Circulating levels of irisin and Meteorin-like protein in PCOS and its correlation with metabolic parameters.

INTRODUCTION: Research on obesity, which results from excessive food consumption and sedentary lifestyle, has focused on increasing energy expenditure. Recently, muscle tissue is being investigated as an endocrine active organ, secreting molecules called myokines. Multiple studies have been performed to assess myokine levels in various disorders, including polycystic ovary syndrome (PCOS) and metabolic syndrome. Irisin and Meteorin-like protein (Metrnl) are particles which, among others, are suggested to play an important role in adipose tissue browning and improving insulin sensitivity. MATERIAL AND METHODS: The study population consisted of 31 women with PCOS and 18 healthy individuals. PCOS was diagnosed based on revised 2003 Rotterdam criteria. Multiple anthropometrical, hormonal, and biochemical parameters were assessed, including oral glucose tolerance test and body composition with dual energy X-ray absorptiometry. Serum levels of irisin and Metrnl were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were no differences between the PCOS and control groups according to age, body mass index (BMI), waist-to-hip ratio (WHR), fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), or body mass composition. Assessment of Metrnl and irisin concentrations revealed no significant differences between PCOS and healthy women. The irisin level was negatively correlated with BMI, body fat mass, fasting glucose, and insulin concentrations. No relationship between Metrnl level and metabolic parameters was found. CONCLUSIONS: Although irisin seems to be a promising biomarker, inconsistent research limits its value in clinical use in the assessment or treatment of obesity. Metrnl level was not affected in the study population, but it might be connected to the severity of metabolic disturbances.

Influence of C60 Nanofilm on the Expression of Selected Markers of Mesenchymal-Epithelial Transition in Hepatocellular Carcinoma.

The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire the ability to actively migrate via a change to the mesenchymal phenotype. This mechanism occurs in an environment rich in cytokines and reactive oxygen species but poor in nutrients. The aim of this study was to demonstrate that the use of a fullerene C60 nanofilm can inhibit liver cancer cell invasion by restoring their non-aggressive, epithelial phenotype. We employed epithelial and mesenchymal HepG2 and SNU-449 liver cancer cells and non-cancerous mesenchymal HFF2 cells in this work. We used enzyme-linked immunosorbent assays (ELISAs) to determine the content of glutathione and transforming growth factor (TGF) in cells. We measured the total antioxidant capacity with a commercially available kit. We assessed cell invasion based on changes in morphology, the scratch test and the Boyden chamber invasion. In addition, we measured the effect of C60 nanofilm on restoring the epithelial phenotype at the protein level with protein membranes, Western blotting and mass spectrometry. C60 nanofilm downregulated TGF and increased glutathione expression in SNU-449 cells. When grown on C60 nanofilm, invasive cells showed enhanced intercellular connectivity; reduced three-dimensional invasion; and reduced the expression of key invasion markers, namely MMP-1, MMP-9, TIMP-1, TIMP-2 and TIMP-4. Mass spectrometry showed that among the 96 altered proteins in HepG2 cells grown on C60 nanofilm, 41 proteins are involved in EMT and EMT-modulating processes such as autophagy, inflammation and oxidative stress. The C60 nanofilm inhibited autophagy, showed antioxidant and anti-inflammatory properties, increased glucose transport and regulated the ß-catenin/keratin/Smad4/snail+slug and MMP signalling pathways. In conclusion, the C60 nanofilm induces a hybrid mesenchymal-epithelial phenotype and could be used in the prevention of postoperative recurrences.

Cell Line-Dependent Adhesion and Inhibition of Proliferation on Carbon-Based Nanofilms.

Introduction: Disorganisation of the extracellular matrix (ECM) is strongly connected to tumor progression. Even small-scale changes can significantly influence the adhesion and proliferation of cancer cells. Therefore, the use of biocompatible nanomaterials capable of supporting and partially replenishing degraded ECM might be essential to recover the niche after tumor resection. The objective of this study was to evaluate the influence of graphene, graphene oxide, fullerene, and diamond nanofilms on breast cancer and glioblastoma grade IV cell lines. Methods: Nanomaterials were characterized using SEM and TEM techniques; zeta potential analysis was also performed. Nanofilms of graphene, fullerene, and diamond nanoparticles were also characterized using AFM. The toxicity was tested on breast cancer MDA.MB.231 and glioblastoma grade IV U-87 MG cell lines, using LDH assay and by counting stained dead cells in bioprinted 3D models. The following parameters were analyzed: proliferation, adhesion to the nanofilm, and adhesion to particular ECM components covered with diamond nanoparticles. Results and Discussion: Our studies demonstrated that nanofilms of graphene and diamond nanoparticles are characterized by cell-specific toxicity. Those nanomaterials were non-toxic to MDA.MB.231 cells. After applying bioprinted 3D models, diamond nanoparticles were not toxic for both cell lines. Nanofilms made of diamond nanoparticles and graphene inhibit the proliferation of MDA.MB.231 cells after 48 and 72 hours. Increased adhesion on nanofilm made of diamond nanoparticles was only observed for MDA.MB.231 cells after 30 and 60 minutes from seeding the cells. However, analysis of adhesion to certain ECM components coated with diamond nanoparticles revealed enhanced adhesion to tenascin and vitronectin for both tested cell lines. Conclusion: Our studies show that nanofilm made of diamond nanoparticles is a non-toxic and pro-adhesive nanomaterial that might stabilize and partially replenish the niche after breast tumor resection as it enhances the adhesion of breast cancer cells and inhibits their proliferation.

A Comprehensive Assessment of the Biocompatibility and Safety of Diamond Nanoparticles on Reconstructed Human Epidermis.

Diamond nanoparticles, also known as nanodiamonds (NDs), exhibit remarkable, awe-inspiring properties that make them suitable for various applications in the field of skin care products. However, a comprehensive assessment of their compatibility with human skin, according to the irritation criteria established by the Organization for Economic Cooperation and Development (OECD), has not yet been conducted. The purpose of this study was to evaluate if diamond nanoparticles at a concentration of 25 µg/mL, incubated with reconstituted human epidermis (EpiDermTM) for 18 h, conform to the OECD TG439 standard used to classify chemical irritants. For this purpose, a cell viability test (MTT assay), histological assessment, and analysis of pro-inflammatory cytokine expression were performed. The results indicated that NDs had no toxic effect at the tested concentration. They also did not adversely affect tissue structure and did not lead to a simultaneous increase in protein and mRNA expression of the analyzed cytokines. These results confirm the safety and biocompatibility of NDs for application in skincare products, thereby creating a wide range of possibilities to exert an impact on the advancement of contemporary cosmetology in the future.

Dependence of diamond nanoparticle cytotoxicity on physicochemical parameters: comparative studies of glioblastoma, breast cancer, and hepatocellular carcinoma cell lines.

Reports on the cytotoxicity of diamond nanoparticles (ND) are ambiguous and depend on the physicochemical properties of the material and the tested cell lines. Thus, the aim of this research was to evaluate the influence of thirteen types of diamond nanoparticles, differing in production method, size, and surface functional groups, on their cytotoxicity against four tumor cell lines (T98G, U-118 MG, MCF-7, and Hep G2) and one non-tumor cell line (HFF-1). In order to understand the dependence of diamond nanoparticles on physicochemical properties, the following parameters were analyzed: viability, cell membrane damage, morphology, and the level of intracellular general ROS and mitochondrial superoxide. The performed analyses revealed that all diamond nanoparticles showed no toxicity to MCF-7, Hep G2, and HFF-1 cells. In contrast, the same nanomaterials were moderately toxic for the glioblastoma T98G and U-118 MG cell lines. In general, the effect of the production method did not influence ND toxicity. Some changes in cell response after treatment with modified nanomaterials were observed, with the presence of carboxyl groups having a more detrimental effect than the presence of other functional groups. Although nanoparticles of different sizes caused similar toxicity, nanomaterials with bigger particles caused a more pronounced effect.

Differences in the Cell Type-Specific Toxicity of Diamond Nanoparticles to Endothelial Cells Depending on the Exposure of the Cells to Nanoparticles.

Introduction: Diamond nanoparticles are considered to be one of the most cytocompatible carbon nanomaterials; however, their toxicity varies significantly depending on the analysed cell types. The aim was to investigate the specific sensitivity of endothelial cells to diamond nanoparticles dependent on exposure to nanoparticles. Methods: Diamond nanoparticles were characterized with Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS). Toxicity of diamond nanoparticles was assessed for endothelial cells (HUVEC), human mammary epithelial cells (HMEC) and HS-5 cell line. The effect of diamond nanoparticles on the level of ROS, NO, NADPH and protein synthesis of angiogenesis-related proteins of endothelial cells was evaluated. Results and Discussion: Our studies demonstrated severe cell type-specific toxicity of diamond nanoparticles to endothelial cells (HUVEC) depending on nanoparticle surface interaction with cells. Furthermore, we have assessed the effect on cytotoxicity of the bioconjugation of nanoparticles with a peptide containing the RGD motive and a serum protein corona. Our study suggests that the mechanical interaction of diamond nanoparticles with the endothelial cell membranes and the endocytosis of nanoparticles lead to the depletion of NADPH, resulting in an intensive synthesis of ROS and a decrease in the availability of NO. This leads to severe endothelial toxicity and a change in the protein profile, with changes in major angiogenesis-related proteins, including VEGF, bFGF, ANPT2/TIE-2, and MMP, and the production of stress-related proteins, such as IL-6 and IL-8. Conclusion: We confirmed the presence of a relationship between the toxicity of diamond nanoparticles and the level of cell exposure to nanoparticles and the nanoparticle surface. The results of the study give new insights into the conditioned toxicity of nanomaterials and their use in biomedical applications.

Effect of Melittin Complexes with Graphene and Graphene Oxide on Triple-Negative Breast Cancer Tumors Grown on Chicken Embryo Chorioallantoic Membrane.

One of the components of bee venom is melittin (M), which has strong lysing properties on membranes. M has high toxicity to cancer cells, but it also affects healthy cells, making it necessary to use methods for targeted delivery to ensure treatment. This research is a continuation of previous studies using graphene nanomaterials as M carriers to breast cancer cells. The studies described below are conducted on a more organized biological structure than what is found in vitro cells, namely, cancerous tumors grown on a chicken embryo chorioallantoic membrane. Caspase 3 and 8 levels are analyzed, and the level of oxidative stress markers and changes in protein expression for cytokines are examined. The results show that M complexes with nanomaterials reduce the level of oxidative stress more than M alone does, but the use of graphene (GN) as a carrier increases the level of DNA damage to a greater extent than the increase caused by M alone. An analysis of cytokine levels shows that the use of the M and GN complex increases the level of proteins responsible for inhibiting tumor progression to a greater extent than the increase occasioned by a complex with graphene oxide (GO). The results suggest that the use of GN as an M carrier may increase the toxic effect of M on structures located inside a cell.

Whom to trust? Inferred source credibility and response borrowing in a memory task.

We investigated whether people can discriminate between sources of information that are either credible or respond at random, based only on their own knowledge and the responses provided by these sources. In three experiments, participants were asked to judge the validity of trivia statements. Some statements were accompanied by true/false responses provided by either a credible source or a source whose responses were random. In Experiment 1, participants first saw a set of easy questions, which provided the basis for assessing the relative credibility of the sources, before responding to a set of difficult questions, where response borrowing was assessed. In Experiments 2 and 3, participants solved a test composed of difficult questions only, but only after studying the correct responses to all these questions. In Experiment 2, there was no delay between the study and test phases, whereas in Experiment 3, the delay was 24 hours. In all experiments, more participants explicitly identified the more credible source in the postexperimental questionnaire than misidentified the noninformative source as credible. However, differentiated response borrowing-borrowing more responses from the credible than the noninformative source-emerged only in Experiment 2. Therefore, people can often explicitly infer source credibility from the responses the sources provide. However, using these inferences to regulate response borrowing is relatively less likely and happens only under specific, favorable circumstances.

The Influence of SARS-CoV-2 Infection on the Thyroid Gland.

It is important to acknowledge the impact that COVID-19 has on the thyroid gland and how the thyroid gland status before and during infection affects SARS-CoV-2 severity. To this day those dependencies are not fully understood. It is known that the virus uses angiotensin-converting enzyme-2 as the receptor for cellular entry and it can lead to multiple organ failures due to a cytokine storm. Levels of proinflammatory molecules (such as cytokines and chemokines) which are commonly elevated during infection were significantly higher in observed SARS-CoV-2-positive patients. In terms of hypothyroidism, hyperthyroidism, and autoimmune thyroid diseases, there is no proof that those dysfunctions have a direct impact on the more severe courses of COVID-19. Regarding hyper- and hypothyroidism there was no consequential dependency between the frequency of SARS-CoV-2 infection morbidity and more severe post-infectious complications. When it comes to autoimmune thyroid diseases, more evaluation has to be performed due to the unclear relation with the level of antibodies commonly checked in those illnesses and its binding with the mentioned before virus. Nonetheless, based on analyzed works we found that COVID-19 can trigger the immune system and cause its hyperactivity, sometimes leading to the new onset of autoimmune disorders. We also noticed more acute SARS-CoV-2 courses in patients with mainly reduced free triiodothyronine serum levels, which in the future, might be used as a mortality indicating factor regarding SARS-CoV-2-positive patients. Considering subacute thyroiditis (SAT), no statistically important data proving its direct correlation with COVID-19 infection has been found. Nevertheless, taking into account the fact that SAT is triggered by respiratory tract viral infections, it might be that SARS-CoV-2 can cause it too. There are many heterogenous figures in the symptoms, annual morbidity distribution, and frequency of new cases, so this topic requires further evaluation.

Guessing can benefit memory for related word pairs even when feedback is delayed.

Trying to guess what the correct answer to a question might be can facilitate future learning of this answer when presented in the form of corrective feedback. One issue that determines the effectiveness of guessing as a learning strategy is the timing of the presentation of feedback: it can be presented either immediately after the guess, or after a delay. Whereas the timing of feedback is of little importance for complex materials such as trivia questions, previous research suggests that for simpler materials such as related word pairs guessing seems to benefit learning only when feedback is immediate. In order to test whether this always has to be the case, we conducted two experiments in which we increased the richness of study materials by superimposing the to-be-learned word pairs over unrelated context pictures. We then manipulated the match between contexts at study and at test (Experiment 1) and at the time of feedback delivery (Experiment 2). Contrary to previous studies showing no benefits of guessing with delayed feedback, our results show that learning related word pairs can benefit from guessing even when feedback is delayed. These benefits of guessing occur if participants are reminded via reinstated contexts of the guessing stage at the time of feedback delivery. Our results help constrain theories of guessing benefits and extend theories of reminding.

Elaboration by superposition: From interference in working memory to encoding in long-term memory.

Distraction embedded in working memory tasks leads to impaired performance. This impairment is mitigated when targets and distractors that follow them share common features-a signature effect of interference by superposition. Here we propose that target-distractor similarity modulates not only forgetting from working memory but also encoding into long-term memory. In five experiments, we test this elaboration-by-superposition hypothesis, demonstrating that semantic relatedness between targets and distractors benefits delayed category-cued recall performance (Experiments 1a and 1b), which is not due to carry-over effects from working memory testing (Experiment 2). Just as in the case of working memory, this long-term memory effect is reduced when distractors precede targets (Experiment 3). Finally, we show that while high target-distractor similarity reduces forgetting from working memory, it produces net benefits for long-term memory performance (Experiment 4). Together, the results suggest that common mechanisms underlie encoding into working and long-term memory, and that bindings between features of spatiotemporal context and features of to-be-remembered items play a crucial role. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Acromegaly Caused by Ectopic Growth Hormone Releasing Hormone Secretion: A Review.

Introduction: Ectopic acromegaly is a rare condition caused most frequently by growth hormone releasing hormone (GHRH) secretion from neuroendocrine tumors. The diagnosis is often difficult to establish as its main symptoms do not differ from those of acromegaly of pituitary origin. Objectives: To determine most common clinical features and diagnostic challenges in ectopic acromegaly. Patients and Methods: A search for ectopic acromegaly cases available in literature was performed using PubMed, Cochrane, and MEDline database. In this article, 127 cases of ectopic acromegaly described after GHRH isolation in 1982 are comprehensively reviewed, along with a summary of current state of knowledge on its clinical features, diagnostic methods, and treatment modalities. The most important data were compiled and compared in the tables. Results: Neuroendocrine tumors were confirmed in 119 out of 121 patients with histopathological evaluation, mostly of lung and pancreatic origin. Clinical manifestation comprise symptoms associated with pituitary hyperplasia, such as headache or visual field disturbances, as well as typical signs of acromegaly. Other endocrinopathies may also be present depending on the tumor type. Definitive diagnosis of ectopic acromegaly requires confirmation of GHRH secretion from a tumor using either histopathological methods or GHRH plasma concentration assessment. Hormonal evaluation was available for 84 patients (66%) and histopathological confirmation for 99 cases (78%). Complete tumor resection was the main treatment method for most patients as it is a treatment of choice due to its highest effectiveness. When not feasible, somatostatin receptor ligands (SRL) therapy is the preferred treatment option. Prognosis is relatively favorable for neuroendocrine GHRH-secreting tumors with high survival rate. Conclusion: Although ectopic acromegaly remains a rare disease, one should be aware of it as a possible differential diagnosis in patients presenting with additional symptoms or those not responding to classic treatment of acromegaly.

The Thousand Polish Genomes-A Database of Polish Variant Allele Frequencies.

Although Slavic populations account for over 4.5% of world inhabitants, no centralised, open-source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for clinical genetics, biomedical research, as well as archeological and historical studies. The Polish population, which is homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a genetic reference for the Slavic nations. In this study, we analysed whole genomes of 1222 Poles to identify and genotype a wide spectrum of genomic variation, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups, and de novo variants. Common variant analyses showed that the Polish cohort is highly homogenous and shares ancestry with other European populations. In rare variant analyses, we identified 32 autosomal-recessive genes with significantly different frequencies of pathogenic alleles in the Polish population as compared to the non-Finish Europeans, including C2, TGM5, NUP93, C19orf12, and PROP1. The allele frequencies for small and structural variants, calculated for 1076 unrelated individuals, are released publicly as The Thousand Polish Genomes database, and will contribute to the worldwide genomic resources available to researchers and clinicians.

Effect of Quinoline on the Phospholipid Profile of Curvularia lunata and Its Microbial Detoxification.

Quinoline is an N-heterocyclic compound commonly found in wastewater, especially that derived from coal processing, chemical, and pharmaceutical industries. In the present study, the microscopic fungus Curvularia lunata IM 4417, which is known to degrade various xenobiotics, was used. The aim of the research was to study the elimination of quinoline and its influence on fungal phospholipids, which are considered to be excellent indicators of environmental monitoring. Quinoline biodegradation products and phospholipid contents were analyzed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. C. lunata IM 4417 degraded quinoline, which led to the formation of conjugates of glucose with hydroxylated derivatives of the compound. Toxicity tests (Artoxkit M and Microtox assay) indicated that the elimination of lower concentrations of quinoline was efficient and led to a reduction in sample toxicity. The presence of quinoline also significantly affected the profile of fatty acids and phospholipids. The addition of quinoline to a culture of C. lunata IM 4417 caused an increase in the content of phosphatidylcholine (PC) and a decrease in the amount of phosphatidylethanolamine (PE), two major structural lipids. Additionally, decreases in the contents of phosphatidylinositol (PI) and phosphatidylserine (PS), which are responsible for tolerance to toxic substances, cell viability, and signal transduction, were noted. Thus, it can be concluded that the presence of quinoline modifies the membrane composition, and this change may be an important indicator of the presence of N-heterocyclic compounds or other toxins in the environment.

NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis.

Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis. The aim of the study was to reveal genetic factors responsible for thyroid maldevelopment in two siblings with THA. None of the family members presented with congenital heart defect. The samples were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Enrichment Kit, San Diego, CA 92121, USA). An ultra-rare variant c.839C>T (p.Pro280Leu) in NKX2-5 gene (NM_004387.4) was identified in both affected children and an unaffected father. In the mother, the variant was not present. This variant is reported in population databases with 0.0000655 MAF (GnomAD v3, dbSNP rs761596254). The affected amino acid position is moderately conserved (positive scores in PhyloP: 1.364 and phastCons: 0.398). Functional prediction algorithms showed deleterious impact (dbNSFP v4.1, FATHMM, SIFT) or benign (CADD, PolyPhen-2, Mutation Assessor). According to ACMG criteria, variant is classified as having uncertain clinical significance. For the first time, NKX2-5 gene variants were found in two siblings with THA, providing evidence for its potential contribution to the pathogenesis of this type of thyroid dysgenesis. The presence of the variant in an unaffected parent, carrier of p.Pro280Leu variant, suggests potential contribution of yet unidentified additional factors determining the final penetrance and expression.

The Synergistic Effect of Triterpenoids and Flavonoids-New Approaches for Treating Bacterial Infections?

Currently, the pharmaceutical industry is well-developed, and a large number of chemotherapeutics are being produced. These include antibacterial substances, which can be used in treating humans and animals suffering from bacterial infections, and as animal growth promoters in the agricultural industry. As a result of the excessive use of antibiotics and emerging resistance amongst bacteria, new antimicrobial drugs are needed. Due to the increasing trend of using natural, ecological, and safe products, there is a special need for novel phytocompounds. The compounds analysed in the present study include two triterpenoids ursolic acid (UA) and oleanolic acid (OA) and the flavonoid dihydromyricetin (DHM). All the compounds displayed antimicrobial activity against Gram-positive (Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Listeria monocytogenes ATCC 19115) and Gram-negative bacteria (Escherichia coli ATCC 25922, Proteus hauseri ATCC 15442, and Campylobacter jejuni ATCC 33560) without adverse effects on eukaryotic cells. Both the triterpenoids showed the best antibacterial potential against the Gram-positive strains. They showed synergistic activity against all the tested microorganisms, and a bactericidal effect with the combination OA with UA against both Staphylococcus strains. In addition, the synergistic action of DHM, UA, and OA was reported for the first time in this study. Our results also showed that combination with triterpenoids enhanced the antimicrobial potential of DHM.

You won't guess that: On the limited benefits of guessing when learning a foreign language.

Guessing the meaning of a foreign word before being presented with the right answer benefits recognition performance for the translation compared to reading the full translation outright. However, guessing does not increase memory for the foreign-word-to-translation associations, which is crucial for language acquisition. In this study, we aimed to investigate whether this disadvantage of guessing for performance in cued-recall tests would be eliminated if a restudy phase was added. In Experiments 1-3, we consistently demonstrated that guessing resulted in lower cued-recall performance compared to reading, both before and after restudy. Even for items for which participants successfully recalled their initial guesses on the cued-recall test, accuracy levels did not exceed those from the reading condition. In Experiment 4, we aimed to generalize our findings concerning restudy to a different set of materials - weakly associated word pairs. Even though this time guessing led to better performance than reading, consistent with previous studies, this guessing benefit was not moderated by adding a restudy phase. Our results thus underscore the importance of the initial learning phase for future learning and retention, while undermining the usefulness of the learning-through-guessing strategy for acquiring foreign language vocabulary.

Evaluation of the Antimicrobial Potential and Toxicity of a Newly Synthesised 4-(4-(Benzylamino)butoxy)-9H-carbazole.

One of the greatest threats to human and animal health is posed by infections caused by drug-resistant bacterial strains. Therefore, newly synthesised substances are tested for their antimicrobial activity. Carbazole derivatives seem to be promising antibacterial agents. This study aimed at investigating the toxicity and activity of newly synthesised, functionalised carbazole derivative 2 (4-(4-(benzylamino)butoxy)-9H-carbazole) against various microorganisms. Its antimicrobial potential against Gram-positive and Gram-negative bacteria, yeast, and filamentous fungi was examined according to CLSI (Clinical and Laboratory Standards Institute) standards. The tested compound was found to efficiently inhibit the growth of Gram-positive strains. The addition of carbazole derivative 2 at the concentration of 30 µg/mL caused inhibition of bacterial growth by over 95%. Moreover, about 50 and 45% limitation of Pseudomonas aeruginosa and Aspergillus flavus growth was observed in the samples incubated with the addition of 20 and 60 µg/mL of the compound, respectively. Its addition to the microbial cultures caused an increase in the permeability of the cellular membrane. Slight haemolysis of red blood cells was observed after 24-h treatment with carbazole derivative 2. On the other hand, human fibroblasts were found to be more sensitive to its effects. The activity of the tested compound indicates a possibility of its further modification in order to obtain effective drugs, especially against drug-resistant staphylococci.

Comparison of the Toxicity of Pristine Graphene and Graphene Oxide, Using Four Biological Models.

There are numerous applications of graphene in biomedicine and they can be classified into several main areas: delivery systems, sensors, tissue engineering and biological agents. The growing biomedical field of applications of graphene and its derivates raises questions regarding their toxicity. We will demonstrate an analysis of the toxicity of two forms of graphene using four various biological models: zebrafish (Danio rerio) embryo, duckweed (Lemna minor), human HS-5 cells and bacteria (Staphylococcus aureus). The toxicity of pristine graphene (PG) and graphene oxide (GO) was tested at concentrations of 5, 10, 20, 50 and 100 µg/mL. Higher toxicity was noted after administration of high doses of PG and GO in all tested biological models. Hydrophilic GO shows greater toxicity to biological models living in the entire volume of the culture medium (zebrafish, duckweed, S. aureus). PG showed the highest toxicity to adherent cells growing on the bottom of the culture plates-human HS-5 cells. The differences in toxicity between the tested graphene materials result from their physicochemical properties and the model used. Dose-dependent toxicity has been demonstrated with both forms of graphene.

CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy.

The relationship between congenital defects of the brain and facial anomalies was proven. The Hedgehog signaling pathway plays a fundamental role in normal craniofacial development in humans. Mutations in the sonic hedgehog (SHH) signaling gene CDON have been recently reported in patients with holoprosencephaly and with pituitary stalk interruption syndrome (PSIS). This study's aim was an elucidation of an 18-year-old patient presenting PSIS, multiple pituitary hormone deficiency, and congenital unilateral facial and abducens nerve palsy. Additionally, bilateral sensorineural hearing loss, dominating at the right site, was diagnosed. From the second year of life, growth deceleration was observed, and from the age of eight, anterior pituitary hormone deficiencies were gradually confirmed and substituted. At the MRI, characteristic triad for PSIS (anterior pituitary hypoplasia, interrupted pituitary stalk and ectopic posterior lobe) was diagnosed. We performed a comprehensive genomic screening, including microarrays for structural rearrangements and whole-exome sequencing for a monogenic defect. A novel heterozygous missense variant in the CDON gene (c.1814G > T; p.Gly605Val) was identified. The variant was inherited from the mother, who, besides short stature, did not show any disease symptoms. The variant was absent in control databases and 100 healthy subjects originating from the same population. We report a novel variant in the CDON gene associated with PSIS and congenital cranial nerve palsy. The variant revealed autosomal dominant inheritance with incomplete penetrance in concordance with previous studies reporting CDON defects.