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.

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.

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.

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.

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.

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).

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.

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.

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.

Self-management using crude herbs and the health-related quality of life among adult patients with hypertension living in a suburban setting of Malaysia.

PURPOSE: To determine the prevalence of crude herbs' use in the self-management of hypertension and the health-related quality of life (HRQOL) in patients with hypertension. METHODS: This cross-sectional study was performed among patients with hypertension attending a government health clinic. Socio-demographic characteristics, lifestyle modifications, medical history and predictors of crude herbs users were obtained. The diversity of crude herbs used was assessed using a modified international complementary and alternative medicine questionnaire (I-CAM-Q) and the HRQOL was assessed using the SF36 instrument. RESULTS: Out of the 294 patients recruited, 52.4% were female, 41.5% were Malay and 38.8% were within the 60 to69 age category. The prevalence of crude herbs users was 30.6% and the most common herbs used were pegaga (Centella asiatica), peria (Momordica charantia) and betik (Carica papaya). Using the regression analysis, significantly higher odds of using crude herbs are noted among Malay or Indian patients who have these characteristics: attained secondary education, experienced falls or muscle pain, and had systolic blood pressure of more than 140 mmHg. There was no significant difference in HRQOL domains between the crude herb users and non-users (p>0.05). CONCLUSION: Besides taking allopathic medications, certain patients with hypertension use crude herbs as a form of self-management. Although patients are adamant about integrating crude herbs as a form of self-management, the effects of doing so have not been properly investigated. This implies that the healthcare staff members need to communicate with the patients regarding the use of crude herbs together with conventional drugs.

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.

Traditional Chinese Medicine Body Constitutions and Psychological Determinants of Depression among University Students in Malaysia: A Pilot Study.

Depression is commonly observed in university students, who are a high risk group for developing psychiatric disorders during adulthood. This study aimed to determine the prevalence of depression and its traditional Chinese medicine body constitutions and psychological determinants among university students in Malaysia. A cross-sectional pilot study was conducted between 9 and 28 September 2020 among 80 university students in Malaysia. Participants completed online survey questionnaires, including the validated Patient Health Questionnaire (PHQ-9), Constitution in Chinese Medicine Questionnaire (CMCQ), Dysfunctional Attitude Scale (DAS), Depression Anxiety Stress Scale (DASS-21) stress subscale, Perceived Stress Scale (PSS-10), and Rosenberg Self-Esteem Scale (RSES), which assess depression, body constitution, dysfunctional attitude, stress, perceived stress, and self-esteem. Multiple linear regression analyses were performed to determine the associated risk factors for depression. The overall prevalence of depression among university students was 33.8%. The multiple regression analysis showed a significant relationship between depression and qi-stagnation constitution (B = 0.089, p = 0.011), balanced constitution (B = -0.077, p = 0.049), and self-esteem (B = -0.325, p = 0.001). Our findings suggest that some traditional Chinese medicine body constitutions and self-esteem are significant risk factors affecting depression among university students. Identifying risk factors of depression is vital to aid in the early detection of depression among university students.

Effect of Hydrolyzed Bird's Nest on ß-Cell Function and Insulin Signaling in Type 2 Diabetic Mice.

Type 2 diabetes mellitus is characterized by both resistance to the action of insulin and defects in insulin secretion. Bird's nest, which is derived from the saliva of swiftlets are well known to possess multiple health benefits dating back to Imperial China. However, it's effect on diabetes mellitus and influence on the actions of insulin action remains to be investigated. In the present study, the effect of standardized aqueous extract of hydrolyzed edible bird nest (HBN) on metabolic characteristics and insulin signaling pathway in pancreas, liver and skeletal muscle of db/db, a type 2 diabetic mice model was investigated. Male db/db diabetic and its euglycemic control, C57BL/6J mice were administered HBN (75 and 150 mg/kg) or glibenclamide (1 mg/kg) orally for 28 days. Metabolic parameters were evaluated by measuring fasting blood glucose, serum insulin and oral glucose tolerance test (OGTT). Insulin signaling and activation of inflammatory pathways in liver, adipose, pancreas and muscle tissue were evaluated by Western blotting and immunohistochemistry. Pro-inflammatory cytokines were measured in the serum at the end of the treatment. The results showed that db/db mice treated with HBN significantly reversed the elevated fasting blood glucose, serum insulin, serum pro-inflammatory cytokines levels and the impaired OGTT without affecting the body weight of the mice in all groups. Furthermore, HBN treatment significantly ameliorated pathological changes and increased the protein expression of insulin, and glucose transporters in the pancreatic islets (GLUT-2), liver and skeletal muscle (GLUT-4). Likewise, the Western blots analysis denotes improved insulin signaling and antioxidant enzyme, decreased reactive oxygen species producing enzymes and inflammatory molecules in the liver and adipose tissues of HBN treated diabetic mice. These results suggest that HBN improves ß-cell function and insulin signaling by attenuation of oxidative stress mediated chronic inflammation in the type 2 diabetic mice.

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.

Effect of Traditional Chinese Medicine on Musculoskeletal Symptoms in Breast Cancer: A Systematic Review and Meta-Analysis.

CONTEXT: Traditional Chinese Medicine (TCM) has been widely used as a complementary medical treatment for arthralgia and other types of pain. The available literature on the effectiveness of TCM on breast cancer patients with musculoskeletal symptoms reports controversial results. OBJECTIVES: The objective of this review is to assess the effectiveness of TCM as a treatment option for musculoskeletal symptoms in patients with breast cancer who were treated with aromatase inhibitors (AIs). METHODS: A comprehensive literature search was conducted using PubMed, the Cochrane Library, SAGE journals, Scopus, EMBASE, Web of Science, Medline, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Wanfang, and Chinese Medical Journal Database (CMJ) from May 2020 to November 2020. The literature review included randomized controlled trials (RCTs) of TCM for AI-related musculoskeletal symptoms. RESULTS: Four RCTs incorporating TCM were assessed by meta-analysis and reported favorable effects in reducing worst pain score (n = 284, mean difference [MD]: 2.31; 95% CI, 1.74 to 2.88; P < 0.00001). Three trials showed favorable effects of TCM in reducing pain interference (n = 211, MD: 2.62; 95% CI, 1.29 to 3.94; P = 0.0001), while two trials reported no significant effects of TCM on stiffness (n = 147, MD: 1.21; 95% CI, -0.39 to 2.82; P = 0.14). The meta-analysis of three trials also found no significant effect of TCM on bone mineral density (n = 214, MD, -0.01; 95% CI, -0.07 to 0.05; P = 0.71). The physical aspect of quality of life was significantly increased in breast cancer patients after TCM treatment (n = 220, MD, 5.13; 95% CI, 2.04 to 8.22; P = 0.001). In addition, three RCTs reported minimal TCM-related adverse events. CONCLUSION: The results suggest that TCM could be an effective treatment in relieving pain especially worst pain and pain interference as well as improving quality of life caused by AI-related musculoskeletal symptoms. However, further investigation of the molecular pathway involved and in-depth safety profile are needed.

Comparative transcriptome analysis to identify candidate genes involved in 2-methoxy-1,4-naphthoquinone (MNQ) biosynthesis in Impatiens balsamina L.

Impatiens balsamina L. is a tropical ornamental and traditional medicinal herb rich in natural compounds, especially 2-methoxy-1,4-naphthoquinone (MNQ) which is a bioactive compound with tested anticancer activities. Characterization of key genes involved in the shikimate and 1,4-dihydroxy-2-naphthoate (DHNA) pathways responsible for MNQ biosynthesis and their expression profiles in I. balsamina will facilitate adoption of genetic/metabolic engineering or synthetic biology approaches to further increase production for pre-commercialization. In this study, HPLC analysis showed that MNQ was present in significantly higher quantities in the capsule pericarps throughout three developmental stages (early-, mature- and postbreaker stages) whilst its immediate precursor, 2-hydroxy-1,4-naphthoquinone (lawsone) was mainly detected in mature leaves. Transcriptomes of I. balsamina derived from leaf, flower, and three capsule developmental stages were generated, totalling 59.643 Gb of raw reads that were assembled into 94,659 unigenes (595,828 transcripts). A total of 73.96% of unigenes were functionally annotated against seven public databases and 50,786 differentially expressed genes (DEGs) were identified. Expression profiles of 20 selected genes from four major secondary metabolism pathways were studied and validated using qRT-PCR method. Majority of the DHNA pathway genes were found to be significantly upregulated in early stage capsule compared to flower and leaf, suggesting tissue-specific synthesis of MNQ. Correlation analysis identified 11 candidate unigenes related to three enzymes (NADH-quinone oxidoreductase, UDP-glycosyltransferases and S-adenosylmethionine-dependent O-methyltransferase) important in the final steps of MNQ biosynthesis based on genes expression profiles consistent with MNQ content. This study provides the first molecular insight into the dynamics of MNQ biosynthesis and accumulation across different tissues of I. balsamina and serves as a valuable resource to facilitate further manipulation to increase production of MNQ.

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.