Warning: This article does not contain any medical advice. It merely presents a review of the literature, expressed in plain language with the author’s commentary. The aim is to provide the reader with general information.

Stress, in modern life we have to cope with that. It is a feeling that many of us experience when we have an exam, a job interview, when we’re stuck in traffic, when we face difficulties in our relationships, or when we encounter any daily problem. All of these are sources of stress. The word “stress” generally conjures up negative associations for us, but stress comes in different forms. Whilst good stress (eustress) has a motivating effect, bad stress (distress) can physically exhaust us and make us more susceptible to illness.

Defining Stress: Hans Selye’s Theory of Stress

There are many studies on what stress is. However, the most famous of these is Hans Selye’s work. Hans Selye, an endocrinologist, proposed this theory in 1936 whilst conducting experiments on mice, by evaluating the mice’s responses to the experiments. He realised that these responses were an expression of Bernard’s concepts of the internal environment and homeostasis, and cleverly linked the hypothalamic-pituitary-adrenal axis to the body’s way of coping with stress.

In addition, a syndrome described by Hans Selye as the General Adaptation Syndrome (GAS) outlines the three stages of stress:

• Alarm Reaction Stage (Shock/Counter-shock): The immediate reaction to a stressor. The body releases adrenaline and cortisol, increasing heart rate and blood pressure to prepare for “fight-or-flight”.

• Stage of Resistance (Adaptation): If the stressor continues, the body attempts to adapt. It remains on high alert but tries to normalize functions, leading to reduced emotional regulation, irritability, and frustration.

• Stage of Exhaustion: Prolonged exposure to stress depletes the body’s energy and resources. This stage can lead to severe health issues, including burnout, depression, anxiety, or physical illness.

The final stage of this syndrome in particular—namely, the exhaustion stage—has adverse effects on our immune system. It is at this stage that we become susceptible to many illnesses. Research indicates that one of these illnesses is cancer.

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Cancer & Stress

When we are stressed, we release certain hormones and neurotransmitters. The general term for these is catecholamines. Catecholamines bind to specific receptors found in cells. These receptors are also found in cancer cells. Catecholamines regulate various activities within cells. In cancer cells, this can lead to metastasis, growth or faster proliferation. In addition, apoptosis (programmed cell death) may be disrupted, and the cells become more prone to metastasising.

This has been demonstrated in a study conducted on mice. Stress hormones trigger a series of cellular reactions. These reactions ultimately lead to the activation of PKA (Protein Kinase A). This activation affects certain proteins. These proteins disrupt the cell’s functioning. Consequently, this leads to the effects I mentioned earlier. In other words, metastasis increases, tumours grow, and apoptosis is disrupted.

In addition, excessive catecholamine release has a detrimental effect on DNA. A gene called TP53 in the human body is responsible for the production of a protein called p53. This protein prevents cancer cells from developing by disrupting their genetic structure. However, excessive catecholamines disrupt the structure of the p53 protein. In other words, they disrupt the mechanism that kills cancer cells.

A paper published in 2024 in the journal Cold Spring Harbor Laboratory (CSHL) reported that a team working with Professors Linda Van Aelst, David Spector and Christopher Vakoc from CSHL had discovered that stress causes certain white blood cells, known as neutrophils, to form sticky, web-like structures that make body tissues more susceptible to metastasis.

The team found that stress hormones called glucocorticoids acted on the neutrophils. These “stressed” neutrophils formed spider-web-like structures called NETs (neutrophil extracellular traps). NETs form when neutrophils expel DNA. Normally, they can defend us against invading microorganisms. However, in cancer, NETs create a metastasis-friendly environment.

-”Chronic stress spreads cancer … here’s how”,(CSHL), 22 February 2024

This discovery highlights the effect of stress on metastasis.

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So, what can we do?

This is a very important question. Today’s world is one where many things have changed compared to the past. However, some things pose serious risks to our health. Among young people, pressure from school, career expectations, anxiety about the future, and unrealistic beauty standards are causing significant stress. Particularly due to the influence of social media, a constant sense of ‘inadequacy’ lingers in young people’s minds. Amirali Banani addresses this issue in his latest article. Taking up a hobby, socialising in communities outside of school and home, and engaging in sport and the arts have positive effects on the brains of adolescents.

In addition, politicians need to prioritise this issue. I believe that initiatives such as designing education systems to create less pressure, offering young people multiple career options, and providing access to psychological and psychiatric support will yield significant results. This will have a significant impact not only on cancer but also on the prevention and treatment of many mental and physical illnesses. Because stress lowers immunity and mentally exhausts the individual.

In middle and older age, making psychological and psychiatric support more widely available and encouraging politicians to be more sensitive to issues such as financial hardship generally helps to reduce people’s chronic stress.

In short, what we can do individually in this regard is not to hesitate to seek psychological support when needed and to explore alternative options for our lives.

What we can do as a society is to draw the attention of local and central authorities in democratic societies to ensure that the necessary support is provided.

We must not forget that when we feel pain in any part of our body, we take it seriously and go to the doctor. We should do the same when we are feeling mentally unwell. This is because our brain chemistry has a significant impact on our physical well-being.

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[1] Chronic stress spreads cancer … here’s how, Cold Spring Harbor Laboratory, 22 February 2024

[2] Abate, M., Citro, M., Caputo, M., Pisanti, S., & Martinelli, R. (2020). Psychological stress and cancer: new evidence of an increasingly strong link. Translational Medicine@ UniSa, 23, 53.

[3] At the Lab Episode 18: The stress of cancer, Cold Spring Harbor Laboratory, 6 August 2024

[4] Tan SY, Yip A. Hans Selye (1907-1982): Founder of the stress theory. Singapore Med J. 2018 Apr;59(4):170-171. doi: 10.11622/smedj.2018043. PMID: 29748693; PMCID: PMC5915631.

My STEM Quest 3.0 Adventure! What happened and why was it important?

If you knew me before I started writing on Substack, you’ll know that I gave a presentation at STEM Quest 3.0 on 17 December 2025. First of all, I must say that this was tremendous for me. It feels great to make your voice heard by people all over the world, to talk about my work, to teach people something, to discuss a topic. It was difficult but equally enjoyable to present a topic I had researched in depth for the first time in my life in English, which is not my native language. In today’s post, I won’t be teaching you anything new about science. However, I will explain how valuable the activities organised by communities like the Youth STEM Initiative are.

First of all, I must say that Amirali Banani and Abeer Iftikhar have done a wonderful job. It is no easy task to bring together people from all over the world who are interested in science (mostly young people). Yes, the Youth STEM Initiative is not a community that will be successful on its own in areas such as ‘world peace’ or ‘raising social awareness’. But I am someone who believes that small steps can lead to big results. For this reason, I think that small organisations also have an important place in issues such as raising social awareness and world peace. Events like STEM Quest 3.0 remind us that physical boundaries are not an obstacle to interacting with people, that there is much that can be done even if you only have internet access, that what is necessary for us to understand each other is shared feelings and thoughts rather than a common language, that people have different perspectives, and that humanity is stronger together. The world we live in today is hell for some people. Today, babies are dying in Gaza, children are living in fear in Ukraine, and people in Iran are fighting for their basic rights. Muslims in East Turkestan are being tortured. The reason for all this is that people hold rock-solid prejudices and see themselves as superior to others. In fact, no race (which doesn’t even exist biologically; the concept of race today is political) is superior to another. They just look different because of where they live.

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Let’s face it, humanity is greedy. You could give them the world and it still wouldn’t be enough. It invents its own tales and denies even the right to live to those who are not like itself. Such people are the most dangerous creatures in nature. Such people have shed much blood in the past and left behind many painful memories. They left only evil in this world and died like all living creatures. But today we are more hopeful than yesterday; today we are more united than yesterday. If we want to be more united, we must unite with science. Science unites us and teaches us tolerance. Those who are interested in science know this:

What makes a person important is not the language they speak, the religion they believe in, or their ethnic origin; every human being is important simply because they are human, and what increases their importance is their contribution to humanity. This could be finding a cure for cancer or planting a sapling.

At STEM Quest 3.0, I didn’t just give a presentation; I saw dozens of faces looking to the future with hope. I saw dozens of listeners and speakers who wanted to contribute to humanity. For me, this is more important than people’s academic achievements. That’s why, from the outset of this post, I’m talking about the social contributions of the event rather than its academic contributions. But I don’t want to be misunderstood; STEM Quest 3.0 was also a very valuable event academically. For this reason, I would like to thank everyone involved in the organisation and our valued listeners. United by the science!

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What did STEM Quest 3.0 contribute to me?

Before Amirali offered me the opportunity to speak at STEM Quest 3.0, I was going through a period of anxiety. If you are an 11th grade student in Türkiye, you have to prepare for a university entrance exam that is quite gruelling and difficult. In addition, the changed exam system increases uncertainty, triggering anxiety and stress in many students. I was one of those students, and the stress and anxiety took a toll on my body. Before speaking at STEM Quest 3.0, stress caused me to experience some health problems.

I often did not get along well with most of my peers at school. My constant obeying of school rules, not gossiping, and not giving people bad nicknames greatly reduced my interaction with them. I ended up talking to very few friends. This isolated me, but it gave me the opportunity to get to know myself and realise who my true friends were. I started to stop caring about what people thought of me. I discovered new hobbies and returned to old ones that I had given up to study. One of the hobbies I returned to was biology. I had written an article during the summer holidays but hadn’t published it. (The Physiological and Psychological Effects of the Relationship Between Cryptochromes and Circadian Rhythm on Mammals and Plants). I decided to publish my article in the Youth STEM Initiative. And I gave a talk on the topic I covered in my article at STEM Quest 3.0.

In summary:

Through STEM Quest 3.0, I gained skills such as presentation skills, communication, problem-solving, asking questions, and academic research. Following my presentation, I was a guest on the Across STEM with YSI podcast series, marking my first time appearing on a podcast. Being part of a community like Youth STEM Initiative is truly a wonderful feeling. I believe that other members and I will undertake many projects in the future.

Follow the Youth STEM Initiative and join in if you’re interested in science!

Warning: This post does not contain any physical or mental health advice. If you think you need support, contact your nearest medical institution

Love, some people describe this word as a “magical feeling”. On the other hand some people can describe as a “dissapointment” .But it is a fact that love is such a powerful emotion that it can cause wars to start or end, the writing of the most tragic stories or the happiest of tales, or the occurrence of many events deemed impossible. These days, people are preparing for Valentine’s Day. Some of my readers may be happy, while others may be overcome with sadness. I extend my best wishes to my happy readers. To my dear readers who are feeling gloomy, I hope you find happiness soon. Today, we will examine the effects of love and berakups on our bodies.

“How little we know, how much to discover, what chemical forces flow from lover to lover”

- Frank Sinatra

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How do we fall in love?

Falling in love is not something that happens all at once. On the contrary, it is a physical process that develops gradually. When we first become interested in someone, testosterone and oestrogen trigger desire or lust and excite us when we see that person. That is the reason for those childish feelings.

Eventually, we may begin to feel an attraction towards that person. People describe this as love intoxication or excitement. Indeed, the feeling of attraction can lead to feelings of excitement. At this stage, our body releases dopamine, adrenaline and noradrenaline, which causes joy, excitement and, in general, increased alertness, arousal and attention. It can also give a person that “butterflies in the stomach” feeling.

Finally, the bond we will form with our one true love will bring us closer together. As this bond is formed, the hormones oxytocin and vasopressin will be released. Oxytocin and vasopressin are secreted more as the couple spends time together. This enables the couple to bond more closely.

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The tragic end of love: Breakup

Love can seem very enchanting, and spending a lifetime with someone you love can be a wonderful feeling. However, not every love story has a happy ending. Sometimes disagreements can arise. Fairytale romances can come to an end. This process can be very exhausting. This process has psychological as well as biological effects.

When you have a breakup conversation, your limbic system becomes active (fight, flight, freeze). The amygdala becomes hyperactive and scans for emotional danger. You may feel anxious, overly alert, or emotionally overwhelmed. This is because your body tries to protect you from even abstract things like abandonment or rejection. This is a legacy passed down to us from our ancestors.

Some people call to “love” as a “drug”. They are not entirely wrong about this. When we experience separation, our brain experiences a dopamine deficiency. Love stimulates the brain’s reward system. During a romantic relationship, the ventral tegmental area (VTA) floods the brain with dopamine. When a relationship ends, this source of dopamine disappears, and withdrawal symptoms similar to those seen in substance addiction emerge. This is why obsessive thoughts, cravings, and emotional breakdowns occur.

When the body experiences loss, grief, or intense emotional stress, the vagus nerve may switch to dorsal vagal mode. This mode is associated with the parasympathetic nervous system’s freeze and withdraw responses. In such a state, the individual may feel immobile, drained of energy, and disconnected. If this persists for a long time, symptoms such as chronic fatigue, numbness, digestive problems, feelings of hopelessness, and mental fogginess may arise. (Important reminder: do not hesitate to seek professional support if you are unable to cope with your emotions!)

In addition, you may develop a condition known as “broken heart syndrome”. This means you may actually experience heart pain. The causes of broken heart syndrome include the death of a loved one or a breakup. Broken heart syndrome can cause chest pain or shortness of breath. In such a case, it would be best to consult a doctor. In addition, breakups negatively affect our immune system because they increase cortisol levels.

Love, with all its ups and downs!

Love is an extremely innocent and beautiful feeling. It brings two strangers together to become the closest people in each other’s lives. This feeling, which makes “Butterflies in your stomach”, is absolutely essential for the continuation of our species. However, sometimes it ends in disappointment. Big dreams are dashed. I want to remind you, my dear readers: In life, things don’t always go according to plan. You may think you’ve found the love of your life, but that’s not always the case. Sometimes people grow tired of love. Sometimes it’s hard to deal with emotions. In such situations, seeking psychological support is important. I wish you all a wonderful love life!

Happy Valentine’s Day!

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Have you ever heard a baby who has 3 parrents? At first it sounds impossible, However it is possible with new IVF (in vitro fertilization)! Even a baby boy was born in 2016 the USA. This technology is called Mitochondrial Replacement Therapy. This technology is a type of “mitochondrial DNA transfer.” With this technology, the biological mother’s egg, from which the mitochondrial DNA has been removed, is combined with the mitochondrial DNA of a donor woman and fertilized with the father’s sperm.

A Jordanian couple has been trying to start a family for almost 20 years. Ten years after they married, she became pregnant, but it ended in the first of four miscarriages.

In 2005, the couple gave birth to a baby girl. It was then that they discovered the probable cause of their fertility problems: a genetic mutation in the mother’s mitochondria. Their daughter was born with Leigh syndrome, which affects the brain, muscles and nerves of developing infants. Sadly, she died aged six. The couple’s second child had the same disorder, and lived for 8 months.12

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Leigh syndrome is inherited through mitochondrial DNA, which prevented them from having children. Consequently, John Zhang and his team applied to the New Hope Fertility Centre in New York.

John Zhang and his team began working on mitochondrial replacement therapy (MRT) techniques, known as the ‘three-parent’ technique. They initially proposed the pronuclear transfer method, which is legally accepted in the UK (detailed below), but the family did not accept this method for religious reasons. The spindle nuclear transfer method was then proposed (described below). The family accepted this technique.

The baby born after the birth was perfectly healthy, which means John Zhang and his team succeeded.

What ist the Mitochondrial replacement therapy?

Mitochondrial replacement therapy (MRT) is an assisted reproductive technology performed within the framework of in vitro fertilization (IVF). It involves transferring the nuclear DNA (nDNA) of a prospective mother from an egg or zygote containing defective mitochondrial DNA (mtDNA) into a donor egg or zygote that contains healthy, non-pathogenic mtDNA and has had its own nuclear DNA removed. The female donor must have no personal, familial, or genetic evidence of pathogenic mtDNA mutations. This technique enables women with mtDNA mutations to have genetically related children while preventing the transmission of mitochondrial DNA–inherited diseases from mother to child.

The techniques used for mitochondrial replacement therapy are called mitochondrial replacement techniques. The three most popular of these techniques are as follows:

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Maternal Spindle Transfer (MST): Maternal Spindle Transfer is a mitochondrial replacement technique based on the removal of nuclear chromosomes arranged in spindle fibers from an egg cell belonging to a prospective mother with damaged mtDNA and a donor egg cell with healthy mtDNA. After the nuclear material of the donor oocyte is removed, the nuclear chromosomes of the prospective mother are transferred to this oocyte, and the reconstituted oocyte is fertilized via IVF.

Pronuclear Transfer (PNT): Pronuclear Transfer (PNT) is a technique used to prevent the transmission of mitochondrial diseases. In this method, the egg cells of both the prospective mother and a donor with healthy mitochondria are fertilized in the laboratory to create two separate zygotes. Next, the pronuclei (nuclear precursors) carrying the genetic information from the mother and father are removed from both zygotes. The pronuclei from the prospective mother are transferred to the donor zygote, which has healthy mitochondria and has had its nucleus removed. The resulting embryo is developed and, once confirmed to be healthy, is transferred to the mother’s uterus.

Polar Body Transfer (PBT): Polar Body Transfer (PBT) is a technique aimed at preventing the transmission of mitochondrial diseases and can be applied in two different ways. In the first method, the first polar body, which appears during the formation of the mother’s egg and carries the nuclear DNA, is transferred to a donor egg that has healthy mitochondria and has had its nucleus removed; this egg is then fertilized to form an embryo. In the second method, both the prospective mother’s and the donor’s eggs are fertilized, and the second polar body from the prospective mother is transferred to a healthy donor zygote with its nucleus removed. In both methods, the resulting embryos are developed and, once confirmed to be healthy, are transferred to the mother’s uterus.

There are other techniques besides these three, but I didn’t want to overwhelm you with details. (For more, see ref.3)

What will happend in future?

Today, some of these techniques are permitted in certain countries, while others are forbidden. However, the ethical issues surrounding such practices are gradually being resolved and becoming more commonplace. Although ethical debates about these techniques continue, they appear to hold promise for the future. My personal opinion is that in the future we will prevent many hereditary diseases with this type of treatment.

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WARNING: This article does not contain any medical advice. It refers to a new treatment currently found in the literature.

Nowadays, there is still no cure for cancer. Many scientists are conducting research in this field. One of them is Prof. Dr. Aziz Sancar and his team. Professor Aziz Sancar, who won the 2015 Nobel Prize in Chemistry for his research mapping how cells repair damaged DNA and preserve genetic information, has recently made significant strides in his work on glioblastoma (GBM), one of the most aggressive forms of brain cancer.

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Temozolomide (TMZ) is a drug used in the standard chemotherapy treatment for glioblastoma. This drug attempts to render tumours ineffective by damaging cell DNA, but tumours can become resistant to it over time. Furthermore, treatment is difficult due to factors such as the inability of most chemotherapy drugs to cross the blood-brain barrier (BBB) and the presence of more resistant cells due to genomic heterogeneity.

Sancar and his team, who are lecturers at the University of North Carolina, mentioned in their article titled “Combinatorial treatment of glioblastoma with temozolomide (TMZ) plus 5-ethynyl-2′ -deoxyuridine (EdU)”, published on 31 December 2025, discussed the potential use of a combination of temozolomide and a molecule called EdU in the treatment of glioblastoma.

Thanks to this drug combination, life expectancy in mice increased from 24 days in the control group to 121 days with 5mg/kg TMZ + 200mg/kg EdU. This means that this treatment was found to increase life expectancy.

Sancar made a statement on his X account about his study, pointed out that the treatment is currently effective in mice, and that it will be possible to develop a safe and effective treatment for humans only after extensive clinical trials, which will take at least two years.

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References

[1] Kaanoglu H, Akyel YK, Adefolaju A, et al. Combinatorial treatment of glioblastoma with temozolomide (TMZ) plus 5-ethynyl-2′-deoxyuridine (EdU). Proc Natl Acad Sci U S A. 2025 Dec 31;123(1):e2532187123. doi: 10.1073/pnas.2532187123

[2] “Aziz Sancar’dan Glioblastom Tedavisinde Yenilikçi Bir Yaklaşım: “Nafile Döngü” ile Direnci Kırmak”, https://www.drozdogan.com/aziz-sancardan-dikkat-cekici-yeni-calisma-beyin-kanserinde-direnci-kirmak/

Abstract—The circadian rhythm is extremely important for the health of living organisms. Disruption of the circadian rhythm has many adverse effects on living organisms. This review discusses the connection between cryptochromes and the circadian rhythm and the physiological effects of this connection on plants and mammals. In addition, in the final section, This review discusses mood disorders observed in humans associated with circadian rhythm. It has been observed that cryptochromes are particularly involved in activities related to the day-night cycle and, consequently, regulate various metabolic activities.

I. INTRODUCTION

Crys (Cryptochromes) are found in many kingdoms, from bacteria to mammals. This enables many light-dependent physiological events to occur in living organisms. For example, Crys proteins repair DNA damage caused by ultraviolet radiation through a mechanism known as photoreactivation. In addition, they can regulate circadian rhythms (circa= about, dies=day), flowering times, and light morphogenesis in plants across all major evolutionary kingdoms.

In mammals, Crys play a role in regulating behavioural rhythms. They are also involved in controlling sleep, which is extremely important for our mental health. For example, they play an indirect role in the emergence of diseases such as several types of cancer, elevated incidence of cardiovascular and metabolic disorders, as well as increased prevalence of behavioural health and psychiatric disorders, which can be seen in relation to sleep. [1]

II. METHODOLOGY

The fundamental question in this study was ‘What are the consequences of the relationship between circadian rhythms and cryptochromes?’ Based on this question, studies in the literature concerning their effects in plants and mammals were identified. Subsequently, the information in the literature was compiled and this article was written in an accessible language.

III. RELATIONSHIP BETWEEN CRYPTOCHROMES AND CIRCADIAN RYTHM

It should first be noted that the circadian rhythm is not solely dependent on the sleep-wake cycle. The circadian rhythm is dependent on environmental factors known as ‘zeitgebers’. However, light is the most important zeitgeber for the circadian rhythm. In fact, it is the most important zeitgeber for the Suprachiasmatic Nucleus located in the hypothalamus region of mammals. [8]

The circadian rhythm,which enables organisms to respond to changing conditions throughout the day and prepare in advance, has provided them with an evolutionaryadvantage. Inplants,itcontrolsimportantmechanismssuchasflowering time and seed dispersal time. In mammals, it is crucial for regulating metabolism.Crys collaborate with numerous genes and proteins to regulate the circadian rhythm. These aspects will be discussed in detail.

A. Cryptochromes and the effect of circadian rhythm on plants

Important differences exist between systematic, and non- systematic reviews which especially arise from methodologies used in the description of the literature sources. A non-systematic review means use of articles collected for years with the recommendations of your colleagues, while systematic review is based on struggles to search for and find the best possible research which will respond to the questions predetermined at the start of the review.

In plants, the clock core that generates the 24-h rhythm includes a highly complex network of genes that act as repressors and/or activators, creating multiple interlocked transcriptional feedback loops formed by transcription factors.

Clock genes exhibit temporal expression waves that reach high activity at different times of the day. They regulate each other’s transcription by modulating many fundamental physiological processes such as flowering time, phytohormone synthesis, growth control, metabolic activities, and biotic and abiotic stress responses. MYB-like transcription factors CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY)

reach their expression peak around dawn; They suppress the transcription of PSEUDORESPONSE REGULATOR (PRR) genes (also known as 9,7,5 and 1, Timing of CAB expression 1 (TOC1)), which are expressed in the afternoon. When TOC1 reaches its highest level in the evening, it suppresses the expression of CCA1/LHY, ensuring the cycle continues. It also affects certain genes referred to as the ‘evening complex,’ such as ELF3 (EARLY FLOWERING3), ELF4 (EARLY FLOWERING 4), and LUX (LUX ARRHYTHMO). These three genes show maximum transcription at night; at this time of day, they suppress several morning and afternoon genes, leading to further feedback loops. MYB-like factors such as the REVEILLE family (4,6,8) support the transcription of PRR genes and the evening complex; in particular, the complex formed by RVE8 with LNK1 and LNK2 increases the transcription of PRR5 and TOC1 in the afternoon. Thus, the PRR genes repress CCA1/LHY again, and the rhythm continues until morning. In another part of the cycle, TOC1 promotes the degradation of the ZTL protein throughout the night, while during the day, the GIGANTEA protein stabilises ZTL, blocking this interaction. [3,4]

Circadian genes regulate each other in this manner to create a rhythmic wave of expression at different times of the day, while light receptors play an important role in synchronising these cycles with external signals. Cryptochromes trigger the reduction of the chromophore to its ‘signal state’ by initiating an electron transfer reaction involving blue light photoactivation, conserved tryptophan residues and/or cellular metabolites. This controls the general light development programme in plants. In a second mechanism, light-activated cry2 interacts with transcription factors CRY2 INTERACTING bHLH (CIB1, 2, 4, 5) and directly activates FLOWERING LOCUS T (FT) transcription to promote flowering. This provides specialised control over the timing of flowering. [3,4]

B. Physiological effects of cryptochromes and circadian rhythms in mammals

The circadian rhythm regulates numerous mechanisms in mammals. The mechanisms controlled by the circadian rhythm have physiological and behavioural effects on mammals. For example, the SCN (suprachiasmatic nucleus) located in the hypothalamus region of mammals is responsible for the secretion of many hormones. For example, the SCN plays an important role in the expression of sex steroids (This topic will be addressed subsequently). This allows for the control of mechanisms that affect the continuity of the species, such as fertility in mammals. In addition, circadian rhythms affect the metabolism of living organisms, and their disruption can cause various physiological diseases and mood disorders (This topic will be addressed subsequently too).[1,4,8,14]

At the molecular level, the cell-autonomous molecular clock is controlled by two intertwined transcriptional/ translational positive and negative feedback loops (TTFL) in mammals. CLOCK (Circadian Locomotor Output Cycles Kaput) and BMAL1 (for brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)like protein 1) are transcription factors that bind E-box (CACGTG) to initiate the transcription of clock-controlled genes including the Periods and Cryptochromes.[8]

The PER and CRY proteins produced from these genes then enter the cell nucleus and suppress the activity of CLOCK and BMAL1, thereby shutting down the system. In a second control loop, retinoid-related orphan receptors (ROR a,b,g) proteins initiate the transcriptional activation of Bmal1, while REV-ERBs suppress these activities. This dual effect allows the biological clock to be finely tuned. Furthermore, the constant chemical modifications these proteins undergo within the cell, such as phosphorylation, ubiquitination, sumoylation, and acetylation, are essential for the rhythm to function regularly. In particular, PER:CRY ubiquitin- dependent degradation contributes to the precise regulation of the molecular clock. [8]

It must be emphasized that one of the most important factors in regulating the circadian rhythm in mammals is the sleep-wake cycle. I have previously mentioned that many diseases and biological irregularities can arise in relation to the sleep-wake cycle. Fertility is the first topic addressed.

Menstrual irregularities, dysmenorrhea, increased time to, and reduced rates for, conception, increased miscarriages, lower birth weights are among the adverse reproductive health outcomes that have been linked to circadian rhythm disorders in studies. At this point, the factor that most disrupts the circadian rhythm is sleep. To examine the effects of the circadian rhythm on fertility, the mechanism by which sleep disrupts this rhythm must be considered. [14].

There are at least three possible ways in which sleep disorders may be associated with infertility: 1) HPA axis activation, which triggers sleep disorders, may also affect reproduction. Changes in sleep duration and/or sleep continuity disorders may themselves impair reproduction or lead to further increases in HPA axis activation; 3) HPA axis activation may cause infertility independently of (or in interaction with) sleep duration and/or sleep continuity disorder. The effect of sleep on fertility in women is extensive and detailed. This article summarizes this topic. (For more information, see reference [14])

However, there is one point I would like to highlight in this regard: melatonin. Evidence has been presented regarding the beneficial effects of melatonin on reproductive functions in animals and humans. Melatonin is thought to have significant effects, particularly in seasonally breeding mammals, facilitating oocyte quality and development, ovulation, luteal function, and embryo development. Findings have been made regarding the antioxidant effects of melatonin and its ability to increase fertility. Melatonin is highlighted here due to its effect on it has an effect on many reproductive hormones. Fertility in women is not solely dependent on the melatonin hormone. There are many hormones regulated by sleep. For example, hormones such as Thyroid Stimulating Hormone (TSH), Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin (PRL), Testosterone, Oestradiol, Anti-Mullerian Hormone (AMH), and Progesterone have effects on reproductive mechanisms in women. [14] However, the details of these are not provided in this article.

The effect of circadian rhythm on fertility in males is similar to that in females. A decrease in sperm quality and count has been observed in males with poor sleep duration and quality. The main reason for this is hormonal changes related to sleep. Testosterone levels are highest during the day and lowest in the evening. There is evidence that sleeping less than 6 hours at night reduces sperm concentration. It has been observed that lack of sleep reduces testosterone release but increases corticosterone and cortisol levels. This mechanism has not been fully elucidated. However, it is thought that sleep deprivation activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing cortisol and corticosterone levels, and that this feedback inhibits the hypothalamic-pituitary-gonadal (HPG) axis, reducing testosterone secretion. Due to the extensive nature of this topic, the effect of circadian rhythm on fertility in women is summarized rather than discussed in detail. (Reference [14,15])

In humans, sleep-related disorders can lead to various illnesses. Sleep irregularities can cause numerous health problems, including cardiovascular disease, hypertension, glucose irregularities, cancer, depression, and anxiety disorders.[14]

This article selectively examines the effect of the circadian rhythm-cryptochrome relationship on metabolism, summarizing its connection with diabetes. Psychiatric disorders associated with this relationship are addressed in the subsequent section.

In mammals, the CLOCK and BMAL1 transcription factors regulate the central oscillator in the hypothalamus and even in peripheral tissues; however, the connection between cellular rhythms and organismal homeostasis, including the stability of energy and fuel utilisation cycles, remains unresolved. In humans, one of the most important physiological characteristics is the daily variability of glucose tolerance and insulin sensitivity throughout the 24-hour day. More importantly, disruption of the circadian oscillation of glucose metabolism can cause type 2 diabetes. [5] Biological clocks located in the structure of the pancreas regulate the secretion of metabolism-related hormones (This detail is not covered in this article see reference [5]).

C. The effects of circadian rhythms and cryptochromes on human psychology

As I mentioned previously, the sleep-wake cycle has very important effects on human health. One of these effects is on mental health. As I mentioned in the previous section, the sleep-wake cycle plays a role in regulating many activities in the human body. As a result, the changes that occur in our bodies affect our mental health.

This article provides a summary of mental illnesses; no details are given. (For more information, see reference [1])

The most significant factor disrupting the sleep-wake cycle is light. Nowadays, many people are exposed to artificial light. Artificial light can come from technological devices such as phones and tablets, or from artificial lighting sources.

The first condition I wish to discuss is major depressive disorder (MDD). Major depressive disorder is characterised by mood changes, typically increased sadness and/or irritability, and is accompanied by at least one of the following psychophysiological symptoms: changes in sleep, appetite or sexual desire, loss of pleasure, slowed speech or movement, crying and suicidal thoughts. [1]

MDD relates to countries’ levels of modernity. The prevalence of factors disrupting the circadian rhythm (night lighting, shift work, jet lag, etc.) may reflect the interaction between circadian rhythm disorders and other environmental factors. [1]

The second condition I would like to mention is anxiety. Numerous studies suggest that jet lag and night shifts trigger anxiety. A series of studies have been conducted on the relationship between circadian rhythm and anxiety. [1] Findings from studies conducted on mice and hamsters in particular have revealed that behavioural patterns associated with increased anxiety were observed following changes in environmental factors that disrupt the circadian rhythm (such as exposure to light). However, these findings are not discussed in this paper (for more information, see reference [1].

IV. Conclusions

The relationship between circadian rhythms and cryptochromes has very important effects on living organisms. Changes occurring in living organisms in accordance with the day-night cycle enable them to adapt quickly to changing environmental conditions and thus make the most efficient use of the day. This situation has provided living organisms with an evolutionary advantage.

This relationship has physiological effects in plants, such as flowering and seed production, and in mammals, such as metabolism, fertility, and certain diseases. In addition to physiological effects, this relationship has psychological effects in mammals (especially in humans).

This article represents an interdisciplinary study that addresses the common link between various topics.

Explaining this relationship without going into excessive detail has enabled the general readership to better understand the subject and become more knowledgeable about it.

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