This review is aimed to provide a comprehensive overview of the physicochemical properties and extraction processes of red palm oil, its nutritional properties and applications in food. Crude palm ...oil is firstly extracted from the fruit mesocarp and processed into red palm oil using pre-treatment of crude palm oil, with deacidification steps, and deodorization via short-path distillation. These processes help to retain β-carotene and vitamin E in red palm oil. Palmitic, stearic and myristic acids are the saturated fatty acids in red palm oil, while the unsaturated fatty acids are oleic, linoleic and linolenic acids. It is reported to overcome vitamin A deficiency, promote heart health and have anti-cancer properties.
P110α is a member of the phosphoinositide 3-kinase (PI3K) enzyme family that functions downstream of RAS. RAS proteins contribute to the activation of p110α by interacting directly with its RAS ...binding domain (RBD), resulting in the promotion of many cellular functions such as cell growth, proliferation and survival. Previous work from our lab has highlighted the importance of the p110α/RAS interaction in tumour initiation and growth. Here we report the discovery and characterisation of a cyclic peptide inhibitor (cyclo-CRVLIR) that interacts with the p110α-RBD and blocks its interaction with KRAS. cyclo-CRVLIR was discovered by screening a "split-intein cyclisation of peptides and proteins" (SICLOPPS) cyclic peptide library. The primary cyclic peptide hit from the screen initially showed a weak affinity for the p110α-RBD (K
about 360 µM). However, two rounds of amino acid substitution led to cyclo-CRVLIR, with an improved affinity for p110α-RBD in the low µM (K
3 µM). We show that cyclo-CRVLIR binds selectively to the p110α-RBD but not to KRAS or the structurally-related RAF-RBD. Further, using biophysical, biochemical and cellular assays, we show that cyclo-CRVLIR effectively blocks the p110α/KRAS interaction in a dose dependent manner and reduces phospho-AKT levels in several oncogenic KRAS cell lines.
The Hippo signalling pathway is dysregulated across a wide range of cancer types and, although driver mutations that directly affect the core Hippo components are rare, a handful is found within ...pleural mesothelioma (PM). PM is a deadly disease of the lining of the lung caused by asbestos exposure. By pooling the largest‐scale clinical datasets publicly available, we here interrogate associations between the most prevalent driver mutations within PM and Hippo pathway disruption in patients, while assessing correlations with a variety of clinical markers. This analysis reveals a consistent worse outcome in patients exhibiting transcriptional markers of YAP/TAZ activation, pointing to the potential of leveraging Hippo pathway transcriptional activation status as a metric by which patients may be meaningfully stratified. Preclinical models recapitulating disease are transformative in order to develop new therapeutic strategies. We here establish an isogenic cell‐line model of PM, which represents the most frequently mutated genes and which faithfully recapitulates the molecular features of clinical PM. This preclinical model is developed to probe the molecular basis by which the Hippo pathway and key driver mutations affect cancer initiation and progression. Implementing this approach, we reveal the role of NF2 as a mechanosensory component of the Hippo pathway in mesothelial cells. Cellular NF2 loss upon physiological stiffnesses analogous to the tumour niche drive YAP/TAZ‐dependent anchorage‐independent growth. Consequently, the development and characterisation of this cellular model provide a unique resource to obtain molecular insights into the disease and progress new drug discovery programs together with future stratification of PM patients.
Stratifying pleural mesothelioma (PM) patients reveals active YAP/TAZ is associated with poor clinical outcomes.
An isogenic cell‐line model of PM driver mutations is developed that faithfully recapitulates clinical PM characteristics.
NF2 regulates YAP/TAZ mesothelial activity in response to stresses, including sensing mechanical cues, while BAP1 appears to regulate a stem‐cell‐like transcriptional program.
Using data from the International Satellite Cloud Climatology Project (ISCCP), we examine how near-global (60°N–60°S) high cloud fraction varies over time in the past three decades. Our focus is on ...identifying dominant modes of variability and associated spatial patterns, and how they are related to sea surface temperature. By performing the principal component analysis, we find that the first two principal modes of high cloud distribution show strong imprints of the two types of El Niño–Southern Oscillation (ENSO)—the canonical ENSO and the ENSO Modoki. Comparisons between ISCCP data and 14 models from the Atmospheric Model Intercomparison Project Phase 5 (AMIP5) show that models simulate the spatial pattern and the temporal variations of high cloud fraction associated with the canonical ENSO very well but the magnitudes of the canonical ENSO vary among the models. Furthermore, the multi-model mean of the second principal mode in the AMIP5 simulations appears to capture the temporal behavior of the second mode but individual AMIP5 models show large discrepancies in capturing observed temporal variations. A new metric, defined by the relative variances of the first two principal components, suggests that most of the AMIP5 models overestimate the second principal mode of high clouds.
The human body is a home to thousands of microbiotas. It is defined as a community of symbiotic, commensal and pathogenic microorganisms that have existed in all exposed sites of the body, which have ...co-evolved with diet, lifestyle, genetic factors and immune factors. Human microbiotas have been studied for years on their effects with relation to health and diseases.
Relevant published studies, literature and reports were searched from accessible electronic databases and related institutional databases. We used keywords, viz; microbiome, microbiota, microbiome drug delivery and respiratory disease. Selected articles were carefully read through, clustered, segregated into subtopics and reviewed.
The traditional belief of sterile lungs was challenged by the emergence of culture-independent molecular techniques and the recently introduced invasive broncho-alveolar lavage (BAL) sampling method. The constitution of a lung microbiome mainly depends on three main ecological factors, which include; firstly, the immigration of microbes into airways, secondly, the removal of microbes from airways and lastly, the regional growth conditions. In healthy conditions, the microbial communities that co-exist in our lungs can build significant pulmonary immunity and could act as a barrier against diseases, whereas, in an adverse way, microbiomes may interact with other pathogenic bacteriomes and viromes, acting as a cofactor in inflammation and host immune responses, which may lead to the progression of a disease. Thus, the use of microbiota as a target, and as a drug delivery system in the possible modification of a disease state, has started to gain massive attention in recent years. Microbiota, owing to its unique characteristics, could serve as a potential drug delivery system, that could be bioengineered to suit the interest. The engineered microbiome-derived therapeutics can be delivered through BC, bacteriophage, bacteria-derived lipid vesicles and microbe-derived extracellular vesicles. This review highlights the relationships between microbiota and different types of respiratory diseases, the importance of microbiota towards human health and diseases, including the role of novel microbiome drug delivery systems in targeting various respiratory diseases.
•Microbiome-based therapeutics deeply impact pharmaceutical and medical fields.•Engineered bacteriophage has potential antibiotic adjuvant activity.•Crosstalk between lung and gut microbiota influences immune response.•These bio-systems has potential to improve patient compliance and drug profile.
Targeting the interaction of proteins with weak binding affinities or low solubility represents a particular challenge for drug screening. The NanoLuc
® Binary Technology (NanoBiT
®) was ...originally developed to detect protein-protein interactions in live mammalian cells. Here we report the successful translation of the NanoBit cellular assay into a biochemical, cell-free format using mammalian cell lysates. We show that the assay is suitable for the detection of both strong and weak protein interactions such as those involving the binding of RAS oncoproteins to either RAF or phosphoinositide 3-kinase (PI3K) effectors respectively, and that it is also effective for the study of poorly soluble protein domains such as the RAS binding domain of PI3K. Furthermore, the RAS interaction assay is sensitive and responds to both strong and weak RAS inhibitors. Our data show that the assay is robust, reproducible, cost-effective, and can be adapted for small and large-scale screening approaches. The NanoBit Biochemical Assay offers an attractive tool for drug screening against challenging protein-protein interaction targets, including the interaction of RAS with PI3K.
This review is aimed to provide a comprehensive overview of the physicochemical properties and extraction processes of red palm oil, its nutritional properties and applications in food. Crude palm ...oil is firstly extracted from the fruit mesocarp and processed into red palm oil using pre-treatment of crude palm oil, with deacidification steps, and deodorization via short-path distillation. These processes help to retain β-carotene and vitamin E in red palm oil. Palmitic, stearic and myristic acids are the saturated fatty acids in red palm oil, while the unsaturated fatty acids are oleic, linoleic and linolenic acids. It is reported to overcome vitamin A deficiency, promote heart health and have anti-cancer properties.
Targeting the interaction of proteins with weak binding affinities or low solubility represents a particular challenge for drug screening. The NanoLuc
® Binary Technology (NanoBiT
®) was originally ...developed to detect protein-protein interactions in live mammalian cells. Here we report the successful translation of the NanoBit cellular assay into a biochemical, cell-free format using mammalian cell lysates. We show that the assay is suitable for the detection of both strong and weak protein interactions such as those involving the binding of RAS oncoproteins to either RAF or phosphoinositide 3-kinase (PI3K) effectors respectively, and that it is also effective for the study of poorly soluble protein domains such as the RAS binding domain of PI3K. Furthermore, the RAS interaction assay is sensitive and responds to both strong and weak RAS inhibitors. Our data show that the assay is robust, reproducible, cost-effective, and can be adapted for small and large-scale screening approaches. The NanoBit Biochemical Assay offers an attractive tool for drug screening against challenging protein-protein interaction targets, including the interaction of RAS with PI3K.
To evaluate the potential for diagnosing colorectal cancer (CRC) from faecal metagenomes.
We performed metagenome-wide association studies on faecal samples from 74 patients with CRC and 54 controls ...from China, and validated the results in 16 patients and 24 controls from Denmark. We further validated the biomarkers in two published cohorts from France and Austria. Finally, we employed targeted quantitative PCR (qPCR) assays to evaluate diagnostic potential of selected biomarkers in an independent Chinese cohort of 47 patients and 109 controls.
Besides confirming known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with CRC, we found significant associations with several species, including Parvimonas micra and Solobacterium moorei. We identified 20 microbial gene markers that differentiated CRC and control microbiomes, and validated 4 markers in the Danish cohort. In the French and Austrian cohorts, these four genes distinguished CRC metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77, respectively. qPCR measurements of two of these genes accurately classified patients with CRC in the independent Chinese cohort with AUC=0.84 and OR of 23. These genes were enriched in early-stage (I-II) patient microbiomes, highlighting the potential for using faecal metagenomic biomarkers for early diagnosis of CRC.
We present the first metagenomic profiling study of CRC faecal microbiomes to discover and validate microbial biomarkers in ethnically different cohorts, and to independently validate selected biomarkers using an affordable clinically relevant technology. Our study thus takes a step further towards affordable non-invasive early diagnostic biomarkers for CRC from faecal samples.
•Systematic analysis of all emission streams and established mass balance of reaction reagents, bromide and carbon.•Limited difficulties in emission treatment due to sole destination of ...pollutants.•Excellent environmental sustainability by bromide recovery from the Washing Liquid.•Provide evaluation criteria for waste recycling process development.
The short life span of electrical and electronic equipments (EEE) produces a tremendous amount of waste electrical and electronic equipments (WEEE) globally at an overwhelming rate. Currently, the recycling of waste printed circuit board (WPCB) is an emerging and sensitive environmental issue since traditional treatment methods have been proved to be inappropriate. Also, the recovery of valuable components from WPCB is limited by the environmental emissions from the recycling process, which have been seriously neglected by the research community before. To analyze the environmental emission impacts and set evaluation criteria, a newly developed aluminosilicate adsorbent production process is discussed in this work. It is proved to be capable to recycle the NMF of WPCB as the feedstock of the functionalization process. Besides, the mass balance of reaction reagents, bromide and carbon were established with clear pathways and destinations by various analytical chemistry methods. The debromination process in functionalization significantly reduced the total toxicity by giving inorganic bromide and bisphenol A (BPA) as two main products. The results confirm this process to be an environmentally friendly process which can provide a basis for evaluating recycling processes.
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