Establishment of humanised xenograft models as in vivo study for lung metastasis of osteosarcoma.

Humanised xenograft models and cancer cell lines are widely used for preclinical drug evaluation, biological studies, and targeted therapy strategies in cancer research. A humanised mouse model is a laboratory mouse that has been genetically modified to contain specific human genes, cells, or tissues. By introducing human-specific elements into rodents, researchers can create a more accurate representation of human physiological and pathological processes. Lacking an appropriate animal model for osteosarcoma (OS), hindered understanding of underlying mechanisms in OS metastasis progression. Markedly, metastasis influences the prognosis and treatment of osteosarcoma. Gaining insight into the mechanisms and occurrences of metastasis could potentially facilitate oncologists in improving therapies. Hence, it is important to develop a lung metastatic OS model to study the basic biology of its progression. This study has established a tumour-bearing mouse model using HOS-143B cell line which was injected into male NOD.SCID gamma (NSG) mice at two locations; intramuscularly (hind leg) and subcutaneously (back) respectively. The primary and metastatic tumour size was monitored by palpating the area of tumour induced and quantified using digital calliper. H&E staining was performed by pathologist to confirm metastasis. Our results showed that mice injected with 1 million cancer cells were unable to produce tumours. Meanwhile, mice injected with three million cancer cells showed tumour development and lung metastasis after 25 days of cancer cell inoculation. In conclusion, this study has successfully established a lung metastatic OS mouse model that could be useful for biological studies of OS. These findings imply that this model is essential for safety and efficacy before clinical trials, accelerate the translation from basic research to therapeutic applications.

Palm-based tocotrienol-rich fraction (TRF) supplementation modulates cardiac sod1 expression, fxr target gene expression, and tauro-conjugated bile acid levels in aleptinemic mice fed a high-fat diet.

Tocotrienol-rich fraction (TRF) has been reported to protect the heart from oxidative stress-induced inflammation. It is, however, unclear whether the protective effects of TRF against oxidative stress involve the activation of farnesoid X receptor (fxr), a bile acid receptor, and the regulation of bile acid metabolites. In the current study, we investigated the effects of TRF supplementation on antioxidant activities, expression of fxr and its target genes in cardiac tissue, and serum untargeted metabolomics of high-fat diet-fed mice. Mice were divided into high-fat diet (HFD) with or without TRF supplementation (control) for 6 weeks. At the end of the intervention, body weight (BW), waist circumference (WC), and random blood glucose were measured. Heart tissues were collected, and the gene expression of sod1, sod2, gpx, and fxr and its target genes shp and stat3 was determined. Serum was subjected to untargeted metabolomic analysis using UHPLC-Orbitrap. In comparison to the control, the WC of the TRF-treated group was higher (p >0.05) than that of the HFD-only group, in addition there was no significant difference in weight or random blood glucose level. Downregulation of sod1, sod2, and gpx expression was observed in TRF-treated mice; however, only sod1 was significant when compared to the HFD only group. The expression of cardiac shp (fxr target gene) was significantly upregulated, but stat3 was significantly downregulated in the TRF-treated group compared to the HFD-only group. Biochemical pathways found to be influenced by TRF supplementation include bile acid secretion, primary bile acid biosynthesis, and biotin and cholesterol metabolism. In conclusion, TRF supplementation in HFD-fed mice affects antioxidant activities, and more interestingly, TRF also acts as a signaling molecule that is possibly involved in several bile acid-related biochemical pathways accompanied by an increase in cardiac fxr shp expression. This study provides new insight into TRF in deregulating bile acid receptors and metabolites in high-fat diet-fed mice.

Trends on Human Norovirus Virus-like Particles (HuNoV-VLPs) and Strategies for the Construction of Infectious Viral Clones toward In Vitro Replication.

Most acute gastroenteritis (AGE) outbreaks and sporadic cases in developing countries are attributable to infection by human norovirus (HuNoV), the enteric virus mainly transmitted via fecal-contaminated water. However, it has been challenging to study HuNoV due to the lack of suitable systems to cultivate and replicate the virus, hindering the development of treatments and vaccines. Researchers have been using virus-like particles (VLPs) and infectious viral clones to overcome this challenge as alternatives to fresh virus isolates in various in vitro and ex vivo models. VLPs are multiprotein structures that mimic the wild-type virus but cannot replicate in host cells due to the lack of genetic materials for replication, limiting downstream analysis of the virus life cycle and pathogenesis. The development of in vitro cloning systems has shown promise for HuNoV replication studies. This review discusses the approaches for constructing HuNoV-VLPs and infectious viral clones, the techniques involved, and the challenges faced. It also highlights the relationship between viral genes and their protein products and provides a perspective on technical considerations for producing efficient HuNoV-VLPs and infectious viral clones, which could substitute for native human noroviruses in future studies.

Application of Conductive Hydrogels on Spinal Cord Injury Repair: A Review.

Spinal cord injury (SCI) causes severe motor or sensory damage that leads to long-term disabilities due to disruption of electrical conduction in neuronal pathways. Despite current clinical therapies being used to limit the propagation of cell or tissue damage, the need for neuroregenerative therapies remains. Conductive hydrogels have been considered a promising neuroregenerative therapy due to their ability to provide a pro-regenerative microenvironment and flexible structure, which conforms to a complex SCI lesion. Furthermore, their conductivity can be utilized for noninvasive electrical signaling in dictating neuronal cell behavior. However, the ability of hydrogels to guide directional axon growth to reach the distal end for complete nerve reconnection remains a critical challenge. In this Review, we highlight recent advances in conductive hydrogels, including the incorporation of conductive materials, fabrication techniques, and cross-linking interactions. We also discuss important characteristics for designing conductive hydrogels for directional growth and regenerative therapy. We propose insights into electrical conductivity properties in a hydrogel that could be implemented as guidance for directional cell growth for SCI applications. Specifically, we highlight the practical implications of recent findings in the field, including the potential for conductive hydrogels to be used in clinical applications. We conclude that conductive hydrogels are a promising neuroregenerative therapy for SCI and that further research is needed to optimize their design and application.

Increased ENT2 expression and its association with altered purine metabolism in cell lines derived from different stages of colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent malignant cancer types worldwide. Although the purine metabolism pathway is vital for cancer cell survival, little is known about the role of equilibrative nucleoside transporter 2 (ENT2) in CRC development and its association with purine metabolites. The aim of the present study was to evaluate the levels of hypoxanthine phosphoribosyl transferase (HPRT), hypoxanthine and uric acid (UA), as well as xanthine oxidase (XO) activity, and investigate their association with ENT2 expression levels in a normal human colon cell line and CRC cell lines derived from different stages of CRC. These analyses were performed using the normal colon CCD-841CoN cell line and a panel of human CRC cell lines comprising SW480, HCT15 and HCT116, which represent Dukes' B, C and D stages, respectively. Reverse transcription-quantitative PCR was performed to determine the level of ENT2 mRNA expression. In cells of all CRC stages, the levels of HPRT and hypoxanthine were significantly higher (P<0.05), while XO activity and UA levels were significantly decreased (P<0.05), compared with those in the CCD-841CoN cell line. ENT2 expression was found to be elevated in cells derived from all stages of CRC. The Dukes' D stage cell line had higher levels of HPRT and hypoxanthine, although its ENT2 level was not significantly lower than that of the Dukes' B and C stage cell lines. Increased levels of HPRT and hypoxanthine in various stages of CRC may indicate an increase in the activity of the salvage pathway. The increased expression of ENT2 implies the importance of the ENT2 protein in facilitating hypoxanthine transport, which is required for enhanced DNA synthesis via hypoxanthine recycling. In conclusion, ENT2 may have potential as a target in the development of CRC therapeutics.

Antimicrobial Effects of Tetraspanins: A New Turnabout in Treatment of Microorganisms.

Tetraspanins, a transmembrane protein is a 'molecular organiser' with diverse functions that promote a network of signalling involved in the cellular and pathological processes. Tetraspanins-enriched microdomains (TEMs) are the crucial feature for the protein-protein interactions in the cell membrane and are vulnerable to pathogens exploitation. Targetting the tetraspanins has shown to be effective against microbial infections although more research is needed to be performed. This article will review previous evidence that has successfully demonstrated the potential mechanism to target tetraspanins as an antimicrobial agent.

TCGA-My: A Systematic Repository for Systems Biology of Malaysian Colorectal Cancer.

Colorectal cancer (CRC) ranks second among the most commonly occurring cancers in Malaysia, and unfortunately, its pathobiology remains unknown. CRC pathobiology can be understood in detail with the implementation of omics technology that is able to generate vast amounts of molecular data. The generation of omics data has introduced a new challenge for data organization. Therefore, a knowledge-based repository, namely TCGA-My, was developed to systematically store and organize CRC omics data for Malaysian patients. TCGA-My stores the genome and metabolome of Malaysian CRC patients. The genome and metabolome datasets were organized using a Python module, pandas. The variants and metabolites were first annotated with their biological information using gene ontologies (GOs) vocabulary. The TCGA-My relational database was then built using HeidiSQL PorTable 9.4.0.512, and Laravel was used to design the web interface. Currently, TCGA-My stores 1,517,841 variants, 23,695 genes, and 167,451 metabolites from the samples of 50 CRC patients. Data entries can be accessed via search and browse menus. TCGA-My aims to offer effective and systematic omics data management, allowing it to become the main resource for Malaysian CRC research, particularly in the context of biomarker identification for precision medicine.

Palm tocotrienol rich fraction with palm kernel oil supplementation prevents development of liver steatosis in high fat diet ICR mice.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in Asian countries is increasing at concerning level. Currently, no specific treatment available to prevent its oxidative stress and progression except for diet and lifestyle changes. Vitamin E such as tocotrienol-rich fraction (TRF) has a promising potential in preventing NAFLD progression. TRF is a potent antioxidant but has low bioavailability due to the use of long-chain triglycerides (LCT) as its carrier. Testing of potential therapeutic agents such as TRF are commonly carried out using animal models. These animal models are often costly due to limited access to the supply especially Asian countries and predisposed to high transportation cost. Lower expenditure of NAFLD model should be investigated without forfeiting the outcome of study. Therefore, this study addresses the gap by utilizing the ICR mice as NAFLD model through dietary modification and testing on the newly formulated TRF with combination of palm kernel oil (PKO) as a medium-chain triglycerides (MCT) carrier. METHODS: Fifteen ICR strain mice were randomly group into two control and one treatment group. Control groups received high-fat diet (HFD) only and standard diet while treatment group was given HFD with TRF (200 mg/kg/day). Study was carried out for 10 weeks. Weights were recorded twice a week. At the end of study, all mice were euthanized and data such weights, waist circumference and random blood glucose were recorded. Liver from each mouse were prepared for histology assessment. RESULTS: Mice mean weights and random blood sugar showed no difference between group (P>0.05) while significance waist circumference was larger in HFD and TRF groups compared to SD (P<0.05). Histology assessment showed steatosis in TRF group had lower severity compared to HFD group. NAFLD activity score (NAS) was lower in treatment group compared to HFD group. CONCLUSIONS: TRF showed promising potential as an agent to reduce NAFLD progression in ICR mice. Further study at gene and protein levels are required to fully elucidate the mechanism of this new TRF formulation in reducing NAFLD progression.

Untargeted serum metabolites profiling in high-fat diet mice supplemented with enhanced palm tocotrienol-rich fraction using UHPLC-MS.

Excessive high fat dietary intake promotes risk of developing non-alcoholic fatty liver disease (NAFLD) and predisposed with oxidative stress. Palm based tocotrienol-rich fraction (TRF) has been reported able to ameliorate oxidative stress but exhibited poor bioavailability. Thus, we investigated whether an enhanced formulation of TRF in combination with palm kernel oil (medium-chain triglycerides) (ETRF) could ameliorate the effect of high-fat diet (HFD) on leptin-deficient male mice. All the animals were divided into HFD only (HFD group), HFD supplemented with ETRF (ETRF group) and HFD supplemented with TRF (TRF group) and HFD supplemented with PKO (PKO group). After 6 weeks, sera were collected for untargeted metabolite profiling using UHPLC-Orbitrap MS. Univariate analysis unveiled alternation in metabolites for bile acids, amino acids, fatty acids, sphingolipids, and alkaloids. Bile acids, lysine, arachidonic acid, and sphingolipids were downregulated while xanthine and hypoxanthine were upregulated in TRF and ETRF group. The regulation of these metabolites suggests that ETRF may promote better fatty acid oxidation, reduce oxidative stress and pro-inflammatory metabolites and acts as anti-inflammatory in fatty liver compared to TRF. Metabolites regulated by ETRF also provide insight of its role in fatty liver. However, further investigation is warranted to identify the mechanisms involved.

Metabolomic characterization of colorectal cancer cell lines highlighting stage-specific alterations during cancer progression.

Introduction: Metabolomic studies on various colorectal cancer (CRC) cell lines have improved our understanding of the biochemical events underlying the disease. However, the metabolic profile dynamics associated with different stages of CRC progression is still lacking. Such information can provide further insights into the pathophysiology and progression of the disease that will prove useful in identifying specific targets for drug designing and therapeutics. Thus, our study aims to characterize the metabolite profiles in the established cell lines corresponding to different stages of CRC. Methods: Metabolite profiling of normal colon cell lines (CCD 841 CoN) and CRC cell lines corresponding to different stages, i.e., SW 1116 (stage A), HT 29 and SW 480 (stage B), HCT 15 and DLD-1 (stage C), and HCT 116 (stage D), was carried out using liquid chromatography-mass spectrometry (LC-MS). Mass Profiler Professional and Metaboanalyst 4.0 software were used for statistical and pathway analysis. METLIN database was used for the identification of metabolites. Results: We identified 72 differential metabolites compared between CRC cell lines of all the stages and normal colon cells. Principle component analysis and partial least squares discriminant analysis score plot were used to segregate normal and CRC cells, as well as CRC cells in different stages of the disease. Variable importance in projection score identified unique differential metabolites in CRC cells of the different stages. We identified 7 differential metabolites unique to stage A, 3 in stage B, 5 in stage C, and 5 in stage D. Conclusion: This study highlights the differential metabolite profiling in CRC cell lines corresponding to different stages. The identification of the differential metabolites in CRC cells at individual stages will lead to a better understanding of the pathophysiology of CRC development and progression and, hence, its application in treatment strategies.

Global metabolomics profiling of colorectal cancer in Malaysian patients.

Introduction: The serum metabolomics approach has been used to identify metabolite biomarkers that can diagnose colorectal cancer (CRC) accurately and specifically. However, the biomarkers identified differ between studies suggesting that more studies need to be performed to understand the influence of genetic and environmental factors. Therefore, this study aimed to identify biomarkers and affected metabolic pathways in Malaysian CRC patients. Methods: Serum from 50 healthy controls and 50 CRC patients were collected at UKM Medical Centre. The samples were deproteinized with acetonitrile and untargeted metabolomics profile determined using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOFMS, Agilent USA). The data were analysed using Mass Profiler Professional (Agilent, USA) software. The panel of biomarkers determined were then used to identify CRC from a new set of 20 matched samples. Results: Eleven differential metabolites were identified whose levels were significantly different between CRC patients compared to normal controls. Based on the analysis of the area under the curve, 7 of these metabolites showed high sensitivity and specificity as biomarkers. The use of the 11 metabolites on a new set of samples was able to differentiate CRC from normal samples with 80% accuracy. These metabolites were hypoxanthine, acetylcarnitine, xanthine, uric acid, tyrosine, methionine, lysoPC, lysoPE, citric acid, 5-oxoproline, and pipercolic acid. The data also showed that the most perturbed pathways in CRC were purine, catecholamine, and amino acid metabolisms. Conclusion: Serum metabolomics profiling can be used to identify distinguishing biomarkers for CRC as well as to further our knowledge of its pathophysiological mechanisms.

Equilibrative Nucleoside Transporter 2: Properties and Physiological Roles.

Equilibrative nucleoside transporter 2 (ENT2) is a bidirectional transporter embedded in the biological membrane and is ubiquitously found in most tissue and cell types. ENT2 mediates the uptake of purine and pyrimidine nucleosides and nucleobase besides transporting a variety of nucleoside-derived drugs, mostly in anticancer therapy. Since high expression of ENT2 has been correlated with advanced stages of different types of cancers, consequently, this has gained significant interest in the role of ENT2 as a potential therapeutic target. Furthermore, ENT2 plays critical roles in signaling pathway and cell cycle progression. Therefore, elucidating the physiological roles of ENT2 and its properties may contribute to a better understanding of ENT2 roles beyond their transportation mechanism. This review is aimed at highlighting the main roles of ENT2 and at providing a brief update on the recent research.

The impacts of intrauterine Bisphenol A exposure on pregnancy and expression of miRNAs related to heart development and diseases in animal model.

This study aimed to examine the impact of BPA exposure on pregnancy and foetuses on cardiac tissues and the expression of cardiac microRNAs (miRNAs) related to heart development and diseases. Pregnancy is known to be the "critical windows" in determining the offspring physical and cells development in their life after birth. The increment of the risk of cardiovascular disease (CVD) in a later stage of life has been reported by few studies demonstrated from prenatal exposure of BPA. BPA has been shown to alter miRNAs expression profiles for organ development, regeneration and metabolic functions. These alterations have been associated with the risk of CVDs. However, the associations between pregnancy outcomes and miRNAs expression in cardiac of mother- and foetuses-exposed to BPA are still not entirely explored. In BPA-exposed pregnant rat groups, a significant weight gained was observed in comparison to control (p < 0.05). Interestingly, significant changes in systolic and diastolic blood pressure between the first and third trimester of BPA-exposed pregnant rats were also observed (p < 0.05). In BPA-exposed pregnant rats, miR-499-5p was significantly altered in the heart (p < 0.01). Meanwhile, altered miR-17-5p, -208-3p, and -210-3p expressions were observed in all heart of the foetuses from BPA-exposed pregnant rats (p < 0.05). In H&E staining, BPA-exposed foetal hearts showed a sign of fibrosis while BPA-exposed pregnant rats showed muscle remnant. Masson trichrome staining further confirmed the presence of fibrosis observed in BPA-exposed foetal heart and reduced expression of cardiac troponin I (cTnI) was also observed in BPA-exposed foetal heart. In summary, altered cardiac miRNAs with histological changes were observed in both mother- and foetus-exposed BPA These findings put forward the importance of future work to further understand how prenatal BPA exposure affect foetuses in their later stage of life.

Global serum metabolomics profiling of colorectal cancer.

Accurate diagnosis of colorectal cancer (CRC) relies on the use of invasive tools such as colonoscopy and sigmoidoscopy. Non-invasive tools are less sensitive in detecting the disease, particularly in the early stage. A number of researchers have used metabolomics analyses on serum/plasma samples of patients with CRC compared with normal healthy individuals in an effort to identify biomarkers for CRC. The aim of the present review is to compare reported serum metabolomics profiles of CRC and to identify common metabolites affected among these studies. A literature search was performed to include any experimental studies on global metabolomics profile of CRC using serum/plasma samples published up to March 2018. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to assess the quality of the studies reviewed. In total, nine studies were included. The studies used various analytical platforms and were performed on different populations. A pathway enrichment analysis was performed using the data from all the studies under review. The most affected pathways identified were protein biosynthesis, urea cycle, ammonia recycling, alanine metabolism, glutathione metabolism and citric acid cycle. The metabolomics analysis revealed levels of metabolites of glycolysis, tricarboxylic acid cycle, anaerobic respiration, protein, lipid and glutathione metabolism were significantly different between cancer and control samples. Although the majority of differentiating metabolites identified were different in the different studies, there were several metabolites that were common. These metabolites include pyruvic acid, glucose, lactic acid, malic acid, fumaric acid, 3-hydroxybutyric acid, tryptophan, phenylalanine, tyrosine, creatinine and ornithine. The consistent dysregulation of these metabolites among the different studies suggest the possibility of common diagnostic biomarkers for CRC.

The Roles of Low-Density Lipoprotein Receptor-Related Proteins 5, 6, and 8 in Cancer: A Review.

Low-density lipoprotein receptor (LDLR) has been an object of research since the 1970s because of its role in various cell functions. The LDLR family members include LRP5, LRP6, and LRP8. Even though LRP5, 6, and 8 are in the same family, intriguingly, these three proteins have various roles in physiological events, as well as in regulating different mechanisms in various kinds of cancers. LRP5, LRP6, and LRP8 have been shown to play important roles in a broad panel of cancers. LRP5 is highly expressed in many tissues and is involved in the modulation of glucose-induced insulin secretion, bone development, and cholesterol metabolism, as well as cancer progression. Recently, LRP5 has also been shown to play a role in chondroblastic subtype of osteosarcoma (OS) and prostate cancer and also in noncancer case such as osteoporosis. LRP6, which has been previously discovered to share the same structures as LRP5, has also been associated with many cancer progressions such as human triple negative breast cancer (TNBC), primary chronic lymphocytic leukemia (CLL), nonsmall cell lung cancer (NSCL), lung squamous cell carcinoma (LSCC), and hepatocellular carcinoma (HCC). In addition to its role in cancer progression, LRP8 (apolipoprotein E receptor 2 [APOER2]) has also been demonstrated to regulate canonical Wnt/ß-catenin signaling pathway whereby this pathway plays a role in cell migration and development. Therefore, this review aimed to elucidate the role of LRP 5, 6, and 8 in regulating the cancer progression.

Palm Oil in Lipid-Based Formulations and Drug Delivery Systems.

Palm oil is natural oil packed with important compounds and fatty acids ready to be exploited in lipid-based formulations and drug delivery. Palm oil and palm kernel oil contain long-chain and medium-chain triglycerides, respectively, including phytonutrients such as tocotrienol, tocopherol and carotenes. The exploitation of these compounds in a lipid-based formulation would be able to address hydrophobicity, lipophilicity, poor bioavailability and low water-solubility of many current drugs. The utilisation of palm oil as part of the drug delivery system seemed to improve the bioavailability and solubility of the drug, stabilising emulsification of formulation between emulsifier and surfactant, promoting enhanced drug permeability and performance, as well as extending the shelf-life of the drug. Despite the complexity in designing lipid-based formulations, palm oil has proven to offer dynamic behaviour in providing versatility in drug design, form and delivery. However, the knowledge and application of palm oil and its fractions in lipid-based formulation are scarce and interspersed. Therefore, this study aims to focus on the research and outcomes of using palm oil in lipid-based formulations and drug delivery systems, due to the importance of establishing its capabilities and benefits.

Annatto (Bixa orellana) δ-TCT Supplementation Protection against Embryonic Malformations through Alterations in PI3K/Akt-Cyclin D1 Pathway.

Protective action by annatto-derived delta-tocotrienol (δ-TCT) and soy-derived alpha-tocopherol (α-TOC) through the regulation of the PI3K/Akt-cyclin D1 pathway against nicotine-induced DNA damage is the focus of the present study. Nicotine, which has been widely reported to have numerous adverse effects on the reproductive system, was used as a reproductive toxicant. 48 female balb/c mice (6⁻8 weeks) (23⁻25 g) were randomly divided into eight groups (Grp.1⁻Grp.8; n = 6) and treated with either nicotine or/and annatto δ-TCT/soy α-TOC for seven consecutive days. On Day 8, the females were superovulated and mated before euthanization for embryo collection (46 h post-coitum). Fifty 2-cell embryos from each group were used in gene expression analysis using Affymetrix QuantiGene Plex2.0 assay. Findings indicated that nicotine (Grp.2) significantly decreased (p < 0.05) the number of produced 2-cell embryos compared to the control (Grp.1). Intervention with mixed annatto δ-TCT (Grp.3) and pure annatto δ-TCT (Grp.4) significantly increased the number of produced 2-cell embryos by 127% and 79%, respectively compared to Grp.2, but these were lower than Grp.1. Concurrent treatment with soy α-TOC (Grp.5) decreased embryo production by 7%. Supplementations with δ-TCT and α-TOC alone (Grp.6-Grp.8) significantly increased (p < 0.05) the number of produced 2-cell embryos by 50%, 36%, and 41%, respectively, compared to control (Grp.1). These results were found to be associated with alterations in the PI3K/Akt-Cyclin D1 genes expressions, indicating the inhibitory effects of annatto δ-TCT and soy α-TOC against nicotinic embryonic damage. To our knowledge, this is the first attempt in studying the benefits of annatto δ-TCT on murine preimplantation 2-cell embryos.

Vitamin E as an Antioxidant in Female Reproductive Health.

Vitamin E was first discovered in 1922 as a substance necessary for reproduction. Following this discovery, vitamin E was extensively studied, and it has become widely known as a powerful lipid-soluble antioxidant. There has been increasing interest in the role of vitamin E as an antioxidant, as it has been discovered to lower body cholesterol levels and act as an anticancer agent. Numerous studies have reported that vitamin E exhibits anti-proliferative, anti-survival, pro-apoptotic, and anti-angiogenic effects in cancer, as well as anti-inflammatory activities. There are various reports on the benefits of vitamin E on health in general. However, despite it being initially discovered as a vitamin necessary for reproduction, to date, studies relating to its effects in this area are lacking. Hence, this paper was written with the intention of providing a review of the known roles of vitamin E as an antioxidant in female reproductive health.

Metabolomics Profiling on Different Stages of Colorectal Cancer: A Systematic Review.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Early diagnosis and accurate staging of the disease is vital to improve the prognosis. Metabolomics has been used to identify changes in metabolite profiles in the different stages of cancer in order to introduce new non-invasive molecular tools for staging. In this systematic review, we aim to identify the common metabolite changes in human biological samples and the dominant metabolic pathways associated with CRC progression. A broad systematic search was carried out from selected databases. Four reviewers screened and reviewed the titles, abstracts, and full-text articles according to the inclusion and exclusion criteria. Quality assessment was conducted on the eight articles which met the criteria. Data showed that the metabolites involved with redox status, energy metabolism and intermediates of amino acids, choline and nucleotides metabolism were the most affected during CRC progression. However, there were differences in the levels of individual metabolites detected between the studies, and this might be due to the study population, sample preparation, analytical platforms used and statistical tools. In conclusion, this systematic review highlights the changes in metabolites from early to late stages of CRC. Moreover, biomarkers for prognosis are important to reduce CRC-related mortality.

Effects of Nicotine and Tocotrienol-Rich Fraction Supplementation on Cytoskeletal Structures of Murine Pre-Implantation Embryos.

BACKGROUND Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. The objective of this study was to evaluate the effects of nicotine, which is a source of oxidative stress, and subsequent supplementation with Tocotrienol-rich fraction (TRF) on actin and tubulin of 2- and 8-cell murine embryos. MATERIAL AND METHODS Thirty female Balb/C mice were divided into 4 groups: Group 1 received: subcutaneous (sc) injection of 0.9% NaCl; Group 2 received sc injection of 3.0 nicotine mg/kg bw/day; Group 3 received 3.0 sc injection of nicotine mg/kg bw/day +60 mg/kg bw/day TRF; and Group 4 received 60 sc injection of TRF mg/kg bw/day for 7 consecutive days. The animals were superovulated with 5 IU PMSG followed by 5 IU hCG 48 h later. Animals were cohabited with fertile males overnight and euthanized through cervical dislocation at 24 h post coitum. Embryos at the 2- and 8-cell stages were harvested, fixed, and stained to visualize actin and tubulin distributions by using CLSM. RESULTS Results showed that at 2-cell stage, actin intensities were significantly reduced in the nicotine group compared to that of the control group (p<0.001). In Group 3, the intensity of actin significantly increased compared to that of the nicotine group (p<0.001). At 8-cell stage, actin intensity of the nicotine group was significantly lower than that of the control group (p<0.001). The intensities of actin in Group 3 were increased compared to that of nicotine treatment alone (p<0.001). The same trend was seen in tubulin at 2- and 8-cell stages. Interestingly, both actin and tubulin structures in the TRF-treated groups were enhanced compared to the control. CONCLUSIONS This study suggests that TRF prevents the deleterious effects of nicotine on the cytoskeletal structures of 2- and 8-cell stages of pre-implantation mice embryos in vitro.