Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer.

The aim of this review is to provide experimental evidence for the programmed-death activity of Ashwagandha (Withania somnifera) in the anti-cancer therapy of breast cancer. The literature search was conducted using online electronic databases (Google Scholar, PubMed, Scopus). Collection schedule data for the review article covered the years 2004-2024. Ashwagandha active substances, especially Withaferin A (WA), are the most promising anti-cancer compounds. WS exerts its effect on breast cancer cells by inducing programmed cell death, especially apoptosis, at the molecular level. Ashwagandha has been found to possess a potential for treating breast cancer, especially estrogen receptor/progesterone receptor (ER/PR)-positive and triple-negative breast cancer.

Do aluminum, boron, arsenic, cadmium, lipoperoxidation, and genetic polymorphism determine male fertility?

Male infertility is a world multifactorial problem modulated by environmental and genetic factors. Male aspects account for 20-50 % of infertility cases. Our results are unique because they treat the importance of components participating in the determination of male infertility (environmental and immunogenetic determinants, seminological analysis, lipoperoxidation, genetic determinants, role of aluminum, arsenic, cadmium and boron). We analyzed agents affecting male reproductive potential (aluminum, boron, cadmium, arsenic, lipid peroxidation, gene polymorphisms (MTHFRv.C677T (rs1801133) (chromosome-1) and IL-4v.C589T (rs2243250) (chromosome-5) in men with semen disorders (n=76) and with normozoospermia (n=87) from Central Poland. Polymorphisms of MTHFRv.C677T and IL-4v.C589T genes indirectly shape toxic metals concentration and lipoperoxidation but do not exert direct influence on male fertility disorders (monomorphism and lack of differences in genotypes frequency). Men with genotype TT or CC (IL-4v.C589T) show some differentiation in elements concentration and intensity of lipoperoxidation. Analysis of TT or CC (IL-4v.C589T) genotype brought correlations with B, Al, Cd, and lipoperoxidation (P<0.05) and suggesting that mentioned factors jointly shape male reproductive capability. Toxic metals may play an important role in shaping of men genetic polymorphisms, since Cd was identified as a factor increasing risk of qualification to infertile group, predisposing to fertility disorders. B, Al and Cd may be considered as important modulators of reproductive condition. However, lipoperoxidation as an isolated predictive parameter does not produce convincing results in male reproductive potential (higher MDA concentration in healthy men). Our results may be helpful in the diagnosis of male infertility, in the reduction of idiopathic cases of unknown origin and in implementation of targeted and more effective treatment (pharmacological, hormonal). Identification of environmental stressors and their correlations with fertility disorders can help to eliminate or reduce the impact of factors unfavorable to fertility. Our results highlight the importance of environmental and immunogenetic factors in shaping of defensive potential against destruction of spermatozoa and infer a role of oxidative stress in the induction of gene polymorphisms, affecting male fertility.

The Current State of Knowledge Regarding the Genetic Predisposition to Sports and Its Health Implications in the Context of the Redox Balance, Especially Antioxidant Capacity.

The significance of physical activity in sports is self-evident. However, its importance is becoming increasingly apparent in the context of public health. The constant desire to improve health and performance suggests looking at genetic predispositions. The knowledge of genes related to physical performance can be utilized initially in the training of athletes to assign them to the appropriate sport. In the field of medicine, this knowledge may be more effectively utilized in the prevention and treatment of cardiometabolic diseases. Physical exertion engages the entire organism, and at a basic physiological level, the organism's responses are primarily related to oxidant and antioxidant reactions due to intensified cellular respiration. Therefore, the modifications involve the body adjusting to the stresses, especially oxidative stress. The consequence of regular exercise is primarily an increase in antioxidant capacity. Among the genes considered, those that promote oxidative processes dominate, as they are associated with energy production during exercise. What is missing, however, is a look at the other side of the coin, which, in this case, is antioxidant processes and the genes associated with them. It has been demonstrated that antioxidant genes associated with increased physical performance do not always result in increased antioxidant capacity. Nevertheless, it seems that maintaining the oxidant-antioxidant balance is the most important thing in this regard.

Preliminary Report on the Influence of Acute Inflammation on Adiponectin Levels in Older Inpatients with Different Nutritional Status.

Inflammation can be triggered by a variety of factors, including pathogens, damaged cells, and toxic compounds. It is a biological response of the immune system, which can be successfully assessed in clinical practice using some molecular substances. Because adiponectin, a hormone released by adipose tissue, influences the development of inflammation, its evaluation as a potential measure of inflammation in clinical practice is justified. In the present contribution, statistical comparison of adiponectin concentration and selected molecular substances recognized in clinical practice as measures of inflammation were utilized to demonstrate whether adipose tissue hormones, as exemplified by adiponectin, have the potential to act as a measure of rapidly changing inflammation when monitoring older hospitalized patients in the course of bacterial infection. The study showed no statistically significant differences in adiponectin levels depending on the rapidly changing inflammatory response in its early stage. Interestingly, the concentration of adiponectin is statistically significantly higher in malnourished patients than in people with normal nutritional levels, assessed based on the MNA. According to the results obtained, adiponectin is not an effective measure of acute inflammation in clinical practice. However, it may serve as a biomarker of malnutrition in senile individuals.

Immunogenetic and Environmental Factors in Age-Related Macular Disease.

Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment.

The Role of Glutathione in Age-Related Macular Degeneration (AMD).

Age-related macular degeneration (AMD) is a chronic disease that usually develops in older people. Pathogenetic changes in this disease include anatomical and functional complexes. Harmful factors damage the retina and macula. These changes may lead to partial or total loss of vision. The disease can occur in two clinical forms: dry (the progression is slow and gentle) and exudative (wet-progression is acute and severe), which usually starts in the dry form; however, the coexistence of both forms is possible. The etiology of AMD is not fully understood, and the precise mechanisms of the development of this illness are still unknown. Extensive genetic studies have shown that AMD is a multi-factorial disease and that genetic determinants, along with external and internal environmental and metabolic-functional factors, are important risk factors. This article reviews the role of glutathione (GSH) enzymes engaged in maintaining the reduced form and polymorphism in glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase mu-1 (GSTM1) in the development of AMD. We only chose papers that confirmed the influence of the parameters on the development of AMD. Because GSH is the most important antioxidant in the eye, it is important to know the influence of the enzymes and genetic background to ensure an optimal level of glutathione concentration. Numerous studies have been conducted on how the glutathione system works till today. This paper presents the current state of knowledge about the changes in GSH, GST, GR, and GPx in AMD. GST studies clearly show increased activity in ill people, but for GPx, the results relating to activity are not so clear. Depending on the research, the results also suggest higher and lower GPx activity in patients with AMD. The analysis of polymorphisms in GST genes confirmed that mutations lead to weaker antioxidant barriers and may contribute to the development of AMD; unfortunately, a meta-analysis and some research did not confirm that connection. Unspecific results of many of the parameters that make up the glutathione system show many unknowns. It is so important to conduct further research to understand the exact mechanism of defense functions of glutathione against oxidative stress in the human eye.

Concentration of Selected Adipokines and Factors Regulating Carbohydrate Metabolism in Patients with Head and Neck Cancer in Respect to Their Body Mass Index.

Head and neck cancers (HNCs) are a group of tumors not common in European populations. So far, not much is known about the role of obesity, adipokines, glucose metabolism, and inflammation in the pathogenesis of HNC. The aim of the study was to determine the concentrations of ghrelin, omentin-1, adipsin, adiponectin, leptin, resistin, visfatin, glucagon, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), plasminogen activator inhibitor-1 (PAI-1), and gastric inhibitory peptide (GIP) in the blood serum of HNC patients depending on their body mass index (BMI). The study included 46 patients divided into two groups according to their BMI values: the normal BMI group (nBMI) included 23 patients with BMI < 25 kg/m2 and the increased BMI group (iBMI) included patients with BMI ≥ 25 kg/m2. A control group (CG) included 23 healthy people (BMI < 25 kg/m2). Statistically significant differences in the levels of adipsin, ghrelin, glucagon, PAI-1, and visfatin were shown between nBMI and CG. In the case of nBMI and iBMI, statistically significant differences were observed in the concentrations of adiponectin, C-peptide, ghrelin, GLP-1, insulin, leptin, omentin-1, PAI-1, resistin, and visfatin. The obtained results indicate a disruption of endocrine function of adipose tissue and impaired glucose metabolism in HNC. Obesity, which is not a typical risk factor for HNC, may aggravate the negative metabolic changes associated with this type of neoplasm. Ghrelin, visfatin, PAI-1, adipsin, and glucagon might be related to head and neck carcinogenesis. They seem to be promising directions for further research.

The Role of Oxidative Stress Enhanced by Adiposity in Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs), including cardiovascular disease (CVD), metabolic syndrome (MetS), and type 2 diabetes (T2D), are associated with increased morbidity and mortality. The growing prevalence of CVD is mostly attributed to the aging population and common occurrence of risk factors, such as high systolic blood pressure, elevated plasma glucose, and increased body mass index, which led to a global epidemic of obesity, MetS, and T2D. Oxidant-antioxidant balance disorders largely contribute to the pathogenesis and outcomes of CMDs, such as systemic essential hypertension, coronary artery disease, stroke, and MetS. Enhanced and disturbed generation of reactive oxygen species in excess adipose tissue during obesity may lead to increased oxidative stress. Understanding the interplay between adiposity, oxidative stress, and cardiometabolic risks can have translational impacts, leading to the identification of novel effective strategies for reducing the CMDs burden. The present review article is based on extant results from basic and clinical studies and specifically addresses the various aspects associated with oxidant-antioxidant balance disorders in the course of CMDs in subjects with excess adipose tissue accumulation. We aim at giving a comprehensive overview of existing knowledge, knowledge gaps, and future perspectives for further basic and clinical research. We provide insights into both the mechanisms and clinical implications of effects related to the interplay between adiposity and oxidative stress for treating and preventing CMDs. Future basic research and clinical trials are needed to further examine the mechanisms of adiposity-enhanced oxidative stress in CMDs and the efficacy of antioxidant therapies for reducing risk and improving outcome of patients with CMDs.

The Role of Selected Trace Elements in Oxidoreductive Homeostasis in Patients with Thyroid Diseases.

Impaired levels of selenium (Se), zinc (Zn), copper (Cu), iron (Fe), manganese (Mn) and iodine (I) in the organism may adversely affect the thyroid endocrine system. These trace elements play a role in the fight against oxidative stress as components of enzymes. Oxidative-antioxidant imbalance is considered a possible factor in many pathological conditions, including various thyroid diseases. In the available literature, there are few scientific studies showing a direct correlation of the effect of supplementation of trace elements on slowing down or preventing the occurrence of thyroid diseases in combination with the improvement of the antioxidant profile, or through the action of these elements as antioxidants. Among the available studies, it has been shown that an increase in lipid peroxidation levels and a decrease in the overall antioxidant defense status occur during such thyroid diseases as thyroid cancer, Hashimoto's thyroiditis and dysthyroidism. In studies in which trace elements were supplemented, the following were observed: a decrease in the level of malondialdehyde after supplementation with Zn during hypothyroidism and reduction in the malondialdehyde level after Se supplementation with a simultaneous increase in the total activity status and activity of antioxidant defense enzymes in the course of autoimmune thyroiditis. This systematic review aimed to present the current state of knowledge about the relationship between trace elements and thyroid diseases in terms of oxidoreductive homeostasis.

The Influence of Single Whole-Body Cryostimulation on Cytokine Status and Oxidative Stress Biomarkers during Exhaustive Physical Effort: A Crossover Study.

The purpose of the study was to assess the impact of single whole-body cryostimulation (WBC) preceding submaximal exercise on oxidative stress and inflammatory biomarkers in professional, male athletes. The subjects (n = 32, age 25.2 ± 37) were exposed to low temperatures (-130 °C) in a cryochamber and then participated in 40 min of exercise (85% HRmax). Two weeks afterwards, the control exercise (without WBC) was performed. Blood samples were taken before the start of the study, immediately after the WBC procedure, after exercise preceded by WBC (WBC exercise) and after exercise without WBC. It has been shown that catalase activity after WBC exercise is lower in comparison with activity after control exercise. The interleukin 1ß (IL-1-1ß) level was higher after control exercise than after WBC exercise, after the WBC procedure and before the start of the study (p < 0.01). The WBC procedure interleukin 6 (IL-6) level was compared with the baseline level (p < 0.01). The level of Il-6 was higher both after WBC exercise and after control exercise compared with the level recorded after the WBC procedure (p < 0.05). Several significant correlations between the studied parameters were shown. In conclusion, the changes in the cytokine concentration in the athletes' blood confirm that body exposition to extremely low temperatures before exercise could regulate the inflammatory reaction course and secretion of cytokines during exercise. A single session of WBC in the case of well-trained, male athletes does not significantly affect the level of oxidative stress indicators.

The Impact of Diclofenac Gel on Ion Transport in the Rabbit (Oryctolagus cuniculus) Skin: An In Vitro Study.

Diclofenac belongs to the non-steroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory effects. Diclofenac administration on the skin may be associated with the appearance of side effects. The study aimed to evaluate the impact of diclofenac gel on transepithelial electrophysiological parameters of the 55 rabbit abdomen skin specimens. The electric parameters were analyzed in a modified Ussing chamber. The resistance (R) of the skin specimens treated with diclofenac gel significantly increased, which could be related to the reduction in the water content in intercellular spaces and, consequently, tighter adhesion of the cells. Increased electric potential (PD) was also observed in the skin specimens treated with diclofenac gel. The increase in both R and PD measured under stationary conditions was most likely caused by a transient and reversible increase in sodium ion transport, as the R and PD values decreased after the diclofenac gel was washed away. However, diclofenac gel did not affect the maximum and minimum PDs measured during stimulations. Therefore, it seems that diclofenac gel does not affect the perception of stimuli in the model system used.

Application of Multivariate Adaptive Regression Splines (MARSplines) for Predicting Antitumor Activity of Anthrapyrazole Derivatives.

An approach using multivariate adaptive regression splines (MARSplines) was applied for quantitative structure-activity relationship studies of the antitumor activity of anthrapyrazoles. At the first stage, the structures of anthrapyrazole derivatives were subjected to geometrical optimization by the AM1 method using the Polak-Ribiere algorithm. In the next step, a data set of 73 compounds was coded over 2500 calculated molecular descriptors. It was shown that fourteen independent variables appearing in the statistically significant MARS model (i.e., descriptors belonging to 3D-MoRSE, 2D autocorrelations, GETAWAY, burden eigenvalues and RDF descriptors), significantly affect the antitumor activity of anthrapyrazole compounds. The study confirmed the benefit of using a modern machine learning algorithm, since the high predictive power of the obtained model had proven to be useful for the prediction of antitumor activity against murine leukemia L1210. It could certainly be considered as a tool for predicting activity against other cancer cell lines.

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics.

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients' outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes.

Selected Mediators of Inflammation in Patients with Acute Ischemic Stroke.

During a stroke, a series of biochemical and metabolic changes occur which eventually lead to the death of cells by necrosis or apoptosis. This is a multi-stage process involving oxidative stress and an inflammatory response from the first signs of occlusion of a blood vessel until the late stages of regeneration and healing of ischemic tissues. The purpose of the research was to assess the concentration of pro-inflammatory cytokines IL-6 and TNF-α in the blood serum of patients with ischemic stroke (AIS) and to investigate their role as new markers in predicting functional prognosis after thrombolytic therapy. The researches have shown that the concentrations of the measured biomarkers were higher compared to the control group. Serum levels of IL-6 and THF-α before the initiation of intravenous thrombolysis were lower in the subgroup of patients with a favourable functional result (mRS: 0−2 pts) compared to the group of patients with an unfavourable functional result (mRS: 3−6 pts). A positive correlation was found between the concentration of IL-6 and TNF-α in patients with AIS during <4.5 h and on one day after the onset of stroke, which means that the concentration of IL-6 increases with the increase in TNF-α concentration. It has also been shown that higher levels of IL-6 in the acute phase of stroke and on the first and seventh days, and TNF-α during onset, were associated with poorer early and late prognosis in patients treated with intravenous thrombolysis. A relationship was found between the level of IL-6 and TNF-α in the subacute AIS and the severity of the neurological deficit. It has been shown that the investigated biomarkers may be a prognostic factor in the treatment of thrombolytic AIS.

Assessment of the concentration of selected metalloproteinases (MMP-2, MMP-3, MMP-9 and MMP-13) in patients with ulcers as a complication of type 2 diabetes.

Introduction: Impaired chronic wound healing is a great challenge for modern medicine. This process causes ulceration especially in the course of diseases such as type II diabetes mellitus. Aim: This study assesses the concentration of selected matrix metalloproteinases in the example of metalloproteinase 2, 3, 9, 13 in patients with impaired healing of chronic wounds as a complication of type 2 diabetes. Material and methods: Nineteen people took part in the assessment of wound healing in patients with type 2 diabetes. The control group consisted of 21 healthy people. In the blood serum the concentration of MMP-2, MMP-3, MMP-9 and MMP-13 was determined. Results: The concentrations of MMP-2 and MMP-3 in the group of patients with ulcers were significantly higher (61% and 84% accordingly) compared to those in the control group without chronic wounds. No statistically significant differences in MMP-9 and MMP-13 concentrations were observed between the study and control groups. Conclusions: The increase in MMP-2 concentration, which is particularly active in the degradation of type IV collagen, which is the main component of the basal membranes, in patients with type 2 diabetes may impede and delay the healing of chronic wounds and thus contribute to the intensification of vascular complications. In turn, the increase in MMP-3 concentration, which plays a significant role in vascular diseases, in patients with type 2 diabetes may lead to intensification of atherosclerotic changes involving the arteries of the lower extremities and ulceration.

A Novel N-Tert-Butyl Derivatives of Pseudothiohydantoin as Potential Target in Anti-Cancer Therapy.

Tumors are currently more and more common all over the world; hence, attempts are being made to explain the biochemical processes underlying their development. The search for new therapeutic pathways, with particular emphasis on enzymatic activity and its modulation regulating the level of glucocorticosteroids, may contribute to the development and implementation of new therapeutic options in the treatment process. Our research focuses on understanding the role of 11ß-HSD1 and 11ß-HSD2 as factors involved in the differentiation and proliferation of neoplastic cells. In this work, we obtained the 9 novel N-tert-butyl substituted 2-aminothiazol-4(5H)-one (pseudothiohydantoin) derivatives, differing in the substituents at C-5 of the thiazole ring. The inhibitory activity and selectivity of the obtained derivatives in relation to two isoforms of 11ß-HSD were evaluated. The highest inhibitory activity for 11ß-HSD1 showed compound 3h, containing the cyclohexane substituent at the 5-position of the thiazole ring in the spiro system (82.5% at a conc. 10 µM). On the other hand, the derivative 3f with the phenyl substituent at C-5 showed the highest inhibition of 11ß-HSD2 (53.57% at a conc. of 10 µM). A low selectivity in the inhibition of 11ß-HSD2 was observed but, unlike 18ß-glycyrrhetinic acid, these compounds were found to inhibit the activity of 11ß-HSD2 to a greater extent than 11ß-HSD1, which makes them attractive for further research on their anti-cancer activity.

Redox State and Lysosomal Activity in Women with Ovarian Cancer with Tumor Recurrence and Multiorgan Metastasis.

The aim of the study is to evaluate oxidant-antioxidant balance as well as lysosomal and anti-protease activities in ovarian cancer since it has been emphasized that the crucial inducing factor of carcinogenesis may be reactive oxygen/nitrogen species or, more precisely, oxidative stress-induced inflammation. The study involved 15 women with ovarian cancer, aged 59.9 ± 7.8 years, and 9 healthy women aged 56.3 ± 4.3 years (controls). The study material was venous blood collected from fasting subjects. In erythrocytes, the activities of superoxide dismutase, glutathione peroxidase, and catalase, as well as concentrations of conjugated dienes (CDs) and thiobarbituric acid reactive substances (TBARS), were investigated. CD, TBARS, and vitamins A and E plasma concentrations were also determined. Moreover, total antioxidant capacity and concentrations of 4-hydroxynonenal adducts and 8-iso-prostaglandin F2α, as well as activities of acid phosphatase, arylsulfatase, cathepsin D, and α1-antitrypsin, were studied in serum. The vitamin E and 8-iso-prostaglandin F2α concentrations as well as arylsulfatase activity were lower in the women with cancer compared to the controls (p = 0.006, p = 0.03, p = 0.001, respectively). In contrast, cathepsin D activity was lower in the controls (p = 0.04). In the peripheral blood of the women with cancer, oxidant-antioxidant and lysosomal disturbances were observed.

Microbial Synthesis of (S)- and (R)-Benzoin in Enantioselective Desymmetrization and Deracemization Catalyzed by Aureobasidium pullulans Included in the Blossom Protect™ Agent.

In this study, we examined the Aureobasidium pullulans strains DSM 14940 and DSM 14941 included in the Blossom Protect™ agent to be used in the bioreduction reaction of a symmetrical dicarbonyl compound. Both chiral 2-hydroxy-1,2-diphenylethanone antipodes were obtained with a high enantiomeric purity. Mild conditions (phosphate buffer [pH 7.0, 7.2], 30 °C) were successfully employed in the synthesis of (S)-benzoin using two different methodologies: benzyl desymmetrization and rac-benzoin deracemization. Bioreduction carried out with higher reagent concentrations, lower pH values and prolonged reaction time, and in the presence of additives, enabled enrichment of the reaction mixture with (R)-benzoin. The described procedure is a potentially useful tool in the synthesis of chiral building blocks with a defined configuration in a simple and economical process with a lower environmental impact, enabling one-pot biotransformation.

Concentration of proinflammatory cytokines in patients with ulcers as a complication of type 2 diabetes mellitus.

INTRODUCTION: Difficult healing of chronic wounds is a serious problem for modern medicine. It leads to ulceration, especially in conditions such as diabetic foot syndrome or chronic venous insufficiency. This may be a result of chemical, physical, thermal or biological factors, among others. Analysis of mediators and molecular factors released by the abovementioned structure helps to better understand the mechanism of healing of chronic wounds and the formation of ulcers. AIM: To assess excretion of selected cytokines in patients with ulcerations as a complication of diabetes mellitus type 2. MATERIAL AND METHODS: Seventeen patients aged 68-87 took part in the assessment of wound healing in patients with ulceration in the course of diabetes mellitus type 2. The control group consisted of 21 healthy patients aged 32-62. In the blood serum bFGF, TNF-α, IL-4, TGF-ß1, TGF-ß2 and TGF-ß3 were determined. RESULTS: A significant difference was found in bFGF, IL-4, TGF-ß1, TGF-ß2, and TGF-ß3 levels. Concentration of bFGF was 12% lower in patients with ulcers than in the non-ulcerated control group (p = 0.013). IL-4 concentration was 46% lower in patients with ulcers than in the non-ulcerated control group (p = 0.002). TGF-ß1, TGF-ß2 and TGF-ß3 concentrations were also lower in the group of patients with ulcers compared to those in the non-ulcerated control group. CONCLUSIONS: Reduced concentrations of selected cytokines and growth factors may indicate abnormal activity of the cells that secrete them and affect the healing process of chronic wounds, hindering and delaying the healing process.

Effect of chemical structure of benzofuran derivatives and reaction conditions on enantioselective properties of Aureobasidium pullulans microorganism contained in Boni Protect antifungal agent.

Bioorganic asymmetric reduction of carbonyl compounds is one of the most important fundamental and practical reactions for producing chiral alcohols. The stereoselective bioreduction of prochiral ketones of benzofuran derivatives in the presence of yeast-like fungus Aureobasidium pullulans contained in the antifungal Boni Protect agent was studied. Biotransformations were carried out under moderate conditions in an aqueous and two-phase system and without multiplication of the bioreagent. Despite similar chemical structure, each of the used ketone has been reduced with varying efficiency and selectivity. One of the reasons for these results is the presence of a whole set of oxidoreductases in A. pullulans cells that are sensitive to the smallest changes in the structure of prochiral substrate. The unsymmetrical methyl ketones were biotransformed with the highest selectivity. Aureobasidium pullulans microorganism is less effective in the reduction of unsymmetrical halomethyl ketones. The presence of a heteroatom in the alkyl group significantly decreases the selectivity of the process. Finally, as a result of the preferred hydride ion transfer from the dihydropyridine ring of the cofactor to the carbonyl double bond on the re side, secondary alcohols of the S and R configuration were obtained with moderate to high enantioselectivity (55-99%).