Displaying publications 1 - 20 of 72 in total

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  1. Choo SW, Wee WY, Ngeow YF, Mitchell W, Tan JL, Wong GJ, et al.
    Sci Rep, 2014;4:4061.
    PMID: 24515248 DOI: 10.1038/srep04061
    Mycobacterium abscessus (Ma) is an emerging human pathogen that causes both soft tissue infections and systemic disease. We present the first comparative whole-genome study of Ma strains isolated from patients of wide geographical origin. We found a high proportion of accessory strain-specific genes indicating an open, non-conservative pan-genome structure, and clear evidence of rapid phage-mediated evolution. Although we found fewer virulence factors in Ma compared to M. tuberculosis, our data indicated that Ma evolves rapidly and therefore should be monitored closely for the acquisition of more pathogenic traits. This comparative study provides a better understanding of Ma and forms the basis for future functional work on this important pathogen.
  2. Liu K, Wang H, Xiao J, Taha Z
    Comput Intell Neurosci, 2015;2015:158478.
    PMID: 25866500 DOI: 10.1155/2015/158478
    The purpose of this research is to analyse the relationship between nonlinear dynamic character and individuals' standing balance by the largest Lyapunov exponent, which is regarded as a metric for assessing standing balance. According to previous study, the largest Lyapunov exponent from centre of pressure time series could not well quantify the human balance ability. In this research, two improvements were made. Firstly, an external stimulus was applied to feet in the form of continuous horizontal sinusoidal motion by a moving platform. Secondly, a multiaccelerometer subsystem was adopted. Twenty healthy volunteers participated in this experiment. A new metric, coordinated largest Lyapunov exponent was proposed, which reflected the relationship of body segments by integrating multidimensional largest Lyapunov exponent values. By using this metric in actual standing performance under sinusoidal stimulus, an obvious relationship between the new metric and the actual balance ability was found in the majority of the subjects. These results show that the sinusoidal stimulus can make human balance characteristics more obvious, which is beneficial to assess balance, and balance is determined by the ability of coordinating all body segments.
  3. Zheng Y, Wang Q, Zhuang W, Lu X, Miron A, Chai TT, et al.
    Molecules, 2016 Nov 02;21(11).
    PMID: 27827862
    Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water-soluble polysaccharides from lotus seeds (LSPS) were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant inhibitory effects on the mouse gastric cancer MFC cells, human liver cancer HuH-7 cells and mouse hepatocarcinoma H22 cells. The animal studies showed that LSPS inhibited tumor growth in H22 tumor-bearing mice with the highest inhibition rate of 45.36%, which is comparable to that induced by cyclophosphamide (30 mg/kg) treatment (50.79%). The concentrations of white blood cells were significantly reduced in cyclophosphamide-treated groups (p < 0.01), while LSPS showed much fewer side effects according to the hematology analysis. LSPS improved the immune response in H22 tumor-bearing mice by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2. Moreover, LSPS also showed in vivo antioxidant activity by increasing superoxide dismutase activity, thus reducing the malondialdehyde level in the liver tissue. These results suggested that LSPS can be used as an antitumor and immunomodulatory agent.
  4. Zhao J, Xiao J, Lee ML, Ma Y
    Springerplus, 2016;5(1):1633.
    PMID: 27722051
    Slopes are subjected to stress redistributions during underground mining activities, and this may eventually cause deformation or landslide. This paper takes Madaling landslide in Guizhou Province, China as a case study to investigate the failure mechanism and its run-out behaviours by using discrete element method. Previous qualitative analysis indicated that the slope experienced four stages of failure mechanisms: (1) development of tension cracks, (2) development of stepped-like creep cracks, (3) development of potential rupture surfaces, and (4) occurrence of the landslide. PFC2D program was employed to model the pre-failure deformation characteristics in order to verify the failure mechanisms quantitatively. Subsequently, the run-out behaviours of the landslide were analyzed by PFC3D program. The results indicated that the movement could be summarized into four stages: acceleration stage, constant movement stage, rapid movement stage, and deceleration and deposition stage.
  5. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  6. Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, et al.
    COPD, 2017 Oct;14(5):476-483.
    PMID: 28753067 DOI: 10.1080/15412555.2017.1335697
    Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.
  7. Yusof N, Hamid N, Ma ZF, Lawenko RM, Wan Mohammad WMZ, Collins DA, et al.
    Gut Pathog, 2017;9:75.
    PMID: 29255490 DOI: 10.1186/s13099-017-0224-7
    Background: After an environmental disaster, the affected community is at increased risk for persistent abdominal pain but mechanisms are unclear. Therefore, our study aimed to determine association between abdominal pain and poor water, sanitation and hygiene (WaSH) practices, and if small intestinal bacterial overgrowth (SIBO) and/or gut dysbiosis explain IBS, impaired quality of life (QOL), anxiety and/or depression after a major flood.

    Results: New onset abdominal pain, IBS based on the Rome III criteria, WaSH practices, QOL, anxiety and/or depression, SIBO (hydrogen breath testing) and stools for metagenomic sequencing were assessed in flood victims. Of 211 participants, 37.9% (n = 80) had abdominal pain and 17% (n = 36) with IBS subtyped diarrhea and/or mixed type (n = 27 or 12.8%) being the most common. Poor WaSH practices and impaired quality of life during flood were significantly associated with IBS. Using linear discriminant analysis effect size method, gut dysbiosis was observed in those with anxiety (Bacteroidetes and Proteobacteria, effect size 4.8), abdominal pain (Fusobacteria, Staphylococcus, Megamonas and Plesiomonas, effect size 4.0) and IBS (Plesiomonas and Trabulsiella, effect size 3.0).

    Conclusion: Disturbed gut microbiota because of environmentally-derived organisms may explain persistent abdominal pain and IBS after a major environmental disaster in the presence of poor WaSH practices.

  8. Cao H, Chai TT, Wang X, Morais-Braga MFB, Yang JH, Wong FC, et al.
    Phytochem Rev, 2017;16(3):379-440.
    PMID: 32214919 DOI: 10.1007/s11101-016-9488-7
    Ferns are an important phytogenetic bridge between lower and higher plants. Historically they have been used in many ways by humans, including as ornamental plants, domestic utensils, foods, and in handicrafts. In addition, they have found uses as medicinal herbs. Ferns produce a wide array of secondary metabolites endowed with different bioactivities that could potentially be useful in the treatment of many diseases. However, there is currently relatively little information in the literature on the phytochemicals present in ferns and their pharmacological applications, and the most recent review of the literature on the occurrence, chemotaxonomy and physiological activity of fern secondary metabolites was published over 20 years ago, by Soeder (Bot Rev 51:442-536, 1985). Here, we provide an updated review of this field, covering recent findings concerning the bioactive phytochemicals and pharmacology of fern species.
  9. Lau AS, Yanagisawa N, Hor YY, Lew LC, Ong JS, Chuah LO, et al.
    Benef Microbes, 2018 Jan 29;9(1):61-70.
    PMID: 29065707 DOI: 10.3920/BM2017.0063
    This 10-months randomised, double-blind, parallel and placebo-controlled study evaluated the effects of Bifidobacterium longum BB536 on diarrhoea and/or upper respiratory illnesses in 520 healthy Malaysian pre-school children aged 2-6 years old. The subjects randomly received a one-gram sachet containing either BB536 (5×109 cfu) or placebo daily. Data analysis was performed on 219 subjects who fully complied over 10-months (placebo n=110, BB536 n=109). While BB536 did not exert significant effects against diarrhoea in children, Poisson regression with generalised estimating equations model indicated significant intergroup difference in the mean number of times of respiratory illnesses over 10 months. The duration of sore throat was reduced by 46% (P=0.018), with marginal reduction for duration of fever (reduced by 27%, P=0.084), runny nose (reduced by 15%, P=0.087) and cough (reduced by 16%, P=0.087) as compared to the placebo. Principal coordinate analysis at genus level of the gut microbiota revealed significant differences between 0 and 10 months in the BB536 group (P<0.01) but not in placebo group (P>0.05). The abundance of the genus Faecalibacterium which is associated with anti-inflammatory and immuno-modulatory properties was significantly higher in the BB536 group (P<0.05) compared to the placebo group. Altogether, our present study illustrated the potential protective effects of BB536 against upper respiratory illnesses in pre-school Malaysian children, with gut microbiota modulating properties.
  10. Wong FC, Xiao J, Ong MG, Pang MJ, Wong SJ, Teh LK, et al.
    Food Chem, 2019 Jan 15;271:614-622.
    PMID: 30236723 DOI: 10.1016/j.foodchem.2018.07.206
    This study was conducted to identify and characterize antioxidant peptides from the alcalase hydrolysate of the blue-spotted stingray. Purification steps guided by ABTS cation radical (ABTS+) scavenging assay and de novo peptide sequencing produced two peptides, WAFAPA (661.3224 Da) and MYPGLA (650.3098 Da). WAFAPA (EC50 = 12.6 µM) had stronger antioxidant activity than glutathione (EC50 = 13.7 µM) and MYPGLA (EC50 = 19.8 µM). Synergism between WAFAPA and MYPGLA was detected. WAFAPA and MYPGLA surpassed carnosine in their ability to suppress H2O2-induced lipid oxidation. The peptides protected plasmid DNA and proteins from Fenton's reagent-induced oxidative damage. Thermal (25-100 °C) and pH 3-11 treatments did not alter antioxidant activity of the peptides. MYPGLA maintained its antioxidant activity after simulated gastrointestinal digestion, whereas WAFAPA showed a partial loss. The two peptides may have potential applications as functional food ingredients or nutraceuticals, whether used singly or in combination.
  11. El-Seedi HR, Khalifa SAM, Taher EA, Farag MA, Saeed A, Gamal M, et al.
    Pharmacol Res, 2019 03;141:123-175.
    PMID: 30579976 DOI: 10.1016/j.phrs.2018.12.015
    Cardiac glycosides (CGs) are a class of naturally occurring steroid-like compounds, and members of this class have been in clinical use for more than 1500 years. They have been used in folk medicine as arrow poisons, abortifacients, heart tonics, emetics, and diuretics as well as in other applications. The major use of CGs today is based on their ability to inhibit the membrane-bound Na+/K+-ATPase enzyme, and they are regarded as an effective treatment for congestive heart failure (CHF), cardiac arrhythmia and atrial fibrillation. Furthermore, increasing evidence has indicated the potential cytotoxic effects of CGs against various types of cancer. In this review, we highlight some of the structural features of this class of natural products that are crucial for their efficacy, some methods of isolating these compounds from natural resources, and the structural elucidation tools that have been used. We also describe their physicochemical properties and several modern biotechnological approaches for preparing CGs that do not require plant sources.
  12. Ma ZF, Yusof N, Hamid N, Lawenko RM, Mohammad WMZW, Liong MT, et al.
    Benef Microbes, 2019 Mar 13;10(2):111-120.
    PMID: 30525951 DOI: 10.3920/BM2018.0008
    Individuals in a community who developed irritable bowel syndrome (IBS) after major floods have significant mental health impairment. We aimed to determine if Bifidobacterium infantis M-63 was effective in improving symptoms, psychology and quality of life measures in flood-affected individuals with IBS and if the improvement was mediated by gut microbiota changes. Design was non-randomised, open-label, controlled before-and-after. Of 53 participants, 20 with IBS were given B. infantis M-63 (1×109 cfu/sachet/day) for three months and 33 were controls. IBS symptom severity scale, hospital anxiety and depression scale, SF-36 Questionnaire, hydrogen breath testing for small intestinal bacterial overgrowth and stools for 16S rRNA metagenomic analysis were performed before and after intervention. 11 of 20 who were given probiotics (M-63) and 20 of 33 controls completed study as per-protocol. Mental well-being was improved with M-63 vs controls for full analysis (P=0.03) and per-protocol (P=0.01) populations. Within-group differences were observed for anxiety and bodily pain (both P=0.04) in the M-63 per-protocol population. Lower ratio of Firmicutes/Bacteroidetes was observed with M-63 vs controls (P=0.01) and the lower ratio was correlated with higher post-intervention mental score (P=0.04). B. infantis M-63 is probably effective in improving mental health of victims who developed IBS after floods and this is maybe due to restoration of microbial balance and the gut-brain axis. However, our conclusion must be interpreted within the context of limited sample size. The study was retrospectively registered on 12 October 2017 and the Trial Registration Number (TRN) was NCT03318614.
  13. Teng H, Chen Y, Lin X, Lv Q, Chai TT, Wong FC, et al.
    Food Chem Toxicol, 2019 Jul;129:138-143.
    PMID: 31034934 DOI: 10.1016/j.fct.2019.04.043
    The aim of this study was to assess the inhibitory effects of Sonchus olearleu extract on the generation of heterocyclic amines in roasted pork patties cooked by pan-frying. All samples were cooked for two different durations (45 min and 105 min) under 200 °C and 230 °C. 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-ami- no-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinox-aline (4,8-DiMeIQx), harman, and norharman were detected and quantified. In patties cooked at 230 °C for 105 min, S. olearleu extract (0.5%) significantly inhibited the formation of IQ, harman, and norharman by 39%, 67%, and 63%, respectively. In contrast to IQ, the levels of harman and norharman were significantly reduced by the extracts tested. However, no such effects were observed for MeIQx and 4, 8-DiMeIQx. Notably, the inhibitory effect on heterocyclic amines is significantly correlated with the antioxidant potential and total phenolic content of S. olearleu extract.
  14. Zahra MH, Salem TAR, El-Aarag B, Yosri N, El-Ghlban S, Zaki K, et al.
    Molecules, 2019 Jul 08;24(13).
    PMID: 31288458 DOI: 10.3390/molecules24132495
    BACKGROUND/AIM: Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers.

    METHODS: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model.

    RESULTS: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively.

    CONCLUSION: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.

  15. Chai TT, Tan YN, Ee KY, Xiao J, Wong FC
    Crit Rev Food Sci Nutr, 2019;59(sup1):S162-S177.
    PMID: 30663883 DOI: 10.1080/10408398.2018.1561418
    The emergence of bacterial resistance against conventional antibiotics and the growing interest in developing alternative, natural antibacterial agents have prompted the search for plant-derived antibacterial peptides in recent decades. Different classes of endogenous antibacterial peptides have been identified from various plant species. Moreover, protein hydrolysates and hydrolysate-derived peptides with potent antibacterial effects have also been identified from numerous plant sources. Antibacterial peptides are often cationic and amphipathic, consisting of fewer than 100 amino acids. They are able to disrupt bacterial membrane integrity via pore formation and/or compromise bacterial metabolic processes. In this review, we summarize current knowledge on the characteristics and modes of action of antibacterial peptides, as well as salient points concerning the production of antibacterial protein hydrolysates from plant proteins. Examples of plant-derived antibacterial hydrolysates and peptides will be highlighted, with particular attention to less explored seeds, fermented plant foods and agricultural by-products. Promising future research directions with regards to the application of plant-derived antibacterial hydrolysates and peptides in food preservation, farm animal disease management, and nutraceutical/functional food development will be proposed.
  16. Wong FC, Chai TT, Xiao J
    Crit Rev Food Sci Nutr, 2019;59(6):947-952.
    PMID: 29787299 DOI: 10.1080/10408398.2018.1479681
    In our diets, many of the consumed foods are subjected to various forms of heating and thermal processing. Besides enhancing the taste, texture, and aroma of the foods, heating helps to sterilize and facilitate food storage. On the other hand, heating and thermal processing are frequently reported during the preparation of various traditional herbal medicines. In this review, we intend to highlight works by various research groups which reported on changes in phytochemicals and bioactivities, following thermal processing of selected plant-derived foods and herbal medicines. Relevant cases from plant-derived foods (garlic, coffee, cocoa, barley) and traditional herbal medicines (Panax ginseng, Polygonum multiforum, Aconitum carmichaelii Debeaux, Angelica sinensis Radix) will be presented in this review. Additionally, related works using pure phytochemical compounds will also be highlighted. In some of these cases, the amazing formation of new compounds were being reported. Maillard reaction could be concluded as the predominant pathway leading to the formation of new conjugates, along with other possibilities being suggested (degradation, transglycosylation, deglycosylation and dehydration). With collective efforts from all researchers, it is hoped that more details will be revealed and lead to the possible discovery of new, heat-mediated phytochemical conjugates.
  17. Porwal P, Pachade S, Kokare M, Deshmukh G, Son J, Bae W, et al.
    Med Image Anal, 2020 01;59:101561.
    PMID: 31671320 DOI: 10.1016/j.media.2019.101561
    Diabetic Retinopathy (DR) is the most common cause of avoidable vision loss, predominantly affecting the working-age population across the globe. Screening for DR, coupled with timely consultation and treatment, is a globally trusted policy to avoid vision loss. However, implementation of DR screening programs is challenging due to the scarcity of medical professionals able to screen a growing global diabetic population at risk for DR. Computer-aided disease diagnosis in retinal image analysis could provide a sustainable approach for such large-scale screening effort. The recent scientific advances in computing capacity and machine learning approaches provide an avenue for biomedical scientists to reach this goal. Aiming to advance the state-of-the-art in automatic DR diagnosis, a grand challenge on "Diabetic Retinopathy - Segmentation and Grading" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2018). In this paper, we report the set-up and results of this challenge that is primarily based on Indian Diabetic Retinopathy Image Dataset (IDRiD). There were three principal sub-challenges: lesion segmentation, disease severity grading, and localization of retinal landmarks and segmentation. These multiple tasks in this challenge allow to test the generalizability of algorithms, and this is what makes it different from existing ones. It received a positive response from the scientific community with 148 submissions from 495 registrations effectively entered in this challenge. This paper outlines the challenge, its organization, the dataset used, evaluation methods and results of top-performing participating solutions. The top-performing approaches utilized a blend of clinical information, data augmentation, and an ensemble of models. These findings have the potential to enable new developments in retinal image analysis and image-based DR screening in particular.
  18. Bolisetty S, Osborn D, Schindler T, Sinn J, Deshpande G, Wong CS, et al.
    BMC Pediatr, 2020 02 08;20(1):59.
    PMID: 32035481 DOI: 10.1186/s12887-020-1958-9
    BACKGROUND: The first consensus standardised neonatal parenteral nutrition formulations were implemented in many neonatal units in Australia in 2012. The current update involving 49 units from Australia, New Zealand, Singapore, Malaysia and India was conducted between September 2015 and December 2017 with the aim to review and update the 2012 formulations and guidelines.

    METHODS: A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed.

    RESULTS: Five existing preterm Amino acid-Dextrose formulations have been modified and two new concentrated Amino acid-Dextrose formulations added to optimise amino acid and nutrient intake according to gestation. Organic phosphate has replaced inorganic phosphate allowing for an increase in calcium and phosphate content, and acetate reduced. Lipid emulsions are unchanged, with both SMOFlipid (Fresenius Kabi, Australia) and ClinOleic (Baxter Healthcare, Australia) preparations included. The physicochemical compatibility and stability of all formulations have been tested and confirmed. Guidelines to standardise the parenteral nutrition clinical practice across facilities have also been developed.

    CONCLUSIONS: The 2017 PN formulations and guidelines developed by the 2017 Neonatal Parenteral Nutrition Consensus Group offer concise and practical instructions to clinicians on how to implement current and up-to-date evidence based PN to the NICU population.

  19. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Oct 09;125(15):152001.
    PMID: 33095627 DOI: 10.1103/PhysRevLett.125.152001
    Using a data sample of proton-proton collisions at sqrt[s]=13  TeV, corresponding to an integrated luminosity of 140  fb^{-1} collected by the CMS experiment in 2016-2018, the B_{s}^{0}→X(3872)ϕ decay is observed. Decays into J/ψπ^{+}π^{-} and K^{+}K^{-} are used to reconstruct, respectively, the X(3872) and ϕ. The ratio of the product of branching fractions B[B_{s}^{0}→X(3872)ϕ]B[X(3872)→J/ψπ^{+}π^{-}] to the product B[B_{s}^{0}→ψ(2S)ϕ]B[ψ(2S)→J/ψπ^{+}π^{-}] is measured to be [2.21±0.29(stat)±0.17(syst)]%. The ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{0}→X(3872)K^{0}] is found to be consistent with one, while the ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{+}→X(3872)K^{+}] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B^{0} and B_{s}^{0} meson decays compared to B^{+}. The reported observation may shed new light on the nature of the X(3872) particle.
  20. Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, Dragicevic M, et al.
    Phys Rev Lett, 2020 Oct 09;125(15):151802.
    PMID: 33095594 DOI: 10.1103/PhysRevLett.125.151802
    The first observation is reported of the combined production of three massive gauge bosons (VVV with V=W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV. The analysis is based on a data sample recorded by the CMS experiment at the CERN LHC corresponding to an integrated luminosity of 137  fb^{-1}. The searches for individual WWW, WWZ, WZZ, and ZZZ production are performed in final states with three, four, five, and six leptons (electrons or muons), or with two same-sign leptons plus one or two jets. The observed (expected) significance of the combined VVV production signal is 5.7 (5.9) standard deviations and the corresponding measured cross section relative to the standard model prediction is 1.02_{-0.23}^{+0.26}. The significances of the individual WWW and WWZ production are 3.3 and 3.4 standard deviations, respectively. Measured production cross sections for the individual triboson processes are also reported.
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