Immunolocalization of Matrix Metalloproteinases 2 and 9 and Their Inhibitors in the Hearts of Rats Treated with Immunosuppressive Drugs-An Artificial Intelligence-Based Digital Analysis.

BACKGROUND: Immunosuppressive agents represent a broad group of drugs, such as calcineurin inhibitors, mTOR inhibitors, and glucocorticosteroids, among others. These drugs are widely used in a number of conditions, but lifelong therapy is crucial in the case of organ recipients to prevent rejection. To further increase the safety and efficacy of these agents, their off-target mechanisms of action, as well as processes underlying the pathogenesis of adverse effects, need to be thoroughly investigated. The aim of this study was to examine the impact of various combinations of cyclosporine/tacrolimus/mycophenolate with rapamycin and steroids (CRG, TRG, MRG), on the morphology and morphometry of rats' cardiomyocytes, together with the presence of cardiac collagen and the immunoexpression of MMPs and TIMPs. METHODS: Twenty-four rats were divided into four groups receiving different immunosuppressive regiments. After six months of treatment, the hearts were collected and analyzed. RESULTS: Cardiomyocytes from the CRG cohorts demonstrated the most pronounced morphological alterations. In addition, chronic immunosuppression reduced the width and length of cardiac cells. However, immunosuppressive therapy did not alter the presence of cardiac collagen fibers. Nevertheless, we observed significant alterations regarding MMP/TIMP homeostasis. CONCLUSIONS: Chronic immunosuppression seems to disturb the MMP/TIMP balance in aspects of immunolocalization in the hearts of rats. Further studies are required to analyze other mechanisms and pathways affected by the use of immunosuppressants.

Evaluation of Arsenic and Cobalt Levels in Pediatric Patients Receiving Long-Term Parenteral Nutrition.

This study continues the research in which we determined the concentration of aluminum in children receiving long-term parenteral nutrition (LPN). Since our results were interesting, we decided to assay arsenic (As) and cobalt (Co) in the collected material, which, like aluminum, constitute contamination in the mixtures used in parenteral nutrition. Excesses of these trace elements in the human body are highly toxic, and deficiencies, particularly in the case of Co, can lead to various complications. The aim of this study was to determine the impact of LPN in children on their serum levels of As and Co, as well as the excretion of these elements in urine, and to compare them with a control group of healthy children. The study group consisted of 83 children receiving home parenteral nutrition from two Polish centers, while the control group included 121 healthy children. In both groups, the levels of As and Co in serum and urine were measured. The elemental compositions of the samples were determined using inductively coupled plasma mass spectrometry (ICP-MS). It was demonstrated that the children receiving LPN did not have increased As exposure compared to the controls. Greater exposure compared to the control group was shown for Co. In conclusion, children receiving LPN are not exposed to As, and even though the concentrations of Co in serum and urine were higher in the LPN group than in the healthy controls, neither trace element poses a health threat to children requiring LPN.

The Effects of Chronic Immunosuppressive Treatment on Morphological Changes in Cardiac Tissue and the Balance between Matrix Metalloproteinases (MMP-2 and MMP-9) and Their Inhibitors in the Rat Heart.

Using different three-drug immunosuppressive treatment regimens in a rat model, we aimed to determine the effects of long-term therapy on metalloproteinase-2 and metalloproteinase-9 activity and the expression of their inhibitors, as well as to assess the morphology of the animals' cardiac tissue. Our results suggest that chronic use of immunosuppressive drugs disrupts the balance between the activity of MMPs and TIMPs. Depending on the type of drug regimen used, this leads to abnormalities in the cardiac structure, collagen fiber accumulation, or cardiomyocyte hypertrophy. The information obtained in the present study allows us to conclude that the chronic treatment of rats with the most common clinical immunosuppressive regimens may contribute to abnormalities in the myocardial structure and function. The results presented in this study may serve as a prelude to more in-depth analyses and additional research into the optimal selection of an immunosuppressive treatment with the lowest possible risk of cardiovascular complications for patients receiving organ transplants.

Effects of Letrozole Treatment and Vitamin C Supplementation on Morphology, Endoplasmic Reticulum Stress, Programmed Cell Death, and Oxidative Stress in the Small Intestine of Adult Male Rats.

Estrogens are hormones that play an important role in the digestive tract, including in men. Letrozole is an inhibitor of cytochrome P450 aromatase, an enzyme converting androgens to estrogens. The use of letrozole may cause oxidative stress and endoplasmic reticulum stress in the cells. Factors modulating cellular stress may include vitamin C. The purpose of this study was to examine whether letrozole and/or vitamin C supplementation can affect the morphology of the small intestine, the parameters of endoplasmic reticulum stress, programmed cell death markers, and oxidative damage. Three-month-old male rats were divided into four groups and treated with the following: (I) CTRL-water; (II) CTRL+C-L-ascorbic acid; (III) LET-letrozole; and (IV) LET+C-letrozole + L-ascorbic acid. The morphometrical measurements included epithelial thickness, crypt and lumen area, crypt perimeter, nuclei number in the crypt, and the cell size of crypts. The expression levels of PERK, caspase-3, and catalase were determined. Significant differences in the morphometrical measurements and immunoexpression were observed. This may indicate that chronic treatment with letrozole can affect morphology and induce ER stress, oxidative stress, and programmed cell death in the epithelial cells of the small intestine of adult male rats. Vitamin C supplementation exerts an effect on some parameters of the molecular processes.

Glioblastoma multiforme influence on the elemental homeostasis of the distant organs: the results of inter-comparison study carried out with TXRF method.

Glioblastoma (GBM) is a fast-growing and aggressive brain tumor which invades the nearby brain tissue but generally does not spread to the distant organs. Nonetheless, if untreated, GBM can result in patient death in time even less than few months from the diagnosis. The influence of the tumor progress on organs other than brain is obvious but still not well described. Therefore, we examined the elemental abnormalities appearing in selected body organs (kidney, heart, spleen, lung) in two rat models of GBM. The animals used for the study were subjected to the implantation of human GBM cell lines (U87MG and T98G) characterized by different levels of invasiveness. The elemental analysis of digested organ samples was carried out using the total reflection X-ray fluorescence (TXRF) method, independently, in three European laboratories utilizing various commercially available TXRF spectrometers. The comparison of the data obtained for animals subjected to T98G and U87MG cells implantation showed a number of elemental anomalies in the examined organs. What is more, the abnormalities were found for rats even if neoplastic tumor did not develop in their brains. The most of alterations for both experimental groups were noted in the spleen and lungs, with the direction of the found element changes in these organs being the opposite. The observed disorders of element homeostasis may result from many processes occurring in the animal body as a result of implantation of cancer cells or the development of GBM, including inflammation, anemia of chronic disease or changes in iron metabolism. Tumor induced changes in organ elemental composition detected in cooperating laboratories were usually in a good agreement. In case of elements with higher atomic numbers (Fe, Cu, Zn and Se), 88% of the results were classified as fully compliant. Some discrepancies between the laboratories were found for lighter elements (P, S, K and Ca). However, also in this case, the obtained results fulfilled the requirements of full (the results from three laboratories were in agreement) or partial agreement (the results from two laboratories were in agreement).

Current Status Regarding Immunosuppressive Treatment in Patients after Renal Transplantation.

Renal transplantation is now the best treatment for end-stage renal failure. To avoid rejection and prolong graft function, organ recipients need immunosuppressive therapy. The immunosuppressive drugs used depends on many factors, including time since transplantation (induction or maintenance), aetiology of the disease, and/or condition of the graft. Immunosuppressive treatment needs to be personalised, and hospitals and clinics have differing protocols and preparations depending on experience. Renal transplant recipient maintenance treatment is mostly based on triple-drug therapy containing calcineurin inhibitors, corticosteroids, and antiproliferative drugs. In addition to the desired effect, the use of immunosuppressive drugs carries risks of certain side effects. Therefore, new immunosuppressive drugs and immunosuppressive protocols are being sought that exert fewer side effects, which could maximise efficacy and reduce toxicity and, in this way, reduce both morbidity and mortality, as well as increase opportunities to modify individual immunosuppression for renal recipients of all ages. The aim of the current review is to describe the classes of immunosuppressive drugs and their mode of action, which are divided by induction and maintenance treatment. An additional aspect of the current review is a description of immune system activity modulation by the drugs used in renal transplant recipients. Complications associated with the use of immunosuppressive drugs and other immunosuppressive treatment options used in kidney transplant recipients have also been described.

Prenatal Exposition to Different Immunosuppressive Protocols Results in Vacuolar Degeneration of Hepatocytes.

Immunosuppressive drugs are essential for transplant recipients, since they prolong proper function of graft; however, they affect the morphology and function of organs, including liver. One commonly observed alteration in hepatocytes is vacuolar degeneration. Numerous medications are contraindicated in pregnancy and breastfeeding, mostly due to a lack of data concerning their advert effects. The aim of the current study was to compare the effects of prenatal exposition to different protocols of immunosuppressants on vacuolar degeneration in the hepatocytes of livers of rats. Thirty-two livers of rats with usage of digital analysis of the images were examined. Area, perimeter, axis length, eccentricity and circularity regarding vacuolar degeneration were analysed. The most prominent vacuolar degeneration in hepatocytes in the aspects of presence, area and perimeter was observed in rats exposed to tacrolimus, mycophenolate mofetil and glucocorticoids, and cyclosporine A, everolimus with glucocorticoids.This is the first study that demonstrates the results of the influence of multidrug immnunosuppression distributed in utero on the hepatic tissue of offspring.

The Effect of the Gut Microbiota on Transplanted Kidney Function.

The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.

Can longitudinal strain analysis differentiate between Takotsubo syndrome and acute coronary syndrome?

BACKGROUND: Takotsubo syndrome (TTS) is characterized by transient abnormalities of myocardial contractility. Noninvasive tests are currently being sought to differentiate TTS from acute coronary syndrome (ACS). THE AIM OF THE STUDY: To evaluate the prevalence of TTS and echocardiographic parameters to distinguish apical TTS from acute anterior wall infarction. MATERIAL AND METHODS: The medical records of patients with suspected TTS, hospitalized in the Department of Cardiology (TTS group n = 18) were analyzed. The control group included patients with STEMI of the left ventricle anterior wall and anterior and lateral wall (STEMI group n = 17). Standard transthoracic echocardiography (TTE) was supplemented with segmental longitudinal strain (LS) assessment with the use of acoustic marker tracking. RESULTS: A statistically significant difference was observed in the second cardiac troponine I (CTNI) measurement (TTS: 3241.2 ng/L vs. STEMI: 12032.6 ng/L; p < 0.05). A significant difference in left and right ventricular size was observed on TTE. Left ventricular end-diastolic and end-systolic volumes were considerably smaller in TTS group; (86.1 vs. 104 ml and 48.1 vs. 74.1 ml, respectively). LS were significantly higher (in absolute values) in patients with TTS than in those with STEMI in the apical and middle lateral segments, LS in the apical four-chamber view (apSept -14.9 vs. -8.9; apLat -14.8 vs. -6.84; midLat -13.26 vs. -9.11). CONCLUSIONS: Patients with TTS are characterized by a different LS pattern in the apical segments of the left ventricle compared to patients with STEMI. TTE examination with LS remains insufficient to distinguish TTS from ACS at the early stage of diagnosis.

Influence of measurement mode on the results of glioblastoma multiforme analysis with the FTIR microspectroscopy.

Fourier Transform Infrared (FTIR) microspectroscopy is well known for its effectiveness in spectral and biochemical analyses of various materials. It enables to determine the sample biochemical composition by assigning detected frequencies, characteristic for functional groups of main biological macromolecules. In analysis of tissue sections one of two measurement modes, namely transmission and transflection, is usually applied. The first one has relatively straightforward geometry, hence it is considered to be more precise and accurate. However, IR-transparent media are very fragile and expensive. Transflection does not require expensive substrates, but is more prone to disruptive influence of Mie scattering as well as electric field standing wave effect. The excessive comparison of spectra' characteristics, obtained via both measurement modes, was performed in this paper. By the means of Mann-Whitney non-parametrical U test and PCA, the comparison of results obtained with both modes and assessment of usefulness of IR spectra obtained with transmission and transflection modes to differentiate between healthy and GBM-affected tissue, were performed. The main objective of the presented research is to compare the results of FTIR analysis of unfixed biological samples performed with transflection and transmission mode. In frame of the study we demonstrated the discrepancies between results of biochemical analysis performed based on data obtained with transmission and transflection. Such observation suggests that caution should be taken in drawing conclusions from the results obtained with transflection geometry, as its more prone to disruptive effects. Despite that, IR spectra developed with both modes allowed to distinguish GBM area from healthy tissue, which proves their diagnostic potential. Especially, application of the ME-EMSC correction of spectra before PCA enhances the performance of both methods to distinguish the analysed tissue areas.

Asymptomatic Left Atrial Myxoma.

Primary tumors of the heart are extremely rare. The most common is the left atrial myxoma. This article presents a case of large asymptomatic left atrial myxoma in an 80-year-old woman. The patient was admitted to the hospital emergency department after a traffic accident. After a performed trauma scan and an echocardiographic examination, a diagnosis of asymptomatic left atrial myxoma was made. The patient was discharged from the hospital with a referral for a consultation at a cardiac surgery center, which the patient did not attend. The treatment of choice for myxomas is surgical removal. The detection of a myxoma usually is considered as an emergency however the tumor described here has the characteristics of myxoma in the complication-free phase. Given the patient's age, reluctance to undergo invasive surgery, and tumor characteristics, it seems that abandoning invasive management in favor of monitoring the patient's condition may be the preferred therapy.

The Effect of Chronic Immunosuppressive Regimens Treatment on Aortal Media Morphology and the Balance between Matrix Metalloproteinases (mmp-2 and mmp-9) and Their Inhibitors in the Abdominal Aorta of Rats.

Immunosuppressive drugs are widely and chronically used to avoid graft rejection in transplant recipients. However, they are also known to have organotoxic effects and can exert numerous side effects. The aim of this study was to assess whether the chronic treatment of rats with the most commonly used clinical immunosuppressive regimens in organ recipients had an effect on the morphology and function of the aorta. The rats were divided into five groups and each group was chronically treated with different sets of three immunosuppressive drugs (TRG, CRG, MRG, CMG, TMG) for 6 months. The changes were most profound in calcineurin inhibitor-based protocols. TMG protocol treatment was characterized by the most numerous alterations such as morphological changes, changes in the thickness of the tunic media, wider distances between elastic lamellae, an increase in the number of vSMCs and changes in collagen deposition. We concluded that the morphological changes were connected with MMP-2 and MMP-9/TIMP-2 and TIMP-1 imbalances, which was also determined and noticed.

The Effects of E-Cigarette Aerosol on Oral Cavity Cells and Tissues: A Narrative Review.

A wealth of research has comprehensively documented the harmful effects of traditional cigarette smoking and nicotine on human health. The lower rate of exposure to harmful chemicals and toxic substances offered by alternative electronic smoking devices (e-cigarettes, vaping, etc.) has made these methods of smoking popular, especially among adolescents and young adults, and they are regarded frequently as safer than regular cigarettes. During vaporization of these so-called e-liquids, toxins, carcinogens and various other chemical substances may be released and inhaled by the user. Data on the potential human health effect attendant on exposure to e-vapor are based mainly on animal and in vitro studies. The oral tissues are the first locus of direct interaction with the components of the inhaled vapor. However, the short-term as well as long-term effects of the exposure are not known. The aim of the review is to briefly present data on the effects of the chemical components and toxins of e-cigarette vapor on oral cavity cells and tissues of oral health.

Tacrolimus-Based Immunosuppressive Therapy Influences Sex Hormone Profile in Renal-Transplant Recipients-A Research Study.

It is estimated that approximately 20% of couples suffer from infertility worldwide and within renal-transplant recipients, this problem is 10 times more common. An intake of immunosuppressants may lead to hormonal imbalance. The aim of the study was to investigate the influence of tacrolimus-based therapy on the hormonal status of grafted patients. Blood samples were obtained from patients from the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University. All 121 patients had stable graft function for over 6 months. The blood plasma concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, estradiol, cortisol were assessed by the electrochemiluminescence method. We observed decreased levels of prolactin (11.9 ng/mL) and cortisol (87.4 µg/mL) in patients under tacrolimus-based therapy. Tacrolimus-based therapy was also associated with increased testosterone and follicle-stimulating hormone in males, 4.04 ng/mL and 6.9 mLU/mL, respectively, and decreased testosterone levels in females, 0.121 ng/mL. We also assessed that immunosuppressive therapy based on tacrolimus is less nephrotoxic in comparison to other regimens. Concluding, tacrolimus-based therapy may influence the hormonal status of transplant recipients in the current study. Results presented here are believed to be helpful for clinicians and patients, especially within the aspect of willingness for biological offspring.

The Effect of Immunosuppressive Drugs on MMPs Activity in The Walls of Blood Vessels - A Systematic Review.

The current study focuses on the role of MMPs in the pathogenesis of the vascular damage and at the same time it offers the review referring to the influence of the immunosuppressive treatment on this interdependence. Contemporary immunosuppressive treatment constitutes of four groups of medications, such as: calcineurin inhibitors including cyclosporine A and tacrolimus; inhibitors of the inosine monophosphate dehydrogenase - the only agent from this group currently used in transplantation is mycophenalate mofetil (MMF); mTOR inhibitors, consisting of everolimus and glucocorticosteroids. Due to the fact that the properties of immunosuppressive drugs still remain unclear and transplant recipients need to use these medicines every day, knowledge of this should be further expanded. The deceases of the patients with the functioning graft who were diagnosed with the cardiovascular system diseases, constitute 50% of all renal transplant recipients. Immunosuppressive treatment leads to many pathological alterations within the organs and tissues and additionally they undoubtedly affect the activity of MMPs in the wall of the vessels.

Global Gene Expression of Cultured Human Dermal Fibroblasts: Focus on Cell Cycle and Proliferation Status in Improving the Condition of Face Skin.

Chronological skin ageing is an inevitable physiological process that results in thin and sagging skin, fine wrinkles, and gradual dermal atrophy. The main therapeutic approaches to soft tissue augmentation involve using dermal fillers, where natural fillers, such as autologous fibroblasts, are involved in generating dermal matrix proteins. The aim of this study was to determine the global transcriptome profile of three passages of dermal autologous fibroblasts from a male volunteer, focusing on the processes of the cell cycle and cell proliferation status to estimate the optimal passage of the tested cells with respect to their reimplantation. We performed K-means clustering and validation of the expression of the selected mRNA by qRT-PCR. Ten genes were selected (ANLN, BUB1, CDC20, CCNA2, DLGAP5, MKI67, PLK1, PRC1, SPAG5, and TPX2) from the top five processes annotated to cluster 5. Detailed microarray analysis of the fibroblast genes indicated that the cell population of the third passage exhibited the highest number of upregulated genes involved in the cell cycle and cell proliferation. In all cases, the results of qRT-PCR confirmed the differences in expression of the selected mRNAs between fibroblasts from the primary culture (C0) and from the first (C1), second (C2), and third (C3) cell passage. Our results thus suggest that these cells might be useful for increasing fibroblast numbers after reimplantation into a recipient's skin, and the method used in this study seems to be an excellent tool for autologous transplantation allowing the rejuvenation of aging skin.

Analysis of Cadmium, Mercury, and Lead Concentrations in Erythrocytes of Renal Transplant Recipients from Northwestern Poland.

Cadmium (Cd), mercury (Hg), and lead (Pb) exhibit highly nephrotoxic properties, and their high concentrations can lead to renal failure. Much research has been conducted on the concentrations of heavy metals, microelements, and macroelements in the blood, but little is known about the concentration of Cd, Pb, and Hg in erythrocytes of renal recipients. The aim of this study is to determine the blood erythrocyte concentrations of toxic metals (Cd, Pb, and Hg) in renal transplant recipients (RTRs). Additionally, we analyzed the effect of selected biological and environmental factors, including the intake of various immunosuppressive drug regimens and smoking, on these xenobiotic concentrations. The material consisted of erythrocyte samples from 115 patients of the Department of Nephrology, Transplantology, and Internal Medicine at Independent Public Clinical Hospital No. 2, Pomeranian Medical University, Szczecin, in northwestern Poland. Cd, Hg, and Pb levels in the erythrocytes were quantified by inductively coupled mass spectroscopy (ICP-MS). Equal concentrations of Cd were found in erythrocytes of both female and male transplant recipients. The highest level of Hg was seen in women, and women overall had statistically higher concentrations of Pb than men. Comparison of metal concentrations between those over 50 years and those under it showed that Pb concentration was also significantly higher in renal transplant recipients over 50. Pb concentration was almost twice as high in RTRs who used tacrolimus with mycophenolate mofetil than in RTRs who used cyclosporine A with mycophenolate mofetil. The highest level of Cd was seen in smokers, who had 3.25 µg/L. This value was significantly higher than in ex-smokers (p = 0.001) and with RTRs who had never smoked. There were significantly higher levels of Pb in the erythrocytes of RTRs who were ex-smokers than in those who had never smoked. A statistically significant correlation was found between Cd and Pb concentrations. Additionally, we have noticed significant positive correlation between Pb and age (R = 0.37), gender (R = 0.24) and significant negative correlation of Pb with GFR (R = -0.33). We have also found significant positive correlation between Hg and age (R = 0.21). In summary, our data suggest that, smoking is associated with Pb and Cd concentrations, and gender, age change depending on Pb concentration in erythrocytes of RTRs. Additionally, this is the first research that suggests that immunosuppressive regimen, depending on type of immunosuppressive drugs combination affects Pb concentration in erythrocytes of RTRs. It seems to be crucial information for patients who use immunosuppressive drugs.

The Effects of E-Cigarette Vapor Components on the Morphology and Function of the Male and Female Reproductive Systems: A Systematic Review.

E-cigarettes, a comparatively new phenomenon, are regarded as a safer alternative to conventional cigarettes. They are increasingly popular among adolescents of both sexes, and many smokers use e-cigarettes in their attempts to quit smoking. There is little understanding of the effects of exposure to e-cigarette vapors on human reproductive health, human development, or the functioning of the organs of the male and female reproductive systems. Data on the effects of the exposure were derived mainly from animal studies, and they show that e-cigarettes can affect fertility. Here, we review recent studies on the effects of exposure to e-cigarettes on facets of morphology and function in the male and female reproductive organs. E-cigarettes, even those which are nicotine-free, contain many harmful substances, including endocrine disruptors, which disturb hormonal balance and morphology and the function of the reproductive organs. E-cigarettes cannot be considered a completely healthy alternative to smoking. As is true for smoking, deleterious effects on the human reproductive system from vaping are likely, from the limited evidence to date.

Serum Selenium, Iron, Zinc, and Copper Concentrations in Renal Transplant Recipients Treated with Mycophenolate Mofetil.

There are data available in the literature on bioelement concentrations in the serum of various groups of patients; however, very little is known about the serum concentration of selenium (Se), iron (Fe), zinc (Zn), and copper (Cu) in renal transplant patients treated with immunosuppressive drugs, including mycophenolate mofetil (MMF). Monitoring of serum bioelement concentrations in renal transplant recipients is of profound importance, as the proper bioelement levels seem to prolong the normal function of the transplanted organ. Thus, the aim of this current study was to examine and carry out comparative analysis involving serum concentrations of Se, Fe, Cu, and Zn of renal transplant recipients treated with MMF and without MMF. The material consisted of blood samples from 115 patients of the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University, in the city of Szczecin in the northwestern Poland. Serum Se, Fe, Cu, and Zn levels were quantified by inductively coupled mass spectroscopy (ICP-MS). Taking into account all patients, MMF increases Cu level. Cu and Fe concentrations were significantly higher in women treated with MMF; in group of younger patients treated with MMF, Se level was significantly lower comparing with those whose regimen did not include MMF. Additionally, MMF in combination with prednisone increased Se concentration in blood of transplant recipients. Our study highlights that trace elements should be monitored to allow for an early detection of trace elements deficits, which can easily be corrected for by an adjusted diet or supplemental intake.

Transcriptome Profile of Human Fibroblasts in an Ex Vivo Culture.

Implantation of autologous fibroblasts is a method used to correct age-related changes in facial skin. The aim of this study was to establish the optimal population of cultured human fibroblasts according to the organization of the extracellular matrix in the dermis. Transcriptome profile analysis of cells derived from three consecutive passages indicated that fibroblasts after the second passage were the population with the greatest number of upregulated genes encoding the critical biological processes responsible for skin regeneration, such as extracellular matrix organization, collagen fibril organization, and cell adhesion. Furthermore, genes encoding proteinases responsible for the degradation of dermal extracellular matrix proteins were noticeably downregulated at this stage of culture. Autologous fibroblasts seem to be an optimal and safe biological filler for the renewal of all skin structures.