Isolation of exosome from the culture medium of Nasopharyngeal cancer (NPC) C666-1 cells using inertial based Microfluidic channel.

Isolation of exosome from culture medium in an effective way is desired for a less time consuming, cost saving technology in running the diagnostic test on cancer. In this study, we aim to develop an inertial microfluidic channel to separate the nano-size exosome from C666-1 cell culture medium as a selective sample. Simulation was carried out to obtain the optimum flow rate for determining the dimension of the channels for the exosome separation from the medium. The optimal dimension was then brought forward for the actual microfluidic channel fabrication, which consisted of the stages of mask printing, SU8 mould fabrication and ended with PDMS microchannel curing process. The prototype was then used to verify the optimum flow rate with polystyrene particles for its capabilities in actual task on particle separation as a control outcome. Next, the microchip was employed to separate the selected samples, exosome from the culture medium and compared the outcome from the conventional exosome extraction kit to study the level of effectiveness of the prototype. The exosome outcome from both the prototype and extraction kits were characterized through zetasizer, western blot and Transmission electron microscopy (TEM). The microfluidic chip designed in this study obtained a successful separation of exosome from the culture medium. Besides, the extra benefit from this microfluidic channels in particle separation brought an evenly distributed exosome upon collection while the exosomes separated through extraction kit was found clustered together. Therefore, this work has shown the microfluidic channel is suitable for continuous separation of exosome from the culture medium for a clinical study in the future.

Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.

Parkinson's disease is one of the most common neurodegenerative diseases affecting the ageing population, with a prevalence that has doubled over the last 30 years. As the mechanism of the disease is not fully elucidated, the current treatments are unable to effectively prevent neurodegeneration. Studies have found that mutations in Leucine-rich-repeat-kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). Moreover, aberrant (higher) LRRK2 kinase activity has an influence in idiopathic PD as well. Hence, the aim of this review is to categorize and synthesize current information related to LRRK2-linked PD and present the factors associated with LRRK2 that can be targeted therapeutically. A systematic review was conducted using the databases PubMed, Medline, SCOPUS, SAGE, and Cochrane (January 2016 to July 2021). Search terms included "Parkinson's disease", "mechanism", "LRRK2", and synonyms in various combinations. The search yielded a total of 988 abstracts for initial review, 80 of which met the inclusion criteria. Here, we emphasize molecular mechanisms revealed in recent in vivo and in vitro studies. By consolidating the recent updates in the field of LRRK2-linked PD, researchers can further evaluate targets for therapeutic application.

Decoding the differentiation of mesenchymal stem cells into mesangial cells at the transcriptomic level.

BACKGROUND: Mesangial cells play an important role in the glomerulus to provide mechanical support and maintaine efficient ultrafiltration of renal plasma. Loss of mesangial cells due to pathologic conditions may lead to impaired renal function. Mesenchymal stem cells (MSC) can differentiate into many cell types, including mesangial cells. However transcriptomic profiling during MSC differentiation into mesangial cells had not been studied yet. The aim of this study is to examine the pattern of transcriptomic changes during MSC differentiation into mesangial cells, to understand the involvement of transcription factor (TF) along the differentiation process, and finally to elucidate the relationship among TF-TF and TF-key gene or biomarkers during the differentiation of MSC into mesangial cells. RESULTS: Several ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. TO-GCN analysis can classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation. Furthermore, it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process. CONCLUSIONS: A systematic analysis for transcriptomic profiling of MSC differentiation into mesangial cells has been established. Key genes or biomarkers, TFs and pathways involved in differentiation of MSC-mesangial cells have been identified and the related biological implications have been discussed. Finally, we further elucidated for the first time the three main stages of mesangial cell differentiation, and the regulatory relationships between TF-TF-key genes involved in the muscle contraction process. Through this study, we have increased fundamental understanding of the gene transcripts during the differentiation of MSC into mesangial cells.

Proteome Heterogeneity in Colorectal Cancer.

Tumor heterogeneity is an important feature of colorectal cancer (CRC) manifested by dynamic changes in gene expression, protein expression, and availability of different tumor subtypes. Recent publications in the past 10 years have revealed proteome heterogeneity between different colorectal tumors and within the same tumor site. This paper reviews recent research works on the proteome heterogeneity in CRC, which includes the heterogeneity within a single tumor (intratumor heterogeneity), between different anatomical sites at the same organ, and between primary and metastatic sites (intertumor heterogeneity). The potential use of proteome heterogeneity in precision medicine and its implications in biomarker discovery and therapeutic outcomes will be discussed. Identification of the unique proteome landscape between and within individual tumors is imperative for understanding cancer biology and the management of CRC patients.

Differential effects of sPLA2-GV and GX on cellular proliferation and lipid accumulation in HT29 colon cancer cells.

Secretory phospholipase A2 (sPLA2) group of enzymes have been shown to hydrolyze phospholipids, among which sPLA2 Group V (GV) and Group X (GX) exhibit high selectivity towards phosphatidylcholine-rich cellular plasma membranes. The enzymes have recently emerged as key regulators in lipid droplets formation and it is hypothesized that sPLA2-GV and GX enhanced cell proliferation and lipid droplet accumulation in colon cancer cells (HT29). In this study, cell viability and lipid droplet accumulation were assessed by Resazurin assay and Oil-Red-O staining. Interestingly, both sPLA2-GV and GX enzymes reduced intracellular lipid droplet accumulation and did not significantly affect cell proliferation in HT29 cells. Incubation with varespladib, a pan-inhibitor of sPLA2-Group IIA/V/X, further suppressed lipid droplets accumulation in sPLA2-GV but have no effects in sPLA2-GX-treated cells. Further studies using catalytically inactive sPLA2 enzymes showed that the enzymes intrinsic catalytic activity is required for the net reduction of lipid accumulation. Meanwhile, inhibition of intracellular phospholipases (iPLA2-γ and cPLA2-α) unexpectedly enhanced lipid droplet accumulation in both sPLA2-GV and GX-treated cells. The findings suggested an interconnected relationship between extracellular and intracellular phospholipases in lipid cycling. Previous studies indicated that sPLA2 enzymes are linked to cancer development due to their ability to induce release of arachidonic acid and eicosanoids as well as the stimulation of lipid droplet formation. This study showed that the two enzymes work in a distinct manner and they neither confer proliferative advantage nor enhanced the net lipid droplet accumulation in HT29 cells.

Effectiveness of herbs taken concurrently with antihypertensive drugs in managing hypertension and lipid outcomes. A systematic review and meta-analysis.

PURPOSE: Hypertension is the primary cause of mortality. Hence globally, there is a growing interest in complementing antihypertensive drugs with herbs to alleviate blood pressure among hypertensive patients. Thus, this review aimed to evaluate the effectiveness of complementing drugs with herbs on blood pressure and lipid profile outcomes, the associated factors and the types of complementary herbs alongside their consumption regimes. METHODS: This review is registered in PROSPERO on the National Institute of Health Database with an ID: CRD42021270481. Using the PICOS (population, intervention, comparison, outcome, study type) mnemonic formula and search strategy, we searched (January 2010 to February 2024) five electronic databases including Pubmed, Scopus, Web of Science, CINAHL (Cumulative Index for Nursing and Allied Health Literature) and Psychology & Behavioral Sciences Collection (PBSC). The inclusion criteria of the review were that all included papers had to be randomised control trials in English among hypertensive adults who complemented antihypertensive drugs with herbs. A Cochrane risk of bias assessment as well as a meta-analysis and narrative synthesis were conducted to answer the objectives. RESULTS: Twenty-five randomised controlled trials involving 1996 participants from 14 countries were included. The risk of bias among included articles was assessed and presented using the Cochrane risk of bias tool and the graphs were generated. The effects of complementing antihypertensive drugs with different herb regimes on blood pressure and lipid profile outcomes were compared to those solely on antihypertensive drugs and placebo via a random model effects meta-analysis using the Revman manager. Systolic blood pressure (SBP) and triglycerides gave a significant reduction in favour of the intervention group which complemented herbs. The overall pooled systolic blood pressure showed a reduction of (SMD=0.81, 95 % CI 0.14-1.47, p < 0.02, p for heterogeneity=0.00001, I2 =97 %) while triglycerides were (SMD=0.73, 95 % CI 0.17-1.28, p < 0.01, p for heterogeneity=0.00001, I2 =85 %). However, diastolic blood pressure, total cholesterol, HDL and LDL did not exert significant outcomes. CONCLUSION: The complemented herbs with antihypertensive drugs did show improvement in overall blood pressure management in the majority of the studies compared to the placebo group. Blood pressure and lipid profiles are the health outcomes that enable access to complementing herbs in controlling high blood pressure. Some limitations of this review are attributed to performance, detection and attrition bias in a few included articles alongside the presence of a high heterogeneity overall.

Epidemiological exploration of the impact of bluetooth headset usage on thyroid nodules using Shapley additive explanations method.

With an increasing prevalence of thyroid nodules globally, this study investigates the potential correlation between the use of Bluetooth headsets and the incidence of thyroid nodules, considering the cumulative effects of non-ionizing radiation (NIR) emitted by these devices. In this study, we analyzed 600 valid questionnaires from the WenJuanXing platform using Propensity Score Matching (PSM) and the XGBOOST model, supplemented by SHAP analysis, to assess the risk of thyroid nodules. PSM was utilized to balance baseline characteristic differences, thereby reducing bias. The XGBOOST model was then employed to predict risk factors, with model efficacy measured by the area under the Receiver Operating Characteristic (ROC) curve (AUC). SHAP analysis helped quantify and explain the impact of each feature on the prediction outcomes, identifying key risk factors. Initially, 600 valid questionnaires from the WenJuanXing platform underwent PSM processing, resulting in a matched dataset of 96 cases for modeling analysis. The AUC value of the XGBOOST model reached 0.95, demonstrating high accuracy in differentiating thyroid nodule risks. SHAP analysis revealed age and daily Bluetooth headset usage duration as the two most significant factors affecting thyroid nodule risk. Specifically, longer daily usage durations of Bluetooth headsets were strongly linked to an increased risk of developing thyroid nodules, as indicated by the SHAP analysis outcomes. Our study highlighted a significant impact relationship between prolonged Bluetooth headset use and increased thyroid nodule risk, emphasizing the importance of considering health impacts in the use of modern technology, especially for devices like Bluetooth headsets that are frequently used daily. Through precise model predictions and variable importance analysis, our research provides a scientific basis for the formulation of public health policies and personal health habit choices, suggesting that attention should be paid to the duration of Bluetooth headset use in daily life to reduce the potential risk of thyroid nodules. Future research should further investigate the biological mechanisms of this relationship and consider additional potential influencing factors to offer more comprehensive health guidance and preventive measures.

Evolution of a self-renewing, participant-centered workshop series in BMB assessment.

We present as a case study the evolution of a series of participant-centered workshops designed to meet a need in the life sciences education community-the incorporation of best practices in the assessment of student learning. Initially, the ICABL (Inclusive Community for the Assessment of Biochemistry and Molecular Biology/BMB Learning) project arose from a grass-roots effort to develop material for a national exam in biochemistry and molecular biology. ICABL has since evolved into a community of practice in which participants themselves-through extensive peer review and reflection-become integral stakeholders in the workshops. To examine this evolution, this case study begins with a pilot workshop supported by seed funding and thoughtful programmatic assessment, the results of which informed evidence-based changes that, in turn, led to an improved experience for the community. Using participant response data, the case study also reveals critical features for successful workshops, including participant-centered activities and the value of frequent peer review of participants' products. Furthermore, we outline a train-the-trainer model for creating a self-renewing community by bringing new perspectives and voices into an existing core leadership team. This case study, then, offers a blueprint for building a thriving, evolving community of practice that not only serves the needs of individual scientist-educators as they seek to enhance student learning, but also provides a pathway for elevating members to positions of leadership.

Cytotoxicity and structure-activity relationships of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora towards nine human cancer cell lines.

The cytotoxic structure-activity relationships among a series of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora were studied. Eleven xanthone derivatives identified as mesuarianone (1), mesuasinone (2), mesuaferrin A (3), mesuaferrin B (4), mesuaferrin C (5), 6-deoxyjacareubin (6), caloxanthone C (7), macluraxanthone (8), 1,5-dihydroxyxanthone (9), tovopyrifolin C (10) and α-mangostin (11) were isolated from the three Mesua species. The human cancer cell lines tested were Raji, SNU-1, K562, LS-174T, SK-MEL-28, IMR-32, HeLa, Hep G2 and NCI-H23. Mesuaferrin A (3), macluraxanthone (8) and α-mangostin (11) showed strong cytotoxicities as they possess significant inhibitory effects against all the cell lines. The structure-activity relationship (SAR) study revealed that the diprenyl, dipyrano and prenylated pyrano substituent groups of the xanthone derivatives contributed towards the cytotoxicities.

Maslinic acid exerts anticancer effects by targeting cancer hallmarks.

BACKGROUND: Natural products have long been regarded as a source of anticancer compounds with low toxicity. Evidence revealed that maslinic acid (MA), a widely distributed pentacyclic triterpene in common foodstuffs, exhibited pronounced inhibitory effects against various cancer cell lines. Most cancer cells thrive by acquiring cancer hallmarks, as coined by Hanahan and Weinberg in 2000 and 2011. PURPOSE: This represents the first systematic review concerning the anticancer properties of MA as these cancer hallmarks are targeted. It aims to summarize the antineoplastic activities of MA, discuss the diverse mechanisms of action based on the effects of MA exerted on each hallmark. METHODS: A comprehensive literature search was conducted using the search terms "maslinic," "cancer," "tumor," and "neoplasm," to retrieve articles from the databases MEDLINE, EMBASE, Web of Science, and Scopus published up to September 2022. Study selection was conducted by three reviewers independently from title and abstract screening until full-text evaluation. Data extraction was done by one reviewer and counterchecked by the second reviewer. RESULTS: Of the 330 articles assessed, 40 papers met the inclusion criteria and revealed that MA inhibited 16 different cancer cell types. MA impacted every cancer hallmark by targeting multiple pathways. CONCLUSION: This review provides insights regarding the inhibitory effects of MA against various cancers and its remarkable biological properties as a pleiotropic bioactive compound, which encourage further investigations.

Factors influencing COVID-19 vaccination intention among university students: A cross-sectional study in Malaysia.

Vaccination is crucial in controlling the spread of the coronavirus disease 2019 (COVID-19) that triggered the pandemic, but herd immunity can only work with high vaccination coverage in the population. This study aims to measure the COVID-19 knowledge level and determine the factors influencing COVID-19 vaccination intention among university students in Malaysia. A cross-sectional online survey was carried out with 1,274 Malaysian university students in July 2021. Univariate and multivariate analyses were employed to examine the relationships between the study variables. Results showed that the majority of university students had an acceptable level of knowledge of COVID-19. The knowledge, risk perception of COVID-19, social norms, and perceived benefit of COVID-19 vaccination were positively associated with vaccination intention. However, perceived trust in information sources of COVID-19 vaccination and the government's response to COVID-19 did not affect the university students' desire to receive the vaccination. These findings are essential for health policymakers and healthcare providers to implement evidence-based interventions to increase COVID-19 vaccination uptake among university students.

Mesua beccariana (Clusiaceae), a source of potential anti-cancer lead compounds in drug discovery.

An investigation on biologically active secondary metabolites from the stem bark of Mesua beccariana was carried out. A new cyclodione, mesuadione, along with several known constituents which are beccamarin, 2,5-dihydroxy-1,3,4-trimethoxy anthraquinone, 4-methoxy-1,3,5-trihydroxyanthraquinone, betulinic acid and stigmasterol were obtained from this ongoing research. Structures of these compounds were elucidated by extensive spectroscopic methods, including 1D and 2D-NMR, GC-MS, IR and UV techniques. Preliminary tests of the in vitro cytotoxic activities of all the isolated metabolites against a panel of human cancer cell lines Raji (lymphoma), SNU-1 (gastric carcinoma), K562 (erythroleukemia cells), LS-174T (colorectal adenocarcinoma), HeLa (cervical cells), SK-MEL-28 (malignant melanoma cells), NCI-H23 (lung adenocarcinoma), IMR-32 (neuroblastoma) and Hep-G2 (hepatocellular liver carcinoma) were carried out using an MTT assay. Mesuadione, beccamarin, betulinic acid and stigmasterol displayed strong inhibition of Raji cell proliferation, while the proliferation rate of SK-MEL-28 and HeLa were strongly inhibited by stigmasterol and beccamarin, indicating these secondary metabolites could be anti-cancer lead compounds in drug discovery.

Phylattrin, a new cytotoxic xanthone from Calophyllum soulattri.

Our continuing studies on secondary metabolites from the stem bark of Calophyllum soulattri has led to the isolation of another new diprenylated xanthone, phylattrin (1), in addition to five other xanthones and two common sterols. The xanthones are soulattrin (2), caloxanthone C (3), macluraxanthone (4), brasixanthone B (5) and trapezifolixanthone (6) while the sterols are stigmasterol (7) and ß-sitosterol (8). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D-NMR, HRESIMS, IR and UV. Compounds 1-7 exhibited moderate cytotoxic activities against SNU-1, HeLa, Hep G2, NCI-H23, K562, Raji, LS174T, IMR-32 and SK-MEL-28 cells.

Traditional Chinese Medicine Body Constitutions as Predictors for Depression: A Systematic Review and Meta-Analysis.

Traditional Chinese medicine body constitution (TCMBC) reflects a person's vulnerability to diseases. Thus, identifying body constitutions prone to depression can help prevent and treat depression. The review aimed to assess and summarize the existing evidence that explores the relationship between TCMBC and depression. Psychology and Behavioral Sciences Collection, MEDLINE, PubMed, CNKI, Wanfang, SinoMed, Embase, VIP, CINAHL, and CMJ were searched from inception to April 2021. Observational studies assessing the association between TCMBC and depression were selected. The quality of the included studies were assessed using the Newcastle-Ottawa Scale (NOS). Eighteen studies were included in the systematic review and thirteen in the meta-analysis. The pooled odd ratios of developing depression for Qi-stagnation, Qi-deficiency, Yang-deficiency, Yin-deficiency, and Balanced constitutions were 3.12 (95% CI, 1.80-5.40; I2 = 94%), 2.15 (95% CI, 1.54-3.01; I2 = 89%), 1.89 (95% CI, 0.71-5.03; I2 = 81%), 1.41 (95% CI, 0.91-2.20; I2 = 57%), and 0.60 (95% CI, 0.40-0.90; I2 = 94%), respectively. The findings suggest that the evaluation of a person's TCMBC could be useful the in prevention and treatment of depression. However, more case-control and cohort studies are required to further confirm the association between TCMBC and depression.

Protective Effects of Alternanthera sessilis Ethanolic Extract against TNF-α or H2O2-Induced Endothelial Activation in Human Aortic Endothelial Cells.

Activation of the endothelium has been shown to contribute to the early stage of vascular diseases such as atherosclerosis and hypertension. In endothelial activation, excess reactive oxygen species (ROS) production and increased expression of cell adhesion molecules cause an increase in vascular permeability. Alternanthera sessilis (L.) R. Br. is an edible traditional herbal plant, which has previously been shown to possess antioxidant and anti-inflammatory effects. However, the effect of A. sessilis on the activation of human aortic endothelial cells (HAECs) remains unknown. This study aimed to investigate the effects of A. sessilis on endothelial permeability, vascular cell adhesion-1 (VCAM-1) expression, production of ROS and hydrogen peroxide (H2O2), and superoxide dismutase (SOD) and catalase (CAT) activities. The viability of HAECs was first determined using the MTT viability assay. The effect of A. sessilis on endothelial permeability was examined using the FITC-dextran permeability assay. Besides, enzyme-linked immunosorbent assay (ELISA) was done to assess soluble VCAM-1 (sVCAM-1) expression. The production of ROS and H2O2 was studied using 2',7'-dichlorodihydrofluorescein diacetate (H2-DCFDA) and Amplex Red fluorescent dyes, respectively. SOD and CAT activities were also measured using commercial kits. Our results showed that 25-200 µg/mL of A. sessilis ethanolic extract did not cause significant death in HAECs. A. sessilis at 200 µg/mL significantly inhibited TNF-α-induced hyperpermeability of HAECs. However, A. sessilis did not reduce increased VCAM-1 expression induced by TNF-α. A. sessilis also significantly reduced TNF-α-induced increased ROS production, but not H2O2 production. Furthermore, 100 µM of H2O2 decreased both SOD and CAT activities in HAECs at 2 h. A. sessilis ethanolic extract dramatically increased both reduced SOD and CAT activities caused by H2O2. The liquid chromatography-mass spectrometry (LC-MS) analysis of A. sessilis ethanolic extract demonstrated the presence of arachidonic acid, azadirachtin, astaxanthin, flavanole base + 3O, 2Prenyl, and vicenin 2, while the gas chromatography-mass spectrometry (GC-MS) analysis showed that the extract contains 1,3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, 3-deoxy-d-mannoic lactone, 4-pyrrolidinobenzaldehyde, and n-hexadecanoic acid. In conclusion, our findings suggest that A. sessilis ethanolic extract protects against endothelial hyperpermeability and oxidative stress elicited by pro-inflammatory or prooxidant stimulus. This study reveals a therapeutic potential of A. sessilis in preventing endothelial activation, which is a key event in early atherosclerosis.

2-Methoxy-1,4-naphthoquinone (MNQ) regulates cancer key genes of MAPK, PI3K, and NF-κB pathways in Raji cells.

2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor κB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

Generating transcriptional regulatory networks from time-ordered stem cell differentiation RNA sequencing data.

We describe steps to 1) identify ascending and descending monotonic key genes from time-ordered stem cell differentiation expression data, 2) construct time-ordered transcriptional regulatory networks, and 3) infer the involvement of transcription factors along the differentiation process. For complete details on the use and execution of this protocol, please refer to Wong et al. (2020).

A new furanoxanthone from the stem bark of Calophyllum inophyllum.

The stem bark extracts of Calophyllum inophyllum furnished one new furanoxanthone, inophinnin (1), in addition to inophyllin A (2), macluraxanthone (3), pyranojacareubin (4), 4-hydroxyxanthone, friedelin, stigmasterol, and betulinic acid. The structures of these compounds were determined by spectroscopic analysis of 1D and 2D NMR spectral data ((1)H, (13)C, DEPT, COSY, HMQC, and HMBC) while EI-MS gave the molecular mass. The new xanthone, inophinnin (1), exhibited some anti-inflammatory activity in nitric oxide assay.

Temporal gene expression profiling of maslinic acid-treated Raji cells.

Maslinic acid is a novel phytochemical reported to target multiple signaling pathways. A complete gene expression profile was therefore constructed to illustrate the anti-tumourigenesis effects of maslinic acid in Raji cells across five time-points. Microarray analysis was used to identify genes that were differentially expressed in maslinic acid treated Raji cells at 0, 4, 8, 12, 24 and 48 h. Extracted RNA was hybridized using the AffymetrixGeneChip to obtain expression profiles. A total of 109 genes were found to be significantly expressed over a period of 48 hours. By 12 hours, maslinic acid regulates the majority of genes involved in the cell cycle, p53 and NF-κB signaling pathways. At the same time, XAF1, APAF1, SESN3, and TP53BP2 were evidently up-regulated, while oncogenes, FAIM, CD27, and RRM2B, were down-regulated by at least 2-fold. In conclusion, maslinic acid shows an hourly progression of gene expression in Raji cells.

Geographical Factor Influences the Metabolite Distribution of House Edible Bird's Nests in Malaysia.

Background: Edible Bird's Nest (EBN) is famously consumed as a food tonic for its high nutritional values with numerous recuperative and therapeutic properties. EBN is majority exploited from swiftlet houses but the differences in terms of metabolite distribution between the production site of house EBN is not yet fully understood. Therefore, this study was designed to identify the metabolite distribution and to determine the relationship pattern for the metabolite distribution of house EBNs from different locations in Malaysia. Methods: The differences of metabolite distribution in house EBN were studied by collecting the samples from 13 states in Malaysia. An extraction method of eHMG was acquired to extract the metabolites of EBN and was subjected to non-targeted metabolite profiling via liquid chromatography-mass spectrometry (LC-MS). Unsupervised multivariate analysis and Venn diagram were used to explore the relationship pattern among the house EBNs in Malaysia. The geographical distribution surrounded the swiftlet house was investigated to understand its influences on the metabolite distribution. Results: The hierarchical clustering analysis (HCA) combined with correlation coefficient revealed the differences between the house EBNs in Malaysia with four main clusters formation. The metabolites distribution among these clusters was unique with their varied combination of geographical distribution. Cluster 1 grouped EBNs from Selangor, Melaka, Negeri Sembilan, Terengganu which geographically distributed with major oil palm field in township; Cluster 2 included Perak and Sarawak with high distribution of oil palm in higher altitude; Cluster 3 included Perlis, Kelantan, Kedah, Penang from lowland of paddy field in village mostly and Cluster 4 grouped Sabah, Pahang, Johor which are majorly distributed with undeveloped hills. The metabolites which drove each cluster formation have happened in a group instead of individual key metabolite. The major metabolites that characterised Cluster 1 were fatty acids, while the rest of the clusters were peptides and secondary metabolites. Conclusion: The metabolite profiling conducted in this study was able to discriminate the Malaysian house EBNs based on metabolites distribution. The factor that most inferences the differences of house EBNs were the geographical distribution, in which geographical distribution affects the distribution of insect and the diet of swiftlet.