ROC analysis of selected matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in psoriatic patients.

INTRODUCTION: Psoriasis is a common, chronic inflammatory disease characterised by typical scaly skin lesions. The role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis and development of this condition have been repeatedly emphasised in available literature. AIM: ROC analysis of selected MMPs (MMP-2, MMP-3, MMP-9, MMP-12, TIMP-2) and TIMPs (TIMP-2, TIMP-3) in psoriasis patients. The area under the ROC curve (AUC) indicates the clinical usefulness of a biomarker and its diagnostic power. MATERIAL AND METHODS: Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were evaluated. Concentrations of MMPs and TIMPs were determined using the enzyme-linked immunosorbent assay (ELISA) while Psoriasis Area and Severity Index (PASI) was used to define disease advancement. RESULTS: In the total psoriasis patients group, the largest area under the ROC curve was obtained for TIMP-3. After the division of the total group based on disease severity, the highest AUC of all tested parameters was observed for patients with mild disease severity and subgroup Ia for TIMP-3, for subgroup Ib for MMP-12, and for individuals with moderate disease severity for MMP-2. The combined analysis of all tested parameters showed an increase in AUC values in the total group examined as well as in all groups of disease severity. CONCLUSIONS: These results indicate the usefulness and high diagnostic power of TIMP-3 in early detection of psoriasis. Additionally, the combination of all tested parameters appeared to be a valuable biomarker panel for the analysed disease.

[The plasma levels and diagnostic utility of matrix metalloproteinase-9 and CA 125 in cervical cancer patients]. / Ocena stezenia i przydatnosci diagnostycznej metaloproteinazy-9 i CA 125 w osoczu chorych na raka szyjki macicy.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, involved in the degradation of extracellular matrix components. The physiological function of MMP-9 is associated with regulation of immune processes, embryogenesis, reproduction and wound healing. MMP-9 also plays a critical role in tumor invasion, degrading the basement membrane, what is observed in different types of cancers: breast, gastrointestinal, and gynecological. AIM: The aim of this study was to investigate the plasma levels and diagnostic utility of MMP-9 and CA 125 in cervical cancer patients. MATERIALS AND METHODS: The study included 72 patients with cervical cancer and 24 healthy women. Plasma levels of the MMP- 9 was determined by enzyme-linked immunosorbent assay (ELISA) and CA 15-3 - by chemiluminescent microparticle immunoassay (CMIA). RESULTS: This studies have shown increase levels of MMP-9 and CA 125 in cervical cancer patients compared to health control group. In addition, the MMP-9 concentration increased with the clinical stage of tumor. The sensitivity and specificity of MMP-9, positive and negative predictive value, were higher or equal than CA 125, but this parameter can not be used as a single marker. Our studies of MMP-9 have shown a high utility to the exclusion of cancer, similarly to CA 125. The combined analysis of MMP-9 and CA 125 significantly increased the ability to diagnose a cervical cancer and the possibility exclusion of cancer. CONCLUSIONS: MMP-9 has shown the usefulness in the diagnosis of cervical cancer, but only in the combined analysis with CA 125, as a new diagnostic panel.

Influence of narrowband ultraviolet-B phototherapy on plasma concentration of matrix metalloproteinase-12 in psoriatic patients.

INTRODUCTION: Matrix metalloproteinase-12 (MMP-12) may play an important role in the pathogenesis and spread of psoriatic disease. AIM: To investigate plasma levels of the selected enzyme in plaque psoriasis patients before and after the course of narrowband UVB (NBUVB) therapy with respect to disease advancement. MATERIAL AND METHODS: The cohort included 49 patients suffering from plaque psoriasis, divided into groups according to severity of the disease. The control group consisted of 40 healthy volunteers. Plasma levels of MMP-12 were determined using immunoenzyme assay (ELISA), while the Psoriasis Area and Severity Index (PASI) was used to define disease advancement. RESULTS: The results have shown a significantly decreased plasma level of MMP-12 in the total psoriasis patient group compared to healthy individuals, declining with the increase in disease advancement. The NBUVB therapy caused a decrease in the concentration of the analyzed enzyme, but this change was not statistically significant in the total group of psoriatic patients, while a significant change was detected in patients with a mild advancement of the disease. CONCLUSIONS: Decreased synthesis of MMP-12 may lead to the stimulation of the epidermal angiogenesis process, which results in the appearance and spread of psoriatic scales. Based on the obtained results, macrophage metalloelastase seems to be a negatively reacting plasma biomarker of the studied disease.

[Anti-cancer properties epigallocatechin-gallate contained in green tea]. / Wlasciwosci antynowotworowe galusanu epigallokatechiny zawartego w zielonej herbacie.

Numerous in vivo and in vitro studies point to the possibility of using green tea's catechins in chemoprevention of cancer. Recent studies show the inhibitory effects of epigallocatechin gallate on the growth of existing tumors including breast cancer, skin cancer and gastrointestinal tract cancers. Another mode of action of biologically active compounds in green tea involves inhibiting the neoplastic process. All these mechanisms may be useful in prevention and inhibition of the cancer processes (initiation, promotion and progress) by the consumption of green tea. However, clinical studies show contradictory results. Several independent factors, such as the temperature of the beverage, the duration of consumption, the amount of consumed tea and the diet used by the analyzed group, have a decisive effect on the final effect of plant polyphenols on the process of carcinogenesis.  

History of autologous platelet-rich plasma: A short review.

BACKGROUND: Platelet-rich plasma (PRP) is a medical material with numerous applications. It produces particularly spectacular effects when applied in cosmetic dermatology. AIM: To illustrate the origin of the treatment. CONCLUSION: The therapy originates from transfusiology, where it is applied as a concentrate of platelets to treat trombocytopenia. PRP treatment is 70 years old and has an increasing number of applications. PRP holds particular promise for cosmetic dermatology.

Perception of smell of a perfume applied to the women skin in course of menstrual cycle.

INTRODUCTION: Perfumes are the cosmetics applied to the skin. Body odor has been shown to be attractive in the fertile days in non-user of contraception. However, contraception pill intake destroy cyclic attractiveness of odors. AIM: The aim was to test attractiveness and intensiveness of perfume applied to the female skin in course of menstrual cycle. MATERIAL AND METHODS: Diluted vanilla extract was applied on forearm of 18 women (9 women users of contraception and 9 non-users of contraception). Thirty minutes occlusion samples were collected and judged for its attractiveness and intensity by 25 men. Samples were collected at 1st, 8th, 14th, and 22nd day of cyclus. RESULTS: Attractiveness of smell of perfume in women, which use contraceptive was statistically significantly higher than in non-user. Furthermore, attractiveness of smell at 15th day of menstrual cycle was second best when perfume was applied in women, which use contraceptive. CONCLUSIONS: Perfume on the skin of women, which apply contraceptive, smell better than on non-contraceptive-user skin. Moreover, women body odor together with perfume is highly attractive in contraceptive-user in the middle of the cyclus.

Plasma Concentrations of Matrilysins MMP-7 and MMP-26 as Diagnostic Biomarkers in Breast Cancer.

Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are members of the MMPs group that show promise as potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the diagnostic utility of studied matrilysins in patients with BC. The study group consisted of 120 patients with BC, and the control group consisted of 40 subjects with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by enzyme-linked immunosorbent assay, and CA 15-3 by chemiluminescent microparticle immunoassay. Plasma levels of MMP-7 were significantly higher in the BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were highest in stages II and IV of the disease. The highest diagnostic sensitivity was observed in stages III and IV BC for the combination of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters combined in the BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) for the combination of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in stages III and IV. Individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of the disease. Study results indicate that MMP-7 could be used as an additional marker that would improve the diagnostic utility of CA 15-3 in early stages of BC. Therefore, the combined assessment of MMP-7 and MMP-26 with CA 15-3 might be useful in determining disease progression. Further studies are needed to evaluate whether matrilysins show promise as potential markers for improving the diagnosis of BC.

C-C motif chemokine ligand 5 and C-C chemokine receptor type 5: possible diagnostic application in breast cancer patients.

The chemokine CCL5 and its receptor CCR5 play important roles in cancer invasion and metastasis. Based on our knowledge, our results were the first that presented the diagnostic usefulness of CCL5 and CCR5 in breast cancer (BC) patients, based on receiver operating characteristic (ROC) curve analysis. We wished to examine further if CCL5 and CCR5 are appropriate to be applied as BC markers for early screening. Values of tested parameters in patients' plasma were determined by CMIA method (Chemiluminescent Microparticle Immunoassay, CA 15-3) as well as by ELISA method (Enzyme-Linked Immunosorbent Assay, CCL5 and CCR5). Levels of CCL5 in the plasma were markedly increased, while those of CCR5 were remarkably lower in BC patients when compared to the control groups. Moreover, higher levels of CCL5 in BC corresponded to advanced tumor stage, while the levels of CCR5 decreased with increasing the disease stage. CCL5 concentration was characterized by high sensitivity (SE) (68.04%) and high specificity (SP) (100.00%) in the BC patients. Results indicated that area under the curve (AUC) corresponding to CCL5 (0.8116) had a higher value than this corresponding to CA 15-3. The AUC value of CCL5 was significantly increased in the early phase of BC (stage I - 0.7089; stage II - 0.8313). The maximum range in the BC patients was observed for the combined analysis of the tested measurands with CA 15-3 (0.8335). In conclusion, our research indicates that examination of plasma CCL5 and CCR5 may be useful in BC diagnosis at the early stage of the disorder, especially when combined with CA 15-3.

Matrilysins and Stromelysins in Pathogenesis and Diagnostics of Cancers.

Matrix metalloproteinases (MMPs) are endopeptidases which are widely studied in terms of their role in the physiological and pathological processes in the organism. In this article, we consider usefulness of matrilysins and stromelysins in pathogenesis and diagnostic of the most common malignancies in the world, e.g., lung, breast, prostate, and colorectal cancers. In all of the mentioned cancers, matrilysins and stromelysins have a pivotal role in their development and also may have diagnostic utility. Influence to the cancerous process is connected with specific dependencies between these enzymes and components of the extracellular matrix (ECM), non-matrix components like cell surface components. All the information provided below allows to take a closer look at matrilysins and stromelysins and their functions in the cancer development.

Hygienic and cosmetic care habits in polish women during COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic influences a lot of aspects of human life. Particularly, hygienic habits are affected. OBJECTIVES: Changes in washing and cosmetic standards during the pandemic toward the past are in the focus of our interest. MATERIAL AND METHODS: The questionnaire study was conducted anonymously in 140 women. The examination concerned pre- and during-pandemic routine hygiene activities such as hands washing, hair washing, bathing, the use of disinfectants, and use of specific type of cosmetics. RESULTS AND DISCUSSION: Compared were data before and during pandemic. Responders declared increased handwashing and taking shower after coming back home and after using local city transportation. We found also that increased use of disinfectants during COVID-19 pandemic. In contrary to that, number of people washing their hair decreased slightly. Work documents that profile of used cosmetics was changed; increasing hand cream use and decreasing in makeup cosmetics. Nearly, half of the respondents declare that they will maintain new habits also after the pandemic has ended.

Possible Diagnostic Application of CXCL12 and CXCR4 as Tumor Markers in Breast Cancer Patients.

BACKGROUND/AIM: Chemokines are cytokines involved not only in inflammatory but also in inappropriate response of the immune system in breast cancer (BC) progression. We examined the diagnostic usefulness of CXCL12, CXCR4 and CA 15-3 in BC patients, based on ROC curve analysis. MATERIALS AND METHODS: The study group consisted of 100 patients with BC; the control group consisted of 35 women with benign breast disease and 35 healthy patients. The median concentration of chemokines was measured by ELISA and that of CA 15-3 by chemiluminescent microparticle immunoassay. RESULTS: The concentrations of CXCL12 and CXCR4 in the BC group were significantly higher than those in the control groups. The AUC value of CXCL12 (0.7502) was the highest of all the chemokines measured in the BC patients. CONCLUSION: There may be a link between CXCL12, CXCR4 and BC that can assist in the diagnosis, markedly when combined with CA 15-3.

Plasma Level of MMP-10 May Be a Prognostic Marker in Early Stages of Breast Cancer.

BACKGROUND: Stromelysins are potential breast cancer biomarkers. The aim of the study was to evaluate if plasma levels of selected metalloproteinases (MMPs) (stromelysin-1 (MMP-3) and stromelysin-10 (MMP-10)) and cancer antigen 15-3 (CA 15-3) used separately and in combination demonstrated diagnostic usefulness in breast cancer (BC). METHODS: The study group consisted of 120 patients with BC, while the control group included 40 patients with benign breast cancer and 40 healthy individuals. Concentrations of MMP-3 and MMP-10 were determined by enzyme-linked immunosorbent assay; CA 15-3 was determined by chemiluminescent microparticle immunoassay. RESULTS: In the group of patients with BC, the area under the curve (AUC) was significantly higher for all markers (except MMP-3) and all sets of markers. At the earliest disease stage, only MMP-10 had a significantly higher AUC (AUC = 0.8692, p < 0.001). Moreover, MMP-10 had the highest AUC (0.9166) among parameters tested separately. The highest AUC was observed for the combination of MMP-10 + CA 15-3 and MMP-3 + MMP-10 + CA 15-3 in line with disease progression (stage I 0.8884 and 0.8906, stage II 0.9244 and 0.9308, stages III + IV 0.9919 and 0.9944, respectively, p < 0.001 in all cases). CONCLUSIONS: The results suggest that MMP-10 could be a potential marker in early stages of BC. Moreover, plasma concentration of MMP-10 and MMP-3 in combination with CA 15-3 may improve diagnosis of this type of cancer.

Improvements in the perception of facial attractiveness following surgical aesthetic treatment; study based on online before and after photos.

BACKGROUND: Aesthetic surgery procedures such as lip augmentation, eyelid correction, face-lifting, or Botox treatment for lines and wrinkles are an important part of cosmetic surgery. OBJECTIVES: The aim of the study was to estimate improvement in appearance following plastic surgery using modern collective intelligence methods of validation. METHODS: A total of 108 photographs showing 54 patients prior to and following cosmetic surgery were downloaded from Internet web presentations of several unnamed plastic surgeons. The same number of photographs depicted each of the four investigated areas of treatment-26 lip enhancement, 26 blepharoplasty, 26 face-lift, 26 botulinum toxin injection. Attractiveness of depicted individuals was assessed by 167 observers. Each photograph was judged separately. RESULTS: Blepharoplasty produced the most remarkable improvement in attractiveness amounting to 32.79 (SD ± 26.35). Improvement following Botox treatment stood at 30.29 (SD ± 24.55), whereas face-lifting produces improvement of 28.70 (SD ± 22.76). Improvement following lip augmentation was estimated at 12.70 (SD ± 29.8). Highest Spearman's rank correlation coefficient was obtained for face-lift and Botox (0.24 and 0.22, respectively). CONCLUSIONS: Blepharoplasty, face-lifting, and Botox deliver a significant improvement in facial attractiveness. Additionally, face-lifting and Botox are distinguished by a high level of reproducibility. Our results indicate that lip augmentation is a treatment with a statistically significant, but less marked improvement in attractiveness.

Impact of face proportions on face attractiveness.

BACKGROUND: Proportions of face components appear to play a role in facial attractiveness. AIMS: The aim of the study was to establish the best proportions of face components in relation to whole face shape for facial attractiveness. METHODS: Only one face component (eye, nose, or lips) of a model in a series of photographs was altered using a computer program. Alterations consisted of size reduction or augmentation by 5% or 10%. Each photograph depicted a particular face component altered to either 90%, 95%, 100%, 105%, or 110% of its original size. Collages of photographs were shown to 167 individuals (male and female) for a fixed period of 7 seconds. Their task was to indicate the most attractive photograph of a model in a presented collage. RESULTS: In total, 48.1% of individuals preferred enhanced eyes both in males and females. We found that the preferred mean eye size in women was statistically significantly higher than that in men. In total, 64.8% of respondents preferred reduced nose proportions in women (27.5% found a reduction to 90% of the original size more attractive while 37.3% preferred a reduction to 95%). It was demonstrated that the preferred mean nose size was statistically significantly lower in females in comparison with males. Respondents expressed a greater preference for nose reduction in women in comparison with men. 38.4% of respondents (in regard to both male and female mouth) preferred reduced mouth. 40.7% of respondents preferred reduced mouth in the female model. CONCLUSIONS: Our work delivers statistically significant evidence that facial attractiveness increases together with the enlargement of the uncovered eye surface as well as the reduction in nose and lip size. Data were obtained using modern collective intelligence methods of validation. Written consent was obtained from all study participants.

Plasma Chemokine CCL2 and Its Receptor CCR2 Concentrations as Diagnostic Biomarkers for Breast Cancer Patients.

The aim of this study was to investigate plasma levels and applicability of CCL2, CCR2, and tumor marker CA 15-3 in breast cancer (BC) patients and in relation to the control groups: patients with benign breast tumor and healthy subjects. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay (ELISA) and CA 15-3 by Chemiluminescent Microparticle Immunoassay (CMIA). The median levels of CCL2 in entire group of BC were significantly higher compared to the control groups, similarly as median levels of CA 15-3. CCR2 is a negative marker whose levels were significantly lower in BC group compared to healthy women. The concentration of CCL2 in BC increases with advancing tumor stage, while a median level of CCR2 decreases with advancing stage. CCL2 showed the highest value of sensitivity (SE) (64.95%) in entire BC group and also in early stages of disease. The highest specificity (SP) was obtained by CA 15-3 (85.71%). The area under the ROC curve (AUC) of CCR2 (0.7304) was the largest of all the tested parameters (slightly lower than CA 15-3) in the entire BC group, but a maximum range was obtained for the combination of all tested parameters with CA 15-3 (0.8271). In early stages of BC the highest AUC of all tested parameters was observed in CCL2 or CCR2 (stage I: 0.6604 and 0.6564; respectively; stage II: 0.7768, respectively, for CCR2). The findings of this study suggest that there may be applicability of CCL2, CCR2 in diagnosis of BC patients, particularly in conjunction with CA 15-3.

Narrowband ultraviolet B light treatment changes plasma concentrations of MMP-3, MMP-9 and TIMP-3 in psoriatic patients.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are thought to be associated with the pathogenesis and spread of psoriatic disease. This study was designed to investigate the plasma levels of MMP-3, MMP-9 and TIMP-3 in plaque psoriasis patients prior to and following a course of ultraviolet B narrowband treatment with respect to disease advancement. METHODS: Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were evaluated. Concentrations of MMP-3, MMP-9 and TIMP-3 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index was used to define disease advancement. RESULTS: Plasma levels of MMP-3, MMP-9 and TIMP-3 were significantly elevated in psoriasis patients compared to healthy individuals. A course of ultraviolet B narrowband treatment resulted in a significant decline in the studied metalloproteinases. Furthermore, the concentration of selected tissue inhibitors was negatively correlated with baseline Psoriasis Area and Severity Index score. CONCLUSION: Our research highlights the meaningful role of MMP-3, MMP-9 and TIMP-3 in psoriasis pathogenesis and clearance of disease symptoms. Furthermore, plasma levels of the analyzed metalloproteinases seem to be a valuable psoriasis biomarker.

Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol.

AIM: The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. MATERIALS AND METHODS: Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA. Cell viability was examined using methyl thiazolyl tetrazolium (MTT) assay and NC-300 Nucleo-Counter. Imaging of the cells using a fluorescence microscope Pathway 855 was performed to measure FAK expression. RESULTS: Depending on the dosage, ethanol decreased cell viability and activated the process of apoptosis in human skin fibroblasts. HA prevented the negative influence of ethanol on cell viability and prevented apoptosis. The analysis of fluorescence imaging using BD Pathway 855 High-Content Bioimager showed the inhibition of FAK migration to the cell nucleus, depending on the increasing concentration of ethanol. CONCLUSION: This study proves that downregulation of signaling pathway of FAK is involved in ethanol-induced apoptosis in human skin fibroblasts. The work also indicates a protective influence of HA on FAK activity in human skin fibroblasts exposed to ethanol.

Therapy of psoriasis with narrowband ultraviolet-B light influences plasma concentrations of MMP-2 and TIMP-2 in patients.

BACKGROUND: Matrix metalloproteinases (MMPs), which show a significant ability to cleave the components of extracellular matrix, and tissue inhibitors of metalloproteinases (TIMPs), which slow down the activity of those enzymes, may be implicated in the pathogenesis and spread of psoriatic disease. This study aims to analyze plasma levels of MMP-2 and TIMP-2 in plaque psoriasis patients before and after the course of narrowband ultraviolet-B (NBUVB) therapy with respect to disease advancement. PATIENTS AND METHODS: A total of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were enrolled into the study. Plasma levels of MMP-2 and TIMP-2 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index (PASI) was used to define the disease advancement. RESULTS: The results showed increased plasma levels of MMP-2 and TIMP-2, but this change was significant only in case of MMP-2 in total psoriatic group compared to healthy subjects. Moreover, there was an increase in the concentrations of chosen factors with an increase in the severity of the disease. The NBUVB therapy causes a decline in the concentration of the analyzed enzyme and its inhibitor, although this change was statistically significant in the total psoriatic group only in case of MMP-2. There was also a positive correlation between MMP-2, TIMP-2, and PASI score value. CONCLUSION: Our study highlights a possible important role of MMP-2 in the activity of psoriasis and clearance of disease symptoms. Moreover, plasma MMP-2 seems to be a valuable psoriasis biomarker.

Hyaluronic acid abrogates ethanol-dependent inhibition of collagen biosynthesis in cultured human fibroblasts.

INTRODUCTION: The aim of the study was to evaluate the effect of ethanol on collagen biosynthesis in cultured human skin fibroblasts, and the role of hyaluronic acid (HA) in this process. Regarding the mechanism of ethanol action on human skin fibroblasts we investigated: expression of ß1 integrin and insulin-like growth factor 1 receptor (IGF-IR), signaling pathway protein expression: mitogen-activated protein kinases (MAPKs), protein kinase B (Akt), nuclear factor kappa B (NF-κB) transcription factor, cytotoxicity assay and apoptosis, metalloproteinase activity, as well as the influence of HA on these processes. MATERIALS AND METHODS: Collagen biosynthesis, activity of prolidase, DNA biosynthesis, and cytotoxicity were measured in confluent human skin fibroblast cultures that have been treated with 25, 50, and 100 mM ethanol and with ethanol and 500 µg/mL HA. Western blot analysis and zymography were performed to evaluate expression of collagen type I, ß1 integrin receptor, IGF-IR, NF-κB protein, phospho-Akt protein, kinase MAPK, caspase 9 activity, and matrix metalloproteinases (MMP-9 and MMP-2). RESULTS: Ethanol in a dose-dependent manner lead to the impairment of collagen biosynthesis in fibroblast cultures through decreasing prolidase activity and expression of ß1 integrin and IGF-IR. This was accompanied by an increased cytotoxicity, apoptosis and lowered expression of the signaling pathway proteins induced by ß1 integrin and IGF-IR, that is, MAPK (ERK1/2) kinases. The lowered amount of synthesized collagen and prolidase activity disturbance may also be due to the activation of NF-κB transcription factor, which inhibits collagen gene expression. It suggests that the decrease in fibroblast collagen production may be caused by the disturbance in its biosynthesis but not degradation. The application of HA has a protective effect on disturbances caused by the examined substances. It seems that regulatory mechanism of ethanol-induced collagen aberration take place at the level of collagen biosynthesis, since no effect of ethanol and HA was found on process of collagen degradation by MMP-2 and MMP-9. CONCLUSION: This study provides evidence that ethanol impairs collagen metabolism in human skin fibroblasts, leading to a significant decrease in the amount of produced protein. This mechanism probably is due to downregulation of prolidase activity, expression of ß1 integrin and IGF-IR receptors, and the signaling pathway proteins induced by these receptors.