May 14;19(1):198.
PMID: 31088368 DOI: 10.1186/s12870-019-1803-1

BACKGROUND: Lonicera japonica Thunb. flower has been used for the treatment of various diseases for a long time and attracted many studies on its potential effects. Transcription factors (TFs) regulate extensive biological processes during plant development. As the restricted reports of L. japonica on TFs, our work was carried out to better understand the TFs' regulatory roles under different developmental stages in L. japonica.
RESULTS: In this study, 1316 TFs belonging to 52 families were identified from the transcriptomic data, and corresponding expression profiles during the L. japonica flower development were comprehensively analyzed. 917 (69.68%) TFs were differentially expressed. TFs in bHLH, ERF, MYB, bZIP, and NAC families exhibited obviously altered expression during flower growth. Based on the analysis of differentially expressed TFs (DETFs), TFs in MYB, WRKY, NAC and LSD families that involved in phenylpropanoids biosynthesis, senescence processes and antioxidant activity were detected. The expression of MYB114 exhibited a positive correlation with the contents of luteoloside; Positive correlation was observed among the expression of MYC12, chalcone synthase (CHS) and flavonol synthase (FLS), while negative correlation was observed between the expression of MYB44 and the synthases; The expression of LSD1 was highly correlated with the expression of SOD and the total antioxidant capacity, while the expression of LOL1 and LOL2 exhibited a negative correlation with them; Many TFs in NAC and WRKY families may be potentially involved in the senescence process regulated by hormones and reactive oxygen species (ROS). The expression of NAC19, NAC29, and NAC53 exhibited a positive correlation with the contents of ABA and H2O2, while the expression of WRKY53, WRKY54, and WRKY70 exhibited a negative correlation with the contents of JA, SA and ABA.
CONCLUSIONS: Our study provided a comprehensive characterization of the expression profiles of TFs during the developmental stages of L. japonica. In addition, we detected the key TFs that may play significant roles in controlling active components biosynthesis, antioxidant activity and flower senescence in L. japonica, thereby providing valuable insights into the molecular networks underlying L. japonica flower development.
Comparative proteomics of Mesembryanthemum crystallinum guard cells and mesophyll cells in transition from C3 to CAM

Guan Q, Kong W, Zhu D, Zhu W, Dufresne C, Tian J, et al.

J Proteomics, 2021 01 16;231:104019.
PMID: 33075550 DOI: 10.1016/j.jprot.2020.104019

Salinity can induce Mesembryanthemum crystallinum to shift its photosynthesis from C3 to crassulacean acid metabolism (CAM), leading to enhanced plant water use efficiency. Studying how M. crystallinum changes its carbon fixation pathways is important for potential translation into crops and enhancing crop resilience. In this study, we examined proteomic changes in guard cells and mesophyll cells in the course of the C3 to CAM transition. We collected enriched guard cells and mesophyll cells during a short period of transition. A total of 1153 proteins were identified and quantified in the two cell-types. During the transition, proteins in the guard cells and mesophyll cells exhibited differential changes. For example, we observed nocturnal carbon fixation in mesophyll cells and proteins involved in cell growth in the two cell-types. Proteins involved in osmotic adjustment, ion transport, energy metabolism and light response may play important roles in the C3 to CAM transition. Real-time PCR experiments were conducted to determine potential correlations between transcript and protein levels. These results have highlighted potential molecular mechanisms underlying the C3 to CAM transition of guard cells and mesophyll cells of the important facultative CAM plant. BIOLOGICAL SIGNIFICANCE: Fresh water resource for agricultural food production is a global challenge. Nature has evolved crassulacean acid metabolism (CAM) plants with enhanced water use efficiency. Using single cell-type proteomics, this study revealed molecular changes taking place in guard cells and mesophyll cells during the shift of ice plant photosynthesis from C3 to CAM. The results have provided important insights into the CAM transition and may facilitate effort toward enhancing crop resilience for global food security.
Fulltext Capilliposide B blocks VEGF-induced angiogenesis in vitro in primary human retinal microvascular endothelial cells

Han H, Yang Y, Wu Z, Liu B, Dong L, Deng H, et al.

Biomed Pharmacother, 2021 Jan;133:110999.
PMID: 33227710 DOI: 10.1016/j.biopha.2020.110999

Abnormal angiogenesis is associated with intraocular diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, and current therapies for these eye diseases are not satisfactory. The purpose of this study was to determine whether capilliposide B (CPS-B), a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl, can inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis signaling events and cellular responses in primary human retinal microvascular endothelial cells (HRECs). Our study revealed that the capilliposide B IC50 for HRECs was 8.5 μM at 72 h and that 1 μM capilliposide B specifically inhibited VEGF-induced activation of VEGFR2 and its downstream signaling enzymes Akt and Erk. In addition, we discovered that this chemical effectively blocked VEGF-stimulated proliferation, migration and tube formation of the HRECs, suggesting that capilliposide B is a promising prophylactic for angiogenesis-associated diseases such as proliferative diabetic retinopathy.
Molecular Characterization of a Geranyl Diphosphate-Specific Prenyltransferase Catalyzing Stilbenoid Prenylation from Morus alba

Zhong Z, Zhu W, Liu S, Guan Q, Chen X, Huang W, et al.

Plant Cell Physiol, 2018 Nov 01;59(11):2214-2227.
PMID: 30020500 DOI: 10.1093/pcp/pcy138

Pharmaceutically active compounds from medical plants are attractive as a major source for new drug development. Prenylated stilbenoids with increased lipophilicity are valuable secondary metabolites which possess a wide range of biological activities. So far, many prenylated stilbenoids have been isolated from Morus alba but the enzyme responsible for the crucial prenyl modification remains unknown. In the present study, a stilbenoid-specific prenyltransferase (PT), termed Morus alba oxyresveratrol geranyltransferase (MaOGT), was identified and functionally characterized in vitro. MaOGT recognized oxyresveratrol and geranyl diphosphate (GPP) as natural substrates, and catalyzed oxyresveratrol prenylation. Our results indicated that MaOGT shared common features with other aromatic PTs, e.g. multiple transmembrane regions, conserved functional domains and targeting to plant plastids. This distinct PT represents the first stilbenoid-specific PT accepting GPP as a natural prenyl donor, and could help identify additional functionally varied PTs in moraceous plants. Furthermore, MaOGT might be applied for high-efficiency and large-scale prenylation of oxyresveratrol to produce bioactive compounds for potential therapeutic applications.
Fulltext Chalcomoracin is a potent anticancer agent acting through triggering Oxidative stress via a mitophagy- and paraptosis-dependent mechanism

Han H, Chou CC, Li R, Liu J, Zhang L, Zhu W, et al.

Sci Rep, 2018 06 22;8(1):9566.
PMID: 29934599 DOI: 10.1038/s41598-018-27724-3

Chalocomoracin (CMR), one of the major secondary metabolites found in fungus-infected mulberry leaves, is a potent anticancer agent. However, its anticancer mechanism remains elusive. Here, we demonstrated the potent anti-tumor activity and molecular mechanism of CMR both in vitro and in vivo. We showed for the first time that CMR treatment markedly promoted paraptosis along with extensive cytoplasmic vacuolation derived from the endoplasmic reticulum, rather than apoptosis, in PC-3 and MDA-MB-231cell lines. Additional studies revealed that ectopic expression of Myc-PINK1 (PTEN-induced kinase 1), a key regulator of mitophagy, rendered LNCap cells susceptible to CMR-induced paraptosis, suggesting that the mitophagy-dependent pathway plays a crucial role in inducing paraptosis by activating PINK1. CMR treatment directly upregulated PINK1 and downregulated Alix genes in MDA-MB-231 and PC-3 cell lines. Furthermore, mitophagy signaling and paraptosis with cytoplasmic vacuolation could be blocked by antioxidant N-acetylcysteine (NAC), indicating the novel pathway was triggered by reactive oxygen species (ROS) production. An in vivo MDA-MB-231 xenograft tumor model revealed that CMR suppressed tumor growth by inducing vacuolation production through the same signal changes as those observed in vitro. These data suggest that CMR is a potential therapeutic entity for cancer treatment through a non-apoptotic pathway.
New Determination Method of Two Bioactive Saponins in Lysimachia capillipes Hemsl. by Quantitative Analysis of Multi-Components by Single-Marker

Zhang X, Chen X, Jin J, Gong M, He Q, Li S, et al.

J Chromatogr Sci, 2021 Oct 29;59(10):941-948.
PMID: 33728454 DOI: 10.1093/chromsci/bmab028

Capilliposide B (CPS-B) and Capilliposide C (CPS-C), as the key components in Lysimachia capillipes Hemsl., increasingly aroused the interest and research concern of many researchers due to the good bioactivities. Nowadays, the reference standards of CPS-B and CPS-C yield were very limited. Due to the deficit of reference standards, the determination could be difficult to carry out, and the quality control and evaluation would be restrained afterwards. To solve this urgent problem, a quantitative analysis of multi-components by single-marker (QAMS) method was proposed and established based on high-performance liquid-chromatography tandem evaporative light-scattering detector. In this QAMS method, the content of the two bioactive components could be calculated by buddlejasaponin IV, which is applied as an external standard and readily obtained. And the methodological experiments were evaluated and indicated accuracy, stability and feasibility of this QAMS method. Therefore, in this study, this built method would properly meet the requirement of determination of CPS-B, CPS-C and quality control of the L. capillipes Hemsl. plant.
RNA-Seq transcriptomic analysis of the Morus alba L. leaves exposed to high-level UVB with or without dark treatment

Guan Q, Yu J, Zhu W, Yang B, Li Y, Zhang L, et al.

Gene, 2018 Mar 01;645:60-68.
PMID: 29274907 DOI: 10.1016/j.gene.2017.12.045

Ultraviolet-B (UVB) irradiation induces oxidative stress in plant cells due to the generation of excessive reactive oxygen species. Morus alba L. (M. abla) is an important medicinal plant used for the treatment of human diseases. Also, its leaves are widely used as food for silkworms. In our previous research, we found that a high level of UVB irradiation with dark incubation led to the accumulation of secondary metabolites in M. abla leaf. The aim of the present study was to describe and compare M. alba leaf transcriptomics with different treatments (control, UVB, UVB+dark). Leaf transcripts from M. alba were sequenced using an Illumina Hiseq 2000 system, which produced 14.27Gb of data including 153,204,462 paired-end reads among the three libraries. We de novo assembled 133,002 transcripts with an average length of 1270bp and filtered 69,728 non-redundant unigenes. A similarity search was performed against the non-redundant National Center of Biotechnology Information (NCBI) protein database, which returned 41.08% hits. Among the 20,040 unigenes annotated in UniProtKB/SwissProt database, 16,683 unigenes were assigned 102,232 gene ontology terms and 6667 unigenes were identified in 287 known metabolic pathways. Results of differential gene expression analysis together with real-time quantitative PCR tests indicated that UVB irradiation with dark incubation enhanced the flavonoid biosynthesis in M. alba leaf. Our findings provided a valuable proof for a better understanding of the metabolic mechanism under abiotic stresses in M. alba leaf.
Fulltext Comparative Proteomic Analysis Reveals Elevated Capacity for Photosynthesis in Polyphenol Oxidase Expression-Silenced Clematis terniflora DC. Leaves

Chen X, Yang B, Huang W, Wang T, Li Y, Zhong Z, et al.

Int J Mol Sci, 2018 Dec 05;19(12).
PMID: 30563128 DOI: 10.3390/ijms19123897

Polyphenol oxidase (PPO) catalyzes the o-hydroxylation of monophenols and oxidation of o-diphenols to quinones. Although the effects of PPO on plant physiology were recently proposed, little has been done to explore the inherent molecular mechanisms. To explore the in vivo physiological functions of PPO, a model with decreased PPO expression and enzymatic activity was constructed on Clematis terniflora DC. using virus-induced gene silencing (VIGS) technology. Proteomics was performed to identify the differentially expressed proteins (DEPs) in the model (VC) and empty vector-carrying plants (VV) untreated or exposed to high levels of UV-B and dark (HUV-B+D). Following integration, it was concluded that the DEPs mainly functioned in photosynthesis, glycolysis, and redox in the PPO silence plants. Mapman analysis showed that the DEPs were mainly involved in light reaction and Calvin cycle in photosynthesis. Further analysis illustrated that the expression level of adenosine triphosphate (ATP) synthase, the content of chlorophyll, and the photosynthesis rate were increased in VC plants compared to VV plants pre- and post HUV-B+D. These results indicate that the silence of PPO elevated the plant photosynthesis by activating the glycolysis process, regulating Calvin cycle and providing ATP for energy metabolism. This study provides a prospective approach for increasing crop yield in agricultural production.
Counteracting mental fatigue for athletes: a systematic review of the interventions

Sun H, Soh KG, Mohammadi A, Toumi Z, Zhang L, Ding C, et al.

BMC Psychol, 2024 Feb 09;12(1):67.
PMID: 38336843 DOI: 10.1186/s40359-023-01476-w

The deleterious effects of mental fatigue (MF) on athletes have been carefully studied in various sports, such as soccer, badminton, and swimming. Even though many researchers have sought ways to ameliorate the negative impact of MF, there is still a lack of studies that review the interventions used to counteract MF among athletes. This review aims to report the current evidence exploring the effects of interventions on MF and sport-specific performance, including sport-specific motor performance and perceptual-cognitive skills. Web of Science, Scopus, PubMed, and SPORTDicus (EBSCOhost) were combed through to find relevant publications. Additionally, the references and Google Scholar were searched for any grey literature. For the current review, we included only randomized controlled trials that involved athletes, a primary task to induce MF, interventions to counter MF with comparable protocols, and the outcomes of sport-specific motor performance and perceptual-cognitive skill. The selection criteria resulted in the inclusion of 10 articles. The manipulations of autonomous self-control exertion, person-fit, nature exposure, mindfulness, and transactional direct current stimulation showed that positive interventions counteract MF and improve sport-specific performance in different domains, including strength, speed, skill, stamina, and perceptual-cognitive skills. The selected interventions could significantly counteract MF and improve subsequent sport-specific performance. Moreover, self-regulation and attention resources showed the importance of the potential mechanisms behind the relevant interventions.
Fulltext A Novel Benzofuran Derivative Moracin N Induces Autophagy and Apoptosis Through ROS Generation in Lung Cancer

Gao C, Sun X, Wu Z, Yuan H, Han H, Huang H, et al.

Front Pharmacol, 2020;11:391.
PMID: 32477104 DOI: 10.3389/fphar.2020.00391

Introduction: The leaves of Morus alba L is a traditional Chinese medicine widely applied in lung diseases. Moracin N (MAN), a secondary metabolite extracted form the leaves of Morus alba L, is a potent anticancer agent. But its molecular mechanism remains unveiled.
Objective: In this study, we aimed to examine the effect of MAN on human lung cancer and reveal the underlying molecular mechanism.
Methods: MTT assay was conducted to measure cell viability. Annexin V-FITC/PI staining was used to detect cell apoptosis. Confocal microscope was performed to determine the formation of autophagosomes and autolysosomes. Flow cytometry was performed to quantify cell death. Western blotting was used to determine the related-signaling pathway.
Results: In the present study, we demonstrated for the first time that MAN inhibitd cell proliferation and induced cell apoptosis in human non-small-cell lung carcinoma (NSCLC) cells. We found that MAN treatment dysregulated mitochondrial function and led to mitochondrial apoptosis in A549 and PC9 cells. Meanwhile, MAN enhanced autophagy flux by the increase of autophagosome formation, the fusion of autophagsomes and lysosomes and lysosomal function. Moreover, mTOR signaling pathway, a classical pathway regualting autophagy, was inhibited by MAN in a time- and dose-dependent mannner, resulting in autophagy induction. Interestingly, autophagy inhibition by CQ or Atg5 knockdown attenuated cell apoptosis by MAN, indicating that autophagy serves as cell death. Furthermore, autophagy-mediated cell death by MAN can be blocked by reactive oxygen species (ROS) scavenger NAC, indicating that ROS accumulation is the inducing factor of apoptosis and autophagy. In summary, we revealed the molecular mechanism of MAN against lung cancer through apoptosis and autophagy, suggesting that MAN might be a novel therapeutic agent for NSCLC treatment.
Fulltext Identification of hidden N4-like viruses and their interactions with hosts

Zheng K, Liang Y, Paez-Espino D, Zou X, Gao C, Shao H, et al.

mSystems, 2023 Sep 13;8(5):e0019723.
PMID: 37702511 DOI: 10.1128/msystems.00197-23

The N4-like viruses, which were recently assigned to the novel viral family Schitoviridae in 2021, belong to a podoviral-like viral lineage and possess conserved genomic characteristics and a unique replication mechanism. Despite their significance, our understanding of N4-like viruses is primarily based on viral isolates. To address this knowledge gap, this study has established a comprehensive N4-like viral data sets comprising 342 high-quality N4-like viruses/proviruses (144 viral isolates, 158 uncultured viruses, and 40 integrated N4-like proviruses). These viruses were classified into 97 subfamilies (89 of which are newly identified), 148 genera (100 of which are newly identified), and 253 species (177 of which are newly identified). The study reveals that N4-like viruses inhibit the polar region, oligotrophic open oceans, and the human gut, where they infect various bacterial lineages, such as Alpha/Beta/Gamma/Epsilon-proteobacteria in the Proteobacteria phylum. Although N4-like viral endogenization appears to be prevalent in Proteobacteria, it has also been observed in Firmicutes. Additionally, the phylogenetic analysis has identified evolutionary divergence within the hallmark genes of N4-like viruses, indicating a complex origin of the different conserved parts of viral genomes. Moreover, 1,101 putative auxiliary metabolic genes (AMGs) were identified in the N4-like viral pan-proteome, which mainly participate in nucleotide and cofactor/vitamin metabolisms. Of these AMGs, 27 were found to be associated with virulence, suggesting their potential involvement in the spread of bacterial pathogenicity. IMPORTANCE The findings of this study are significant, as N4-like viruses represent a unique viral lineage with a distinct replication mechanism and a conserved core genome. This work has resulted in a comprehensive global map of the entire N4-like viral lineage, including information on their distribution in different biomes, evolutionary divergence, genomic diversity, and the potential for viral-mediated host metabolic reprogramming. As such, this work significantly contributes to our understanding of the ecological function and viral-host interactions of bacteriophages.
Fulltext Saline lakes on the Qinghai-Tibet Plateau harbor unique viral assemblages mediating microbial environmental adaption

Gu C, Liang Y, Li J, Shao H, Jiang Y, Zhou X, et al.

iScience, 2021 Dec 17;24(12):103439.
PMID: 34988389 DOI: 10.1016/j.isci.2021.103439

The highest plateau on Earth, Qinghai-Tibet Plateau, contains thousands of lakes with broad salinity and diverse and unique microbial communities. However, little is known about their co-occurring viruses. Herein, we identify 4,560 viral Operational Taxonomic Units (vOTUs) from six viromes of three saline lakes on Qinghai-Tibet Plateau, with less than 1% that could be classified. Most of the predicted vOTUs were associated with the dominant bacterial and archaeal phyla. Virus-encoded auxiliary metabolic genes suggest that viruses influence microbial metabolisms of carbon, nitrogen, sulfur, and lipid; the antibiotic resistance mediation; and their salinity adaption. The six viromes clustered together with the ice core viromes and bathypelagic ocean viromes and might represent a new viral habitat. This study has revealed the unique characteristics and potential ecological roles of DNA viromes in the lakes of the highest plateau and established a foundation for the recognition of the viral roles in plateau lake ecosystems.

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