33 research outputs found
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
In vivo and in vitro studies of efficient mephedrone adsorption over zirconium-based metal-organic frameworks corroborated by DFT+D modeling
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 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
Mephedrone and Nicotine: Oxidative Stress and Behavioral Interactions in Animal Models
Cyclodextrin Metal–Organic Frameworks as a Drug Delivery System for Selected Active Pharmaceutical Ingredients
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
Verification of the analgesic properties of natural compounds of cannabinoid origin in Danio rerio model of nociception
The use of Cannabis sativa in human history dates back thousands of years, with various historical and cultural applications. However, at the beginning of the 20th century, many countries enacted regulations to criminalize and restrict the use of cannabis, leading to a significant reduction in research on its medical applications. A novel approach to pain studies involves Danio rerio-based nociception models. These models use different methods to induce pain, with fish larvae often subjected to incubation in acetic acid solution, resulting in epidermal tissue damage. Nociceptive responses are then observed by tracking fish movement. Our research aimed to develop a simple and accessible Danio rerio (zebrafish) model of nociception to study the potential analgesic properties of CBD (cannabidiol) and CBG (cannabigerol) in comparison to the commonly known painkiller ibuprofen. This research seeks to contribute to our understanding of the potential therapeutic applications of cannabinoids in pain management