Fractionation of Carlina acaulis L. Root Methanolic Extract as a Promising Path towards New Formulations against Bacillus cereus and Methicillin-Resistant Staphylococcus aureus.

The root of Carlina acaulis L. has been widely used in traditional medicine for its antimicrobial properties. In this study, the fractionation of methanol extract from the root was conducted. Four fractions (A, B, C, and D) were obtained and tested against a range of bacteria and fungi. The results showed promising antibacterial activity, especially against Bacillus cereus, where the minimal inhibitory concentration (MIC) was determined to be equal to 0.08 mg/mL and 0.16 mg/mL for heptane (fraction B) and ethyl acetate (fraction C), respectively. In the case of the methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 strain, the same fractions yielded higher MIC values (2.5 and 5.0 mg/mL, respectively). This was accompanied by a lack of apparent cytotoxicity to normal human BJ foreskin fibroblasts, enterocytes derived from CaCo2 cells, and zebrafish embryos. Further analyses revealed the presence of bioactive chlorogenic acids in the fractionated extract, especially in the ethyl acetate fraction (C). These findings support the traditional use of the root from C. acaulis and pave the way for the development of new formulations for treating bacterial infections. This was further evaluated in a proof-of-concept experiment where fraction C was used in the ointment formulation, which maintained high antimicrobial activity against MRSA and displayed low toxicity towards cultured fibroblasts.

Can cannabidiol have an analgesic effect?

BACKGROUND: Cannabis, more commonly known as marijuana or hemp, has been used for centuries to treat various conditions. Cannabis contains two main components cannabidiol (CBD) and tetrahydrocannabinol (THC). CBD, unlike THC, is devoid of psychoactive effects and is well tolerated by the human body but has no direct effect on the receptors of the endocannabid system, despite the lack of action on the receptors of the endocannabid system. OBJECTIVES AND METHODS: We have prepared a literature review based on the latest available literature regarding the analgesic effects of CBD. CBD has a wide range of effects on the human body. In this study, we will present the potential mechanisms responsible for the analgesic effect of CBD. To the best of our knowledge, this is the first review to explore the analgesic mechanisms of CBD. RESULTS AND CONCLUSION: The analgesic effect of CBD is complex and still being researched. CBD models the perception of pain by acting on G protein-coupled receptors. Another group of receptors that CBD acts on are serotonergic receptors. The effect of CBD on an enzyme of potential importance in the production of inflammatory factors such as cyclooxygenases and lipoxygenases has also been confirmed. The presented potential mechanisms of CBD's analgesic effect are currently being extensively studied.

Melanin-The Éminence Grise of Melanoma and Parkinson's Disease Development.

A common feature of Parkinson's disease (PD) and melanoma is their starting points being based on cells capable of converting tyrosine into melanin. Melanocytes produce two types of melanin: eumelanin and pheomelanin. These dyes are designed to protect epidermal cells from the harmful effects of UV radiation. Neurones of the substantia nigra, which degenerate during PD, produce neuromelanin, the physiological role of which is not fully explained. This article discusses the potential role of melanins in the pathogenesis of both diseases. Melanins, due to their ability to accumulate toxic substances, may become their sources over time. The use of glutathione for the synthesis of pheomelanins and neuromelanins may reduce the antioxidant capacity of cells, leading to an excessive synthesis of free radicals. This study also tested the hypothesis that certain drugs used in the treatment of PD (L-DOPA, MAO-B and COMT inhibitors, and amantadine), aimed at increasing dopamine concentration, could potentially contribute to the development of melanoma. The role and properties of melanins should continue to be researched. Whether excessive melanin synthesis or its accumulation in the extracellular space may be factors initiating the development of diseases remains an open question.

The influence of silver nanoparticles on the process of epithelial transition in the context of cancer metastases.

BACKGROUND: Exposure to nanoparticles (NPs) can occur in a variety of occupational situations. Ultrafine particles of natural and anthropological origin toxicity has been described in epidemiological studies. Meanwhile, the risks associated with NPs exposure are not comprehensively assessed. A wide spectrum of NPs toxicity has been demonstrated, mainly through the induction of oxidative stress and inflammatory mediators. Among the newly described mechanisms of NPs toxicity is the induction of fibrosis via the epithelial-mesenchymal transition (EMT), which is also a key mechanism of cancer metastasis. The effect of NPs on EMT in the context of metastasis has not been sufficiently described so far, and the results of studies do not allow for the formulation of unambiguous conclusions. Therefore, the aim of the work was to determine the biological activity of silver NPs against MDA-MB-436 triple-negative breast cancer cells. MATERIAL AND METHODS: Exposure to nanoparticles (NPs) can occur in a variety of occupational situations. Ultrafine particles of natural and anthropological origin toxicity has been described in epidemiological studies. Meanwhile, the risks associated with NPs exposure are not comprehensively assessed. A wide spectrum of NPs toxicity has been demonstrated, mainly through the induction of oxidative stress and inflammatory mediators. Among the newly described mechanisms of NPs toxicity is the induction of fibrosis via the epithelial-mesenchymal transition (EMT), which is also a key mechanism of cancer metastasis. The effect of NPs on EMT in the context of metastasis has not been sufficiently described so far, and the results of studies do not allow for the formulation of unambiguous conclusions. Therefore, the aim of the work was to determine the biological activity of silver NPs against MDA-MB-436 triple-negative breast cancer cells. RESULTS: Silver nanoparticles (AgNPs) cause a statistically significant increase in relative expression of all tested mesenchymal EMT markers - cadherin 2, vimentin, matrix metalloproteinase 2 and matrix metalloproteinase 9. At the same time, reduction of epithelial cadherin 1 expression was observed. The level of MDA-MB-436 migration and TGF-beta 1 secretion was slighty increased in AgNPs-treated cells, with no influence on invasion potential. CONCLUSIONS: Potentially prometastatic effect of AgNPs encourages further work on the safety of nanomaterials. Med Pr Work Health Saf. 2023;74(6):541-8.

Exposure to Chlorpyrifos Alters Proliferation, Differentiation and Fatty Acid Uptake in 3T3-L1 Cells.

Organophosphorus pesticides (OPs) are important factors in the etiology of many diseases, including obesity and type 2 diabetes mellitus. The aim of this study was to investigate the effect of a representative of OPs, chlorpyrifos (CPF), on viability, proliferation, differentiation, and fatty acid uptake in 3T3-L1 cells. The effect of CPF exposure on preadipocyte proliferation was examined by the MTT, NR, and BrdU assays. The impact of CPF exposure on the differentiation of preadipocytes into mature adipocytes was evaluated by Oil Red O staining and RT-qPCR. The effect of CPF on free fatty acid uptake in adipocytes was assessed with the fluorescent dye BODIPY. Our experiments demonstrated that exposure to CPF decreased the viability of 3T3-L1 cells; however, it was increased when the cells were exposed to low concentrations of the pesticide. Exposure to CPF inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. CPF exposure resulted in decreased lipid accumulation, accompanied by down-regulation of the two key transcription factors in adipogenesis: C/EBPα and PPARγ. Exposure to CPF increased basal free fatty acid uptake in fully differentiated adipocytes but decreased this uptake when CPF was added during the differentiation process. Increased free fatty acid accumulation in fully differentiated adipocytes may suggest that CPF leads to adipocyte hypertrophy, one of the mechanisms leading to obesity, particularly in adults. It can therefore be concluded that CPF may disturb the activity of preadipocytes and adipocytes, although the role of this pesticide in the development of obesity requires further research.

Can cannabidiol (CBD) help with low back pain?

INTRODUCTION AND OBJECTIVE: Low back pain (LBP) is a major cause of disability and the main reason why individual patients need medical attention. Pharmacological treatment options for LBP are limited and are often associated with serious side-effects. This makes it necessary to search for new painkillers. One potential therapeutic agent is cannabidiol (CDB). Cannabidiol and tetrahydrocannabinol are the most researched components of cannabis, the plant more commonly known as marijuana or hemp. To the best of our knowledge, this is the first narrative review of the effects of CBD alone on acute and chronic back pain. REVIEW METHODS: Based on the guidelines provided by the Primary Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), the PubMed/ MEDLINE database was used to identify articles for analysis from the last 30 years. Due to the limited number of studies on this topic, all types of studies that met the inclusion criteria were included. After analysis, 10 studies were included in this review. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Currently, the use of medical marijuana continues to increase and the Food and Drug Administration (FDA) has already approved four cannabis-based drugs. Cannabidiol (CBD) is a relatively safe substance for humans and generally well tolerated. It is a substance that is easily available and often taken by patients with LBP. SUMMARY: Evidence for the effectiveness of CBD in the treatment of acute low back pain is lacking. There was only one clinical trial conducted in the Emergency Department that showed no superiority of CBD over placebo in acute LBP. The majority of studies concern chronic rather than acute LBP. Although most of the results suggest a beneficial effect of cannabinoids in relieving chronic LBP, hard evidence is lacking. Rigorous randomized controlled trials are needed.

Can Bee Venom Be Used as Anticancer Agent in Modern Medicine?

Honey bee venom in its composition contains many biologically active peptides and enzymes that are effective in the fight against diseases of various etiologies. The history of the use of bee venom for medicinal purposes dates back thousands of years. There are many reports in the literature on the pharmacological properties of bee venom and/or its main components, e.g., anti-arthritic, anti-inflammatory, anti-microbial or neuroprotective properties. In addition, both crude venom and melittin exhibit cytotoxic activity against a wide range of tumor cells, with significant anti-metastatic activity in pre-clinical studies. Due to the constantly increasing incidence of cancer, the development of new therapeutic strategies in oncology is a particular challenge for modern medicine. A review paper discusses the various properties of bee venom with an emphasis on its anticancer properties. For this purpose, the PubMed database was searched, and publications related to "bee", "venom", "cancer" from the last 10 years were selected.

Esketamine and Psilocybin-The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review.

This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment-psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those substances as novel antidepressant agents. The PubMed/MEDLINE database was used to identify articles for systematic review, using the following search terms: (depression) AND (psilocybin) OR (ketamine). From 617 items, only 12 articles were obtained in the final analyses. Three articles were devoted to psilocybin in depression treatment and nine to esketamine. In most studies, esketamine showed a significant reduction in both depressive symptoms and suicidal ideation shortly after intake and after a month of treatment compared to baseline and to standard-of-care antidepressant agents. Psilocybin's antidepressive effects occurred one day after intake and after 6-7 weeks of treatment and were maintained for up to 6 or 8 months of follow-up. One study indicated that psilocybin's effects are comparable with and may be superior to escitalopram treatment. Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and, after overcoming some limitations, may be considered as novel antidepressant agents in future.

Carlina oxide inhibits the interaction of SARS-CoV-2 S glycoprotein with angiotensin-converting enzyme 2.

Carlina acaulis plant is a potential target for the industrial production of phytochemicals that display applicability in pharmacy and medicine. The dry roots of C. acaulis contain up to 2 % of essential oil, the main component (up to 99 %) of which is carlina oxide [2-(3-phenylprop-1-ynyl)furan]. This compound shows multidirectional biological activity, including antibacterial and antifungal properties. Here, we evaluated the capacity of carlina oxide to inhibit the interaction between SARS-CoV-2 and its human receptor in vitro and in silico. A bioluminescent immunoassay was used to study the interaction between the receptor binding domain (RBD) of viral spike protein and the human angiotensin-converting enzyme 2 (ACE2), which serves as a receptor for viral entry. A dose-effect relationship was demonstrated, and a concentration of carlina oxide causing half-maximal inhibition (IC50) of the RBD:ACE2 interaction was determined to be equal to 234.2 µg/mL. Molecular docking suggested the presence of carlina oxide binding sites within the RBD and at the interface between RBD and ACE2. Finally, this study expands the list of potential applications of C. acaulis as a crop species.

Antiproliferative Properties of Triterpenoids by ECIS Method-A New Promising Approach in Anticancer Studies?

Electric cell-substrate impedance sensing is an advanced in vitro impedance measuring system which uses alternating current to determine behavior of cells in physiological conditions. In this study, we used the abovementioned method for checking the anticancer activities of betulin and betulinic acid, which are some of the most commonly found triterpenes in nature. In our experiment, the threshold concentrations of betulin required to elicit antiproliferative effects, verified by MTT and LDH release methods, were 7.8 µM for breast cancer (T47D), 9.5 µM for lung carcinoma (A549), and 21.3 µM for normal epithelial cells (Vero). The ECIS results revealed the great potential of betulin and betulinic acid's antitumor properties and their maintenance of cytotoxic substances to the breast cancer T47D line. Moreover, both substances showed a negligible toxic effect on healthy epithelial cells (Vero). Our investigation showed that the ECIS method is a proper alternative to the currently used assay for testing in vitro anticancer activity of compounds, and that it should thus be introduced in cellular routine research. It is also a valuable tool for live-monitoring changes in the morphology and physiology of cells, which translates into the accurate development of anticancer therapies.

Bee Venom Effect on Glioblastoma Cells Viability and Gelatinase Secretion.

BACKGROUND: The involvement of MMP-2 and MMP-9 in the pathogenesis of various kinds of cancers including glioblastoma is well documented. The evaluation of the anticancer potential of honey bee (Apis mellifera) venom (BV) consisting of the inhibition of MMP-2 and MMP-9 secretion in a glioblastoma cell culture model was the aim of the study. METHODS: 8-MG-BA and GAMG human primary glioblastoma cell lines vs. HT-22 mouse hippocampal neuronal cells were applied for the study. The BV dose (0.5, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, and 5.0 µg/ml) and time-dependent (24, 48, 72 h) cytotoxicity was evaluated with the tetrazolium-based colorimetric assay (MTT test). MMP-2 and MMP-9 activities in the cell culture medium under different BV concentrations were determined by gelatin zymography. RESULTS: A dose and time-dependent BV effect on cytotoxicity of both glioblastoma cell lines and hippocampus line was observed. The weakest, but statistically important effect was exerted by BV on HT-22 cells. The greatest cytotoxic effect of BV was observed on the 8-MG-BA line, where a statistically significant reduction in viability was observed at the lowest BV dose and the shortest incubation time. The reduction of both gelatinases secretion was observed at 8-MG-BA and GAMG lines without significant effect of HT-22 cell line. CONCLUSION: In vitro studies indicate that BV has both cytotoxic and inhibitory effects on the secretion of MMP-2 and MMP-9 in selected lines of glioma, suggesting anticancer properties of BV.

Osteoarthritis of the knee - biochemical aspect of applied therapies: a review.

The most prevalent form of arthritis is osteoarthritis (OA) of the knee, which is characterized by a degeneration of articular cartilage resulting in the development of osteophytes, or bone spurs. Main goals of OA treatment are to reduce pain, slow the disease progression, and improve joint function and the quality of life. The purpose of this study was to verify all the therapies recommended by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) from the biochemical point of view. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesis of eicosanoids, whereas paracetamol prevents the production of prostaglandin (PG) by interacting with peroxidase (POX) site of the prostaglandin H2 synthase complex. Tramadol is an opioid that has a dual mechanism of action: it binds to the µ-opioid receptor and it inhibits serotonin and adrenaline. Corticosteroids, which are also prescribed for OA pain, inhibit the activity of phospholipase A2 and block the synthesis of arachidonate-derived eicosanoids. Symptomatic slow-acting drugs for osteoarthritis (SYSADOA) are drugs that are well tolerated by patients and help to restore proteoglycan matrix of the cartilage. These drugs include compounds that naturally build articular cartilage. The articular cartilage, as well as the bone located around the cartilage, are destroyed as osteoarthritis progresses. Thus, bisphosphonates, commonly used in the treatment of osteoporosis, were evaluated as potential therapy. However, there is no official recommendation for their use in therapy. The aim of the study was to analyze the biochemical mechanisms of principal drugs used for the treatment of knee OA. Therefore, a narrative review summarizing the current knowledge regarding the applied therapies was prepared.

Alterations in Kynurenine and NAD+ Salvage Pathways during the Successful Treatment of Inflammatory Bowel Disease Suggest HCAR3 and NNMT as Potential Drug Targets.

A meta-analysis of publicly available transcriptomic datasets was performed to identify metabolic pathways profoundly implicated in the progression and treatment of inflammatory bowel disease (IBD). The analysis revealed that genes involved in tryptophan (Trp) metabolism are upregulated in Crohn's disease (CD) and ulcerative colitis (UC) and return to baseline after successful treatment with infliximab. Microarray and mRNAseq profiles from multiple experiments confirmed that enzymes responsible for Trp degradation via the kynurenine pathway (IDO1, KYNU, IL4I1, KMO, and TDO2), receptor of Trp metabolites (HCAR3), and enzymes catalyzing NAD+ turnover (NAMPT, NNMT, PARP9, CD38) were synchronously coregulated in IBD, but not in intestinal malignancies. The modeling of Trp metabolite fluxes in IBD indicated that changes in gene expression shifted intestinal Trp metabolism from the synthesis of 5-hydroxytryptamine (5HT, serotonin) towards the kynurenine pathway. Based on pathway modeling, this manifested in a decline in mucosal Trp and elevated kynurenine (Kyn) levels, and fueled the production of downstream metabolites, including quinolinate, a substrate for de novo NAD+ synthesis. Interestingly, IBD-dependent alterations in Trp metabolites were normalized in infliximab responders, but not in non-responders. Transcriptomic reconstruction of the NAD+ pathway revealed an increased salvage biosynthesis and utilization of NAD+ in IBD, which normalized in patients successfully treated with infliximab. Treatment-related changes in NAD+ levels correlated with shifts in nicotinamide N-methyltransferase (NNMT) expression. This enzyme helps to maintain a high level of NAD+-dependent proinflammatory signaling by removing excess inhibitory nicotinamide (Nam) from the system. Our analysis highlights the prevalent deregulation of kynurenine and NAD+ biosynthetic pathways in IBD and gives new impetus for conducting an in-depth examination of uncovered phenomena in clinical studies.

The influence of erythropoietin on apoptosis and fibrosis in the early phase of chronic pancreatitis in rats.

INTRODUCTION: Chronic pancreatitis (CP) is a continuing, inflammatory process of the pancreas, characterised by irreversible morphological changes. The identification of pancreatic stellate cells resulted in the development of research on the pathogenesis of CP. Erythropoietin (Epo) regulates the interaction between apoptosis and inflammation of the brain, kidney, and heart muscle. Erythropoietin receptors were also found in the pancreas, in particular on the islet cells. Our objective was to evaluate the influence of Epo on fibrosis and apoptosis in experimental CP. MATERIAL AND METHODS: The experiments were performed on 48 male Wistar rats (250-350 g). The animals were divided into six equal groups (I - control, II - chronic cerulein - induced pancreatitis, III - 1 ml of Epo sc, IV - 0.5 ml of Epo sc, V - CP treated with 1 ml Epo, VI - CP treated with 0.5 ml Epo). The blood for gelatinases and pancreata for the morphological examinations and immunohistochemistry were collected. RESULTS: A slight reduction of interstitial oedema and less severe fibrosis were noticed in the groups treated with Epo. Reduced expression of caspase-3 and α-actin, and a lack of Bcl-2 expression were observed in areas with inflammation. There was no expression of caspase-9 observed in all groups. There were no statistically significant differences between the groups in the activity of gelatinases. CONCLUSIONS: Erythropoietin seems to have the effect of reducing fibrosis and apoptosis in an experimental model of CP.

Evaluation of Antioxidative Mechanisms In Vitro and Triterpenes Composition of Extracts from Silver Birch (Betula pendula Roth) and Black Birch (Betula obscura Kotula) Barks by FT-IR and HPLC-PDA.

Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.

The role of matrix metalloproteinases in pathogenesis of human bladder cancer.

Matrix metalloproteinases (MMPs) play an important role in many physiological and pathological processes, including neoplastic processes. They belong to a group of enzymes called endopeptidases and have the ability to hydrolyze all proteins in the extracellular matrix (ECM). They are produced in most connective tissue cells, macrophages, leukocytes, endothelial cells, microglial cells and in cancer cells. Neoplastic diseases are one of the main causes of death in Poland and in the world, therefore learning about the process of carcinogenesis seems to be particularly important. The process of carcinogenesis is currently widely studied and MMPs play one of the key roles in the development of cancer. They do this by regulating local tumor growth, stromal invasion, stimulating angiogenesis and metastasis formation. Bladder cancer is the 7th most common cancer in the male population and the 11th most common cancer in the world. In bladder cancer, most studies have been devoted to MMP-2 and MMP-9, that are enzymes responsible for the degradation of type IV collagen in the first place, which through the destruction of basement membranes and ECM, play an essential role in the tumor invasion process. Since bladder cancer is characterized by the ability to relapse, from the point of view of clinical practice it seems particularly important to develop a marker of early bladder tumor recurrence. MMPs detected in the urine and serum of patients with bladder cancer are potential factors that could play such a role.

Role of matrix metalloproteinases and their tissue inhibitors in the pathological mechanisms underlying maxillofacial cystic lesions.

Cystic lesions are considered to be one of the most common pathologies of the maxillofacial region, and matrix metalloproteinases (MMPs) may represent potential etiological factors. The aim of the present study was to elucidate the role of MMP-2 and MMP-9, and their endogenous tissue inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, respectively, in the pathogenesis of maxillofacial cystic lesions. A total of 25 patients diagnosed with radicular cysts (RCs; n=20), dentigerous cysts (n=3) and retention cysts (RtCs; n=7) were enrolled in the present study. Gelatin zymography was performed to assess the gelatinolytic activity of MMP-2 and MMP-9, and commercial ELISA kits were used to determine TIMP-1 and TIMP-2 concentrations. Gelatin zymography revealed the presence of both MMP-2 and MMP-9 in all types of samples analyzed. An increase in MMP-9 activity, TIMP-1 concentration and MMP-9/TIMP-1 ratio was observed in the fluid obtained from RCs compared with that obtained from RtCs. In conclusion, MMP-9 may be involved in the pathogenesis of RCs, whereas the activity of MMP-2 in the wall of RtCs was low, and this gelatinase did not appear to significantly affect the development of this type of lesion.

Chlorpyrifos alters expression of enzymes involved in vitamin D3 synthesis in skin cells.

Skin acts as a mechanical barrier between human body and environment. Epidermal cells are regularly exposed to many physiological and environmental stressors, such as pesticides, like chlorpyrifos (CPS). It is recognised that CPS may affect metabolism of other exo- and endogenous substances by affecting enzyme activity and expression. This study aims to investigate the effect of CPS on expression of CYP27A1, CYP27B1 and CYP24A1, the enzymes involved in synthesis and metabolism of vitamin D3, in human keratinocytes HaCaT and human fibroblasts BJ. Synthesis of vitamin D3 in cells was initiated by irradiating with UVB. Expression of CYP27A1, CYP27B1 and CYP24A1 was evaluated by RT-qPCR and Western blot. Our experiments revealed that expression of all tested cytochrome P450 isoforms in cells exposed to CPS changed significantly. Exposure of HaCaT keratinocytes to CPS decreased CYP27A1 mRNA levels, but increased CYP27B1 and CYP24A1 mRNA levels. This was confirmed at the protein level, except for the CYP27A1 expression. Outcome for the BJ cells was however less conclusive. Though exposure to CPS decreased CYP27A1 and CYP27B1 mRNA levels, at protein level increasing concentration of CPS and UVB intensity induced expression of CYP27A1 and CYP24A1. The expression of CYP27B1 isoform decreased in line with mRNA level. Nevertheless, it can be concluded that CPS may therefore interrupt vitamin D3 metabolism in skin cells, but further studies are required to better understand such mechanisms.

Activity of selected metalloproteinases in neurodegenerative diseases of the central nervous system as exemplified by dementia and schizophrenia. / Aktywnosc wybranych metaloproteinaz w chorobach neurodegeneracyjnych osrodkowego ukladu nerwowego na przykladzie otepienia i schizofrenii.

OBJECTIVES: The aim of the study was to determine and analyze the correlation between the concentrations of selected metalloproteinases and their inhibitors (TIMP-1 and TIMP-2) in patients with dementia and schizophrenia. METHODS: The concentration of two collagenases and metalloendopeptidase was determined in the study. The study included 29 patients with lateonset dementia, 25 patients with paranoid schizophrenia and 25 healthy controls who were age-matched with the study groups. Symptoms of dementia were evaluated using the Short Mental State Assessment Scale, whereas the symptoms of schizophrenia were assessed using the Positive and Negative Assessment Scale. Blood samples were collected from the participants and the concentrations of MMP-1, MMP7, MMP-13, TIMP-1, and TIMP-2 in the blood serum were evaluated using ELISA method. RESULTS: A two-fold increase in the concentration of MMP-1 and a slight increase in MMP-13 was observed in dementia patients compared to other groups, as well as a lower level of MMP-7 and TIMP-1 and a higher level of TIMP-2 compared to the control group. Patients with schizophreniashowed lower MMP-7 and higher TIMP-2 serum level compared to the controls. No differences in the concentration of MMP-1, MMP-13 and TIMP-1 levels were noticed. In people with late onset dementia an increase in collagenolytic activity was demonstrated. CONCLUSIONS: Increase in collagenolytic activity may indicate an increased remodeling within the central nervous system in late onset dementia. The differencein the fluctuation of the concentrations of the studied enzymes and their inhibitors in dementia and schizophrenia indicates their different involvement in the pathogenesis of these disorders.

Serum miR-210-3p can be used to differentiate between patients with pancreatic ductal adenocarcinoma and chronic pancreatitis.

Patients with chronic pancreatitis (CP) are at risk of developing pancreatic ductal adenocarcinoma (PDAC). To the best of our knowledge, there are no suitable non-invasive biomarkers for differentiation between CP and PDAC; however, potential molecular candidates include circulating miRNAs due to ease of extraction, their stability and tissue specificity. Therefore, the aim of the present study was to identify potential serum marker(s) that may be used for differentiating between CP and PDAC. In total, 77 patients were enrolled in the present study; 34 patients with CP, 26 patients with PDAC and a control group of 17 healthy individuals. Expression of miR-10b-5p, miR-106b-5p, miR-210-3p and miR-216a-5p in serum was determined by reverse transcription-quantitative PCR. Serum miRNA expression levels in patients with CP, PDAC and in the control group were compared. Routine biochemical blood parameters were determined and correlation analysis of these parameters with miRNA expression was performed. Expression of miR-210-3p was increased in the sera of patients with PDAC compared with the CP patients (P=0.015) and with the control group (P<0.001). MiR-106b-5p (P=0.056) and miR-10b-5p (P=0.080) were not significantly upregulated in patients with PDAC compared with those with CP. Analysis of miRNA expression in relation to laboratory blood parameters showed positive correlations between miR-210-3p with alkaline phosphatase (r=0.605; P=0.022) and with γ-glutamyltranspeptidase (r=0.529; P=0.029) in PDAC. The novel finding of the present study was that miR-10b-5p was positively correlated with C-reactive protein (r=0.429; P=0.047) in patients with PDAC and with carbohydrate antigen 19-9 (r=0.483; P=0.005) in CP. Based on the preliminary data obtained in the present study, it was concluded that miR-210-3p may be used as a non-invasive biomarker that can be used to distinguish between patients with PDAC and CP.