Brain-Heart Axis: Brain-Derived Neurotrophic Factor and Cardiovascular Disease-A Review of Systematic Reviews.

BACKGROUND: The brain-heart axis is an intra- and bidirectional complex that links central nervous system dysfunction and cardiac dysfunction. In recent decades, brain-derived neurotrophic factor (BDNF) has emerged as a strategic molecule involved in both brain and cardiovascular disease (CVD). This systematic review of systematic reviews aimed to (1) identify and summarize the evidence for the BDNF genotype and BDNF concentration in CVD risk assessment, (2) evaluate the evidence for the use of BDNF as a biomarker of CVD recovery, and (3) evaluate rehabilitation approaches that can restore BDNF concentration. METHODS: A comprehensive search strategy was developed using PRISMA. The risk of bias was assessed via ROBIS. RESULTS: Seven studies were identified, most of which aimed to evaluate the role of BDNF in stroke patients. Only two systematic reviews examined the association of BDNF concentration and polymorphism in CVDs other than stroke. CONCLUSIONS: The overall evidence showed that BDNF plays a fundamental role in assessing the risk of CVD occurrence, because lower BDNF concentrations and rs6265 polymorphism are often associated with CVD. Nevertheless, much work remains to be carried out in current research to investigate how BDNF is modulated in different cardiovascular diseases and in different populations.

The Role of Brain-Derived Neurotrophic Factor (BDNF) in Depression and Cardiovascular Disease: A Systematic Review.

BACKGROUND: Several studies have been conducted to prove the bidirectional relationship between cardiovascular disease (CVD) and depression. These two major illnesses share several common risk factors such that the development of either condition may increase the risk of the occurrence of the other. Brain-derived neurotrophic factor (BDNF) has been suggested as a reliable biomarker for depression and a strong predictor of CVD because it plays an important role in neuron survival and growth, serves as a neurotransmitter modulator, and promotes neuronal plasticity. The aim of this systematic review was to examine the bidirectional relationship between CVD and depression, focusing on the potential role of low serum BDNF levels in the development of either disease in the presence of the other. METHODS: A systematic search strategy was developed using PRISMA guidelines. RESULTS: Six studies (comprising 1251 patients) were identified, all of which examined the association between CVD and depression. CONCLUSIONS: It was found that there may be a strong association between low serum BDNF levels and the risk of post-stroke depression. However, the studies on the role of altered serum BDNF levels and other types of CVD are few. Therefore, the inverse association between depression and CVD cannot be proven.

The role of arts engagement in reducing cognitive decline and improving quality of life in healthy older people: a systematic review.

In recent years, arts engagement has been proposed as a non-pharmacological approach to reduce cognitive decline and increase well-being and quality of life in specific populations such as the elderly or patients with severe disease. The aim of this systematic review was to assess the effects of receptive or active arts engagement on reducing cognitive decline and improving quality of life and well-being in healthy populations, with a particular focus on the role of arts engagement in the long term. A comprehensive search strategy was conducted across four databases from February to March 2023. Ten studies with a total of 7,874 participants were incorporated in accordance with the PRISMA guidelines. Active and receptive arts engagement was found to be an effective approach to reduce cognitive decline and improve well-being and quality of life in healthy populations. The role of the positive effects of arts engagement could be determined by the combination of several factors such as exposure to cultural activities and the group effect. There is limited evidence of the protective effects of active arts engagement over a long period of time. Given the increasing demand for preventive programmes to reduce the negative effects of population ageing, more research on arts engagement should be conducted to identify its mechanisms and long-term effects.

Impact of low-dose Brain-Derived Neurotrophic Factor (BDNF) on atrial fibrillation recurrence.

BACKGROUND: Atrial fibrillation is the most common arrhythmia worldwide and is associated with significant morbidity and mortality. Despite the effectiveness of catheter-based ablation, periprocedural complication and recurrences remain a concern. In this context, we aim to appraise the potential impact of brain-derived neurotrophic factor (BDNF) on reducing episodes of paroxysmal atrial fibrillation (PAF). METHODS: 22 patients with an established diagnosis of PAF and without structural heart disease were considered. Every patient received 20 drops of GUNA-BDNF administered in the morning. During the 24 months of follow-up, the arrhythmic burden was measured by the average monthly duration of PAF episodes. RESULTS: At the end of the follow-up period (24 months), data from 22 patients, of whom 17 men and five women, were analyzed. The arrhythmic burden, measured in terms of average monthly duration of PAF episodes, was found significantly reduced after the administration of low dose BDNF (9.5 vs. 65.3 minutes per month, P<0.001). A total of 17 out of 22 patients saw their arrhythmic burden eliminated or consistently reduced, furthermore two patients underwent a drastic reduction of the average monthly duration of AF (more than 200 minutes compared to the baseline). Only four patients, despite the administration of BDNF, still experienced an arrhythmic burden of 20 minutes or more. Considering the age groups, the major reduction was observed in people aged 70 or more, who were also the most represented in the sample. These results are coherent with the poor literature currently available. CONCLUSIONS: BDNF low dose therapy has shown to have an impacting role in reducing the arrhythmic burden and recurrences of AF, with a particular effectiveness in patients over 70 and without structural heart disease. We should welcome this work, despite it limitations. Further clinical and molecular studies are needed before-considering BDNF low dose as a tool against PAF.

A mathematical model for imaging and killing cancer cells by using concepts of the Warburg effect in designing a Graphene system.

According to the Warburg effect, there are some significant differences between metabolisms, products and process of respirations of cancer cells and normal cells. For example, normal cells absorb oxygen and glucose and give water molecules, carbon dioxide, ATP molecules and some number of spinors; while cancer cells take glucose and give lactate, less number of ATP molecules and different number of spinors. Using this property, we can design a system from two graphene sheets that are connected by pairing the fourth free electrons of carbons. Then, we can break some pairs and produce some holes. The number of these holes should be equal to the number of radiated spinors by normal cells. Near a normal cell, all holes are filled and the graphene system doesn't emit any electrical current or wave. However, near a cancer cell, some extra holes or spinors remain that their motions produce some electrical currents. These currents force on cancer cell membranes and destroy them and consequently, cause the cell death. Also, these currents emit some electromagnetic waves which detectors could take them out of the human's body and consequently, they could play the main role in imaging.

A model for analyzing evolutions of neurons by using EEG waves.

It is known that differences between potentials of soma, dendrites and different parts of neural structures may be the origin of electroencephalogram (EEG) waves. These potentials may be produced by some excitatory synapses and currents of charges between neurons and then thereafter may themselves cause the emergence of new synapses and electrical currents. These currents within and between neurons emit some electromagnetic waves which could be absorbed by electrodes on the scalp, and form topographic images. In this research, a model is proposed which formulates EEG topographic parameters in terms of the charge and mass of exchanged particles within neurons, those which move between neurons, the number of neurons and the length of neurons and synapses. In this model, by knowing the densities of the frequencies in different regions of the brain, one can predict the type, charge and velocity of particles which are moving along neurons or are exchanged between neurons.

Regulation of Inflammatory Reaction in Health and Disease.

Inflammation is a key mechanism for the clearance of infective agents and other inflammatory triggers and is pivotal for the repairing processes of the affected tissues. Inflammation is a multistep process driven by a great number of mediators which regulate specific aspects of the inflammatory response, in agreement with a well-defined chronobiological program. A great number of inflammation-related diseases show a deeply altered immune chronobiology (e.g., COVID-19-related cytokines storm). This aspect highlights the need for a deeper understanding of the inflammatory phenomenon. It is fundamental to study inflammation as a multilevel phenomenon. Of particular interest is the low-grade chronic inflammation, which is an etiological factor of many chronic diseases. Nowadays, the therapeutic approach to low grade chronic inflammation is one of the great challenges of traditional pharmacology. Currently, no drugs specifically designed for the treatment of chronic inflammatory forms are available. Today, bioregulatory systems medicine (BrSM) and low dose medicine (LDM), two pharmacological paradigms grounded in systems medicine, potentially represent new tools for the treatment of inflammation-related diseases. Scientific research has assessed the effectiveness and safety of both these therapeutic approaches, in particular for the management of chronic inflammatory conditions and chronic immunological dysregulations.

Quantum information teleportation through biological wires, gravitational micro-bio-holes and holographic micro-bio-systems: A hypothesis.

Biological systems like cells, bacteria, chloroplasts and other micro-organisms could exchange quantum particles like electrons, photons and gravitational waves and have large distant information teleportation. This is because that their DNAs and membranes are formed from quantum particles like electrons and protons and by their motions, some currents and waves are emerged. These waves have the main role in information teleportation. There are different methods which could be used for quantum information teleportation in biological system. Some of these mechanisms are: 1. Microbes, micro-bubbles and some other biological molecules like to form some biological lines specially near the cellular gates. Also, some biological lines may be formed between two cells. These biological lines could play the role of wires which transmit information from a place to another one. For example, some signatures of this quantum information teleportation could be seen in biological lines which are emerged near the plant cell walls or gates or close to chloroplasts. Chloroplasts shoot some spinors which maybe confined within the micro-bubbles or absorb by microbes. These bubbles and microbes may join to each other and form some biological lines which may be strengthen from a plant cell to another. These biological lines could be seen near the plant cell walls or on a metal which connects two parts of a leaf. 2. Some another signatures of "quantum photon exchange or quantum information teleportation" could be seen between microbes under the objective lenses and macro-objects on the eye lenses of a light microscope. It seems that as microscope make big images from microbes for us, produce small pictures of macro-objects for microbes such as they could diagnose them and interact with them. This property could be used in controlling microbes. 3. Another way for controlling microbes is using of virtual shapes which are induced by a special light source. For example, using a multi-gonal lamp, one can induce multi-gonal shape within the micro-bubbles. Also, this special lamp could force microbes and micro-bubbles to build multi-gonal colonies on a metal-glass slide. Maybe, by using this property, one can build a light source with the shape of anti-microbial matter and induce anti-microbial property within micro-bubbles. 4. Another main way for quantum teleportation is using of gravitational holes which may be emerged by increasing concentration of microbes and heavy cells in some points. These holes absorb microbes and micro-bubbles and conduct them to the heavy cells. Usually, there are some white holes near these dark holes which as a proposal, one can assume that these white holes are another end of gravitational holes and emit photons which are entered from dark end. 5. And finally, a very main mechanism for quantum information teleportation with microbes and controlling them is using of a holography and inducing virtual microbes and biological molecules in biological systems. For example, by a combinations of two lights with different colors under a light microscope in a dark room, one may induce some non-virtual microbes in biological systems such as each microbe interacts with a virtual microbe. This is because that light waves take photos of microbes, collide with lenses of microscopes and return to the slide and form virtual microbes or biological molecules. This technique could be used in curing diseases. Although, results of our experiments show the correctness of these mechanisms and theories, however, for the moment, we propose them only as a proposal and hypothesis and hope that other scientists do similar experiments. Also, some of our experiments may be at preliminary stages; however they could be used as a hypothesis, proposal and guidance.

Modelling the dynamics of exchanged novel coronavirus (2019-nCov) between regions in terms of time and space.

To date, many models have been proposed which estimate the transmission risk of COVID-19 in terms of time; however, its dependency on space dimensions has been ignored. In this research, by multiplying risk parameters in certain regions and bridging, we obtain a stable action, which means that the transmission risk worldwide could shrink to a constant. Thus, by increasing the risk parameters in one region, the risk parameters in other regions decrease. Then, by adding space dimensions to the parameters in transmission risk models, and using the wave equations of manifolds for the regions, we obtain the dynamics of the exchanged novel coronavirus (2019-nCov) between countries. We calculate the risk factors of COVID19 for different regions in this model, and observe that they are in good agreement with experimental data.

A new medical imaging technique for diagnosing dermatologic diseases: A clue to treatment choices.

Recently, it has been shown that DNA could emit some waves which carry main information about its evolution. Using this idea, we design a new method to image the behavior of skin cells, especially melanocytes, and diagnose their damage. In this method, we make use of a circuit which is formed from DNAs within the damaged melanocytes, a graphene sheet, DNAs within the healthy cells, and a scope. To amplify exchanged waves between hexagonal and pentagonal manifolds of DNAs, we induce some defects in the graphene sheets and replace some hexagonal molecules by pentagonal ones to build a structure similar to the structure of DNAs. We show that unprotected exposure to UVA and UVB damages the DNA in melanocyte cells, producing genetic defects, or mutations, that can lead to exchanged waves between cells and the emergence of a current in our circuit. By analyzing the evolution of this current, we can estimate the rate of destruction in melanocytes, and predict the emergence of cancer.

The information isn't lost in gene expression.

The present question is the possibility of information loss in gene expression? Information loss in the gene expression disrupts the cellular dynamics and can lead to serious defects, including cancer. Using Gottesman and Preskill method for calculating information loss in black holes,a mechanism for calculating the amount of information transformation in gene expression is proposed. In this proposal, there are three different Hilbert spaces that belong to degrees of freedom of DNA, RNA, and protein. The genetic sequence of the DNA is transcribed into protein at two stages. At first stage it is shown that the internal stationary state of the cell can be represented by a maximally entangled two-mode squeezed state of DNA and mRNA.At second stage, the state of the cell is described by a maximally entangled two-mode squeezed state of mRNA and protein. The amount of information transformation can be obtain by projecting the state at first stage on the state at second stage. Evidently for all finite values of the transcription factor concentration y, binding energy E and free energy F of the transcription factor, the information isn't lost in gene expression.

Clinical Applications of System Regulation Medicine.

Increasing incidence and poor outcome of chronic non-communicable diseases in western population would require a paradigm shift in the treatments. Guidelines-based medical approaches continue to be the standard rule in clinical practice, although only less than 15% of them are based on high-quality research. For each person who benefits from the 10 best-selling drugs in the USA, a number between 4 and 25 has no one beneficial effect. The reductionist linear medicine method does not offer solutions in the non-manifest preclinical stage of the disease when it would still be possible to reverse the pathological progression and the axiom "a drug, a target, a symptom" are still inconclusive. Needs additional tools to address these challenges. System Medicine considers the disease as a dysregulation of the biological networks that changes throughout the evolution of the pathological process and with the comorbidities development. The strength of the networks indicates their ability to withstand dysregulations during the perturbation phases, returning to the state of stability. The treatment of dysregulated networks before the symptomatological manifestation emerges offers the possibility of treating and preventing pathologies in the preclinical phase and potentially reversing the pathological process, stopping it or preventing comorbidities. Furthermore, treating shared networks instead of individual phenotypic symptoms can reduce drug use, offering a solution to the problem of ineffective drug use.

The Impact of Immunological Factors on Depression Treatment - Relation Between Antidepressants and Immunomodulation Agents.

It is determined that 30% of patients with depression are resistant to antidepressant medication. The increased concentration of inflammation factors, such as C-reactive protein, and pro-inflammatory cytokines, have been detected in serum in these patients. It is necessary to establish new therapeutic possibilities and protocols that are created to overcome the difficulties caused by increased concentration of inflammatory biomarkers in depressive patients. The Selective Serotonin Reuptake Inhibitors (SSRIs) are considered to be the most powerful antidepressants, increasing the level of serotonin in endogenous depression, as well as in that caused by immunological mechanisms. It is believed that agents that influence cytokines, immunological signal pathways and cytokine syntheses, like the inhibitors of cyclooxygenase enzyme and other non-steroidal anti-inflammatory drugs (NSAIDs), are very important in the potential treatment of residual symptoms of depression. Treatment with cytokine antagonists is one of the potential adjuvant therapies, along with antidepressants. Signal pathways blockers, such as the inhibitors of cyclooxygenase and other NSAIDs, are in the phase of research, in terms of their antidepressant effects. Also, it has been shown that the inhibition of indolamin-2,3 deoxygenase (IDO) and kynurenine (KYN) signal pathways in the synthesis of neurotransmitters, by application of IDO antagonists, are leading to suppression of pro-inflammatory cytokine effects. Antidepressants may have anti-inflammatory effects, depending on dose and type, and they achieve this effect through the decrease of pro-inflammatory cytokine production and increase of anti-inflammatory cytokines. Also, antidepressants modulate the humoral and cellular immune system. This work aims to summarise certain neurobiological and neuroimmunological specificities that have been observed in patients with depression, antidepressants and immunomodulation agents. The understanding of complex and heterogenic pathophysiology of depression through the prism of the altered immune system, is of major importance, in terms of better optimisation of pharmacotherapy, and options for a personalised approach in depressive disorder treatment.

A Black Hole at the Center of Earth Plays the Role of the Biggest System of Telecommunication for Connecting DNAs, Dark DNAs and Molecules of Water on 4+N- Dimensional Manifold.

Recently, some scientists from NASA have claimed that there may be a black hole like structure at the centre of the earth. We show that the existence of life on the earth may be a reason that this black hole like object is a black brane that has been formed from biological materials like DNA. Size of this DNA black brane is 109 times longer than the size of the earth's core and compacted interior it. By compacting this long object, a curved space-time emerges, and some properties of black holes emerge. This structure is the main cause of the emergence of the large temperature of the core, magnetic field around the earth and gravitational field for moving around the sun. Also, this structure produces some waves which act like topoisomerase in biology and read the information on DNAs. However, on the four-dimensional manifold, DNAs are contracted at least four times around various axis's and waves of earth couldn't read their information. While, by adding extra dimensions on 4 +n-dimensional manifold, the separation distance between particles increases and all of the information could be recovered by waves. For this reason, each DNA has two parts which one can be seen on the four-dimensional universe, and another one has existed in extra dimensions, and only it's e_ects is observed. This dark part of DNA called as a dark DNA in an extra dimension. These dark DNAs not only exchange information with DNAs but also are connected with some of the molecules of water and helps them to store information and have memory. Thus, the earth is the biggest system of telecommunication which connects DNAs, dark DNAs and molecules of water.

Recovery of Brain in Chick Embryos by Growing Second Heart and Brain.

To recover chick embryos damaged the brain, two methods are presented. In both of them, somatic cells of an embryo introduced into an egg cell and an embryo have emerged. In one method, injured a part of the brain in the head of an embryo is replaced with a healthy part of the brain. In the second method, the heart of brain embryo dead is transplanted with the embryo heart. In this mechanism, new blood cells are emerged in the bone marrow and transmit information of transplantation to subventricular zone (SVZ) of the brain through the circulatory system. Then, SVZ produces new neural stem cells by a subsequent dividing into neurons. These neurons produce new neural circuits within the brain and recover the injured brain. To examine the model, two hearts of two embryos are connected, and their effects on neural circuits are observed.

In Ovo Sexing of Chicken Eggs by Virus Spectroscopy.

Recently, some new methods for sexing of chicken eggs by fluorescence and Raman spectroscopy through the shell membrane have been proposed. On the other hand, in another investigation, a new virus medical imaging has been suggested. In this research, summing over these considerations, a new technique for sexing of chicken eggs by virus spectroscopy through the shell membrane is proposed. It is shown that viruses outside the shell of egg can communicate with materials inside it and determine the gender of chick embryo and it's evolutions.

DNA Waves and Their Applications in Biology.

AIM: In this research, we show that DNA waves have many applications in biology. DNA is formed by the joining of quantum particles like electrons and charged atoms. DNA has different motions during transcription, translation, and replication, in which the charged particles move, accelerate, and emit waves. Thus, DNA could emit quantum waves. METHODS: Two methods are proposed to observe the effect of DNA waves. The first proposed method measures DNA waves emitted by bacteria suspended in the milk. The vessel of milk is placed in the interior of an inductor. One side of the vessel is connected to a generator and another side to a scope. By sending a current to the inductor, an input electromagnetic field is produced. Bacteria interact with the input field, change it and produce new output signals. Using the scope, the output signals are observed and compared with the input signals. The number of DNA waves produced also depends on temperature. RESULTS: At lower temperatures, bacterial replication is less, and fewer DNA waves are produced. Conversely, more bacteria are generated at higher temperatures, and more DNA waves are produced. The second proposed method acquires and images of DNA signals of chick embryos. In this method, a circuit is constructed that consists of a graphene or metal tube, generator, inductor, scope, DNA in the interior of eggs and DNA exterior to the eggs. Magnetic waves pass the interior and exterior DNA as well as the graphene. The DNA is excited and the exciting interior/exterior DNA exchanges waves. Some of these waves interact with electrons in the graphene tube, and a current is generated. Properties of the chick embryo DNA can be explored by analysing changes in the waves that emerge from the eggs. CONCLUSION: It is concluded that DNA waves could be used extensively in imaging and provide for us the exact information about evolutions of DNAs interior of biological systems.

Formation of Neural Circuits in an Expanded Version of Darwin's Theory: Effects of DNAs in Extra Dimensions and within the Earth's Core on Neural Networks.

AIM: In this paper, inspiring Darwin's theory, we propose a model which connects evolutions of neural circuits with evolutions of cosmos. In this model, in the beginning, there are some closed strings which decay into two groups of open strings. METHODS: First group couple to our universe from one side and produce matters like some genes of DNAs and couple to an anti-universe from another side with opposite sign and create anti-matters like some anti-genes of anti-DNAs. Second group couple to the star and planet's cores like the earth's core from one side and produce anti-matters like stringy black anti-DNA and couple to outer layers of stars and planets like the earth from other side and produce matters like some genes of DNAs on the earth. Each DNA or anti-DNA contains some genetic circuits which act like the circuits of receiver or sender of radio waves. To transfer waves of these circuits, some neurons emerge which some of them are related to genetic circuits of anti-DNAs in anti-universe, and some are related to genetic circuits of stringy black anti-DNA within the earth's core. A collection of these neural circuits forms the little brain on the heart at first and main brain after some time. RESULTS: To examine the model, we remove effects of matters in outer layers of earth in the conditions of microgravity and consider radiated signals of neural circuits in a chick embryo. We observe that in microgravity, more signals are emitted by neural circuits respect to normal conditions. This is a signature of exchanged waves between neural circuits and structures within the earth's core. CONCLUSION: These communications help some animals to predict the time and place of an earthquake.

A Mathematical Model for the Signal of Death and Emergence of Mind Out of Brain in Izhikevich Neuron Model.

AIM: In this paper, using a mathematical model, we will show that for special exchanged photons, the Hamiltonian of a collection of neurons tends to a constant number and all activities is stopped. These photons could be called as the dead photons. To this aim, we use concepts of Bio-BIon in Izhikevich Neuron model. METHODS: In a neuron, there is a page of Dendrite, a page of axon's terminals and a tube of Schwann cells, axon and Myelin Sheath that connects them. These two pages and tube form a Bio-Bion. In a Bio-Bion, exchanging photons and some charged particles between terminals of dendrite and terminals of axon leads to the oscillation of neurons and transferring information. This Bion produces the Hamiltonian, wave equation and action potential of Izhikevich Neuron model. Also, this Bion determines the type of dependency of parameters of Izhikevich model on temperature and frequency and obtains the exact shape of membrane capacitance, resting membrane potential and instantaneous threshold potential. RESULTS: Under some conditions, waves of neurons in this BIon join to each other and potential shrinks to a delta function. Consequently, total Hamiltonian of the system tends to a constant number and system of neuron act like a dead system. Finally, this model indicates that all neurons have the ability to produce similar waves and signals like waves of the mind. CONCLUSION: Generalizing this to biology, we can claim that neurons out of the brain can produce signals of minding and imaging and thus mind isn't confined to the brain.

Stress and Inflammation in Coronary Artery Disease: A Review Psychoneuroendocrineimmunology-Based.

Recent findings have deeply changed the current view of coronary heart disease, going beyond the simplistic model of atherosclerosis as a passive process involving cholesterol build-up in the subintimal space of the arteries until their final occlusion and/or thrombosis and instead focusing on the key roles of inflammation and the immune system in plaque formation and destabilization. Chronic inflammation is a typical hallmark of cardiac disease, worsening outcomes irrespective of serum cholesterol levels. Low-grade chronic inflammation correlates with higher incidence of several non-cardiac diseases, including depression, and chronic depression is now listed among the most important cardiovascular risk factors for poor prognosis among patients with myocardial infarction. In this review, we include recent evidence describing the immune and endocrine properties of the heart and their critical roles in acute ischaemic damage and in post-infarct myocardial remodeling. The importance of the central and autonomic regulation of cardiac functions, namely, the neuro-cardiac axis, is extensively explained, highlighting the roles of acute and chronic stress, circadian rhythms, emotions and the social environment in triggering acute cardiac events and worsening heart function and metabolism in chronic cardiovascular diseases. We have also included specific sections related to stress-induced myocardial ischaemia measurements and stress cardiomyopathy. The complex network of reciprocal interconnections between the heart and the main biological systems we have presented in this paper provides a new vision of cardiovascular science based on psychoneuroendocrineimmunology.