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Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The exciting potential of mRNA vaccines 03/12/24, 12:19 Last updated: Unleashing the power of mRNA: revolutionising medicine with personalised vaccines Basic mRNA vaccine pharmacology Basic mRNA vaccine pharmacology involves the study of two types of RNA used as vaccines: non-replicating mRNA and self-amplifying RNA. Non-replicating mRNA-based vaccines encode the antigen of interest and contain untranslated regions (UTRs) at both ends. Self-amplifying RNAs, on the other hand, encode both the antigen and the viral replication machinery, allowing for intracellular RNA amplification and abundant protein expression. For successful protein production in mRNA therapeutics, the optimal translation of in vitro transcribed (IVT) mRNA is crucial. Factors such as the length of the poly(A) tail, codon usage, and sequence optimization can influence translation efficiency and accuracy. Adding an optimal length of poly(A) to mRNA is necessary for efficient translation. This can be achieved by directly incorporating it from the encoding DNA template or by using poly(A) polymerase. Codon usage also plays a role in protein translation. Replacing rare codons with frequently used synonymous codons, which have abundant cognate tRNA in the cytosol, can enhance protein production from mRNA. However, the accuracy of this model has been subject to questioning. Optimally translated IVT mRNA encoding mRNA IVT mRNA plays a crucial role in mRNA vaccines as it is designed for optimal translation, ensuring efficient protein production. To achieve this, a 5ʹ cap structure is added, which is essential for efficient protein synthesis. Different versions of 5ʹ caps can be added during or after the transcription process. Furthermore, the poly(A) tail plays a significant regulatory role in mRNA translation and stability. Sequence optimization is another critical factor that can enhance mRNA levels and protein expression. Increasing the G:C content has been shown to elevate steady-state mRNA levels in vitro and improve protein expression in vivo. Furthermore, modifying the codon composition or introducing modified nucleosides can positively influence protein expression. However, it is important to note that these sequence engineering techniques may impact mRNA secondary structure, translation kinetics, accuracy, protein folding, as well as the expression of alternative reading frames and cryptic T-cell epitopes. Sequence optimization for protein translation Sequence optimization plays a crucial role in the development of mRNA vaccines. It involves modifying the mRNA sequence to improve the efficiency of protein translation. By optimizing the sequence, researchers can enhance the expression and stability of therapeutic mRNAs. However, the immunogenicity of exogenous mRNA is a concern, as it can trigger a response from various innate immune receptors. In some cases, encoding mRNA in the hypothalamus may even elicit a physiological response. Despite initial promising outcomes, the development of mRNA therapeutics has been hindered by concerns regarding mRNA instability, high innate immunogenicity, and inefficient in vivo delivery. As a result, DNA-based and protein-based therapeutic approaches have been preferred in the past. Modulation of immunogenicity Modulation of immunogenicity is a crucial aspect of mRNA vaccine development. Researchers aim to design mRNA vaccines that elicit a strong immune response while minimizing adverse reactions. This involves careful selection of antigens and optimization of the mRNA sequence to enhance immunogenicity. Self-replicating RNA vaccines and adjuvant strategies, such as TriMix, have shown increased immunogenicity and effectiveness. The immunostimulatory properties of mRNA can be further enhanced by including adjuvants. The size of the mRNA-carrier complex and the level of innate immune sensing in targeted cell types can influence the immunogenicity of mRNA vaccines. Advantages of mRNA vaccines mRNA vaccines offer several advantages over conventional vaccine approaches. First, they have high potency, meaning they can induce a strong immune response. Second, they have a capacity for rapid development, allowing for quick vaccine production in response to emerging infectious diseases or new strains. Third, mRNA vaccines have the potential for rapid, inexpensive, and scalable manufacturing, mainly due to the high yields of in vitro transcription reactions. Additionally, mRNA vaccines are minimal genetic vectors, avoiding anti-vector immunity, and can be administered repeatedly. However, recent technological innovations and research investments have made mRNA a promising therapeutic tool in vaccine development and protein replacement therapy. mRNA has several advantages over other vaccine platforms, including safety and efficacy. It is non-infectious and non-integrating, reducing the risk of infection and insertional mutagenesis. mRNA can be regulated in terms of in vivo half-life and immunogenicity through various modifications and delivery methods. Production of mRNA vaccines The production of mRNA vaccines involves in vitro transcription (IVT) of the optimized mRNA sequence. This process allows for the rapid and scalable manufacturing of mRNA vaccines. High yields of IVT mRNA can be obtained, making the production process cost-effective. Making mRNA more stable and highly translatable is achievable through modifications. Efficient in vivo delivery can be achieved by formulating mRNA into carrier molecules. The choice of carrier and the size of the mRNA-carrier complex can also modulate the cytokine profile induced by mRNA delivery. Current mRNA vaccine approaches ( Figure 1 ) There are several current mRNA vaccine approaches being explored. These include the development of mRNA vaccines against infectious diseases and various types of cancer. mRNA vaccines have shown promising results in both animal models and humans. Cancer vaccines Cancer vaccines are a type of immunotherapy that aim to stimulate the body's immune system to recognize and destroy cancer cells. These vaccines work by introducing specific antigens, which are substances that can stimulate an immune response, into the body. The immune system then recognizes these antigens as foreign and mounts an immune response against them, targeting and destroying cancer cells that express these antigens. There are different types of cancer vaccines, including personalized vaccines and predefined shared antigen vaccines. Personalized vaccines are tailored to each patient and are designed to target specific mutations or antigens present in their tumor. These vaccines are created by identifying tumor-specific antigens by sequencing the patient's tumor DNA and predicting which antigens are most likely to elicit an immune response. These antigens are then used to create a vaccine that is specific to that patient's tumor. On the other hand, predefined shared antigen vaccines are designed to target antigens that are commonly expressed in certain types of cancer. These vaccines can be used in multiple patients with the same type of cancer and are not personalized to each individual. The antigens used in these vaccines are selected based on their ability to induce an immune response and their potential to be recognized by T cells. Despite the promising potential of cancer vaccines, their clinical progress is limited, and skepticism surrounds their effectiveness. While there have been some examples of vaccines that have shown systemic regression of tumors and prolonged survival in small clinical trials, many trials have yielded marginal survival benefits. Challenges such as small trial sizes, resource-intensive approaches, and immune escape of heterogeneous tumors have hindered the field's progress. However, it is important to note that other immunotherapies, such as monoclonal antibodies and chimeric antigen receptor (CAR) T-cell therapies, have also faced challenges and setbacks before eventually achieving success. Therefore, cancer vaccines may also have the potential for eventual success, given their clear rationale and compelling preclinical data. To improve the efficacy of cancer vaccines, researchers are exploring various strategies. These include optimizing antigen presentation and immune activation by using adjuvants or agonists of pattern-recognition receptors. Additionally, advancements in sequencing technologies and computational algorithms for epitope prediction allow for the identification of more specific tumor mutagens and the production of personalized neo-epitope vaccines. Neo-epitope vaccines are a type of personalized vaccine that target specific mutations or neo-epitopes present in a patient's tumor. These vaccines exploit the most specific tumor mutagens identified through computational methods and prioritize highly expressed neo-epitopes. They can be given with adjuvants to enhance their immunogenicity. Hence, cancer vaccines hold promise as a potential standard anti-cancer therapy. While their progress has been limited, a clear rationale and compelling preclinical data support their further development. Personalized vaccines targeting specific mutations or antigens present in a patient's tumor, as well as predefined shared antigen vaccines targeting commonly expressed antigens, are being explored. Future of mRNA vaccines mRNA vaccines have emerged as a promising alternative to traditional vaccine approaches due to their high potency, rapid development capabilities, and potential for low-cost manufacture and safe administration. Recent technological advancements have addressed the challenges of mRNA instability and inefficient in vivo delivery, leading to encouraging results in the development of mRNA vaccine platforms against infectious diseases and various types of cancer. Looking ahead, the future of mRNA vaccines holds great potential for further advancements and widespread therapeutic use. Efficient in vivo delivery of mRNA remains a critical area of focus for future development. Researchers are working on improving delivery systems to ensure targeted delivery to specific cells or tissues, thereby enhancing the effectiveness of mRNA vaccines. This includes the development of lipid nanoparticles, viral vectors, and other delivery mechanisms to optimize mRNA delivery and cellular uptake. The success of mRNA vaccines against infectious diseases and cancer has opened doors to exploring their potential in other areas of medicine. Future research may involve the development of mRNA vaccines for autoimmune disorders, allergies, and chronic diseases. The versatility of mRNA technology allows for the rapid adaptation of vaccine candidates to address various medical conditions. One exciting prospect for mRNA vaccines is their potential for personalized medicine. The ability to easily modify the genetic sequence of mRNA allows for the development of personalized vaccines tailored to an individual's specific genetic makeup or disease profile. This could revolutionize preventive medicine by enabling targeted immunization strategies. Combining mRNA vaccines with other treatment modalities, such as immunotherapies or traditional therapies, could lead to synergistic effects and improved clinical outcomes. The unique properties of mRNA vaccines, such as their ability to induce potent immune responses and modulate the expression of specific proteins, make them attractive candidates for combination therapies. Continued advancements in manufacturing processes will be crucial for the widespread adoption of mRNA vaccines. Efforts are underway to optimize and scale up the production of mRNA vaccines, making them more accessible and cost-effective. This includes refining in vitro transcription reactions and implementing efficient quality control measures. The regulatory landscape surrounding mRNA vaccines will evolve as the field progresses. Regulatory agencies will need to establish guidelines and frameworks specific to mRNA vaccine development and approval. Ensuring safety, efficacy, and quality control will be essential to gain widespread acceptance and public trust in mRNA vaccines. Conclusion mRNA vaccines have shown great potential in revolutionizing the field of medicine, particularly in the areas of personalized medicine and preventive medicine. The ability to easily modify the genetic sequence of mRNA allows for the development of personalized vaccines tailored to an individual's specific genetic makeup or disease profile. Furthermore, the unique properties of mRNA vaccines, such as their ability to induce potent immune responses and modulate the expression of specific proteins, make them attractive candidates for combination therapies. However, there are still challenges to overcome, such as ensuring safety, efficacy, quality control, addressing concerns regarding immunogenicity. Nonetheless, with continued advancements in manufacturing processes and regulatory guidelines, the future of mRNA vaccines holds great promise for further advancements and widespread therapeutic use. Efforts to improve in vivo delivery systems and explore the potential of mRNA vaccines in other areas of medicine, such as autoimmune disorders and chronic diseases, further contribute to the promising outlook for this technology. Written by Sara Maria Majernikova Related articles: Potential malaria vaccine / Bioinformatics in COVID vaccine production / Personalised medicine REFERENCES Lin, M.J., Svensson-Arvelund, J., Lubitz, G.S. et al. Cancer vaccines: the next immunotherapy frontier. Nat Cancer 3, 911–926 (2022). https://doi.org/10.1038/s43018-022-00418-6 Pardi, N., Hogan, M., Porter, F. et al. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov 17 , 261–279 (2018). DOI: https://doi.org/10.1038/nrd.2017.243 Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Artificial Intelligence in Drug Research and Discovery 13/12/24, 11:30 Last updated: Using the new technology AI to develop drugs Drug research has been transformed by artificial intelligence (AI), which has become a game-changing technology in several industries. Only a small portion of potential drugs make it to the market after the lengthy and expensive traditional drug discovery process. A drug's discovery and development can take over ten years and cost an average of US$2.8 billion. Even then, nine out of 10 medicinal compounds fall short of passing regulatory approval and Phase II clinical trials. The use of AI in this process, however, has the potential to greatly improve effectiveness, accuracy, and success rates. Given that AI can help with rational drug design, support decision-making, identify the best course of treatment for a patient, including personalised medicines, manage the clinical data generated, and use it for future drug development, it is reasonable to assume that it will play a role in the development of pharmaceutical products from the laboratory bench to bedside table. There are several ways in which AI is currently being used to enhance the drug discovery process. One of the primary applications is virtual screening ( Figure 2 ), which involves using machine learning algorithms to analyse large libraries of chemical compounds and predict which ones are likely to be effective against a specific disease target. This can significantly reduce the time and cost required for drug discovery by narrowing down the number of compounds that need to be tested in the lab. Another way AI is being used in drug discovery is through generative models, which use deep learning algorithms to design molecules that are optimised for specific therapeutic targets. This approach can be used to design molecules that are effective against a specific target while also minimising toxicity or other undesirable properties. Data analysis is another area where AI can be applied in drug discovery. By analysing large datasets of biological and chemical information, AI can help researchers identify patterns and relationships that may be relevant to drug discovery. For example, AI can be used to analyse genomic data to identify potential drug targets or to analyse drug-drug interactions to identify potential safety issues. However, one of the main challenges is the need for high-quality data, as AI models rely on large amounts of data to make accurate predictions. Additionally, there is a risk that AI models may miss important insights or make incorrect predictions if the data used to train them is biased or incomplete. Nevertheless, the continued development of AI and its amazing tools seeks to lessen the difficulties experienced by pharmaceutical firms, impacting both the medication development process and the full lifecycle of the product, which may account for the rise in the number of start-ups in this industry. The importance of automation will increase as a result of using the most up-to-date AI-based technologies, which will not only shorten the time needed for products to reach the market but also enhance product quality, increase overall production process safety, and make better use of available resources while also being cost-effective. In conclusion, the use of AI in drug discovery has the potential to revolutionize the field and significantly improve the success rate of potential drug candidates. Despite the challenges and limitations, the continued research and development of AI in drug discovery will undoubtedly lead to faster, cheaper, and more accurate drug development. Written by Navnidhi Sharma Related articles: A breakthrough procedure in efficient drug discovery / AI in medicinal chemistry / AI advancing genetic disease diagnosis Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The Hippo signalling pathway 05/09/24, 10:41 Last updated: It plays a key role in many cancers Introduction The Hippo signalling pathway controls tissue growth, and it is also a vital pathway involved in many cancers. It is a serine/threonine kinase pathway, which regulates tissue growth by the control of cell proliferation and apoptosis. It was first discovered in a Drosophila genetic screen and was named Hippo, as a loss of Hippo results in an overgrowth (or hippopotamus) phenotype. When the Hippo pathway is ‘on,’ YAP and TAZ (transcription factors/activators) are degraded in the cytoplasm. This occurs via phosphorylation: Sterile 20-related (MST) kinases are phosphorylated, which in turn phosphorylate Large tumour suppressor 1 and 2 (LATS1/2). LATS phosphorylation then causes phosphorylation of YAP/TAZ. In turn, YAP/TAZ then bind to 14-3-3 proteins in the cytoplasm and are broken down by ubiquitin-dependent degradation (see fig. 1). YAP/TAZ has also been shown to activate transcription of YAP/TAZ regulators, such as LATS1/2, in a negative feedback loop. Conversely, when Hippo is ‘off,’ YAP/TAZ are unphosphorylated and are free to move to the nucleus, where they bind to Transcriptional enhanced associate domain (TEAD). YAP/TAZ-TEAD then are able to bind DNA and be involved in transcription of genes such as Axl, c-Myc, survivin, CTGF , and Cyr61 , which are anti-apoptotic or proliferative. Hippo pathway in cancer YAP/TAZ have been shown to be crucial for cancer initiation, progression, and metastasis. They are known to be involved in many cancers, including prostate, bone, eye, brain, spinal cord, breast, and liver cancers. They are also involved in the rare blood vessel cancer epithelioid hemangioendothelioma (EHE). Interestingly, it appears YAP/TAZ act differently depending on the cell type. YAP/TAZ are oncogenic transcription factors in many solid tumours, but surprisingly, they are thought to act as tumour suppressors in some blood cancers e.g. Multiple myeloma (it is still unknown why this is). Therefore, for YAP/TAZ to behave in a regular manner (i.e. non-oncogenic), they must be tightly regulated. Regulation of the Hippo pathway Hippo signalling is regulated by tight/adherens junctions, mechanical signals, and growth factors/receptors. Tight junctions exist where there is a permeability barrier between adjoining cells, and proteins bind to these membranes for a range of different functions. A protein which binds to these adherens junctions is Merlin (encoded by the gene, NF2 ), which is another regulator of the Hippo pathway and a well-known tumour suppressor. Merlin is known to bind to adherens junction proteins in confluent cells, and loss of Merlin causes a lack of development of adherens junctions. Merlin is also an important component involved in contact inhibition during proliferation. Contact inhibition is where cell growth is inhibited upon contact with other cells. The specific mechanism by which Merlin regulates the Hippo pathway and contact inhibition is still unknown. Another regulator of the Hippo pathway is mechanical signals. Fluid shear stress is the frictional force between flowing blood and endothelial cells lining the blood vessels and is known to cause vascular growth, remodelling and maintenance. This stress can result in changes to endothelial cell shape and cause the activation of transcription factors, leading to gene expression. An additional regulator of the Hippo pathway is growth factors/receptors. Growth factors, such as Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are both part of the phospholipids growth factor family. They bind to the S1P receptor and LPA receptor, respectively, inhibiting LATS and causing activation of YAP/TAZ. Whereas molecules, such as glucagon and epinephrine have been shown to suppress YAP/TAZ. Cytokines, vascular endothelial growth factors (VEGF), epidermal growth factors (EGF), Wnt, bone morphogenic protein (Bmp), insulin, and transforming growth factor β (TGF-β) have also been shown to regulate the Hippo pathway, which suggests that regulation of the Hippo pathway is complex and linked to several different other pathways. Conclusion The Hippo pathway is a vitally important pathway regulating tissue growth. YAP/TAZ, which are part of the Hippo pathway, are oncogenic factors in many solid tumours but can act as tumour suppressors in some blood cancers. As YAP/TAZ are involved in transcription in this pathway, they are crucial for cancer initiation, growth and metastasis. Hence, targeting of this pathway could lead to further cancer treatments. For example, TEAD inhibitors may offer a therapeutic avenue of treatment and are currently being investigated. In the future, further research on targeting the Hippo pathway may improve on the current targeted therapeutic landscape, realising the need for diverse treatment options for such a complex disease as cancer. Written by Eleanor R. Markham Related article: Epitheliod hemnagioendothelioma Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link A breakthrough in prostate cancer treatment 10/01/25, 11:33 Last updated: Treatment that effectively controls tumours and prolongs survival without side effects Introduction Prostate cancer is a devastating disease that affects millions of men worldwide. Despite advancements in treatment options, aggressive forms of the disease, such as metastatic castrate-resistant prostate cancer (mCRPC), remain a major challenge. However, a recent study conducted by researchers at the University of Chicago Medicine Comprehensive Cancer Centre has established a promising "proof-of-concept" for a new treatment approach that could revolutionize the field. The study, published in Clinical Cancer Research, demonstrated the remarkable effectiveness of this novel treatment in a mouse model of advanced prostate cancer. The researchers achieved complete tumour control and long-lasting survival without any side effects. These ground-breaking findings have paved the way for further investigation in human clinical trials. Finding the exact cancer cell and then destroying it but leaving the healthy tissue untouched. In theory, it could be like aiming and shooting at someone in the video game but real world is a bit different, isn’t it? Overcoming Resistance to Hormonal Therapy Hormonal therapy, specifically androgen deprivation therapy (ADT), is the standard treatment for metastatic prostate cancer. However, the majority of patients eventually develop resistance to this therapy, leading to castrate-resistant prostate cancer. This resistance poses a significant challenge for clinicians and leaves patients with limited treatment options. Dr. Akash Patnaik, an accomplished physician-scientist and renowned expert in prostate cancer research and treatment, and his team at the University of Chicago Medical Centre have been exploring new strategies to overcome this resistance. Their research focuses on harnessing the immune system's ability to combat cancer cells. Targeting Macrophages to Control Cancer Growth Dr. Patnaik's team discovered that macrophages, a type of immune cell, play a crucial role in promoting the growth of prostate cancer. These macrophages express a molecule called PD-1, which suppresses the anti-cancer immune response. By targeting these macrophages, the researchers aimed to control the growth of the cancer. In a previous study, the team found that co-targeting the PI3K and PD-1 pathways enhanced the effects of hormonal therapy in PTEN-deficient prostate cancer, a particularly aggressive form of the disease. However, a significant portion of the mice remained resistant to this therapy. Further investigations revealed that the activation of the Wnt/β-catenin pathway restored lactate production in these treatment-resistant cancers, leading to macrophages promoting tumour growth. A Novel Therapeutic Approach Building on their previous findings, Dr. Patnaik and his team developed a novel therapeutic approach. By co-targeting the PI3K, MEK, and Wnt/β-catenin signalling pathways, they achieved an impressive 80% response rate in mouse models. However, a small percentage of the mice still showed resistance due to the restoration of lactate production in the treatment-resistant cancers. This led the researchers to investigate further and uncover the mechanism behind this resistance. They discovered that lactate can interact with macrophages and modify them through a process called histone lactylation, making the macrophages immunosuppressive and promoting cancer growth. In their latest study, the researchers found that targeting lactate as a macrophage phagocytic checkpoint can effectively control the growth of PTEN/p53-deficient prostate cancer. Through intermittent dosing of the three drugs, they achieved complete tumor control and significantly prolonged survival without the long-term toxicity associated with continuous drug administration. These groundbreaking findings provide "proof-of-concept" for a new treatment approach that holds great promise for the most aggressive forms of prostate cancer. The researchers believe that their strategy of harnessing the ability of macrophages to eliminate cancer cells could revolutionize cancer therapy. By flipping the switch in macrophages, the cancer cells can be effectively controlled and eliminated. The next step for Dr. Patnaik and his team is to translate these findings into clinical trials. They plan to develop a phase 1 clinical trial to test the efficacy of the intermittent dosing approach in human patients. If successful, this approach could potentially offer a new therapeutic option for patients with metastatic castrate-resistant prostate cancer, who currently have limited treatment options. The potential of this novel therapeutic approach extends beyond prostate cancer. The researchers have also uncovered new therapeutic opportunities by perturbing signaling pathways in cancer cells that affect the metabolic output of the cancer cell and its interaction with tumor-promoting macrophages. This opens up new avenues for research and the development of targeted therapies for various types of cancer. Conclusion The research conducted by Dr. Patnaik and his team has demonstrated the effectiveness of co-targeting multiple signaling pathways in treating aggressive forms of prostate cancer. Their findings provide a solid foundation for further investigation in human clinical trials and offer hope for patients with limited treatment options. This novel therapeutic approach has the potential to revolutionize cancer therapy and pave the way for more targeted and effective treatments in the future. Written by Sara Maria Majernikova Related article: A breakthrough drug discovery in cancer treatment References: Chaudagar, K., et al . (2023) Suppression of tumor cell lactate-generating signaling pathways eradicates murine PTEN/p53-deficient aggressive-variant prostate cancer via macrophage phagocytosis. Clinical Cancer Research . doi.org/10.1158/1078-0432.CCR-23-1441 Chetta, P., Sriram, R. and Zadra, G. (2023) ‘Lactate as key metabolite in prostate cancer progression: What are the clinical implications?’, Cancers , 15(13), p. 3473. doi: https://doi.org/10.3390/cancers15133473 . Mathieu (2023) Revolutionary breakthrough in prostate cancer treatment at the University of Bern , Greater Geneva Bern area . Available at: https://ggba.swiss/en/revolutionary-breakthrough-in-prostate-cancer-treatment-at-the-university-of-bern/(Accessed: 29 September 2023). Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The endless possibilities of iPSCs and organoids 31/10/24, 11:44 Last updated: iPSCs are one of the most powerful tools of biosciences On the 8th of October 2012, the Nobel Prize in Physiology was given to Shinya Yamanaka and John B. Gurdon for a groundbreaking discovery; induced Pluripotent Stem Cells (iPSCs). The two scientists discovered that mature, specialised cells can be reprogrammed to their initial state and consequently transformed into any cell type. These cells can be used to study disease, examine genetic variations and test new treatments. The science behind iPSCs The creation of iPSCs is based on the procedure of cell potency during mammalian development. While the organism is still in the embryonic stage, the first cell developed is a totipotent stem cell, which has the unique ability to differentiate into any cell type in the human body. “Totipotent” refers to the cell’s potential to give rise to all cell types and tissues needed to develop an entire organism. As the totipotent cell grows, it develops into the pluripotent cell, which can differentiate into the three types of germ layers; the endoderm line, the mesoderm line and the ectoderm line. The cells of each line then develop into multipotent cells, which are derived into all types of human somatic cells, such as neuronal cells, blood cells, muscle cells, skin cells, etc. Creation of iPSCs and organoids iPSCs are produced through a process called cellular reprogramming, which involves the reprogramming of differentiated cells to revert to a pluripotent state, similar to that of embryonic stem cells. The process begins with selecting any type of somatic cell from the individual (in most cases, the individual is a patient). Four transcription factors, Oct4, Sox2, Klf4 and c-Myc, are introduced into the selected cells. These transcription factors are important for the maintenance of pluripotency. They are able to activate the silenced pluripotency genes of the adult somatic cells and turn off the genes associated with differentiation. The somatic cells are now transformed into iPSCs, which can differentiate into any somatic cell type if provided with the right transcription factor. Although iPSCs themselves have endless applications in biosciences, they can also be transformed into organoids, miniature three-dimensional organ models. To create organoids, iPSCs are exposed to a specific combination of signalling molecules and growth factors that mimic the development of the desired organ. Current applications of iPSCs As mentioned earlier, iPSCs can be used to study disease mechanisms, develop personalised therapies and test the action of drugs in human-derived tissues. iPSCs have already been used to model cardiomyocytes, neuronal cells, keratinocytes, melanocytes and many other types of cells. Moreover, kidney, liver, lung, stomach, intestine, and brain organoids have already been produced. In the meantime, diseases such as cardiomyopathy, Alzheimer’s disease, cystic fibrosis and blood disorders have been successfully modelled and studied with the use of iPSCs. Most importantly, the use of iPSCs in all parts of scientific research reduces or replaces the use of animal models, promising a more ethical future in biosciences. Conclusion iPSCs are one of the most powerful tools of biosciences at the moment. In combination with gene editing techniques, iPSCs give accessibility to a wide range of tissues and human disorders and open the doors for precise, personalised and innovative therapies. iPSCs not only promise accurate scientific research but also ethical studies that minimise the use of animal models and embryonic cells. Written by Matina Laskou Related articles: Organoids in drug discovery / Introduction to stem cells Project Gallery

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The science and controversy of water fluoridation 24/09/24, 13:20 Last updated: Diving deep In the pursuit of national strategies to improve oral health, few interventions have sparked as much debate and divided opinions as water fluoridation. Whilst some have voiced concerns about water fluoridation in recent years, viewing it as mass medicalisation and an intrusion into personal choice, researchers and dental professionals continue to champion its benefits as a cost-effective, population-wide approach that can significantly reduce tooth decay and enhance the oral health of communities across the country. The statistics from 2021-2022 paint a concerning picture, with a staggering 26,741 extractions performed on 0-19-year-olds under the NHS due to preventable tooth decay, amounting to an estimated cost of £50 million. With the NHS bearing the responsibility of providing dental care to millions of people nationwide, the introduction of water fluoridation stands out as a promising ally in the quest for more efficient healthcare and the alleviation of the burden on our already-strained healthcare system, all while improving dental health in a cost-effective manner. Fluoride is a naturally occurring chemical element found in soil, plants and groundwater, which can reduce dental decay through a dual mechanism; fluoridating water reduces dental decay by both impeding demineralisation of enamel and enhancing remineralisation of teeth following acid attacks in the mouth. When sugars from food or drinks enter the mouth, the bacteria present in plaque act to convert these sugars to acid, demineralising the outer surface of teeth and leading to the formation of cavities. The incorporation of fluoride into the structure of tooth enamel during remineralisation strengthens and hardens the outer layer of teeth, rendering teeth less susceptible to damage and more resistant to acid-induced demineralisation. Moreover, fluoride has also been proven to reverse early tooth decay by repairing and remineralising weakened enamel, thus averting the need for restorative dental procedures such as fillings. The inhibition of demineralisation and encouragement of remineralisation overall prevents cavities forming and preserves the vitality of our smiles. The main adverse effect of fluoridating water is the risk of dental fluorosis, which affects the appearance of teeth. Dental fluorosis is a cosmetic dental condition caused by excessive fluoride exposure, resulting in changes in tooth colour and texture. It presents as small opaque white spots or streaks on the tooth surface. It is important to note that these conditions generally occur at fluoride levels significantly higher than those recommended for water fluoridation. Opponents of water fluoridation also argue on ethical grounds, citing concerns about mass medication infringing on personal choice and the right to decide whether to use fluoride or dental products containing fluoride. In some cases, opposition is rooted in conspiracy theories and scepticism about government motives. Findings from the Office for Health Improvement and Disparities and the UK Health Security Agency highlight the benefits of water fluoridation. The data collected illustrates young populations in areas of England with higher fluoride concentrations are up to 63% less likely to be admitted to hospital for tooth extractions due to decay compared to their counterparts in areas of lower fluoridation levels. This disparity is most pronounced in the most deprived areas, where children and young adults benefit the most from the addition of fluoride to the water supply. These findings strongly support the evidence for the advantages of water fluoridation and highlight how this simple method can substantially improve health outcomes for our population. While fluoridation has proven beneficial for communities, especially those from deprived backgrounds, it has demonstrated successful outcomes for individuals across all demographics, irrespective of age, education, employment, or oral hygiene habits. It's essential to emphasize that water fluoridation should not replace other essential oral health practices such as regular tooth brushing, prudent sugar intake, and dental appointments. Instead, it should complement these practices, working in synergy to optimize oral health. As of now, approximately 10% of the population in England receives water from a fluoridation scheme. While the protective and beneficial effects of fluoridation are well-established, the decision to move towards a nationwide water fluoridation scheme ultimately rests with the Secretary of State for Health in the coming years. Written by Isha Parmar Project Gallery

Go back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link How metal organic frameworks are used to deliver cancer drugs in the body Last updated: 14/11/24 Metal ions and organic ligands are able to connect to form metallic organic frameworks on a nanoscale (Nano-MOFs) for cancer drug delivery. Metal Organic Frameworks (MOFs) are promising nanocarriers for the encapsulation of cancer drugs for drug delivery in the body. Cancer affects people globally with chemotherapy remaining the most frequent treatment approach. However, chemotherapy is non-specific, being cytotoxic to patients’ normal DNA cells causing severe side effects. Nanoscale Metal Organic Frameworks (Nano-MOFs) are highly effective for encapsulating cancer drugs for controlled drug delivery, acting as capsules that deliver cancer drugs to only tumorous environments. MOFs are composed of metal ions linked by organic ligands creating a permanent porous network. MOFs are able to form one-, two-, or three-dimensional structures building a coordination network with cross-links. When synthesized MOFs are crystalline compound and can sometimes be observed as a cubic structure when observed on a scanning electron microscope (SEM) image. In particular the novel zeolitic 2-methylimidazole framework (ZIF-8) MOF has received attention for drug delivery. ZIF-8 is composed of Zn2+ ions and 2-methylimidazole ligands, making a highly crystalline structure. ZIF-8 MOFs are able to deliver cancer drugs like doxorubicin to tumorous environments as it possesses a pH-sensitive degradation property. ZIF-8’s framework will only degrade in pH 5.0-5.5 which is a cancerous pH environment, and will not degrade in normal human body pH 7.4 conditions. This increases therapeutic efficacy for the patients having less systemic side effects, an aspect that nanomedicine has been extensively researching. As chemotherapy will damage health DNA cells as well as cancer cells, MOFs will only target cancer cells. Additionally the ZIF-8 MOF has a high porosity property due to the MOFs structures that is able to uptake doxorubicin successfully. Zn2+ is used in the medical field having a low toxicity and good biocompatibility. Overall MOFs and metal-organic molecules are important for the advancement of nanotechnology and nanomedicine. MOFs are highly beneficial for cancer research being a less toxic treatment method for patients. ZIF-8 MOFs are a way forward for biotechnology and pharmaceutical companies that research treatments that are more tolerable for patients. Such research shows the diversity of chemistry as the uses of metals and organic molecules are able to expand to medicine. Written by Alice Davey Related article: Anti-cancer metal compounds

Maths Articles Brush up on your mathematical knowledge with informative articles ranging from statistics and topology, to latent space transformations and Markov chain models. You may also like: Economics , Physics , Engineering and Technology Unlocking the power of statistics What statistics are and its importance Latent spac e transformations Their hidden power in machine learning Topology In action Teaching maths How we can apply maths in our lives How to excel in maths A useful resource for students studying the subject Cognitive decision-making The maths involved Cross-curricular maths The game of life The maths behind trading A comprehensive guide to the Relative Strength Index (RSI) Markov chain models Named after the Russian mathematician, Andrei Markov, who had first studied them

Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Exploring food at a molecular level 06/01/25, 14:10 Last updated: Molecular gastronomy Imagine taking a bite of your favourite dish, not just savouring the flavours, but peering into the very essence of its existence. That's the realm of molecular gastronomy, a fascinating exploration of food through the lens of science. This article takes you on a journey at the microscopic level of what fuels the human body. The foundation of all food lies in macromolecules, large molecules formed from the intricate assembly of smaller ones. Carbohydrates, proteins, and lipids are the main players, each with unique structures and roles. Carbohydrates: These sugary giants, like starches and sugars, provide our bodies with energy. Imagine them as long chains of sugar molecules linked together, like beads on a necklace. Proteins: The workhorses of the cellular world, proteins are responsible for countless functions. They're built from amino acids, each with a distinct side chain, creating a diverse and essential cast of characters. Lipids: Fats and oils, these slippery molecules store energy and form cell membranes. Think of them as greasy chains with attached rings, like chubby tadpoles swimming in oil. The symphony of cooking and the final dance Applying heat, pressure, and chemical reactions, chefs become culinary alchemists at the molecular level. Water, the universal solvent, facilitates the movement and interaction of these molecules. As we cook, proteins unfold and rearrange, starches break into sugars, and fats melt and release flavours. Maillard Reaction: This browning phenomenon, responsible for the delicious crust and crunch on your food, arises from the dance between sugars and amino acids. Imagine them waltzing and exchanging partners, creating new flavorful molecules that paint your food with golden hues. Emulsification: Oil and water don't mix, but lecithin, a molecule found in egg yolks, acts as a matchmaker. It bridges the gap between these unlikely partners, allowing for the creation of creamy sauces and fluffy cakes. Think of lecithin as a tiny cupid, shooting arrows of attraction between oil and water droplets. Saponification: Techniques like spherification use alginate and calcium to create edible spheres filled with liquid, transforming into playful pearls that burst with flavor in your mouth. A world of potential Understanding food at the molecular level unlocks a treasure trove of possibilities. It can help us create healthier, more sustainable food choices, develop personalized nutrition plans, and even combat foodborne illnesses. By peering into the microscopic world of our meals, we gain a deeper appreciation for the magic that happens on our plates, bite after delicious bite. So next time you savor a meal, remember the intricate dance of molecules that brought it to life. From the building blocks of carbohydrates to the symphony of cooking, food is a story written in the language of chemistry, waiting to be deciphered and enjoyed. Written by Navnidhi Sharma Related articles: Emotional chemistry on a molecular level / Food prices and malnutrition / Vitamins References and further readings: Chapter 2: Protein structure . (2019, July 10). Chemistry. https://wou.edu/chemistry/courses/online-chemistry-textbooks/ch450-and-ch451-biochemistry-d efining-life-at-the-molecular-level/chapter-2-protein-structure/ Gan, J., Siegel, J. B., & German, J. B. (2019). Molecular annotation of food - Towards personalized diet and precision health. Trends in Food Science & Technology , 91 , 675–680. https://doi.org/10.1016/j.tifs.2019.07.016 Grant, P. (2020, August 4). Sugar, fiber, starch: What’s A carbohydrate? — Pamela Grant, L.Ac , NTP. Pamela Grant, L.Ac , NTP . https://pamela-grant.com/blog-ss/sugar-fiber-starch Helmenstine, A. (2022, October 25). Examples of carbohydrates . Science Notes and Projects. https://sciencenotes.org/examples-of-carbohydrates/ Project Gallery

Curriculum Vitae (CV) Looking to apply for a job after your graduation, internship, or placement? Read below our CV information and advice! What are CVs? A CV entails a person's notable accomplishments - for example, their education history, work experience, certifications, volunteering experience, projects, and more. They are normally made on Microsoft Word and should be one page long , however someone extremely experienced in their field of work may choose to make their CV as two pages. But isn't this a resumé? ... ... No. CVs contain a more comprehensive breakdown of education, work experience etc; a resum é is not as detailed. A resum é also excludes date of birth, address, and contact info, whereas a CV includes this. Why should you write a good CV? There are several reasons as to why you should write a good CV, with just a few listed below: Professionalism A well organised, polished CV reflects your attention to detail and makes you more likely to be considered by employers for the advertised job. First impression and employability Employers spend less than 9 seconds looking at a CV! Hence, a well-designed CV is important as it will make you stand out and increase chances of securing an interview. Career progression A CV is not only for getting a job. It shows how you have generally developed as an employee, from what new skills you have gained to the responsibilities you have picked up. Networking Having a strong CV will allow you to share your background in a quick and efficient matter at, for example, career fairs or industry events. How do I know if my CV is to the right standard? Read below to find out more. We can check your CV for free! 1. Style We will make sure your writing is coherent and flows in the correct way, such as in chronological order. We will also recommend fonts, font sizes, appropriate headings that employers prefer and more, as layout is incredibly important to consider. 2. Spelling, punctuation and grammar It is easy to make small errors that can be easily overlooked! However, we will proofread your work to make sure your sentences make sense whilst being straight to the point. 3. Sections to include More than one would think, some may include sections that are of no relevance to the employer or put lack of detail in the ones that matter most. We will help make sure you don't fall into this trap. 4. Helping you make a start It is completely normal to feel like you don't know where to start from, too! Our advisors can ask you personalised questions regarding your experience, education, and so on to give you a 'template' to work on. This can then be reviewed and personalised feedback will be given until you are satisfied. 5. Other neat tricks... There are some features of a CV that individuals may not focus on but employers actually look for (hint: super- and extracurricular). Find out more from us if you're interested! Example universities where some of our advisors attend/have graduated from: Queen Mary University of London, Imperial College London, University of Liverpool and so on. Some of these students have secured placements, internships, and jobs with companies such as GSK and STATIC St. Andrews ! Just like personal statements , our expert advisors offer to review your CV in a time-efficient manner, by providing feedback on the following: Fill the form out below and we will contact you* * Alternatively, you can email us at scientianewsorg@gmail.com . Please keep the subject as 'CVs'. Email Subject Your message Send Thanks for submitting!