#WearingWhite: Cancer immunotherapy

#WearingWhite: Cancer immunotherapy

This Sunday is World Cancer Day. Staff here at the University of Southampton have been wearing white in order to raise awareness of the life-saving research being performed behind the laboratory doors. In fact, today the University of Southampton are celebrating hitting the £25m target for the UK’s first dedicated Centre for Cancer Immunology!

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Why white?!

We have a lot of different cells in our body, in fact there’s thought to be approximately 200 different types of cells, but today I’m talking about our white blood cells. White bloods cells are the superhero cells, their role is to protect us from infection, disease and foreign invaders to keep us healthy. Here in Southampton, these white blood cells are being used in laboratory research to develop new therapies to fight cancer. The research is being applied into the clinic, and results from clinical trials is showing a lot of promise!

Wearing White

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We are the cure

Immunology is a pretty complex field, and so I’m not going to go into the details (you’d be sat here reading for hours trying to get a grip on a lot of different molecules), but basically, researchers have found that our immune system could actually be used to cure cancer. That’s pretty neat right?!

A type of treatment called immunotherapy harnesses the power of the body’s immune system to recognise and destroy cancer cells (see video below). Cancer cells have the ability to switch off or confuse our killer T cells which then enable the cancer cells to grow. Cancer cells are very hard to defeat! Immunotherapy switches these killer T cells back on and so those useful killer T cells become back in action. They are then able to detect the invasive cancer cells (and potentially any hidden cancer cells!) and destroy them, providing long lasting action to protect against cancer growth. There are different types of immunotherapy including the use of monoclonal antibodies, vaccines, cytokines and adoptive cell transfer and you can read more about these here! They’re all about enhancing the ability of the T cells to recognise the cancer cells. Immunotherapy has the potential to provide us with a lifetime immunity to cancer.

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Successes

Cancer is one of the leading causes of death worldwide, but the results from cancer immunology clinical trials suggest great hope for controlling and curing most cancers.

Immunotherapy clinical trial patients in Southampton:

  • As many as half of the patients with difficult and terminal cancers (often just given months to live) are showing dramatic improvements.
  • 20% patients are cancer free.
  • Drugs for advanced and terminal cancers, such as lung, skin (melanoma), blood (lymphoma), head and neck cancers and childhood cancer (neuroblastoma) are showing outstanding results.

“The cure for Cancer? You’re it.”

– University of Southampton

To read the stories of patients, researchers, fundraisers and donors click here and scroll down the page.

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For extra info click the following links: Cancer Research UK & Cancer Research Institute.

If you are interested in taking part in an immunotherapy clinical trial please contact your GP or cancer specialist.

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If you want to learn some more interesting science then check out my previous science blog posts here.

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Disease can originate from early development?!

Disease can originate from early development?!

Last week’s blog post was all about the #uosIDS 10 year celebrations here at the Institute of Developmental Sciences. We’re also the home of DOHaD (Developmental Origins of Health and Disease). But what is this? What is this hypothesis that forms the basis to the majority of research here? Well, I’ll enlighten you with some science!

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It’s well known that ‘bad genes’ and poor lifestyle choices affect our health and wellbeing in adulthood. But is it that simple? Is that all that determines our health? Professor David Barker, a Southampton based clinical epidemiologist, challenged these traditional ideas. In 1990 he proposed that poor nutrition in the womb resulted in common chronic diseases and ‘The Barker Hypothesis’ was born, which is now known as the ‘DOHaD Hypothesis’. He suggested that the environment during fetal and early life is what ‘programmes’ our health and risk of disease from infancy to adulthood. It is thought that the fetus adapts to the nutrient supply available during pregnancy. Some will have to adapt to a more restricted supply, which is associated with an increased risk of chronic diseases.

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Early life health. Photo: Pexels

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The science behind the hypothesis

UK lower socioeconomic areas – infant mortality rates in the early 20th century correlated with cardiovascular deaths 60-70 years later.

The Hertfordshire Study – Barker revealed that low birth weight (indicator of poor maternal environment) was associated with higher blood pressure, increased death by coronary heart disease, type 2 diabetes and osteoporosis.

Helsinki, India and Amsterdam – studies revealed similar relationships between maternal nutrition/childhood growth and chronic disease.

The Dutch Winter Famine (1944-1945) – people including pregnant women were restricted to only 400–800 calories per day. Famine during early pregnancy lead to larger and heavier babies with an increased risk of coronary heart disease in adulthood. However, exposure during mid-late pregnancy resulted in babies with reduced birth weight, a reduced ability to handle blood glucose levels and risk of type 2 diabetes.

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Over the past 25 years a wealth of research (both human and animal studies) has contributed to Barker’s theory. Effects of maternal stress, obesity and hypoxia (low oxygen) during pregnancy on offspring health are a few conditions being researched today. Research is still on going in Southampton as a result of Barker’s work. The Princess Ann Cohort and the Southampton Women’s Survey found a correlation between low maternal vitamin D levels and lower childhood bone mass and grip strength, respectively. These results have lead to interventional trials involving vitamin D supplementation during pregnancy.

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Human beings are like motor cars. They break down either because they are being driven on rough roads or because they were badly made in the first place. Rolls-Royce cars do not break down no matter where they are being driven. How do we build stronger people? By improving the nutrition of babies in the womb. The greatest gift we could give the next generation is to improve the nutrition and growth of girls and young women

Prof. David Barker

The power of epigenetics

For years scientists have studied single genes and how alterations in them affect our health status. Recent research suggests that there are factors (epigenetic factors) which in turn alter the function of these genes. Some epigenetic markers have been associated with the natural ageing process and some have been associated with diseases such as cancer and diabetes.

So what are epigenetic factors? Epigenetic changes modify our DNA, causing some genes to be switched on or off, and consequently causing more or less of the corresponding protein to be produced. Environmental factors such as undernutrition, overnutrition, stress and inflammation can alter our epigenetics. We know these factors experienced by the mother can lead to an increased risk of cardiovascular and metabolic diseases for the child in later life. Epigenetic changes in critical developmental time frames are thought to cause long term effects and consequently increased susceptibility to disease throughout the life course.

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Human placenta. Turquoise= trophoblast (placental) cells, purple= connective tissue, pink= fetal blood vessels. Photo: Placenta Lab and Biomedical Imaging Unit, University of Southampton.

The placenta is the interface between mother and baby, and the source of all the baby’s nutrients during pregnancy. Transfer of amino acids (the building blocks of protein) via amino acid transporters are vital for fetal growth. A suboptimal placenta can therefore cause problems for the baby in later life. Research here at the IDS is currently investigating how epigenetic changes impact the placenta and these amino acid transporters. Studies are also looking into the epigenetic modifications leading to changes in gene expression associated with the risk of obesity and metabolic disease in later life, which is very relevant to our current population.

 

The hypothesis can lead to good things!…

The DOHaD hypothesis has lead to a huge amount of research over the years exploring the reasons for and why conditions during pregnancy affect the long term health of the child. This understanding which is constantly growing can have a huge positive impact…

  • shift the focus of public health interventions – should not just be focusing on the health during childhood and adulthood, but also during pregnancy.
  • opportunity to reassess education, availability of health services and professional training.
  • Enhance education in the importance of nutrition, exercise and emotional health.
  • Enhanced support for the mother during pregnancy. Stress and emotional struggles can have a serious knock to maternal wellbeing and result in severe consequences to offspring health.
  • Research focusses – researching genetic predisposition and epigenetic monitoring would enhance our ability to target chronic diseases more effectively in the future.

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Additional nutritional intervention studies are vital in order to further our understanding of chronic disease risk factors and the epigenetics which play a role in exacerbating these health complications.

David Barker and his hypothesis have really made scientists change their way of thinking. It has lead to ground breaking science and provides a foundation to improve public health services in order to enhance the health and wellbeing of future generations.

… And of course it’s formed the basis for my very own PhD research.

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Fancy reading a little more on this? Click here.

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World Diabetes Day

World Diabetes Day

Today is World Diabetes Day.

Diabetes is a condition which occurs when the body cannot regulate glucose (sugar) properly. The cells within the body are not able to respond and ‘use’ the glucose in a normal way, which leads to large amounts of glucose in the blood. It is the high blood glucose levels which can cause serious health conditions.

“Estimated 422 million people are living with diabetes in the world, 1 in 11 of the world’s adult population.”

– Word Health Organisation

So what stops these cells from utilising the glucose properly?

Let’s talk about insulin. Insulin is a hormone produced by the pancreas. After we eat a meal we digest our food and the carbohydrates get broken down into glucose. This glucose needs to be utilised by our cells (particularly in fat tissue, the liver and skeletal muscle) in order to generate energy. Insulin is what allows the glucose to move into our cells.

Diabetes is often explained via a lock and key mechanism. Insulin being the key which enables the door of the cells to open and allow glucose to enter.

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Diabetes lock and key

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This lock and key mechanism is different in those with diabetes compared to those without it. This mechanism is also impaired in different way in the two main types of diabetes:

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Type 1 diabetes:

Insulin just isn’t produced by the pancreas so there’s no key to open the lock on the cells.

Type 1 diabetes affects 10% of diabetic patients in the UK. It’s what we call an autoimmune condition. The insulin-producing cells in the pancreas are destroyed which means that insulin is not produced by the body.

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Type 2 diabetes:

Insulin (the key) may not be able to unlock the door to the cells optimally, or it could be that it’s readily available but the lock isn’t working properly.

Type 2 diabetes is often associated with being overweight and affects 90% of UK diabetic patients.

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There’s also something called pre-diabetes. This is when someone has blood sugar levels above the normal range but not enough to be diagnosed as diabetic. Having pre-diabetes increases the risk of developing diabetes.

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What’s the treatment?

Sadly there is currently no cure for diabetes. HOWEVER, amazing scientific advancements has lead to the discovery of insulin (lowers blood glucose levels) and it’s use as a treatment (particularly for type 1), and the development of other medication and devices which are vital in managing diabetes. If diabetes is not managed and high blood glucose levels persist, it can lead to a plethora of health disorders such as cardiovascular disease, stroke, nerve damage, chronic kidney disease, foot ulcers and visual impairment.

Diabetes management

As I said, type 2 diabetes (most common form of diabetes) is often associated with being overweight. So eating healthily, exercising regularly and monitoring blood glucose levels is important…

Adults should do 150 minutes of moderate to vigorous physical activity a week. Muscle strengthening activity should also be included twice a week.

– recommended by The Department of Health

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… so hello #150mins campaign.

The lovely Krishana (@beyond.the.ivory.tower) over on Instagram has set up an inspiring campaign to raise awareness of diabetes throughout the month of November. Her campaign is to encourage others to work towards 150 minutes of exercise a week and to share their efforts on social media to inspire others. Here’s what she shared with the IG world:

150mins campaign

I’ve been sharing my workouts on my IG stories along with many others, so head over and join us by using the hashtags #150mins and #diabetesawareness! Krishana has also been doing fun daily diabetes-related Q&As, so give her a follow and learn something new!

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If you’d like to seek help with managing diabetes please talk to your doctor or visit the following websites:

http://www.diabetes.co.uk

http://www.nhs.uk/conditions/diabetes/

http://www.diabetes.org.uk/home

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Seasonal affective disorder

Seasonal affective disorder

In the UK, our clocks went back an hour last night. Summer is officially over, autumn is upon us and we are moving into winter. Many of you may be enjoying the fresh mornings wrapped up in cosy jumpers indulging in hot chocolates, but the shorter days and longer hours of darkness can make life a real struggle for some people.

It’s totally normal to feel happier and more energetic during the longer summer days, and feel that you want to stay cocooned in your duvet and sleep-in longer during the winter months. However, some people experience these dips in mood a lot more intensely than others.

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What is seasonal affective disorder?

Seasonal affective disorder (SAD) is a unique type of mental health disorder and some call it the “winter depression”. As the name suggests, the time of year has a significant impact on a person’s general mood and energy levels, with symptoms similar to depression. It causes feelings of despair, irritability, heightened carbohydrate cravings and a loss of enjoyment in daily activities.

 

“It’s as if my mood turns grey the same time as the sky”

– Mind UK

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What are the causes?

Altered body clock: As discussed in a previous blog post, our bodies have an internal clock. When light is sensed at the back of the eye on the retina, signals are sent to a region in the brain called the SCN (suprachiasmatic nucleus). The SCN then sends signals to all our others cells in our body to tells them what processes they should be carrying out. Basically, daylight tells our body we should be awake, and darkness tells our body we should be asleep, this is called our circadian rhythm. The circadian rhythm helps to regulate food digestion, appetite, energy levels, sleep, and mood. However, people with SAD are thought to have a disruption to this rhythm.

Low serotonin: Serotonin, one of the “happy hormones”, is a neurotransmitter that controls how happy we are and boosts our mood. It’s thought to be low in patients with SAD during the winter. Research shows that people with SAD have higher levels of the serotonin transporter (SERT) which carries serotonin away from the site of action. Higher levels of SERT, means lower available serotonin to induce its effects, and increased feelings associated with depression are experienced.

High melatonin: Melatonin is another neurotransmitter, but it affects our sleep quantity and quality as well as our mood. Normally, melatonin is inhibited during the day, and as it gets darker its production increases. This is why we feel sleepy at night-time. Patients with SAD produce melatonin at higher levels disrupting how awake they are during the day.

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What can help to alleviate SAD?

The aim is to get better hormonal regulation. Here’s a few options:

  • Lightbox therapy: A lamp emitting the same wavelength of light as the sun. They artificially extend the photo period (amount of light) in your day. This helps to suppress melatonin production.
  • Diet high in tryptophan: Tryptophan is an amino acid and it’s a building block for serotonin. More tryptophan = more serotonin production. Foods such as turkey, chicken, tuna, salmon and seeds are high in this amino acid.
  • Regular exercise: Exercise decreases stress levels via increasing serotonin levels.

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Click on the links below for a little more reading if you wish…

1.  Molecular mechanisms controlling the circadian rhythm. Click here.

2. Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder. Click here.

3. The Effects of Dietary Tryptophan on Affective Disorders. Click here.

4. Bright-Light Therapy in the Treatment of Mood Disorders. Click here.

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Healthy foundations: Making time to exercise

Healthy foundations: Making time to exercise

Regular exercise and staying fit is so important to living a healthy life, but how often do you exercise? Since starting my blog and sharing my science journey through Instagram, it’s made me aware of how many people rarely get that heart rate up – and yes grad school students, I’m looking at you!

Too much to do, too little time right? I’m going to be that devil on your shoulder and say, sorry, you can always find time! I know people don’t like to hear that, but bare with me…

In this blog post we’ll explore the positive effects of exercise and I’ll be dishing out some tips to help you get more fitness into your busy schedule.

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The wonders of exercise…

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Improves brain function

Studies have found that exercise helps to improve learning and memory. Physical activity leads to an increase in the expression of a protein called brain-derived neurotrophic factor (BDNF) in areas of the brain including the hippocampus (brain centre for memory). It is known to support the growth of new neurones, neural survival and synaptic plasticity. Exercise also stimulates other growth factors which promote the growth of brain cells and slows down age-related decline. If you want to nerd-out, read more about exercise and the brain in this review article.

Fun fact: Different exercises have different mental gains!

Ulitmate brain workout
Image: New Scientist

 

Positive mindset

Exercise can alleviate stress by stimulating the release of that feel-good molecule serotonin and other endorphins. They essentially act as natural painkillers which in turn improve our mood and mental health. Exercise also helps us to sleep better, consequently lowering those stress levels.

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Movement/mobility

Daily desk job workers – how does your body feel when you’re sat down most of the working day? After a while, probably not fantastic. Having good mobility is required to perform everyday activities. Developing bad postural habits and limiting your joint mobility is not going to do you any favours! Staying active and regular stretching will really help to prevent mobility issues in the future.

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Lowers disease risk

Exercise is great for our general health! It improves our muscular, cardiorespiratory, and bone health. It lowers the risk of developing complications such as high blood pressure, coronary heart disease, heart attacks, obesity and type-II diabetes. Weight training strengthens our muscles and helps to maintain our muscle mass. This is important as it slows down the rate of decline in muscle mass and strength that we experience as we get older (sarcopenia) leading to falls and fractures.

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yoga

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My top tips to get fitness into your routine:

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Schedule in exercise time!

Just like you plan your work and social plans, schedule in the time to exercise as well. Planning when you’re going to go for a run or lift those weights in the gym will help you to focus on work beforehand and create more of a balance.

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Start small, build it up.

If you’re new to this whole exercise thing, then don’t go all out to start with! We want it to be a shift in mindset – a new lifestyle choice rather than a phase. Maybe just start off by exercising two/three days a week and gradually build it up.

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Ditch the car, cycle.

Cycling is a great way to get from A to B. You don’t get stuck in the traffic, you’ve exercised before the day has really begun, and you’re helping the environment. Triple win.

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Get some extra steps.

Take the longer route to work. Cut the time you spend in the coffee room for lunch and finish it with a 15-minute walk. If walking isn’t something you usually enjoy, try combining it with listening to a podcast or audiobook you like. Make it fun!

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Find fitness you enjoy!

Hate running but love exercise classes? Then choose the classes! Exercise should be enjoyable. It’s your “me” time so make the most of it and don’t make this part of your day harder for yourself.

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Make it part of your social time

Join a sociable form of exercise, like crossfit or a team sport. Alternatively, get a friend to go with you on that run/walk/fitness class. Exercise can be a social event too! Plus, it keeps you accountable to someone else.

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Create fitness goals

Like I said, we want exercise to become a habit and not a temporary love affair. It’s good to have focusses on other things than work. Whether it’s signing up for a 5k run, climbing up a mountain, getting that 100kg deadlift, set a couple of goals and work towards them. It will keep that motivation to stay fit.

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Are you taking enough time out of your week to stay active? How do you like to stay fit and healthy? As always, please comment below as I love to hear from you…

To read the first in my “Healthy foundations” mini-series all about sleep, click here.

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Healthy foundations: Getting those Zzzs

Healthy foundations: Getting those Zzzs

A lot of people I know (including myself) are mindful about maintaining a healthy lifestyle. What’s been amazing is that quite a few of my followers have asked me to do some blog posts on this, how perfect! So here you are, the first in my mini series “Healthy foundations” which I’m really excited about!

Today’s topic is something we all love – SLEEP!

There are many factors important in promoting good health including hydration, nutrition and exercise. But getting optimal sleep is vital for that all important brain power. It will encourage a more positive mindset for the day which will naturally make you more motivated, focused and productive. So, are you getting enough sleep? Are you functioning optimally?

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Why is sleep so important?

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Sleep is one of the foundations for good health. It’s actually a necessity for us to live. We hear a lot about how sleep affects our wellbeing but here’s a fun fact for you – sleep is still a mystery to scientists! There’s a lot we don’t know. However, we do know that a lack of it affects many biological processes.

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“There is no tissue within the body and no process within the brain that is not enhanced by sleep, or demonstrably impaired when you don’t get enough”

– Matt Walker, Center for Human Sleep Science, Uni of California.

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Research suggests that good quality sleep is associated with:

  • Memory consolidation – strengthens neural connections & reduces unwanted ones.
  • Repair and growth – sleep is healing time! It’s when our bodies reset.
  • Emotional stability – deprivation is associated with depression.
  • Decision making – organises information and switches off the stress response.

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brain
Image credit: Tatiana Shepeleva – Shutterstock

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What about the impact of not getting enough sleep?

Well it definitely has a negative effect on our health, that’s for sure! It’s known to increase inflammation and impair our immune system and appetite. This leads to conditions such as obesity, type 2 diabetes, heart disease and autoimmune disorders. Sleep deprivation has also been linked to mental health disorders such as depression, bipolar disorder and schizophrenia, as well as increasing the risk of neurological conditions such as Alzheimer’s. Toxins, like those associated with Alzheimer’s, are cleared during sleep.

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So, what determines our sleep?

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There are two main factors…

 

Circadian clock

Our bodies have an internal “clock” in the brain which is regulated by our 24-hour biological clock, known as the circadian rhythm. It relies on light, so daylight and darkness determine when we should be awake and when we should be asleep. During the day, light detected by the retina in the back of the eye sends signals to a region in the brain called the SCN (suprachiasmatic nucleus) within the hypothalamus. From here, signals lead to reduced melatonin levels (which when raised initiates the desire to sleep), increased body temperature and an increase in hormones such as the stress hormone cortisol.

Sleep pressure

The longer you’re awake, the more your body is shouting out for you to sleep. A molecule called adenosine increases in the brain throughout the day, which sends signals that make us want to sleep. When we sleep, that sleep pressure is taken off.

 

Image credit: Medscape
Image credit: Medscape

 

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What is the right amount?

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Everyone is different and the optimal amount of sleep varies from person to person. Our genes, age and lifestyle all affect our requirement. But as adults, scientists say that the optimal amount is 7-9 hours.

Warning! More sleep doesn’t always mean you’re better off! Too much of anything can be a bad thing. Some people think they function fine on less than the 7 hours sleep. Yes, some people are able to cope with fewer hours, but they might just be used to the effects of sleep deprivation without realising it! 

Sleep
Image credit: Mindful

A research group looking at students sleeping for only 4 hours on 6 consecutive nights found that the they developed increased blood pressure, levels of that stress hormone cortisol, and an increased insulin resistance, which affects the body’s glucose handling. So chronic sleep deprivation is not doing you any favours!

Those of you who are sleep deprived, I do bring you some good news! This group found that temporary sleep deprivation could be reversed with adequate sleep. Those moments of joy we call ‘naps’ can help to repay this sleep debt but it’s not ideal. Get that good quality 7 hours in to begin with.

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Top tips for better sleep:

  • Don’t use your phone before bed! – I know it’s tempting but blue light (which our phones and laptops emit) stimulate that internal clock I was telling you about. It effectively tricks your brain into thinking it’s daytime, making it harder to sleep. Put a blue filter on, like “f.lux” if you are going to use it.
  • Reduce caffeine intake before bed – caffeine blocks those adenosine receptors in the brain so the desire to sleep will be severely reduced.
  • Be more mindful – be aware of how much of that Zzzz you are getting and how much more you need to get that 7 hours minimum. Having alerts on your phone telling you to get ready for bed will help!
  • Holidays – if you’re in a really bad pattern of consistent sleep deprivation, a holiday will reset you! Lay on a beach, sleep, relax. I went to Fuerteventura in May and it did wonders.
  • Yoga and meditation – it calms the mind and helps prepare your body for sleep.
  • Sleep in a dark and quiet room – reduces those external stimuli.

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Any questions or topics you’d like me to cover in my Science Explained posts, then please comment below! As always, I love to hear what you have to say, your feedback really is valuable to me. It helps me to get the information out there that you like to read!

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Enhancing placental function – my first publication explained

Enhancing placental function  – my first publication explained

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Four years after my Masters of Research in Maternal and Fetal Health at The University of Manchester, our paper is finally published in Theranostics which means I have my first science journal publication! As other scientists will know, this is a very exciting moment in our science journey.

 

The title is “Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling”. What does that mean?! In simple terms, it’s all about targeting the placenta in order to enhance its function by delivering therapeutic molecules to it. Science journals can be very inaccessible to non-scientists but it is so important we relay our scientific findings to the public. I’m going to talk about why an earth we did this research, how we did it, our results and what they mean… and hopefully it all makes sense and you’ve learnt something new!

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The background…

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Many serious pregnancy complications such as pre-eclampsia (high blood pressure and protein present in the urine), fetal growth restriction (FGR; baby is smaller than average) and macrosomia (baby is larger than average) develop as a result of suboptimal growth and development of the placenta. The placenta is the interface between mother and baby for nutrient transfer.

These conditions can lead to preterm delivery which in turn can cause complications. Babies who are born too early have an increased risk of developing cardiovascular and metabolic diseases, but there are currently no treatments available during pregnancy. Administration of a drug via an injection in human pregnancy can cause dangerous side effects and disturbances to the fetus’ development (teratogenicity). We all take pain killers for headaches from time-to-time right? You just pop them into your mouth, and the drug circulates throughout your whole body. This means at the site of pain, the drug is more diluted but may also result in unwanted effects.

This paper is therefore all about trying to target the placenta specifically with a therapeutic to improve placental growth and development. The human placenta has two different layers: the outer syncytium, which is the site of nutrient transfer, and the underlying layer of proliferating cytotrophoblasts (CTB). These CTBs are important for growth and supporting nutritional demands of the growing fetus. These cells divide, and fuse with the syncytium.

  • Low proliferation of CTB = FGR and pre-eclampsia
  • High proliferation of CTB = macrosomia

The rate of growth/proliferation is affected by various hormones and growth factors, but also regulated by small RNA molecules called microRNAs (miRs). These regulate gene expression and consequently alter various biological processes such as cell proliferation. miR-145 and miR-675 are known to cause a reduction in placental growth, and so inhibiting these could improve placental growth in the pregnant women. But how does this get around the issue of teratogenicity? Well, our group have shown it’s possible to deliver a therapeutic molecule, which is packaged in lipids (a liposome), specifically to the placenta with minimising unwanted effects in the mother and fetus. This is done by using a specific placental homing peptide conjugate (a link of small molecules that form the foundations of proteins) which selectively binds to the placental surface. Think of it as a molecular postcode for the placenta!

structure miR inhibitor

So, put two and two together and in this paper we tried to use placental homing peptides to deliver miR-145 and miR-675 inhibitors directly to the placenta with the aim to enhance placental growth.

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What did we do?

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Testing the safety of miR inhibitor delivery

Ensuring that the miR inhibitors can be used as a clinical intervention for poor placental growth and development means prior safety testing. We need to make sure that their delivery doesn’t cause detrimental effects. We exposed pregnant mice to either a short or longer-term treatment of a fluorescent-labelled non-specific inhibitor. With a fluorescence microscope we visualised the presence and localisation of it (miR inhibitor in green) within the mouse placenta. Localisation of the miR inhibitor was found in the short-term treatment and also in the longer term one too.Results2 - fluor distribution writing

The miR inhibitor was not found in fetal tissues which is great! However, we found it localised in some of the maternal tissues suggesting a possibility of off-target effects – something that would need to be investigated further. The non-specific miR inhibitor didn’t cause a change to fetal or placental weight, litter size or the present of fetal abnormalities, so this indicates that it’s tolerated well in pregnancy… phew!

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Testing specific miR inhibitors in mice

Pregnant mice were either injected with a control solution (PBS), the non-specific (scrambled) inhibitor, or the treatments miR-675 inhibitor or miR-145 inhibitor.

Placental weight:

The miR-675 inhibitor did significantly increase placental weight. However, miR-145 did not. Despite this, interestingly a statistical test confirmed that it did reduce variability in placental weight. No placentas fell below the 10th weight centile for either inhibitor, which suggests they have growth-promoting effects.

Fetal weight:

Both miR-675 and miR-145 inhibitors increased fetal weight but the non-specific inhibitor altered the fetal weight distribution as well. At the moment, we aren’t too sure why. One potential reason could be species-specific effects, but if you want to geek out, check out the discussion section of the paper (link below) where other suggestions are discussed!

Results4 - placetnal fetal weight writing

We also tested the two specific miR inhibitors for any changes in litter size and number of miscarriages. Neither had an effect therefore further suggesting that this novel treatment is safe to use in pregnant mice, another step in the right direction!

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Testing the specific inhibitors in human tissue

Placental explants, which are chunks of fresh tissue, from first trimester (early pregnancy) and term (end of pregnancy) were cultured in the miR-675 inhibitor or miR-145 inhibitor with or without the placental homing peptide added on.  Both miR-675 and miR-145 with the peptide significantly increased the placental CTB cell proliferation, but so did their equivalents without the homing peptide, which was interesting. This enhanced cell proliferation was only found in first trimester placental samples.

Results5 - human prolif writing

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Summary

Without getting bogged down in all the intense sciencey discussion of this data (again, feel free to view the link for the actual paper below if you would like to read some more), what can we conclude from this study?

  • We provide evidence that the use of these homing peptides have a favourable therapeutic profile during pregnancy – they appear safe to use!
  • It’s the first piece of evidence for targeted delivery of a miR inhibitor to the placenta.
  • A homing peptide-miRNA inhibitor can be used to increase human placental growth in early pregnancy, which means it should be possible to manipulate the expression of those pesky placental miRs which contribute to pre-eclampsia and FGR.
  • This study suggests that these novel therapeutics may provide a new strategy for targeted treatment of compromised placental development and function.

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Of course further research is required to push the therapeutic potential of placental homing peptide-microRNA inhibitors further in the hope they will enter clinical trials in the future, but this study provides some really interesting data. Watch this space!

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You can find the original paper here!

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This was a much more science-heavy blog post than I normally write. Would you like more science explained posts?

Please comment below as always to let me know what you thought. Your feedback really is valuable to me. It helps me to grow as a science blogger and get the information out there that you like to read!

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