Ultra early molecular biologic diagnosis of malignant and neurodegenerative diseases by the immunospecific profiles of the proteins markers of the surface of the mobilized autologous hematopoietic stem cells.

The comparative study of the protein markers of the membrane surface of the autologous hematopoietic stem cells (СD34+ СD45+) was performed to detect the patterns of the proteomic profiles, if any. The study included five groups. The subpopulations of the hematopoietic stem cells were studied in 569 samples of the mobilized peripheral blood mononuclear cells from adult cancer cases (group 1), 557 samples from children cancer cases (group 2), 66 samples from amyotrophic lateral sclerosis cases (group 3), 5 samples from other neurodegenerative diseases cases (supplementary group 4) and 61 samples isolated from healthy donors (control group 5). The protein markers of the membrane surface of the autologous hematopoietic stem cells were mapped and profiled with flow cytometry. The specific patterns of the proteomic profiles characteristic for cancer and neurodegenerative disease and different from those of healthy donors were identified. The authors suppose that as far as the HSC is the parent cell of the immune system cells, the modification of its proteomic profile speaks of specific immune insufficiency that not only accompanies the disease but presents the key cause for its onset and precedes its clinical manifestation. Thus, the evaluation of the protein markers of the membrane surface of hematopoietic stem cells can be used for ultra early diagnosis of these diseases.

Is the ALS a motor neuron disease or a hematopoietic stem cell disease?

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is also known as motor neuron disease (MND) or Lou Gehrig's disease. It is a fatal neurodegenerative disease the cause of which is not clear. The effective therapy is absent. ALS is diagnosed through clinical examination and neurophysiologic tests. Clinically, the symptoms manifest when about 80% of motor neurons are dead. MATERIALS AND METHODS: The hematopoietic stem cells are isolated through administration of the granulocyte colony-stimulating factor from three groups: group 1 of 62 ALS cases, group 2 of 54 ALS-free healthy donors and group 3 of 6 ALS-free ALS-family members. The expression of HLA-DR, CD38, CD117, CD13, CD33, CD56, Thy-1, CD45, СD10, CD71 was assessed in 86 samples of HSCs in ALS group, 61 samples of HSCs in healthy group and 6 samples from ALS-free ALS-family members by the multiparameter flow cytometry. RESULTS: The obtained immunophenotypic profiles of HSCs membrane antigens of the ALS group significantly differ from the ALS-free group, while the immunophenotypic profiles of HSCs membrane antigens of the ALS-family members group are close to the ALS group. DISCUSSION: We suppose that the ALS onset as the disease of HSCs and manifests in the genome and proteome of the HSCs. Such immunophenotypic profiling might permit identification of ALS-specific immune insufficiency and become a tool for early diagnostics of the ALS before clinical manifestation of the disease. New options of the updated therapy of ALS might be developed or corrected considering this new evidence. CONCLUSION: Further research with larger samples and deeper examination is required.

Human mind has microwave electromagnetic nature and can be recorded and processed.

INTRODUCTION: In 2014 and 2015 Professor of neurology Andrey Bryukhovetskiy published a novel theory of the information-commutation organization of the human brain in Russia, China and the USA. The theory posits the hypothesis that the higher nervous activity (cognitive, intellectual, mnestic) of the humans and their mind are material and have microwave electromagnetic nature. The theory perceives the human mind as a result of dynamic extracortical information-commutation relations of the super-positions of the electromagnetic waves of ultra high frequency emitted by different areas of the human brain in the inter-membrane cerebrospinal fluid space of the human head at a certain period of time. The inter-membrane cerebrospinal fluid space of the human head (the space between the dura, arachnoid and pia mater filled with the cerebrospinal fluid) of about 10mm size, has all morphological attributes to realize the holography. It is a universal natural bioprocessor for processing, analysis and synthesis of the input data and their record or reproduction on the pia as on the biological holographic membrane. The theory suggested that the processes of the mind can be recorded and digitalized with the last generation contemporary microwave receptors of the UHF band. GOAL: The goal is to experimentally test the theory of the information-commutation organization of the human brain, particularly, the postulate that the human mind has material, and, namely, electromagnetic nature represented by the microwave bioelectric activity; it must be detected, recorded and statistically processed, i.e. its existence must be confirmed. METHODS: On their own initiative, the team of mathematicians, radioengineers and neurologists performed the non-invasive research of the electromagnetic radiation of human brain in the broad frequency range varying from 850MHz to 26.5GHz with the last generation specialized measuring equipment with high sensitivity and recording speed, specialized measuring antennas and low noise amplifying equipment in the anechoic chamber of the 1st class of protection according to the Russian system of certification GOST R 50414-92. RESULTS: The previously unknown microwave electromagnetic radiation of the EHF/UHF range (from 1.5GHz to 4.5GHz) with signal strength of -130dBm .. -100dBm (1e-15 .. 1e-13 W) are discovered. The detected electromagnetic waves have zonal variations in the different areas of the human head and are absent in other areas of the human body. The method of recording of the microwave electromagnetic activity of the human brain is patented in the Russian Federation. The microwave electromagnetic activity of the brain is billion-fold different from the bioelectric activity recorded by the encephalography. CONCLUSION: Discovery of the phenomenon of the microwave radiation of the human brain provides evidence to the idea that thinking and mind are material. This phenomenon has the potential to become a new informational channel of the diagnostics of the functional and pathological state of the higher nervous activity of the human brain. It can provide the basis for the development of the equipment for real-time analysis of the microwave bioelectric activity of the brain in norm and pathology, for objective early diagnostics of the functional and emotional conditions as well as of the psychiatric disorders at the preclinical stage, for the biocontrol of the human brain and the artificial simulators of the human brain. It also can provide the foundation for new systems of the artificial intellect, brain-computer interface and systems of the closed-loop biomanagement of the damaged brain.

Patterns of bone metastases in newly diagnosed colorectal cancer: a real-world analysis in the SEER database.

PURPOSE: To investigate the incidence and the associated factors for bone metastases (BM) development and prognosis in initial colorectal cancer (CRC) with a large sample using Surveillance, Epidemiology, and End Results (SEER) cohort. METHODS: Primary CRC patients, who were initially diagnosed between 2010 and 2015 in the SEER database, were included to analyze BM incidence and risk factors for BM occurrence. The patients with at least 1-year follow-up were involved to investigate the prognostic factors for BM. Multivariable logistic and proportional hazard regression models were used to investigate the risk factors for BM development and prognosis, respectively. RESULTS: A total of 212,787 eligible CRC patients were included and 2557 of them were diagnosed with de novo BM (1.20%). Rectal cancer presented significantly higher BM incidence than right and left colon cancer (χ2 = 107.64, P < 0.001). T1 stage, poor differentiated grade, and brain metastases were homogeneously associated factors for BM development and BM patients' survival. Male gender, higher N stage, rectal site, elevated carcinoembryonic antigen, and lung and liver metastases were positively associated with BM occurrence. Older age, unmarried status, right colon site, and non-surgery were found to positively correlate with the death risk of CRC patients with BM. CONCLUSIONS: BM is rare in CRC patients. Homogeneous and heterogeneous factors were found for BM development and BM patients' survival. The risk factors and prognostic factors can be used for BM screening and patient's prognosis estimation.

Bone Metastases Pattern in Newly Diagnosed Metastatic Bladder Cancer: A Population-Based Study.

Purpose: Based on a large-population analysis, we aimed to estimate the incidence and survival of bone metastases (BM) in initial bladder cancer (BC) patients and to identify the risk and prognostic factors of BC patients with BM. Patients and methods: Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, bladder cancer patients diagnosed between 2010 and 2014 were retrieved. Multivariate logistic and Cox regression analyses were employed to identify risk factors and prognostic factors for BM in BC patients. A Kaplan-Meier analysis with log-rank test was used to estimate the overall survival for BC and the difference between the survival curves. Results: A total of 1,223 (1.39%) BC patients were diagnosed with de novo BM. Variables such as age between 41 to 60 years, black race, unmarried status, higher T stage, higher N stage, poor tumour differentiation grade, lung metastases, liver metastases, and brain metastases were positively associated with BM occurrence. The median survival for BC patients with BM was dramatically decreased to 4.0 months. Factors including advanced age, absence of surgery, and presence of lung, liver, or brain metastases all predicted worse survival. Conclusion: BM can dramatically decrease the survival of bladder cancer patients. The findings of the present study can provide population-based identification of risk and prognostic factors for BC patients with BM at initial diagnosis, which can be used for BM occurrence prediction and individualized treatment plan-making.

Real-World Study of the Incidence, Risk Factors, and Prognostic Factors Associated with Bone Metastases in Women with Uterine Cervical Cancer Using Surveillance, Epidemiology, and End Results (SEER) Data Analysis.

BACKGROUND The aims of this study were to investigate the incidence and risk factors for the development of bone metastases and prognosis in women with cancer of the uterine cervix using database analysis. MATERIAL AND METHODS The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database was analyzed for the incidence and survival rates of women diagnosed with uterine cervical cancer in the United States between 2010-2015. Multivariate logistic regression analysis identified risk factors for bone metastases. Kaplan-Meier analysis estimated the overall survival. Proportional hazard regression analysis estimated prognostic factors associated with bone metastases. RESULTS There were 19,363 women with uterine cervical cancer, and 469 women were diagnosed with bone metastases on initial diagnosis (2.42%). Increased T-stage, N-stage, non-squamous and non-adenocarcinoma histology, high-grade tumors, and the presence of lung, liver, and brain metastases were all significantly associated with early bone metastases. There were 364 patients with cervical cancer and bone metastases on initial diagnosis who were followed-up for at least one year. Multivariate Cox regression analysis showed that unmarried status and lung, liver, and brain metastases were significantly associated with reduced overall survival. No other significant risk or prognostic associations were found. CONCLUSIONS SEER data analysis showed that women with uterine cervical cancer had some standard risk factors associated with bone metastases, and with prognosis, but a heterogeneous group of risk factors was also present. The findings of this study may have clinical application in screening for bone metastases in women with cervical cancer.

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017).

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.

Hematopoietic stem cells as a tool for the treatment of glioblastoma multiforme.

Glioblastoma multiforme is an aggressive malignant brain tumor with terminal consequences. A primary reason for its resistance to treatment is associated with cancer stem cells (CSCs), of which there are currently no effective ways to destroy. It remains unclear what cancer cells become a target of stem cell migration, what the role of this process is in oncogenesis and what stem cell lines should be used in developing antitumor technologies. Using modern post­genome technologies, the present study investigated the migration of human stem cells to cancer cells in vitro, the comparative study of cell proteomes of certain stem cells (including CSCs) was conducted and stem cell migration in vivo was examined. Of all glioblastoma cells, CSCs have the stability to attract normal stem cells. Critical differences in cell proteomes allow the consideration of hematopoietic stem cells (HSCs) as an instrument for interaction with glioblastoma CSCs. Following injection into the bloodstream of animals with glioblastoma, the majority of HSCs migrated to the tumor­containing brain hemisphere and penetrated the tumor tissue. HSCs therefore are of potential use in the development of methods to target CSCs.

Precise Delivery Into Chronic Spinal Cord Injury Syringomyelic Cysts with Magnetic Nanoparticles MRI Visualization.

BACKGROUND: Traumatic spinal cord injury (SCI) often results in the deficiency of glia and neurons in cystic cavities. These syringomyelic cysts can prevent axonal regeneration and sprouting. Details of the mechanism of syringomyelic cyst formation are unknown and an effective treatment for overcoming syringomyelic cysts is not available. MATERIAL AND METHODS: Ten adult female Wistar rats underwent contusion SCI modeling resulting in syringomyelic cyst formation. A novel method for locating the cysts was developed and employed. MRI safe silver needles were inserted through the erector spinae of anesthetized rats to create a stable reference point. MRI images of the rodent spine were taken with the needles in situ. This information was used to accurately locate the cyst and determine the 3-dimensional entry point coordinates for nanoparticle delivery. Nanoparticles were injected into the cyst during a primary injection of 8 ul and a secondary injection of 8 ul, to prove the procedure can be accurately repeated. RESULTS: None of the rats died intra- or post-operatively. The syringomyelic cysts were accurately located with the 3-dimensional entry point coordinates. After nanoparticle delivery twice into each rat, the visualized syringomyelic cyst volume significantly decreased from 5.71±0.21 mm3 to 3.23±0.364 mm3 and to 1.48±0.722 mm3. CONCLUSIONS: The present study describes a novel strategy for precise nanoparticle delivery into a syringomyelic cyst, using measurements obtained from MRI images. This strategy may aid in developing a new method for studying chronic spinal cord injury and a novel treatment for syringomyelic cysts.

Effectiveness of repeated transplantations of hematopoietic stem cells in spinal cord injury.

AIM: To evaluate the short and long-term effects of the complex cell therapy of 202 cases of spinal cord injury (SCI). METHODS: The main arm included 202 cases of SCI and the control arm included 20 SCI cases. For the therapy the hematopoietic stem cells (HSCs) and progenitor cells (PCs) were mobilized to peripheral blood by 8 subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for 4 d and are harvested at day 5. The cells were administered to the main arm intrathecally every 3 mo for a long term (3-5 years) according to the internal research protocol international medical institute of tissue engineering. Magnetic resonance imaging of the site of injury and urodynamic tests were performed every 6 mo. Motor evoked potentials (MEP), somatosensory evoked potentials (SSEP) were evaluated every 3 mo. The patients were evaluated with american spianl injury association (ASIA) index, functional independence measure index, the Medical Research Council Scale, the International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92) and specifically developed scales. The function of bladder was evaluated by a specifically developed clinical scale. The long-term clinical outcomes were assessed for the SCI patients who received no less than 20 intrathecal transplantations of HSCs and hematopoietic precursors (HPs). RESULTS: The restoration of neurologic deficit after HSCs and HPs transplantations was proved stable and evident in 57.4% of the cases. In 42.6% cases no neurologic improvement has been observed. In 50% of the cases the motor restoration began after the first transplantation, which is confirmed in average by 9.9 points improvement in neurologic impairment as compared to the baseline (P < 0.05). Repair of the urinary system was observed in 47.7% of the cases. The sensitivity improved from baseline 124.3 points to 138.4 after the first and to 153.5 points after the second transplantations of HSCs and HPs (P < 0.05, between the stages of research). The evaluation with ASIA index demonstrated regress of neurologic symptoms in 23 cases. Motor progress was also assessed with the ISCISCI-92 motor and sensory scores, and the data coincided with those received with the specifically developed scale. The number of the patients with the signs of locomotive repair was 56.9%. No life threatening complications or adverse effects have been observed. CONCLUSION: The method is safe, effective and considerably improves the life quality of SCI patients. The therapy is approved for clinical use as the treatment of choice.