The Use of Stem Cells as a Potential Treatment Method for Selected Neurodegenerative Diseases: Review.

Stem cells have been the subject of research for years due to their enormous therapeutic potential. Most neurological diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are incurable or very difficult to treat. Therefore new therapies are sought in which autologous stem cells are used. They are often the patient's only hope for recovery or slowing down the progress of the disease symptoms. The most important conclusions arise after analyzing the literature on the use of stem cells in neurodegenerative diseases. The effectiveness of MSC cell therapy has been confirmed in ALS and HD therapy. MSC cells slow down ALS progression and show early promising signs of efficacy. In HD, they reduced huntingtin (Htt) aggregation and stimulation of endogenous neurogenesis. MS therapy with hematopoietic stem cells (HSCs) inducted significant recalibration of pro-inflammatory and immunoregulatory components of the immune system. iPSC cells allow for accurate PD modeling. They are patient-specific and therefore minimize the risk of immune rejection and, in long-term observation, did not form any tumors in the brain. Extracellular vesicles derived from bone marrow mesenchymal stromal cells (BM-MSC-EVs) and Human adipose-derived stromal/stem cells (hASCs) cells are widely used to treat AD. Due to the reduction of Aß42 deposits and increasing the survival of neurons, they improve memory and learning abilities. Despite many animal models and clinical trial studies, cell therapy still needs to be refined to increase its effectiveness in the human body.

Xanthine oxidoreductase activity in platelet-poor and rich plasma as a oxidative stress indicator in patients required renal replacement therapy.

BACKGROUND: Xanthine oxidoreductase (XOR) is a hydroxylase enzyme involved in the metabolism of purines. XOR activity can vary: the homodimer protein can be converted into two different isoforms XD (antioxidant) and XO (prooxidant). Oxidative stress and inflammation that accompanying chronic kidney disease (CKD), dialysis, and kidney transplantation, resulted in platelet activation. Present study aimed to determine the influence of applied renal replacement therapy on xanthine oxidoreductase and its isoforms activity. MATERIALS AND METHODS: The study group consisted of 117 patients, divided into 4 groups: hemodialysis - 30 patients, peritoneal dialysis - 30 patients, kidney transplant patients - 27 and conservative treatment - 30 patients. The control group consisted of 30 healthy volunteers. RESULTS: Significant differences were found in XOR activity in platelet-poor plasma (PPP) within the groups studied (p = 0.001). There was a relationship between the type of renal replacement therapy of all oxidoreductase isoforms in PPP (p < 0.001 all isoforms) and XD (p = 0.008), XO (p < 0.001) in platelet rich-plasma (PRP). A relationship was observed between the activity of all oxidoreductase isoforms in PPP and PRP, and the type of renal replacement therapy and the duration of dialysis and the age of patients. The cause of chronic kidney disease was also reflected differences in XD and XO activity in PPP. CONCLUSIONS: The type of renal replacement therapy used in CKD patients, age of patients, duration of dialysis, CKD causes, and stage of progression significantly affect the activity of XOR and its isoforms.

Effect of renal replacement therapy on selected arachidonic acid derivatives concentration.

BACKGROUND: Platelet activation is an important side effect of dialysis, resulted in a subsequent release of arachidonic acid (AA) from activated platelets. AA is involved in many pathologic conditions, such as inflammation, asthma, cancer, diabetes, hypertension, and the pathogenesis of kidney disease. The aim of this study was to define whether the dialysis type affects the concentration of AA derivatives in patients with chronic kidney disease. METHODS: 117 patients were qualified to the study group. Based on the type of renal replacement therapy, patients were divided into the following groups: hemodialysis (HD A - before/HD B - after hemodialysis), peritoneal dialysis (PD), kidney transplant patients (TE - before/TE A - after transplantation) and conservative treatment (CT) (30; 30; 27; 30 patients, respectively). The control group consisted of 30 healthy volunteers (NK). The ELISA methods were used to measure the concentrations of TXB2, 5-HETE, 12-HETE, and 15-HETE in the blood serum. RESULTS: Renal replacement therapy significantly influences the concentration of TXB2 (mean ± SD [ng/mL]: HD A- 34.6 ± 9; HD B- 28.3 ± 15.2; PD- 28.3 ± 15.2; CT- 34.2 ± 8.0; TE- 36.7 ± 42.9; TE A- 27.9 ± 8.8; NK- 19.6 ± 15; p = 0.010), 5-HETE (mean ± SD [ng/mL]: HD A- 284.2 ± 428.4; HD B- 304.8 ± 516.2; PD - 530.0 ± 553.3; CT- 318.7 ± 366.0; TE- 525.6 ± 358.0; TE A - 409.8 ± 377.1; NK 838.1 ± 497.8; p < 0.001) and 15-HETE (HD A-18.1 ± 8.7; HD B- 42.2 ± 14; PD - 36.3 ± 13.8; CT- 33.7 ± 14.0; TE- 19.5 ± 10.2; TE A - 34.4 ± 16.3; NK 22.2 ± 17.8; p < 0,001). There was a significant relationship between the type of renal replacement therapy and the duration of dialysis, and the concentration of TXB2, 12-HETE acid, and 15-HETE. CONCLUSIONS: The type of renal replacement therapy significantly affects the concentration of AA derivatives. Peritoneal dialysis is the best method of dialysis, taking into account the concentration of arachidonic acid derivatives.

Associations between plasma lysophospholipids concentrations, chronic kidney disease and the type of renal replacement therapy.

BACKGROUND: Lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) are bioactive lysophospholipids involved in the pathogenesis of renal diseases, especially the renal fibrosis. Plasma LPC concentrations in chronic kidney disease (CKD) patients are lower or similar to those observed in control groups, but less is known about the LPA concentrations. The main aim of the study was the analysis of associations of chronic kidney disease and renal replacement therapy with the plasma LPA concentrations. We have also analyzed the relationship between the plasma concentrations of LPA and LPC. MATERIAL AND METHODS: Study group consisted of 110 patients with CKD in stages G3-G5 according to the KDIGO guidelines and was divided into four subgroups: treated conservatively (CT, 30 patients), on hemodialysis (HD, 30 patients), on peritoneal dialysis (PD, 30 patients) and renal transplant recipients (RT, 20 patients). In HD the blood was collected immediately before (HD D1) and after the dialysis (HD D2). In RT the blood was collected immediately before (RT D1) and 3-14 days after the transplantation (RT D2). The control group (Con) consisted of 50 healthy volunteers. Plasma concentrations of LPA and LPC were measured using enzyme-linked immunosorbent assays. RESULTS: In CT, PD and RT D2 plasma concentrations of LPA were significantly higher, compared to Con. In HD, LPA levels did not differ compared to Con and they were significantly lower compared to PD (HD D1 and HD D2), RT D2 (HD D1 and HD D2) and CT (HD D1). However, in most of patients concentrations of LPA were within the range of reference values established in healthy volunteers. Concentrations of LPC were significantly lower in almost all patients subgroups, compared to Con, except in PD. There were no significant correlations between plasma concentrations of LPA and LPC in any of patients subgroups. CONCLUSIONS: Presence of CKD is associated with increased plasma LPA levels and the hemodialysis therapy reduces this influence. However, only in a small percentage of patients with CKD, LPA concentrations are out of the reference range, which makes LPA not useful as a diagnostic marker for CKD. Further studies are needed to confirm and explain observed relationships.

Proteomic and lipidomic biomarkers in the diagnosis and progression of inflammatory bowel disease - a review.

PURPOSE: There is an increasing prevalence of inflammatory bowel disease (IBD) and to date, no effective treatment has been developed and the exact etiology of this disease remains unknown. Nevertheless, a growing number of proteomic and lipidomic studies have identified certain proteins and lipids which can be used successfully in patients to improve diagnoses and monitoring of treatment. EXPERIMENTAL DESIGN: We have focused on the applications of proteins and lipids for IBD diagnostics, including differentiation of Crohn's disease (CD) and ulcerative colitis (UC), treatment monitoring, monitoring of clinical state, likelihood of relapse, and their potential for novel targeted treatments. RESULTS: Analysis of protein and lipid profiles can: improve the availability and use of diagnostic markers; improve understanding of the pathomechanisms of IBD, for example, several studies have implicated platelet dysfunction (PF4), autoimmune responses (granzyme B, perforin), and abnormal metabolism (arachidonic acid pathways); aid in monitoring patient health; and improve therapeutics (experimental phosphatidylcholine therapy has been shown to result in an improvement in intestinal condition). CONCLUSIONS: Despite the enormous progress of proteomics and lipidomics in recent years and the development of new technologies, further research is needed to select some of the most sensitive and specific markers applicable in diagnosing and treating IBD.

Applications of the regenerative capacity of platelets in modern medicine.

Platelets produce platelet growth factors such as PDGF, IGF-1, EGF-, HGF, TGFß, bFGF, and VEGF, which are crucial in regulating all stages of the wound healing process. The source of these substances is platelet-rich plasma (PRP). Over the past five decades, the interest and use of the regenerative properties of platelets have increased significantly in many different fields of medicine around the world. PRP and PRF plate preparations are used in: 1. Dentistry (they reduce bleeding, facilitate and accelerate soft tissue healing and bone regeneration - FGF 2, IGF-1, IGF-2, TGF-ß1, and PDGF); 2. Sports medicine - IGF-1, IGF-2, TGF-ß, VEGF, PDGF and bFGF, EGF); 3. dermatology and cosmetology (treatment of alopecia, hair reconstruction - FGF-7, HGF, acne scars, skin rejuvenation and regeneration, treatment of chronic and poorly healing wounds, burns, and acquired vitiligo); 4. Gynecology and reproductive medicine (treatment of infertility, erectile dysfunction - PDGF-ß, TGF-ß, IGF-1, in sexual dysfunction - PDGF, in vaginal atrophy); 5 Ophthalmology (in the healing of corneal epithelial wounds, in the treatment of dormant corneal ulcers, dry eye syndrome and the reconstruction of the corneal surface; 6. Neurology (regeneration of neurons, pain alleviation, and clinical symptoms - TGF-ß 1, IGF-1, PDGF, VEGF) and FGF). Platelet-rich plasma therapy is a very interesting alternative and complement to traditional methods of treatment. However, the potential for using platelets is still not fully understood. The composition of platelet-rich plasma depends on many factors that may affect its use's efficacy and clinical benefits. Further research is necessary to standardize PRP delivery's preparation procedures and methods for a specific disease entity or clinical case.

Importance of oxidative stress in the pathogenesis, diagnosis, and monitoring of patients with neuropsychiatric disorders, a review.

Oxidative stress is defined as the persistent imbalance between the activity of toxic reactive forms of both oxygen and nitrogen and the antioxidant defense. In low concentrations, they are essential for the proper functioning of the body. Still, their excessive amount contributes to the damage of the biomolecules, consequently leading to various pathologies of the organism. Due to the lipid-rich brain structure, enormous oxygen consumption, and the lack of a sufficient antioxidant barrier make it highly susceptible to oxidative imbalance. Hence, oxidative stress has been linked to various psychiatric disorders. These diseases include all behavioral, emotional, and cognitive abnormalities associated with a significant impediment to social life. Each of the diseases in question: Alzheimer's disease, schizophrenia, depression, and bipolar disorder, is characterized by excessive oxidative stress. Considerable damages to DNA, RNA, proteins, lipids, and mitochondrial dysfunction, are observed. All conditions show increased lipid peroxidation, which appears to be typical of psychiatric disorders because the brain contains large amounts of these types of molecules. In addition, numerous abnormalities in the antioxidant defense are noted, but the results of studies on the activity of antioxidant enzymes differ significantly. The most promising biomarkers seem to be GSH in Alzheimer's disease as an early-stage marker of the disease and thioredoxin in schizophrenia as a marker for therapy monitoring. Data from the literature are consistent with the decrease in antioxidants such as vitamin C, E, uric acid, albumin, etc. Despite these numerous inconsistencies, it seems that oxidative stress is present in the course of psychiatric diseases. Still, it cannot be conclusively determined whether it is the direct cause of development, a consequence of other abnormalities at the biochemical or molecular level, or the result of the disease itself.

Activity of erythrocyte antioxidant enzymes in healthy women depends on age, BMI, physical activity, and diet.

INTRODUCTION: Antioxidant enzymes protect the human body against the harmful effects of oxidative stress. The activity of antioxidant enzymes changes with age and depends on dietary nutrients such as fats and vitamins, which can have a significant impact on minimizing or exacerbating oxidative stress. AIM: To examine the effect of age, BMI, diet, physical activity, and smoking status on the activity of erythrocyte antioxidant enzymes catalase, glutathione reductase, glutathione peroxidase glutathione S-transferase, superoxide dismutase, and glutathione concentrations in healthy women. MATERIAL AND METHODS: This study included 98 healthy women aged between 20 and 65 years. All women underwent anthropometric tests: body weight, height, hip, and waist circumference. Antioxidant activity in erythrocytes was measured by spectrophotometric methods. RESULTS: Catalase activity increased significantly with age (p < 0.001), while superoxide dismutase activities and glutathione decreased with age (p = 0.008, p = 0.023, respectively). Women with a lower BMI (emaciation) had higher superoxide dismutase activity than those in the first degree of obesity (p = 0.009). CONCLUSIONS: (1) Increased catalase activity with age may signify a large amount of hydrogen peroxide resulting from malfunctioning antioxidant systems in old age. (2) A decline in superoxide dismutase activity with age may indicate inactivation of this enzyme, inappropriate SOD function in the presence of excessive amounts of hydrogen peroxide, and glycation of superoxide dismutase molecules. (3) A negative correlation between superoxide dismutase activity and the BMI index may indicate a decreased enzymatic activity in obese people.

Are antioxidant enzymes essential markers in the diagnosis and monitoring of cancer patients - A review.

Reactive oxygen species (ROS) play a significant role in human cells. Excessive ROS production damages important macromolecules such as nucleic acids and can initiate and develop the carcinogenesis process. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and xanthine oxidoreductase (XOR) are responsible for maintaining the balance between the functions of free radical formation and eliminating their excessive amounts. Based on the analyzed literature, the following conclusions can be made: 1. Antioxidant enzymes activity are important for diagnosing neoplastic diseases such as non-small-cell lung cancer, bladder cancer, ovarian cancer, and colon cancer. 2. Non-small-cell lung cancer is usually characterized by decreased SOD and CAT activity and increased glutathione GST activity. Lowered SOD, CAT, and GPx activity is characteristic of bladder cancer. XOR, CAT, SOD and GPx expression is decreased in patients with ovarian cancer. Colorectal cancer is characterized by increased MnSOD expression (in vitro studies) and SOD expression while CAT, GPx, and GR are decreased (in vivo study). 3. SOD, CAT, and XOR are promising prognostic markers in cancer of the lung, bladder, ovarian, and colon.

Regenerative potential of platelets in patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is a systemic disease affecting many organs. Progression of renal failure aggravates ongoing inflammation and increases oxidative stress. In the final stage of CKD, it is necessary to use renal replacement therapy. A side effect of dialysis therapy is the synthesis of proinflammatory factors and increased oxidative stress, which activates platelets and immune cells. AIM OF THE STUDY: To determine the regenerative potential of platelets in patients with CKD based on the analysis of the relationships between substances with potential regenerative action, as well as analysis of the influence of the type of renal replacement therapy used on regeneration of platelets. MATERIALS AND METHODS: The study group consisted of 117 patients. Based on the type of therapy used, patients were divided into four groups: hemodialysis, peritoneal dialysis, kidney transplant patients, and conservative treatment (30, 30, 27, and 30 patients). The control group consisted of 30 healthy volunteers. The concentrations of IGF-1, TGF-ß, and PDGF-B in the blood serum were measured by ELISA methods. RESULTS: It was shown that renal replacement therapy significantly influences the concentration of platelet growth factors (IGF-1: p = 0.025 and PDGF-B: p = 0.012). There was a relationship between the type of renal replacement therapy and the duration of dialysis, and the concentration of IGF-1, PDGF-B (p < 0.00001, p < 0.001). CONCLUSIONS: The type of renal replacement therapy has a different effect on the concentration of platelet-derived growth factors IGF-1 and PDGF-B. PD patients had the highest concentrations of all growth factors, and this may be due to the presence of inflammation induced by dialysis-related advanced end-products of glycosylation (AGE).