Sexual health and sexual well-being of women with Mayer-Rokitansky-Kuester-Hauser syndrome after vaginal reconstruction: a qualitative analysis.

BACKGROUND: Contradictory findings on sexual health in women with Mayer-Rokitansky-Kuester-Hauser syndrome (MRKHS) after vaginal reconstruction point toward the need for more profound assessment of this subject, particularly as it is still unclear what constitutes sexual well-being, especially genital self-image or sexual self-esteem, in women with MRKHS and neovagina. AIM: The aim of this qualitative study was to assess individual sexual health and sexual well-being in the context of MRKHS after vaginal reconstruction, with an emphasis on genital self-image, sexual self-esteem, sexual satisfaction, and coping with MRKHS. METHODS: Qualitative semistructured interviews were conducted with women with MRKHS after vaginal reconstruction (n = 10) with the Wharton-Sheares-George surgical method and a matched control group without MRKHS (n = 20). Women were surveyed about their previous and current sexual activities, perception of and attitudes toward their genitals, disclosure to others, coping with the diagnosis, and perception of surgery. Data were analyzed through qualitative content analysis and compared with the control group. OUTCOMES: The primary outcomes of the study were major categories, such as sexual satisfaction, sexual self-esteem, genital self-image, and dealing with MRKHS, as well as subcategories related to the content analysis. RESULTS: Although half the women in the present study indicated that they were coping well with their condition and were satisfied with sexual intercourse, most felt insecure about their neovagina, were cognitively distracted during intercourse, and showed low levels of sexual self-esteem. CLINICAL IMPLICATIONS: A better understanding of expectations and uncertainties regarding the neovagina might help professionals to support women with MRKHS after vaginal reconstruction to increase sexual well-being. STRENGTHS AND LIMITATIONS: This is the first qualitative study focusing on individual aspects of sexual well-being, especially sexual self-esteem and genital self-image, in women with MRKHS and neovagina. The qualitative study indicates good interrater reliability and data saturation. The limitations of this study include the inherent lack of objectivity resulting from the method but also the fact that all the patients had a particular surgical technique, consequently resulting in limited generalizability of these findings. CONCLUSIONS: Our data indicate that integrating the neovagina into the genital self-image is a prolonged process that is essential for sexual well-being and should thus be the focus of sexual counseling.

Termination of pregnancy for fetal malformation: A traumatic event? A qualitative analysis of women's perception.

Objective: To investigate women's experience of termination of pregnancy (TOP) for severe fetal malformation.We focus on women's individual perception of psychological counselling on decision making, experiencing the birth process, seeing and holding the baby as well as emotional processing. Methods: An explorative study was conducted with 42 women (the age range was between 21 and 45 years [mean 36.17; SD±6.66]) on average twelve months after TOP using semi-structured qualitative interviews. All women received psychological counselling before, during and after the time of TOP (mean 5.2; range 2-11), at the initial counselling session all partners were present. Data were analysed by means of qualitative content analysis by Mayring; the main research question focused on women's perception of psychological counselling on experiencing TOP and coping with this incisive life event. Results: After receiving psychological counselling most of the women felt sufficiently prepared to make a decision, to experience the birth process and to bid farewell to their child. Seeing and holding the baby were perceived as helpful for emotional processing. At the time of the interview, despite the emotional distress,most women reported having positivememories and felt they had coped with the loss. Conclusions: Long-term psychological care from the time of diagnosis through TOP and follow up impacts positively on experiencing TOP, saying farewell to the child and integrating the loss into life. Further studies to detect women at risk for prolonged mourning-reactions are needed.

Sexuality and Multiple Sclerosis: Patient and Doctor Perspectives.

BACKGROUND: Little is known on how to address sexuality in clinical care for patients with multiple sclerosis (pwMS). AIM: To describe and contrast the perception of sexuality and associated aspects of communication in pwMS and their treating neurologists ("MSologists") and provide a standard of care. METHODS: Patients were surveyed using a 13-item questionnaire investigating perception on their own sexuality and opinions on communication about sexuality in context with MS. Certified MSologists in Austria received an 18-item survey regarding their approach to taking a sexual history of their patients. OUTCOMES: We report the frequency of answers given in this survey and propose a possible standard of care how sexuality could be addressed in clinical routine. RESULTS: Ninety-three pwMS (mean age 39 ± 11 years, 57% female) and 75 MSologists (mean age 43 ± 9 years, 63% male) completed this survey. Seventy-six percent of patients report their own sexuality as being (very) important to them and 95% think that sexual dysfunction would influence their quality of life. 84% would like to be asked about their sexuality by their MSologist. In contrast, only 15% of MSologists reported discussing sexuality with every patient. The most common reason for not doing so was a fear of crossing personal borders (34%). There is a strong desire for further medical education on this subject (76%). CLINICAL IMPLICATIONS: Discussing sexuality is important to pwMS and MSologists should consider their patients' wishes and needs to talk about it. STRENGTHS & LIMITATIONS: This is the largest survey contrasting the views of patients and their treating physicians on the topic of communication about sexuality. The use of an empirical unvalidated questionnaire may have introduced bias. Moreover, patients that are open to talk about their sexuality may be potentially overrepresented in this study. CONCLUSION: MSologists should offer their patients an open opportunity and appropriate framework to discuss their sexuality during a consultation. Altmann P, Leithner K, Leutmezer F, et al. Sexuality and Multiple Sclerosis: Patient and Doctor Perspectives. J Sex Med 2021;18:743-749.

The glycerol backbone of phospholipids derives from noncarbohydrate precursors in starved lung cancer cells.

Cancer cells are reprogrammed to consume large amounts of glucose to support anabolic biosynthetic pathways. However, blood perfusion and consequently the supply with glucose are frequently inadequate in solid cancers. PEPCK-M (PCK2), the mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK), has been shown by us and others to be functionally expressed and to mediate gluconeogenesis, the reverse pathway of glycolysis, in different cancer cells. Serine and ribose synthesis have been identified as downstream pathways fed by PEPCK in cancer cells. Here, we report that PEPCK-M-dependent glycerol phosphate formation from noncarbohydrate precursors (glyceroneogenesis) occurs in starved lung cancer cells and supports de novo glycerophospholipid synthesis. Using stable isotope-labeled glutamine and lactate, we show that PEPCK-M generates phosphoenolpyruvate and 3-phosphoglycerate, which are at least partially converted to glycerol phosphate and incorporated into glycerophospholipids (GPL) under glucose and serum starvation. This pathway is required to maintain levels of GPL, especially phosphatidylethanolamine (PE), as shown by stable shRNA-mediated silencing of PEPCK-M in H23 lung cancer cells. PEPCK-M shRNA led to reduced colony formation after starvation, and the effect was partially reversed by the addition of dioleyl-PE. Furthermore, PEPCK-M silencing abrogated cancer growth in a lung cancer cell xenograft model. In conclusion, glycerol phosphate formation for de novo GPL synthesis via glyceroneogenesis is a newly characterized anabolic pathway in cancer cells mediated by PEPCK-M under conditions of severe nutrient deprivation.

Flexibility and Adaptation of Cancer Cells in a Heterogenous Metabolic Microenvironment.

The metabolic microenvironment, comprising all soluble and insoluble nutrients and co-factors in the extracellular milieu, has a major impact on cancer cell proliferation and survival. A large body of evidence from recent studies suggests that tumor cells show a high degree of metabolic flexibility and adapt to variations in nutrient availability. Insufficient vascular networks and an imbalance of supply and demand shape the metabolic tumor microenvironment, which typically contains a lower concentration of glucose compared to normal tissues. The present review sheds light on the recent literature on adaptive responses in cancer cells to nutrient deprivation. It focuses on the utilization of alternative nutrients in anabolic metabolic pathways in cancer cells, including soluble metabolites and macromolecules and outlines the role of central metabolic enzymes conferring metabolic flexibility, like gluconeogenesis enzymes. Moreover, a conceptual framework for potential therapies targeting metabolically flexible cancer cells is presented.

Panobinostat reduces hypoxia-induced cisplatin resistance of non-small cell lung carcinoma cells via HIF-1α destabilization.

BACKGROUND: Lung cancer is one of the most frequent cancer types and the leading cause of cancer death worldwide. Cisplatin is a widely used chemotherapeutic for non-small cell lung carcinoma (NSCLC), however, its positive effects are diminished under hypoxia. We wanted to determine if co-treatment with cisplatin and histone deacetalyse (HDAC) inhibitor panobinostat can reduce hypoxia-induced cisplatin resistance in NSCLC cells, and to elucidate mechanism involved. METHODS: Expression status of different HDACS was determined in two cell lines and in tumor tissue from 20 patients. Cells were treated with cisplatin, panobinostat, or with combination of both under normoxic and hypoxic (1% O(2)) conditions. Cell cycle, viability, acetylation of histones, and activation of apoptosis were determined. HIF-1α stability and its interaction with HDAC4 were analyzed. RESULTS: Most class I and II HDACs were expressed in NSCLC cells and tumor samples. Co-treatment of tumor cells with cisplatin and panobinostat decreased cell viability and increased apoptosis more efficiently than in primary, non-malignant bronchial epithelial cells. Co-treatment induced apoptosis by causing chromatin fragmentation, activation of caspases-3 and 7 and PARP cleavage. Toxic effects were more pronounced under hypoxic conditions. Co-treatment resulted in destabilization and degradation of HIF-1α and HDAC4, a protein responsible for acetylation and de/stabilization of HIF-1α. Direct interaction between HDAC4 and HIF-1α proteins in H23 cells was detected. CONCLUSIONS: Here we show that hypoxia-induced cisplatin resistance can be overcome by combining cisplatin with panobinostat, a potent HDAC inhibitor. These findings may contribute to the development of a new therapeutic strategy for NSCLC.

Stress matters! Psychophysiological and emotional loadings of pregnant women undergoing fetal magnetic resonance imaging.

BACKGROUND: While the application of fetal MRI in high-risk pregnant women is steadily rising, little is known about the psychological consequences of this procedure. The aim of the present study was to investigate emotional and psychophysiological reactions of females undergoing fetal MRI. METHODS: Sixty women (17-44 ys), assigned for fetal MRI, were included. Affective state was assessed by standardized measures of anxiety, emotional states and depressive symptoms. Stress coping strategies were assessed using a self-report questionnaire. Stress responses were determined using skin conductance levels (SCL) during fetal MRI as well as measurement of salivary cortisol levels immediately before and after fetal MRI. RESULTS: Analysis of fast and slow physiological stress measures revealed significant differences between women with and without a supporting person accompanying them to the examination. For SCLs, lower levels of stress during MRI emerged in accompanied women. Women with well-marked stress-coping-strategies experienced lower levels of stress during the examination. Although fast and slow stress measures before and after MRI did not show significant correlations, a significant difference of SCLs pre and post examination was clearly detectable, as well as a trend of decreased cortisol levels for both time points. CONCLUSIONS: The results imply that the elevation of SCLs is an accurate instrument to assess fast stress alterations in patients during fetal MRI. Stress coping strategies and whether women are accompanied or not play an important role in the experience of anxiety and depressive symptoms. These factors should be considered especially in patients with high-risk-pregnancies to improve patient care.

Hypoxia increases membrane metallo-endopeptidase expression in a novel lung cancer ex vivo model - role of tumor stroma cells.

BACKGROUND: Hypoxia-induced genes are potential targets in cancer therapy. Responses to hypoxia have been extensively studied in vitro, however, they may differ in vivo due to the specific tumor microenvironment. In this study gene expression profiles were obtained from fresh human lung cancer tissue fragments cultured ex vivo under different oxygen concentrations in order to study responses to hypoxia in a model that mimics human lung cancer in vivo. METHODS: Non-small cell lung cancer (NSCLC) fragments from altogether 70 patients were maintained ex vivo in normoxia or hypoxia in short-term culture. Viability, apoptosis rates and tissue hypoxia were assessed. Gene expression profiles were studied using Affymetrix GeneChip 1.0 ST microarrays. RESULTS: Apoptosis rates were comparable in normoxia and hypoxia despite different oxygenation levels, suggesting adaptation of tumor cells to hypoxia. Gene expression profiles in hypoxic compared to normoxic fragments largely overlapped with published hypoxia-signatures. While most of these genes were up-regulated by hypoxia also in NSCLC cell lines, membrane metallo-endopeptidase (MME, neprilysin, CD10) expression was not increased in hypoxia in NSCLC cell lines, but in carcinoma-associated fibroblasts isolated from non-small cell lung cancers. High MME expression was significantly associated with poor overall survival in 342 NSCLC patients in a meta-analysis of published microarray datasets. CONCLUSIONS: The novel ex vivo model allowed for the first time to analyze hypoxia-regulated gene expression in preserved human lung cancer tissue. Gene expression profiles in human hypoxic lung cancer tissue overlapped with hypoxia-signatures from cancer cell lines, however, the elastase MME was identified as a novel hypoxia-induced gene in lung cancer. Due to the lack of hypoxia effects on MME expression in NSCLC cell lines in contrast to carcinoma-associated fibroblasts, a direct up-regulation of stroma fibroblast MME expression under hypoxia might contribute to enhanced aggressiveness of hypoxic cancers.

Development of thiolated poly(acrylic acid) microparticles for the nasal administration of exenatide.

The purpose of this study was to develop a microparticulate formulation for nasal delivery of exenatide utilizing a thiolated polymer. Poly(acrylic acid)-cysteine (PAA-cys) and unmodified PAA microparticles loaded with exenatide were prepared via coprecipitation of the drug and the polymer followed by micronization. Particle size, drug load and release of incorporated exenatide were evaluated. Permeation enhancing properties of the formulations were investigated on excised porcine respiratory mucosa. The viability of the mucosa was investigated by histological studies. Furthermore, ciliary beat frequency (CBF) studies were performed. Microparticles displayed a mean size of 70-80 µm. Drug encapsulation was ∼80% for both thiolated and non-thiolated microparticles. Exenatide was released from both thiolated and non-thiolated particles in comparison to exenatide in buffer only within 40 min. As compared to exenatide dissolved in buffer only, non-thiolated and thiolated microparticles resulted in a 2.6- and 4.7-fold uptake, respectively. Histological studies performed before and after permeation studies showed that the mucosa is not damaged during permeation studies. CBF studies showed that the formulations were cilio-friendly. Based on these results, poly(acrylic acid)-cysteine-based microparticles seem to be a promising approach starting point for the nasal delivery of exenatide.

Metabolic heterogeneity in cancer.

Cancer cells rewire their metabolism to survive during cancer progression. In this context, tumour metabolic heterogeneity arises and develops in response to diverse environmental factors. This metabolic heterogeneity contributes to cancer aggressiveness and impacts therapeutic opportunities. In recent years, technical advances allowed direct characterisation of metabolic heterogeneity in tumours. In addition to the metabolic heterogeneity observed in primary tumours, metabolic heterogeneity temporally evolves along with tumour progression. In this Review, we summarize the mechanisms of environment-induced metabolic heterogeneity. In addition, we discuss how cancer metabolism and the key metabolites and enzymes temporally and functionally evolve during the metastatic cascade and treatment.

Men don't cry: The supporting role as necessary for women's well-being after termination of pregnancy.

OBJECTIVES: The present study investigated similarities and differences of grief between men and women as part of the parental couple 1 year after termination of pregnancy (TOP) following a diagnosis of fetal anomaly. METHODS: We applied a method triangulation approach. We assessed several aspects of perinatal grief, depressive symptoms, posttraumatic stress, and anxiety as well as health-related quality of life. In addition, we conducted qualitative interviews with the men to explore the fathers' roles in the partnership during pregnancy, the time of the diagnosis, TOP, and afterwards. RESULTS: Women showed a more elevated grief response compared with men. Qualitative data revealed that men in our sample were mainly concerned with their partners' well-being and concentrated on supporting their partners rather than on their own emotions. In addition, the supportive role of the male partner plays a central role in the well-being of women and the man's coping with the situation. CONCLUSION: In clinical work, but also when developing new questionnaires, the specific role of the male partners needs to be considered more thoroughly. Particular attention should be paid to identify the men who find it difficult to assume the supporting role.

Serine synthesis and catabolism in starved lung cancer and primary bronchial epithelial cells.

Serine and glycine give rise to important building blocks in proliferating cells. Both amino acids are either synthesized de novo or taken up from the extracellular space. In lung cancer, serine synthesis gene expression is variable, yet, expression of the initial enzyme, phosphoglycerate dehydrogenase (PHGDH), was found to be associated with poor prognosis. While the contribution of de novo synthesis to serine pools has been shown to be enhanced by serine starvation, the impact of glucose deprivation, a commonly found condition in solid cancers is poorly understood. Here, we utilized a stable isotopic tracing approach to assess serine and glycine de novo synthesis and uptake in different lung cancer cell lines and normal bronchial epithelial cells in variable serine, glycine, and glucose conditions. Under low glucose supplementation (0.2 mM, 3-5% of normal plasma levels), serine de novo synthesis was maintained or even activated. As previously reported, also gluconeogenesis supplied carbons from glutamine to serine and glycine under these conditions. Unexpectedly, low glucose treatment consistently enhanced serine to glycine conversion, along with an up-regulation of the mitochondrial one-carbon metabolism enzymes, serine hydroxymethyltransferase (SHMT2) and methylenetetrahydrofolate dehydrogenase (MTHFD2). The relative contribution of de novo synthesis greatly increased in low serine/glycine conditions. In bronchial epithelial cells, adaptations occurred in a similar fashion as in cancer cells, but serine synthesis and serine to glycine conversion, as assessed by label enrichments and gene expression levels, were generally lower than in (PHGDH positive) cancer cells. In summary, we found a variable contribution of glucose or non-glucose carbon sources to serine and glycine and a high adaptability of the downstream one-carbon metabolism pathway to variable glucose supply.

Mentalizing in female inpatients with major depressive disorder.

Depression is associated with profound impairments in social and interpersonal functioning. However, little research has addressed deficits in mentalizing capacity that may underlie these impairments. The aim of this study was, therefore, to investigate the capacity for mentalization in female inpatients with depression in comparison with healthy controls. We assessed 46 inpatients with major depressive disorder with regard to psychiatric diagnoses, severity of depression, cognitive impairment, and verbal intelligence. In addition, 20 healthy controls matched for sex, age, and education were included. Mentalization was scored on the Adult Attachment Interview using the Reflective Functioning Scale. The female inpatients with depression showed a significantly lower capacity for mentalization compared with the healthy controls. Mentalization deficits were not restricted to depression-specific topics. Moreover, deficits in mentalizing capacity were related to illness duration, number of admissions, and cognitive impairment. The results indicate severe impairment in the ability of the female inpatients with depression to identify and interpret mental states of the self and others. Correlations with illness duration and number of admissions suggest that a chronic course of depression results in further mentalizing impairments. The investigation of mentalization may be of particular importance for the development of targeted psychotherapeutic interventions for depression.

Psychological reactions related to fetal magnetic resonance imaging: a follow-up study.

AIMS: To assess the women's retrospective perception of fetal magnetic resonance imaging (MRI). METHODS: Thirty-six women were investigated 1 year after fetal MRI. Data was acquired by telephone interviews and standardised rating scales (i.e., Postscan Imaging Distress Questionnaire, mood and anxiety scales). RESULTS: In retrospect, most women felt that fetal MRI was associated with marked psychological distress, notably with significant greater distress than at the time of the actual investigation. In total, 55.6% of the women rated at least one aspect of fetal MRI as "not tolerable" at follow-up. These findings were irrespective of the affective status and of the outcome of the pregnancy. Yet, MRI was rated as "the most important" investigation during the prenatal period by 69.4% of subjects, and 80.6% felt that they had sufficiently been informed about the MRI findings. CONCLUSIONS: The acceptance of fetal MRI was found to be very high; however, fetal MRI is linked with marked psychological distress, which was still present - and in many cases even stronger - 1 year after the investigation. These data highlight the importance of sufficient information about fetal MRI and the necessity of adequate emotional support in this emotional vulnerable patient sample.

HEC-cysteamine particles: influence of particle size, zeta potential, morphology and sulfhydryl groups on permeation enhancing properties.

Within this study, the influence of particle size and zeta potential of hydroxyethyl cellulose-cysteamine particles on permeation enhancing properties was investigated. Particles were prepared by four different methods namely ionic gelation, spray drying, air jet milling and grinding. Particles prepared by grinding were additionally air jet milled. All particles were characterized in terms of particle size and zeta potential. The transport of fluorescein isothiocyanate-dextran 4 (FD4) across Caco-2 cell monolayers in the presence of these particles and the decrease in transepithelial electrical resistance (TEER) was evaluated. The cytotoxic effect of the particles was investigated using resazurin assay. Nanoparticles displaying a zeta potential of 3.3 ± 1.3 mV showed the highest enhancement of FD4 transport among all particles with a 5.83-fold improvement compared to buffer only. Due to the larger particle size, particles generated by grinding exhibited a lower capability in opening of tight junctions compared to smaller particles generated by air jet milling. In addition, the results of the transport studies were supported by the decrease in the TEER. All particle formulations tested were comparatively non-cytotoxic. Accordingly, the zeta potential and particle size showed a significant impact on the opening of tight junctions and hence could play an important role in the design of hydroxyethyl cellulose (HEC)-cysteamine-based nano- and micro-particles as drug delivery systems.

Peroxisome proliferator-activated receptor-ß/δ, the acute signaling factor in prostacyclin-induced pulmonary vasodilation.

As powerful vasodilators, prostacyclin analogues are presently the mainstay in the treatment of severe pulmonary arterial hypertension. Although the hemodynamic effects of prostacyclin analogues are well known, the molecular mechanism of their acute effects on pulmonary vascular tone and systemic vascular tone remains poorly understood. Peroxisome proliferator-activated receptor-ß/δ (PPARß/δ) was previously identified as a putative receptor responsible for the modulation of target gene expression in response to prostacyclin analogues. The present study investigated the signaling pathway of prostacyclin in human pulmonary arterial smooth muscle cells (PASMCs), and sought to define the role of PPARß/δ in the acute vasodilating effect. In human PASMCs, prostacyclin rapidly activated TWIK-related acid-sensitive K channel 1 (TASK-1) and calcium-dependent potassium channels (K(Ca)). This pathway was mediated via the prostanoid I receptor-protein kinase A pathway. The silencing of PPARß/δ demonstrated that the downstream K(Ca) activation was exclusively dependent on PPARß/δ signaling, whereas the activation of TASK-1 was not. In addition, the PPARß/δ-induced activation of K(Ca) was independent of NO. The acute prostacyclin-induced K(Ca) activation is critically dependent on PPARß/δ as a rapid signaling factor. This accounts in part for the vasodilating effect of prostacyclin in pulmonary arteries, and provides insights into a new molecular explanation for the effects of prostanoids.

S-protected thiolated chitosan for oral delivery of hydrophilic macromolecules: evaluation of permeation enhancing and efflux pump inhibitory properties.

The objective of this study was the investigation of permeation enhancing and P-glycoprotein (P-gp) inhibition effects of a novel thiolated chitosan, the so-named S-protected thiolated chitosan. Mediated by a carbodiimide, increasing amounts of thioglycolic acid (TGA) were covalently bound to chitosan (CS) in the first step of modification. In the second step, these thiol groups of thiolated chitosan were protected by disulfide bond formation with the thiolated aromatic residue 6-mercaptonicotinamide (6-MNA). Mucoadhesive properties of all conjugates were evaluated in vitro on porcine intestinal mucosa based on tensile strength investigations. Permeation enhancing effects were evaluated ex vivo using rat intestinal mucosa and in vitro via Caco-2 cells using the hydrophilic macromolecule FD(4) as the model drug. Caco-2 cells were further used to show P-gp inhibition effects by using Rho-123 as P-gp substrate. Apparent permeability coefficients (P(app)) were calculated and compared to values obtained from each buffer control. Three different thiolated chitosans were generated in the first step of modification, which displayed increasing amounts of covalently attached free thiol groups on the polymer backbone. In the second modification step, more than 50% of these free thiol groups were covalently linked with 6-MNA. Within 3 h of permeation studies on excised rat intestine, P(app) values of all S-protected chitosans were at least 1.3-fold higher compared to those of corresponding thiomers and more than twice as high as that of unmodified chitosan. Additional permeation studies on Caco-2 cells confirmed these results. Because of the chemical modification and higher amount of reactive thiol groups, all S-protected thiolated chitosans exhibit at least 1.4-fold pronounced P-gp inhibition effects in contrast to their corresponding thiomers. These features approve S-protected thiolated chitosan as a promising excipient for various drug delivery systems providing improved permeation enhancing and efflux inhibition effects.

In situ gelling properties of anionic thiomers.

The aim of this study was to investigate in situ crosslinking systems of anionic thiolated polymers. In order to accelerate the increase in dynamic viscosity of thiolated polymers (thiomers), they were combined with hydrogen peroxide, carbamide peroxide and ammonium persulfate. Thiomers (pectin-cysteine (Pec-Cys), sodium carboxymethylcellulose-cysteine (NaCMC-Cys) and poly(acrylic acid)-cysteine (PAA-Cys)) were synthesized via amide bond formation between the carboxylic acid group of polymers and the primary amino group of l-cysteine. The rheological properties of 1% (m/v) thiomer solutions with oxidizing agents were compared by oscillatory measurements over time (120 min). Pec-Cys and NaCMC-Cys with hydrogen and carbamide peroxide showed a sol-gel phase transition within a few minutes and scored up to 13,000-fold increase in dynamic viscosity. Furthermore, only thiomers exhibiting a polysaccharide backbone (Pec-Cys and NaCMC-Cys) showed a significant increase in viscosity (p < 0.05). In contrast, measurements of carbohydrate thiomers in combination with ammonium persulfate showed an initial increase in viscosity. Afterwards, a decrease in viscosity was observed likely caused by chain scission. According to these results, carbohydrate thiomer/oxidizing agent systems might be useful for various pharmaceutical applications such as for in situ gelling liquid/semisolid formulations or in tissue engineering.

Circulating microRNAs as molecular biomarkers for lung adenocarcinoma.

BACKGROUND: The potential of microRNAs (miRNAs) as molecular tumor biomarkers for early diagnosis and prognosis in lung cancer is still unclear. OBJECTIVE: To analyze expression of miRNAs in A549 lung adenocarcinoma (LUAD) cells and in primary, non-malignant bronchial epithelial (BE) cells from healthy donors. To analyze the most prominently deregulated miRNAs in plasma samples of LUAD patients and healthy donors. MATERIALS AND METHODS: The expression of 752 miRNAs in LUAD and BE cells was assessed by RT-qPCR with mean-centering restricted normalization. The relative plasma levels of 18 miRNAs in LUAD patients and healthy donors were analyzed using RT-qPCR and normalized to miR-191-5p and miR-16-3p. Putative interactions between miRNAs and their target genes were investigated in silico. RESULTS: Out of 752 miRNAs, 37 miRNAs were significantly deregulated in A549 cells compared to BE cells. MiR-15b-3p, miR-148a-3p, miR-193b-3p, and miR-195-5p were significantly deregulated in plasma samples of LUAD patients compared to donors. The target genes of those four miRNAs are involved in essential mechanisms in cancer development and progression. CONCLUSIONS: There are substantial differences between cancer and control miRNA expression in vitro and in plasma samples of LUAD patients compared to healthy donors. Four deregulated miRNAs are promising as a diagnostic biomarker for adenocarcinoma of the lung.