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*Corresponding Author: A.N. Belousov, Laboratory of Applied Nanotechnology of Belousov, Ukraine.
Citation: A.N. Belousov, E.Yu. Belousova, Ye.V. Lekomtseva, (2024), The Use of a Nanotechnological Drug (Micromage-B) In the Complex Treatment of Multiple Sclerosis, Journal of Clinical and Laboratory Research. 7(1); DOI:10.31579/2768-0487/095
Copyright: © 2024, A.N. Belousov. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 01 November 2023 | Accepted: 01 December 2023 | Published: 01 January 2024
Keywords: multiple sclerosis; treatment; nanodevice; micromagе-b; neurological status assessment; remyelination
Multiple sclerosis (MS) is a serious neurological problem because of its high prevalence, chronic course, frequent disability, and propensity to affect young people. The immunopathogenesis hypothesis underlies the origin of MS. Selective sorption activity of biocompatible magnetite nanoparticles against surface proteins of cell membranes, circulating immune complexes, lymphocytotoxin antibodies, complement system, the effect of increasing phagocytic activity and leukocyte phagocytosis completion index allows the effective use of these nanodevices for immunocorrection. The main goal of the study is to slow down the progression of MS, improve the neurological status and general condition of the patient, and reduce the dynamics of the spread of demyelinating foci in the brain.
Materials and Methods: a patient diagnosed with multiple sclerosis, secondary progressive type of course, cerebro-spinal form, clinical aggravation stage; EDSS neurological status and disability assessment scales; contrast-enhanced MRI of the brain. An oral form of the nanodevice Micromage-B was used as an immunosorbent and immunomodulator. The choice of the regimen and dosage of Micromage-B was personalized. Assessment of the general condition and neurological status was performed every 7 days for 6 months. Contrast-enhanced MRI of the brain was performed at the 5th month of the study. As a result of using Micromage-B in MS treatment, objective improvement of neurological status, reduction of stiffness and rapid fatigability of the lower extremities were observed. Gait and coordination improved, hand tremors decreased, depression and signs of concentration disorders disappeared, appetite restored, and speech improved. During the entire period of Micromage-B application, positive dynamics in the normalization of the neurological status was observed. After 6 months of treatment, the total score dropped by 165 to 35. It was found that the maximum positive effect was observed in the evaluation of the pyramidal system and coordination. The EDSS Disability Scale score decreased from 6.0 to 5.0. Contrast-enhanced MRI brain examination for the first time showed a decrease in the number of new foci of demyelination in the brain by the 4th month of Micromage-B administration. The positive dynamics of normalization of the neurological status correlated with the results of brain MRI. The process of recovery of central nervous system activity in MS is not only due to the immunosuppressive properties of magnetite nanoparticles, but is probably caused by the activation of remyelination mechanisms and oligodendrocyte differentiation through enzymatic methylation. Considering the above, the use of biocompatible nanodevices in the complex treatment of MS is a promising direction. The scheme and method of using biocompatible magnetite nanoparticles to improve the effectiveness of MS treatment require further improvement and study
Multiple sclerosis (MS) is a serious neurological problem due to its widespread occurrence, chronic course, frequent disability of patients and propensity to affect young people. The average age of onset is 30 years. The main hypothesis of immunopathogenesis of MS is that immunological tolerance is violated and autoreactive cells, sensitized to antigens of nervous tissue, actively penetrate through the blood-brain barrier into the brain tissue. B-lymphocytes recognize myelin and order T cells to launch an immune attack [1-7]. T- and B-cells secrete chemicals that attract other immune cells that cause inflammation [8,9]. Plasma cells produce and release antibodies that attack myelin and enlist the help of other immune cells [10,11]. T- and B-cells create a permanent residence in the central nervous system (CNS) and continue the attack [12,13]. There are two hypotheses of MS pathogenesis: the outside-in hypothesis, based on the penetration into the brain tissue of immunocompetent cells activated in the periphery, and inside-out, when the primary is damage to the nervous tissue, the expression of damage receptors - from the family DAMPs (Danger-associated Molecular Patterns), resulting in activation of immunity and failure of tolerance to myelin antigens [14]. Antibodies, which are actively produced by plasma cells, destroy the protective covering of nerve cells. Inflammation develops in the damaged area. After some time, the tissue is scarred, which leads to a disturbance of conduction. As a result of such processes, impulses from the brain do not reach the limbs and organs. Because of this a person loses the ability to control his body [15]. The most common initial clinical symptoms are weakness and impaired sensation in one or more limbs, decreased vision, impaired urination and cerebellar ataxia. Currently, immunomodulatory and immunosuppressive drugs that modify the course of MS form the basis of pathogenetic treatment. Their mechanism of action is related to: 1) selective or 2) complete immunosuppression, 3) prevention of migration of activated cells from lymph nodes or into brain tissue, or 4) a combination of immunoregulatory, anti-inflammatory, antioxidant, and possibly neurotrophic actions. Possible directions in the development of new treatments for MS include selective local immunocorrection, remyelination and neuroprotection, enhancement of neuroplasticity and relocalization of function, evaluation of the effectiveness and safety of cell therapy, individual selection of therapy based on prediction of pathological process variants and possible response to treatment based on the results of molecular and cellular biology of MS [16-22].The development of inflammation and demyelination in MS is caused by an impaired immune response, imbalance of T regulatory and T effector cells, activation of B-cell immunity and microglia. All drugs affecting the course of MS either deplete T- or B-cells or alter the signaling pathways associated with the formation of an immune response [23].
Particular attention has recently been paid to the role of B-cells in the chronic inflammatory process in the CNS, as evidenced by their role in both autoantibody formation and in the presentation of antigens and constant activation of T-cells in the brain parenchyma. Anti-B-cell therapy (Rituximab, Ocrelizumab, Ofatumumab) has proven effective in both remitting and progressive MS. Stimulation of remyelination in MS is associated with the development of new preparations of monoclonal antibodies: anti-Lingo, human immunoglobulin M (IgM). These drugs promote remyelination and differentiation of oligodendrocytes and their precursors [24]. One of the key mechanisms of axonal degeneration is mitochondrial dysfunction. Some drugs (Dimethyl fumarate, Idebenone, Biotin) can be considered promising in this direction [25]. The use of drugs affecting the redistribution of ion channels in the demyelinated axon (Lamotrigine, Amiloride, Fampridine) can help to reduce the energy deficit in the axon and neuron [26]. Recently, biocompatible nanotechnological preparations have been increasingly used in medicine. Since 1998, Ukrainian clinics have been officially using nanodevices developed by Belousov's Applied Nanotechnology Laboratory: Micromage-B, MCS-B and ICNB brands [27]. These nanodevices are based on biocompatible magnetite nanoparticles. The peculiarity of physical and chemical characteristics provides a condition for a wide range of their application in order to influence the quantitative and qualitative compositions of the fluid environment of the body, metabolic and biochemical processes, the energy balance of cells. Selective sorption activity against surface proteins of cell membranes, circulating immune complexes, lymphocytotoxic antibodies, complement system, the effect of increasing phagocytic activity and leukocyte phagocytosis completion index [28] allow the effective use of these nanodevices for immunocorrection. In addition, the nanopreparations presented have an effect on glycolysis processes, the activity of cell membrane ion channels, normalize erythrocyte function, improve microcirculation, reduce platelet aggregation index [29-31], activate the system of antiradical enzymes, and inhibit lipid peroxidation processes [32,33]. The results of these studies are a prerequisite for the development of innovative techniques for the effective and safe use of biocompatible magnetite nanoparticles in the treatment of severe autoimmune diseases, including multiple sclerosis. The main goal of the study is to slow down the progression of MS, improve the neurological status and general condition of the patient, and reduce the dynamics of the spread of demyelinating foci in the brain.
Patient K. was diagnosed with multiple sclerosis, secondary progressive type of course, cerebrospinal form, clinical aggravation stage, pronounced spastic tetraparesis with accent in lower extremities with walking impairment, pronounced urinary-ataxic syndrome, sphincter and sensory disorders. MRI - signs of multifocal diffuse brain lesions (more than 30) of demyelinating nature. Active phase. Diffuse atrophic process in the cerebral cortex. The mean number of relapses during the year before study inclusion was 1.0. The EDSS disability score was 6.0. The duration of the disease since the onset of the first symptoms was 24 years. For 14 years, the patient was regularly treated with vascular and metabolic drugs in combination with hormonal therapy. In the 6th year, against the background of active treatment, the disease transformed into a secondary-progressive type of course. The therapy was supplemented with the immunosuppressive drug Teriflunomide. However, despite all treatment, the patient's general condition progressively worsened. The neurological status has not stabilized. MRI examination showed a progressive increase in the number of new foci of demyelination in the brain over the last 4 years. Considering the above, the complex therapy was supplemented with the prescription of Micromage-B [34]. Micromage-B is an oral form of nanodevice officially registered by the Ministry of Health of Ukraine. Micromage-B is a powder form of magnetite (Fe3O4) nanoparticles, which is designed for the prevention and treatment of various diseases, as well as to increase the body's resistance to adverse environmental factors. Micromage-B it is device of nanotechnology. The size of magnetite nanoparticles is from 6 to 12 nm. The therapeutic effect of the nanopreparation is based on the mechanism of sorption and action of a constant magnetic field on cellular and subcellular structures that causes by magnetite of nanoparticles. The area of the sorption surface of nanoparticles is from 800 to 1200 m2/g, and the value of the induced magnetic field is 300-400 kA/m. The application point of Micromage-B is the microenvironment of the cell aqueous spaces, surface membrane proteins. Magnetite nanoparticles by selective sorption change the quantitative and qualitative composition of cell surface proteins, and the permanent magnetic field induced by magnetite nanoparticles changes the mobility and orientation of hydrogen protons in the water sectors of the cell microenvironment. The latter contributes to the activation of hydrolysis of the phosphate residue ATP. In general, the transmembrane exchange and metabolism of the cell are modified, and its susceptibility is altered. Nanopreparation causes increase of adaptive mechanisms and potential of cell organelles, accelerates of the reparative processes at the level of membranes and macromolecules. Micromage-B significantly increases the level of synthetic intracellular reactions and compensatory possibilities of the organelles of the cells of the renal glomerulus, the epithelial cells of the proximal and distal sections of the nephron, that is structurally expressed in increasing bioenergetic support of synthetic intracellular processes, increasing the reparative and adaptive capabilities of nephrons. By increasing the activity of redox phosphorylation processes, providing energy requirements of synthetic intracellular reactions proceeding at the level of membranes and macromolecules in liver cells, Micromage-B acts as a direct activator of reparative intracellular processes in hepatocytes, enhances glycogenogenesis. This fact allows to use it effectively as a powerful hepatoprotector in the treatment of acute and chronic liver diseases. Micromage-B can act as an active stimulator of erythropoiesis, thereby quickly restoring the level of hemoglobin in the blood. Micromage-B stimulates the synthesis of pulmonary surfactant, which provides stretchability and elasticity of lung tissue. Micromage-B provides the stability of the lungs to negative influences of factors of external and internal environment by means increasing the activity of alveolar macrophages. Clinically and laboratory: Micromage-B improves microcirculation and rheological properties of blood by stabilizing the bioelectric charge of erythrocyte membranes. It has a pronounced immunomodulatory effect. Micromage-B has a selective bacteriostatic effect in relation to the pathogenic microflora, without adversely affecting the normoflora. Delays the growth and reproduction of various kinds of fungi. Stimulates the growth and activity of lactic acid bacteria in the intestine. In 2-3 times increases the effectiveness of antibacterial and antifungal agents. These facts allow the effective use of Micromage-B for the treatment of dysbacteriosis and candidiasis. Nanoparticles of Micromage-B adsorbed toxic substances and circulating immune complexes. It's fact that greatly increases the effectiveness of treatment of various allergic diseases, autoimmune processes (for example, rheumatoid arthritis, acute and chronic polyarthritis, eczema etc.), acute poisoning. Improving the renal blood flow by Micromage-B has a moderate diuretic effect. Having in its nature magnetic moment the magnetite nanoparticles brakes down and promotes the dissolution of stones in the kidneys and bile ducts of the liver, which are subsequently eliminated through the excretory systems of the organism in the form of magnetically sensitive crystals forms. Micromage-B actively contributes to the normalization level of lipids and proteins in blood. Affects the factors of atherogenesis, preventing the development of atherosclerotic processes. Active decline the level of release into the blood of an excessive number of mediators of the aggressive state is result of actions permanent magnetic field of magnetite nanoparticles of the Micromage-B into the macrophage cells. In turn, this causes pronounced anti-inflammatory and moderate analgesic effects. Micromage-B modulates activity of the enzyme link of antioxidant system, sorbs products of the lipid peroxidation, corrects balance between antiradical and proradical products. Under the influence of Micromage-B, the monocytes actively synthesized a tumor necrosis factor (cachexin), which has cytotoxic and cytostatic effects on tumor cells. When topical application (in the form of powders, ointments or aqueous solutions of colloids) the Micromage-B promotes rapid wound healing of mucous membranes and skin, change of wet tissue necrosis to dry. Micromage-B does not cause disturbances in the functional activity of organs and body systems, it is non-toxic [35,36]. Dosing regimen Micromage-B: the first month - 500 mg daily, the second month - 500 mg every other day, subsequent months - 500 mg once every three days. The choice of the scheme and dosage of Micromage-B had an individual approach. The time and speed of the appearance of signs of improvement in the patient's general state and recovery of neurological status were taken into account. The dynamics of changes in the neurological status were studied using a modified Multiple Sclerosis Patient Assessment Scale [37,38]. This scale is based both on the severity of motor disorders and on their combination with other signs of damage to the nervous system. For quantitative assessment of disability, Kurtzke's online EDSS calculator was used [39]. The manifestations of foci of cerebral demyelination were studied using contrast-enhanced MRI.The patient's general condition and neurological status were evaluated every 7 days for 6 months. According to the plan, a contrast-enhanced MRI of the brain was performed once a year. In this case, the timing of the MRI coincided with the 5th month of use of Micromage-B.
One week after the use of Micromage-B, there was a noticeable improvement in the patient's neurological status. The patient noted a significant decrease in stiffness and rapid fatigue in the lower extremities. Objectively, the gait and coordination improved, the hand tremor decreased, depression and concentration disorders completely disappeared, appetite restored, and speech improved. Positive dynamics of normalization of the neurological status was constantly observed during the whole period of Micromage-B application. Evaluation of the neurological status of a patient with multiple sclerosis before and after 6 months of Micromage-B is presented in Table 1.
| 1. Movements (pyramidal system) | |||||
| Input data | Six months after application Micromage-B | Clinical manifestations | |||
| Arm | Leg | Arm | Leg | ||
| 0 | 0 | 0 | 0 | Norma | |
| 5 | 10 | 5* | 10* | Absence of loss symptoms, revival of tendon reflexes, enlargement of reflexogenic zones, clonus, presence of pathological signs, anisoreflexia, (absence of paresis) | |
| 10 | 20 | 10 | 20 | Raises a limb independently, full volume of active movements, signs of pyramidal lesion, overcomes not only the gravity of his own limb, but also an additional obstacle of moderate strength, positive Barre-Rusetsky's symptom | |
| 15 | 40 | 15 | 40 | Raises a limb independently, the volume of active movements is full, cannot hold a limb in a given position for a long time, and cannot overcome an additional obstacle. | |
| 20* | 60* | 20 | 60 | Can pull a limb off the plane, the amount of active movement is limited, cannot hold a limb in a given position. | |
| 40 | 80 | 40 | 80 | Cannot detach a limb from the plane, active movements in the joints of the fingers, ankle and wrist, elbow, knee joints are possible only on the plane. | |
| 50 | 100 | 50 | 100 | Complete absence of movement (paralysis) | |
| 2. Sensitivity | |||||
| Before | After | (a) superficial sensitivity | |||
| 0 | 0* | Norma | |||
| 5 | 0 | Paresthesias, burning sensation, numbness, coldness of a limb (no objective disorders) | |||
| 10* | 10 | Hyperesthesia or hypoesthesia | |||
| 15 | 15 | Anesthesia phenomena | |||
| b) deep sensitivity | |||||
| 0* | 0* | Norma | |||
| 10 | 10 | Disorder of joint and muscle feeling in small joints | |||
| 20 | 20 | Disorder of joint and muscle feeling up to the level of the middle joints (wrist, ankle) | |||
| 40 | 40 | Disorder of joint and muscle feeling up to the level of large joints (elbow, shoulder, knee, hip) | |||
| 3. Coordination | |||||
| 0 | 0 | Norma | |||
| 10 | 10* | Unsteadiness, swaying in the sensitized Romberg's test while standing on one leg, mild intensional trembling (in the complicated test), slight ataxia in the heel-knee test, deviation when walking with eyes closed. | |||
| 40* | 10 | Unsteadiness in simple Romberg's pose, atactic gait with open eyes and legs spread wide apart, "drunkenness," moderately pronounced intensional tremor and ataxia in the heel-knee test. | |||
| 100 | 100 | Because of ataxia, the patient cannot move without assistance, sharp hypotonia of muscles, intensional shaking of the head, trunk, coarse - upper extremities, coarse ataxia during heel-knee test, trembling of upper extremities when trying to perform purposeful movement, chanted speech. | |||
| 4. Psycho-emotional sphere | |||||
| 0 | 0* | Norma | |||
| 10 | 10 | Mild impairment of the intellect in combination with euphoria, rapid change of mood, neurasthenic syndrome. | |||
| 20* | 0 | Euphoria, depression, decreased criticism of one's condition, decreased memory. | |||
| 100 | 100 | Severe mental disorder, complete intellectual disintegration, Korsak's syndrome, etc. | |||
| 5. Nystagmus | |||||
| 0 | 0* | Norma | |||
| 5 | 5 | Nystagmus is detected only in the extreme leads (degree 1) | |||
| 10* | 10 | Nystagmus when looking straight ahead (degree 2) | |||
| 15 | 15 | Sharp beating nystagmus, nystagmus in both directions, even toward the slow component (3rd degree) | |||
| |||||
| 0 | 0* | Norma | |||
| 10* | 10 | Impulsive urges, inability to hold urine for a long time, difficulty urinating | |||
| 20 | 20 | Urinary incontinence, urinary retention, intermittent urination disorders, persistent constipation | |||
| 7. Sexual function | |||||
| 0 | 0* | Norma | |||
| 5* | 5 | Decreased sexual activity in men (intermittent impotence), sexual coldness in women | |||
| 10 | 10 | Total impotence, menstrual disorders in women | |||
| |||||
| 0 | 0 | Norma | |||
| 5 | 5 | Disturbance of vascular pattern, narrowing of arteries, dilation of veins, changes on fluorescence ophthalmoscopy | |||
| 10* | 10* | Partial optic atrophy (bitemporal pallor), optic neuritis | |||
| 15 | 15 | Complete atrophy of the optic nerve | |||
| |||||
| 0 | 0 | Norma (vision within 1.0 or myopia) | |||
| 5 | 5 | Occasional blurring of vision, rapid fatigue when reading and performing work without impaired visual acuity | |||
| 10* | 10* | Visual acuity from 0.9 to 0.7 | |||
| 15 | 15 | Visual acuity from 0.6 to 0.4 | |||
| 20 | 20 | Visual acuity from 0.3 to 0.1 | |||
| 25 | 25 | Visual acuity 0.1 and below | |||
| 100 | 100 | Blindness in one or both eyes | |||
| |||||
| 0 | 0* | Norma (absence of subjective and objective symptoms) | |||
| 5* | 0 | Concealed insufficiency, without visible dysfunction of one of the oculomotor nerves, inter-nuclear ophthalmoplegia syndrome | |||
| 10 | 10 | Mild visible impairment, visible insufficiency of one or more nerves, diplopia, ptosis, anisocoria | |||
| 15 | 15 | Convergent or divergent strabismus | |||
| 20 | 20 | Complete ophthalmoplegia (in one or both eyes) | |||
| 11. The trigeminal nerve | |||||
| 0* | 0* | Norma (отсутствие объективной и субъективной симптоматики) | |||
| 5 | 5 | Наличие субъективных ощущений в виде болей, онемения, чувства «ползания мурашек», стягивание в области лица | |||
| 10 | 10 | Наличие объективных признаков поражения, гипестезия, выпадение или снижение роговичного рефлекса | |||
| 20 | 20 | Грубые нарушения с выпадением всех функций тройничного нерва в сочетании с невралгическими расстройствами или без них | |||
| 12. The facial nerve | |||||
| 0 | 0* | Norma | |||
| 5* | 0 | Moderate weakness of facial muscles (eye closes completely, but cannot actively close it), asymmetry of frontal and nasolabial folds | |||
| 10 | 10 | Moderate weakness of mimic muscles (lagophthalmus, positive Bell's symptom, facial asymmetry in grinning), with preservation, to some extent, of mimic movements | |||
| 20 | 20 | Complete paralysis of facial muscles | |||
| 13.Bulbar group of cranial nerves (nerves 9,10,11,12) | |||||
| 0 | 0* | Norma | |||
| 5* | 5 | Mildly pronounced bulbar phenomena (gagging when taking liquid food, change in speech, without gross organic symptoms of prolapse) | |||
| 10 | 10 | Severe dysphagia, dysarthria, decreased soft palate and posterior pharyngeal wall reflexes | |||
| 100 | 100 | Complete bulbar paralysis | |||
| |||||
| 0* | 0* | Norma | |||
| 5 | 5 | Conversational speech at a distance of 4 to 6 m, whispered speech at a distance of 1 to 3 m. | |||
| 10 | 10 | Speech - from 2 to 4 m, whisper - from 0.5 to 1 m. | |||
| 15 | 15 | Spoken speech 2 m or less, whispered speech 0 to 0.5 m | |||
| 20 | 20 | Complete deafness in one or both ears | |||
| Total: | Total: | ||||
| 210* | 45* | ||||
Table 1: Neurological status assessment scale for patient K. with multiple sclerosis.
Note: * - estimated scores of the neurological status before and after using the Micromage.
The data in Table 1 demonstrate positive dynamics in the normalization of the neurological status after 6 months of using Micromage-B. At the initial stage the total number of points was 210. After 6 months of using Micromage-B - 45. Thus, the total number of points dropped by 165. The maximum positive effect was observed in the evaluation of the pyramidal system and coordination. The EDSS disability scale score decreased from 6.0 to 5.0.Contrast-enhanced MRI examination of the brain after 4 months of use of Micromage-B showed for the first time a decrease in the number of new foci of demyelination in the brain. The positive dynamics of the neurological status correlated with the results of the MRI examination of the brain. Analyzing the data obtained, special attention should be paid to the fact that against the background of the predicted positive clinical effect caused by immunization, the use of magnetite nanoparticles (Micromage-B) actively contributed to the restoration of neurological status. In this case, it can be caused by the processes of remyelination and differentiation of oligodendrocytes. Oligodendrocytes are a type of neuroglia cells that cover the myelin sheath of neurons in the CNS. The molecular mechanisms underlying cell differentiation and specialization are perhaps the most confusing area of cell biology and developmental biology. The development and maturation of many cell types is still poorly understood. However, it is now known that one of the mechanisms of oligodendrocyte maturation is the process of enzymatic methylation - the addition of a methyl group (-CH3) to the nitrogen atom N6 in the nitrogenous base of adenosine, known as m6A-methylation. Such a seemingly insignificant change can have enormous consequences for further stages of protein biosynthesis. The role of m6A-methylation has been shown in many processes related to oligodendrocyte maturation [40]. The universal donor of methyl groups in the body is s-adenosine-methionine, which is formed as a result of the interaction of the amino acid methionine with the ATP molecule. Considering that due to the activation of glycolysis Micromag-B significantly increases the amount of macroergic compound (ATP) [41,42], as well as the formation of the reduced form of the coenzyme nicotinamide-adenindinucleotide phosphate
(NADPH2) with the transition of oxidized form of glutathione to reduced [43], conditions for starting enzymatic methylation processes are created. The latter most likely complements the mechanism of action of magnetite nanoparticles (Micromage-B). Eventually, it ensures differentiation of oligodendrocytes and the remyelination process. It is also necessary to take into account the fact that these magnetite nanoparticles polarize the aqueous sector of the cellular microenvironment [44]. As a result, hydrolysis of the phosphate residue of ATP is activated, a quantum of energy is reset, and ADP is formed.
Taking into account the positive dynamics of the neurological status, it was decided to continue the use of the nanopreparation Micromage-B according to the specified dosage. The therapy was supplemented with a complex of rehabilitation exercises, aimed at the earliest restoration of physical, cognitive and psychosocial functions of a patient with MS.
The results of the study expanded the range of clinical efficacy of biocompatible magnetic nanoparticles in the therapy of severe autoimmune diseases. The use of nanopreparation Micromage-B in the treatment of MS had a pronounced positive clinical effect on the restoration of neurological status, objectively contributed to a reduction in the number of new foci of demyelination in the brain. The process of recovery of CNS activity in MS is not only due to the immunosuppressive properties of magnetite nanoparticles, but is probably caused by the activation of remyelination mechanisms and oligodendrocyte differentiation through enzymatic methylation. The use of biocompatible nanodevices in the complex treatment of multiple sclerosis is a promising direction. The scheme and method of using biocompatible magnetite nanoparticles to improve the effectiveness of MS treatment require further improvement and study.
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Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
