Cytotoxic activity of kenaf (Hibiscus cannabinus L.) seed extract and oil against human cancer cell lines

Objective: To examine the cytotoxic properties of both the kenaf (Hibiscus cannabinus L.) seed extract and kenaf seed oil on human cervical cancer, human breast cancer, human colon cancer and human lung cancer cell lines. Methods: The in vitro cytotoxic activity of the kenaf (Hibiscus cannabinus L.) seed extract and kenaf seed oil on human cancer cell lines was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and sulforhodamine B assays. Cell morphological changes were observed by using an inverted light microscope. Results: The kenaf seed extract (KSE) exhibited a lower IC50 than kenaf seed oil (KSO) in all of the cancer cell lines. Morphological alterations in the cell lines after KSE and KSO treatment were observed. KSE and KSO possessed effective cytotoxic activities against all the cell lines been selected. Conclusions: KSE and KSO could be potential sources of natural anti-cancer agents. Further investigations on using kenaf seeds for anti-proliferative properties are warranted

Effective strengthening of RC beams using bamboo-fibre-reinforced polymer: A finite-element analysis

This paper presents a finite-element model of the structural behaviour of reinforced concrete (RC) beams with and without openings externally strengthened with bamboo-fibre-reinforced composite (BFRC) plates. The simulation was performed using ABAQUS Unified FEA 2021HF8 software. The stress–strain relationship of the RC was modelled using a model code for concrete structures, whereas the concrete-damaged plasticity model was used to simulate concrete damage. The predicted crack pattern of the beams was comparable to that from experimental observations. The ultimate load-bearing capacity of RC beams in flexure was predicted with an error of up to 1.50%, while the ultimate load-bearing capacity of RC beams with openings in shear was predicted with an error ranging from 1.89 to 13.43%. The most successful arrangement for strengthening a beam with openings in the shear zone was to place BFRC plates perpendicular to the crack on both sides of the beam’s surface, which increased the beam’s original load-bearing capacity by 110.06% compared to that of the control beam (CB). The most effective method for strengthening RC beams in flexure is to attach a BFRC plate to the entire bottom soffit of the RC beam. This maximises the ultimate load-bearing capacity at the expense of the beam’s ductility

Induction of cell cycle arrest and apoptosis by copper complex Cu(SBCM)₂ towards oestrogen-receptor positive MCF-7 breast cancer cells

Copper complexes have the potential to be developed as targeted therapy for cancer because cancer cells take up larger amounts of copper than normal cells. Copper complex Cu(SBCM)2 has been reported to induce cell cycle arrest and apoptosis towards triple-negative breast cancer cells. Nevertheless, its effect towards other breast cancer subtypes has not been explored. Therefore, the present study was conducted to investigate the effect of Cu(SBCM)₂ towards oestrogen-receptor positive MCF-7 breast cancer cells. Growth inhibition of Cu(SBCM)₂ towards MCF-7 and human non-cancerous MCF-10A breast cells was determined by MTT assay. Morphological changes of Cu(SBCM)2-treated-MCF-7 cells were observed under an inverted microscope. Annexin V/PI apoptosis assay and cell cycle analysis were evaluated by flow cytometry. The expression of wild-type p53 protein was evaluated by Western blot analysis. The intracellular ROS levels of MCF-7 treated with Cu(SBCM)₂ were detected using DCFH-DA under a fluorescence microscope. The cells were then co-treated with Cu(SBCM)₂ and antioxidants to evaluate the involvement of ROS in the cytotoxicity of Cu(SBCM)2. Docking studies of Cu(SBCM)2 with DNA, DNA topoisomerase I, and human ribonucleotide reductase were also performed. The growth of MCF-7 cells was inhibited by Cu(SBCM)2 in a dose-dependent manner with less toxicity towards MCF-10A cells. It was found that Cu(SBCM)₂ induced G2/M cell cycle arrest and apoptosis in MCF-7 cells, possibly via a p53 pathway. Induction of intracellular ROS was not detected in MCF-7 cells. Interestingly, antioxidants enhance the cytotoxicity of Cu(SBCM)2 towards MCF-7 cells. DNA topoisomerase I may be the most likely target that accounts for the cytotoxicity of Cu(SBCM)₂

The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions.

Summary Background Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01)

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma.

c-MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables METN375S to interact with HER2 in a ligand-independent fashion. The resultant METN375S/HER2 dimer transduces potent proliferative, pro-invasive and pro-metastatic cues through the HER2 signaling axis to drive aggressive squamous cell carcinomas of the head and neck (HNSCC) and lung (LUSC), and is associated with poor prognosis. Accordingly, HER2 blockers, but not c-MET inhibitors, are paradoxically effective at restraining in vivo and in vitro models expressing METN375S. These results establish METN375S as a biologically distinct and clinically actionable molecular subset of SCCs that are uniquely amenable to HER2 blocking therapies

A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma.

c-MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables METN375S to interact with HER2 in a ligand-independent fashion. The resultant METN375S/HER2 dimer transduces potent proliferative, pro-invasive and pro-metastatic cues through the HER2 signaling axis to drive aggressive squamous cell carcinomas of the head and neck (HNSCC) and lung (LUSC), and is associated with poor prognosis. Accordingly, HER2 blockers, but not c-MET inhibitors, are paradoxically effective at restraining in vivo and in vitro models expressing METN375S. These results establish METN375S as a biologically distinct and clinically actionable molecular subset of SCCs that are uniquely amenable to HER2 blocking therapies

Recent Progress and Next Steps for the MATHUSLA LLP Detector

We report on recent progress and next steps in the design of the proposed MATHUSLA Long Lived Particle (LLP) detector for the HL-LHC as part of the Snowmass 2021 process. Our understanding of backgrounds has greatly improved, aided by detailed simulation studies, and significant R&D has been performed on designing the scintillator detectors and understanding their performance. The collaboration is on track to complete a Technical Design Report, and there are many opportunities for interested new members to contribute towards the goal of designing and constructing MATHUSLA in time for HL-LHC collisions, which would increase the sensitivity to a large variety of highly motivated LLP signals by orders of magnitude.Comment: Contribution to Snowmass 2021 (EF09, EF10, IF6, IF9), 18 pages, 12 figures. v2: included additional endorser

Matter manipulation with extreme terahertz light: Progress in the enabling THz technology

Terahertz (THz) light has proven to be a fine tool to probe and control quasi-particles and collective excitations in solids, to drive phase transitions and associated changes in material properties, and to study rotations and vibrations in molecular systems. In contrast to visible light, which usually carries excessive photon energy for collective excitations in condensed matter systems, THz light allows for direct coupling to low-energy (meV scale) excitations of interest, The development of light sources of strong-field few-cycle THz pulses in the 2000s opened the door to controlled manipulation of reactions and processes. Such THz pulses can drive new dynamic states of matter, in which materials exhibit properties entirely different from that of the equilibrium. In this review, we first systematically analyze known studies on matter manipulation with strong-field few-cycle THz light and outline some anticipated new results. We focus on how properties of materials can be manipulated by driving the dynamics of different excitations and how molecules and particles can be controlled in useful ways by extreme THz light. Around 200 studies are examined, most of which were done during the last five years. Secondly, we discuss available and proposed sources of strong-field few-cycle THz pulses and their state-of-the-art operation parameters. Finally, we review current approaches to guiding, focusing, reshaping and diagnostics of THz pulses. (C) 2019 The Author(s). Published by Elsevier B.V

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance