The rtPA increases MMP-9 activity in serum during ischaemic stroke

Background and purpose To find the relationship between rtPA treatment vs. MMP-9 activity, MMP-3, and TIMP-1 serum levels related to patients’ neurological status during acute ischaemic stroke (IS). Material and methods 35 IS patients were enrolled. 14 of them underwent thrombolytic therapy with Actylise (rtPA group). The serum samples were obtained at 3 time-points for rtPA group (time-point 0: 1st–4th hour of stroke; time-point 1 – immediately after rtPA administration; time-point 2 – on day 5–7 from stroke onset). Remaining patients had venous blood collection at two time-points: time-point 1 – 5th–10th hour of stroke and time-point 2 – on day 5–7 of stroke. MMP-9 was analyzed with gelatin zymography, MMP-3 and TIMP-1 serum levels were analyzed with ELISA method. NIHSS improvement ratio (IR) was calculated as a difference between NIHSS score at the admission and discharge of patient. Results The active form of MMP-9 (86kDa) was not observed in any analyzed samples. Total MMP-9 activity was significantly elevated at time-point 1 in rtPA group in comparison with non-rtPA group. MMP-3 serum level significantly decreased during rtPA administration in comparison with non-rtPA group and it was restored at time-point 2. MMP-3 negatively correlated with IR values (p=0.06). Conclusions Thrombolysis applied for IS treatment increases MMP-9 activity in serum, however, rtPA does not facilitate the conversion of pro-MMP-9 into the active form. Our results also suggest the involvement of MMP-3 to the biochemical processes occurring during acute phase of IS

Zirconium-based metal–organic frameworks as acriflavine cargos in the battle against coronaviruses : a theoretical and experimental approach

[Image: see text] In this study, we present a complementary approach for obtaining an effective drug, based on acriflavine (ACF) and zirconium-based metal–organic frameworks (MOFs), against SARS-CoV-2. The experimental results showed that acriflavine inhibits the interaction between viral receptor-binding domain (RBD) of spike protein and angiotensin converting enzyme-2 (ACE2) host receptor driving viral cell entry. The prepared ACF@MOF composites exhibited low (MOF-808 and UiO-66) and high (UiO-67 and NU-1000) ACF loadings. The drug release profiles from prepared composites showed different release kinetics depending on the local pore environment. The long-term ACF release with the effective antiviral ACF concentration was observed for all studied ACF@MOF composites. The density functional theory (DFT) calculations allowed us to determine that π–π stacking together with electrostatic interaction plays an important role in acriflavine adsorption and release from ACF@MOF composites. The molecular docking results have shown that acriflavine interacts with several possible binding sites within the RBD and binding site at the RBD/ACE2 interface. The cytotoxicity and ecotoxicity results have confirmed that the prepared ACF@MOF composites may be considered potentially safe for living organisms. The complementary experimental and theoretical results presented in this study have confirmed that the ACF@MOF composites may be considered a potential candidate for the COVID-19 treatment, which makes them good candidates for clinical trials

Silver is not equal to silver : synthesis and evaluation of silver nanoparticles with low biological activity, and their incorporation into C12C_{12}alanine-based hydrogel

A new type of silver nanoparticles (AgNPs) was prepared and comprehensively studied. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses indicated that 24 nm AgNPs with narrow size distribution were obtained while Z-potential confirms their good stability. The composites of the obtained AgNPs with nontoxic-nature-inspired hydrogel were formed upon cooling of the aqueous solution AgNPs and C12Ala. The thermal gravimetric analysis (TGA) and the differential scanning calorimetry (DSC) do not show significant shifts in the characteristic temperature peaks for pure and silver-enriched gels, which indicates that AgNPs do not strongly interact with C12Ala fibers, which was also confirmed by SEM. Both AgNPs alone and in the assembly with the gelator C12Ala were almost biologically passive against bacteria, fungus, cancer, and nontumor human cells, as well as zebra-fish embryos. These studies proved that the new inactive AgNPs-doped hydrogels have potential for the application in therapy as drug delivery media

Health-promoting properties of compounds derived from Capsicum sp. A review

This article presents multidirectional effects of capsaicin and its natural derivatives as well as natural and synthetic analogs in term of their therapeutic properties. Active agents present in various Capsicum genus plants exert analgesic, anti-inflammatory, antibacterial, antioxidant and gastroprotective effects. Furthermore, capsaicin positively influences the metabolism of lipids. Numerous research show that capsaicinoids inhibit proliferation and migration process of cancer cells, what makes them molecules of high interest in oncology. Among broad range of positive activities, we have focused only on those properties that have already found application in medicine or seemed to be the most probably used in the near future. Even if in low or single doses this compound has been reported successful in numerous therapies, the negative consequences of high doses or prolonged administration is also discussed in the review

Influence of chronic stress in pregnant women on development of eating habits in their offspring in postnatal life

Współcześnie stres stał się integralną częścią życia ludzkiego i towarzyszy mu od momentu poczęcia aż do chwili śmierci. Efekty jego działania na organizm ludzki w bardzo dużym stopniu zależą od zaprogramowanych już w okresie prenatalnym wzorców reakcji. Negatywne bodźce prowadzą do aktywacji osi podwzgórze-przysadka-nadnercza, a także znacznego pobudzenia autonomicznego układu nerwowego. Przewlekłe napięcie skutkuje istotnym podwyższeniem poziomu hormonów „stresu”, które przełamując naturalną, enzymatyczną barierę płodowo-łożyskową wnikają do krwiobiegu płodu, przyczyniając się do powstania istotnych zaburzeń w kształtowaniu zachowań żywieniowych. Konsekwencją tego stanu jest znaczne ryzyko rozwoju nadwagi oraz otyłości w życiu postnatalnym u dzieci matek, które poddawane były chronicznemu stresowi w okresie ciąży. Ekspozycja ciężarnej kobiety na bodźce stresowe wywiera także istotne implikacje na kształtujący się ośrodkowy układ nerwowy. Zaburzenia w rozwoju szlaków przekaźnictwa w obrębie mózgu, a zwłaszcza podwzgórza jako narządu sprawującego wiodącą rolę w centralnej regulacji przyjmowania pokarmu, mogą w istotny sposób wpływać na ilość oraz kaloryczność wybieranych produktów żywnościowych. Podjęcie próby wyjaśnienia złożonych mechanizmów między chronicznym stresem w życiu prenatalnym oraz nadwagą i otyłością w okresie postnatalnym stanowi nadrzędną kwestię z uwagi na narastający w zatrważającym tempie odsetek osób z tymi schorzeniami, głównie wśród dzieci i młodzieży, a także mnogość powikłań obejmujących niemal wszystkie układy organizmu ludzkiego.Nowadays, stress became an integral part of human life and accompanies it from conception to death. Effects of its influence on human organism are mainly dependent on patterns of reaction programmed already in prenatal period. Negative stimuli lead to activation of hypothalamic– pituitary–adrenal axis and autonomic nervous system. Chronic tension results in significant increase in the level of stress hormones which break natural and enzymatic placental barrier and permeate to fetus’ bloodstream thus contributing to significant disorders in development of eating habits. A consequence of this situation is considerable risk of overweight in postnatal life of children of those mothers who were subjected to chronic stress during pregnancy. Exposition of pregnant woman to stress stimuli also has significant implications on developing central nervous system. Disorders in brain transmission pathways, especially of hypothalamus as an organ which has a major role in central regulation of food intake, may significantly influence amount and calorific value of chosen foods. Attempt to explain complex mechanisms between chronic stress in prenatal period and excessive weight in postnatal period is paramount because of rapidly increasing percentage of people with such affliction, mainly among children and teenagers, and multitude of complications involving all systems of human organism

Effect of Commonly Used Cosmetic Preservatives on Healthy Human Skin Cells

Cosmetic products contain preservatives to prevent microbial growth. The various types of preservatives present in skincare products applied on the skin induce many side effects. We tested several types of preservatives such as phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea (IU), the composition of gluconolactone and sodium benzoate (GSB), diazolidinyl urea (DU), and two grapefruit essential oils, one of which was industrially produced and a second which was freshly distilled from fresh grapefruit peels. This study aimed to find the relationship between preservative concentration, cell growth, collagen secretion, and cell viability. We hypothesized that these products induced a decrease in collagen secretion from human dermal fibroblasts. Our research, for the first time, addressed the overall effect of other preservatives on skin extracellular matrix (ECM) by studying their effect on metalloproteinase-2 (MMP-2) activity. Except for cytotoxicity and contact sensitivity tests, there are no studies of their effect on skin ECM in the available literature. These studies show potential antimicrobial activity, especially from the compounds IU and DU towards reference bacteria and the compounds methyl paraben and propyl paraben against reference fungi. The MTS test showed that fibroblasts are more sensitive to the tested group of preservatives than keratinocytes, which could be caused by the differences between the cells’ structures. The grapefruit oils exhibited the most cytotoxicity to both tested cell lines compared to all considered preservatives. The most destructive influence of preservatives on collagen synthesis was observed in the case of IU and DU. In this case, the homemade grapefruit oil turned out to be the mildest one. The results from a diverse group of preservatives show that whether they are natural or synthesized compounds, they require controlled use. Appropriate dosages and evaluation of preservative efficacy should not be the only aspects considered. The complex effect of preservatives on skin processes and cytotoxicity is an important topic for modern people

Proinflammatory Cytokines (IL-1α, IL-6) and Hepatocyte Growth Factor in Patients with Alcoholic Liver Cirrhosis

Background. The aim of the study was to assess the activity of interleukin-1α, interleukin-6, and hepatocyte growth factor protein (HGF) in serum of patients with alcoholic liver cirrhosis. Materials and Methods. Sixty patients with alcoholic liver cirrhosis treated in various hospitals were randomly enrolled. The stage of cirrhosis was assessed according to the Child-Turcotte-Pugh scoring system. The control group consisted of ten healthy persons without liver disease, who did not drink alcohol. Additionally, the group of alcoholics without liver cirrhosis was included in the study. The activity of interleukin-1α, interleukin-6, and HGF in blood plasma of patients and controls was measured using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Results. Higher concentrations of HGF protein were demonstrated in patients with Child class B and Child class C liver cirrhosis, compared to controls and alcoholics without liver cirrhosis. Moreover, significantly higher concentrations of HGF protein were found in patients with Child class C liver cirrhosis compared to patients with Child class A liver cirrhosis p<0.05. The concentrations of interleukin-1α in patients with Child class B and Child class C liver cirrhosis were significantly higher in comparison with controls. Significantly higher concentrations of interleukin-6 were demonstrated in Child class C, compared to Child class A

Activity of MMP-2, MMP-8 and MMP-9 in serum as a marker of progression of alcoholic liver disease in people from Lublin Region, eastern Poland

In alcoholic liver cirrhosis, normal liver cells are replaced by scar tissue (fibrosis). Liver fibrosis is a dynamic process in which activated hepatic stellate cells are involved in the synthesis of matrix proteins and the regulation of matrix degeneration. The aim of the presented study was to assess the usefulness of MMP-2, MMP-8 and MMP-9 as diagnostic markers of alcoholic liver disease. Sixty patients with alcoholic liver cirrhosis were randomly enrolled during hospitalization in departments of hospitals from the Lublin Region in eastern Poland. The stage of cirrhosis was estimated according to Child-Turcotte-Pugh criteria (Child-Pugh score) as P- Ch A, P-Ch B, P-Ch C. The control group consisted of 10 healthy persons without liver disease, who did not drink alcohol. Additionally, a group of alcoholics without liver cirrhosis was included in the study. Blood sample were obtained, and after centrifuge, serum was collected for further analysis. The activity of MMP-2, MMP-8 and MMP-9 in the blood plasma of the patients and the control group were measured by using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Activity of MMP-2, MMP-8 and MMP-9 in patients with liver cirrhosis were increased gradually according to Child-Pugh stages. The activity of MMP-2, MMP-8, MMP-9 were the highest in patients with liver cirrhosis stage C. MMP-2, MMP-8, MMP-9 concentrations in the people with liver cirrhosis (stage C) were significantly increased compared to controls. A significant difference were observed between activity MMP-2 in control group, alcoholics without liver cirrhosis, and those with liver cirrhosis (stages A, B, C according Child-Pugh score). MMP-2, MMP-8 and MMP-9 may be markers of alcoholic liver cirrhosis in the alcoholics. Elevated levels of MMP-2, MMP-8 and MMP-9 in the alcoholic patients indicated that cirrhosis has developed. The most sensitive is MMP-2, because the activity of this parameter is increased in all liver cirrhosis stages. MMP-8 and MMP-9 activity were significantly elevated only in serum patients with advanced liver cirrhosis, compared to controls