Resilience, anxiety, depression, and life satisfaction in women suffering from endometriosis: a mediation model.

The main goal of this cross-sectional study was to assess the relationship between resilience and life satisfaction in women suffering from endometriosis and examine anxiety and depression as mediators in this relationship. The study sample included 349 Caucasian women aged from 18 to 56 years (M = 32.94; SD = 6.74) suffering from endometriosis surgically diagnosed and histologically confirmed. The life satisfaction level was assessed by the Satisfaction with Life Scale (SWLS). Unspecific anxiety was evaluated using the General Anxiety Disorder-7 scale (GAD-7). Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Resilience was measured using the Resilience Assessment Scale (SPP-25). Life satisfaction correlated negatively with anxiety and depression, but positively with resilience. Resilience correlated negatively with anxiety and depression. Anxiety and resilience accounted for 25% of the life satisfaction variance. Depression and resilience explained 35% of the variance in life satisfaction. Among resilience components, personal coping skills, tolerance of negative affect, tolerance of failures and treating life as a challenge, openness to new experiences and a sense of humour, and optimistic life attitude and ability to mobilize in difficult situations were the best predictors of life satisfaction. Anxiety and depression may serve as mediators in the relationship between resilience and life satisfaction. Our results suggested that resilience may be related to life satisfaction in women suffering from endometriosis directly and indirectly as mediated by anxiety and depression.

Gut-Lung Axis in Focus: Deciphering the Impact of Gut Microbiota on Pulmonary Arterial Hypertension.

Recent advancements in the understanding of pulmonary arterial hypertension (PAH) have highlighted the significant role of the gut microbiota (GM) in its pathogenesis. This comprehensive review delves into the intricate relationship between the GM and PAH, emphasizing the influence of gut microbial composition and the critical metabolites produced. We particularly focus on the dynamic interaction between the gut and lung, examining how microbial dysbiosis contributes to PAH development through inflammation, altered immune responses, and changes in the gut-lung axis. Noteworthy findings include variations in the ratios of key bacterial groups such as Firmicutes and Bacteroidetes in PAH and the pivotal roles of metabolites like trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and serotonin in the disease's progression. Additionally, the review elucidates potential diagnostic biomarkers and novel therapeutic approaches, including the use of probiotics and fecal microbiota transplantation, which leverage the gut microbiota for managing PAH. This review encapsulates the current state of research in this field, offering insights into the potential of gut microbiota modulation as a promising strategy in PAH diagnosing and treatment.

Examining the influence of functionalized POSS on the structure and bioactivity of flexible polyurethane foams.

This work reports for the first time on a new class of flexible polyurethane foam hybrids (PUFs) synthesized with the use of less toxic aliphatic hexamethylene diisocyanate (HDI), which have been chemically modified by POSS moieties. The flexible polyurethane foam hybrids (PUFs) chemically modified by functionalized polyhedral oligomeric silsesquioxanes: octa(3-hydroxy-3-methylbutyldimethylsiloxy)POSS (OCTA-POSS) and 1,2-propanediolizo-butylPOSS (PHI-POSS), was obtained. The resulting foams, which contain 0 to 15 wt % POSS, were characterized in terms of their structure, morphology, density and compressive strength. The FT-IR results indicate the chemical incorporation of both OCTAPOSS and PHIPOSS into the polyurethane matrix. SEM-EDS analysis showed that both OCTAPOSS and PHIPOSS nanoparticles are distributed homogeneously in the foam structure; at 15 wt % load PHIPOSS characteristic "crosses" are formed. With the increase of PHIPOSS content in the matrix, the formation of agglomerates is observed, as revealed by WAXD spectra. The introduction of POSS compounds reduces the porosity of the polyurethane, with the number of pores increasing as the amount of modifier increases. Mechanical tests - compressive strength - show that the hardness of modified materials (5 wt % POSS) increases compared to the reference material. An incubation was carried out in a simulated physiological fluid (SBF) to pre-assess the bioactivity of the materials obtained. The obtained results confirmed the formation of a hydroxyapatite layer on the PUF-POSS surface. Cytotoxicity, cell cycle and apoptosis of osteoblast cells and fibroblasts were assessed in the presence of the PUF-POSS materials. Test materials have a cytotoxic effect on both established cell lines. PUF-PHIPOSS samples showed better biocompatibility than reference and PUF-OCTAPOSS samples, as they caused lower mortality of the examined cells.

The non-canonical functions of telomerase: to turn off or not to turn off.

Telomerase is perceived as an immortality enzyme that enables passing the Hayflick limit. Its main function is telomere restoration but only in a limited group of cells, including cancer cells. Since it is found in a vast majority of cancer cells, it became a natural target for cancer therapy. However, it has much more functions than just altering the metabolism of telomeres-it also reveals numerous so-called non-canonical functions. Thus, a question arises whether it is always beneficial to turn it off when planning a cancer strategy and considering potential side effects? The purpose of this review is to discuss some of the recent discoveries about telomere-independent functions of telomerase in the context of cancer therapy and potential side effects.

Molecular analysis of biocompatibility of anodized titanium with deposited silver nanodendrites.

Titanium (>99.6% purity) and its anodically oxidized modifications, with and without deposited silver nanodendrites regarding its biocompatibility were evaluated. In human gingival fibroblasts and osteoblast cell lines grown on tested samples, the level of expression of genes encoding αV (ITGAV) and ß1 (ITGB1) integrin subunits also genes encoding focal adhesion (FAK) and extracellular-signal regulated (ERK) kinases was assessed. For this purpose, the qualitative and quantitative PCR technique was used. The expression of studied genes was dependent on the origin of cell lines and the type of evaluated material. The high expression of PBGD and ITGAV genes in fibroblasts grown on the surface of anodically modified titanium with deposited silver nanodendrites indicates potentially high biocompatibility of these samples for soft tissue cells. The high expression of the ITGB1 and ERK1 genes and the enhanced expression of the FAK gene in osteoblasts cells grown on the tested material was also observed. Summarizing, the nanocrystalline Ti modified with silver deposits showed higher biocompatibility in comparison with the conventional pure Ti samples.

Serum from patients with chronic obstructive pulmonary disease induces senescence-related phenotype in bronchial epithelial cells.

Chronic obstructive pulmonary disease (COPD) is a risk factor for the development of lung cancer (LC). The mechanism of interplay between both diseases remains poorly recognized. This report examines whether COPD may cause a senescence response in human bronchial epithelial cells (HBECs), leading to the progression of LC in a senescence-dependent manner. The results show that HBECs exposed to serum from COPD patients manifest increased expression of markers of cellular senescence, including senescence-associated ß-galactosidase (SA-ß-Gal), histone γ-H2A.X, and p21, as compared to the serum of healthy donors. This effect coincides with an increased generation of reactive oxygen species by these cells. The clinical analysis demonstrated that COPD may cause the senescence, independently on smoking status and disease severity. The concentrations of CXCL5, CXCL8/IL-8 and VEGF were higher in conditioned medium (CM) harvested from HBECs after exposure to COPD serum as compared to controls. In addition, CM treated with serum from COPD patients stimulated adhesion of A549 cancer cells to HBECs, as well as accelerating cancer cell proliferation and migration in vitro. Collectively, these findings indicate that COPD may induce senescence-like changes in HBECs and thus enhance some processes associated with the progression of lung cancer.

Comparison of bioactive compounds content in leaf extracts of Passiflora incarnata, P. caerulea and P. alata and in vitro cytotoxic potential on leukemia cell lines

ABSTRACT Passiflora caerulea L., P. alata Curtis and P. incarnata L. (synonym for P. edulis Sims), are the most popular representatives of the Passiflora genus in South America. In recent years, a growing attention is paid to the biological activity and phytochemical profiles of crude extracts from various species of Passiflora in worldwide. The aim of this study was to evaluate and to compare of anti-leukemic activity of the dry crude extracts from leaves of three Passiflora species from greenhouse of Poland in two human acute lymphoblastic leukemia cell lines: CCRF-CEM and its multidrug resistant variant. Two systems of liquid chromatography in order to assessment of phytochemical composition of extracts were applied. Extracts of P. alata and P. incarnata showed the potent inhibitory activity against human acute lymphoblastic leukemia CCRF-CEM, while P. caerulea not showed activity (or activity was poor). Despite similarities in quality phytochemical profile of extracts from P. caerulea and P. incarnata, differences in quantity of chemical compounds may determine their various pharmacological potency. For the activity of P. alata extract the highest content of terpenoids and a lack of flavones C-glycosides are believed to be crucial. Summarizing, the crude extract from P. alata leaves may be considered as a substance for complementary therapy for cancer patients.

Impact of PKCε downregulation on autophagy in glioblastoma cells.

BACKGROUND: Several efforts have been focused on identification of pathways involved in malignancy, progression, and response to treatment in Glioblastoma (GB). Overexpression of PKCε was detected in histological samples from GB, anaplastic astrocytoma, and gliosarcoma and is considered an important marker of negative disease outcome. In multiple studies on GB, autophagy has been shown as a survival mechanism during cellular stress, contributing to resistance against anti-cancer agents. The main object of this research was to determine the influence of PKCε downregulation on the expression of genes involved in autophagy pathways in glioblastoma cell lines U-138 MG and U-118 MG with high PKCε level. METHODS: We conducted siRNA-mediated knockdown of PKCε in glioblastoma cell lines and studied the effects of autophagy pathway. The expression of autophagy-related genes was analyzed using qPCR and Western blot analysis was carried out to assess protein levels. Immunostaining was used to detect functional autophagic maturation process. RESULTS: We found that these cell lines exhibited a high basal expression of autophagy-related genes. Our results suggest that the loss of PKCε contributes to the downregulation of genes involved in autophagy pathways. Moreover, most of the changes we observed in Western blot analysis and endogenous immunofluorescence experiments confirmed dysfunction of autophagy programs. We found that knockdown of PKCε induced a decrease in the expression of Beclin1, Atg5, PI3K, whereas the expression of other autophagy-related proteins mTOR and Bcl2 was increased. Treatment of control siRNA glioma cells with rapamycin-induced autophagosome formation and increase in LC3-II level and caused a decrease in the expression of p62. Additionally, PKCε siRNA caused a diminution in the Akt phosphorylation at Ser473 and in the protein level in both cell lines. Moreover, we observed reduction in the adhesion of glioblastoma cells, accompanied by the decrease in total FAK protein level and phosphorylation. CONCLUSIONS: Effects of down-regulation of PKCε in glioma cells raised the possibility that the expression of PKCε is essential for the autophagic signal transduction pathways in these cells. Thus, our results identify an important role of PKCε in autophagy and may, more importantly, identifyit as a novel therapeutic target.

Telomerase and drug resistance in cancer.

It is well known that a decreased expression or inhibited activity of telomerase in cancer cells is accompanied by an increased sensitivity to some drugs (e.g., doxorubicin, cisplatin, or 5-fluorouracil). However, the mechanism of the resistance resulting from telomerase alteration remains elusive. There are theories claiming that it might be associated with telomere shortening, genome instability, hTERT translocation, mitochondria functioning modulation, or even alterations in ABC family gene expression. However, association of those mechanisms, i.e., drug resistance and telomerase alterations, is not fully understood yet. We review the current theories on the aspect of the role of telomerase in cancer cells resistance to therapy. We believe that revealing/unravelling this correlation might significantly contribute to an increased efficiency of cancer cells elimination, especially the most difficult ones, i.e., drug resistant.

Nanoscale size effect in in situ titanium based composites with cell viability and cytocompatibility studies.

Novel in situ Metal Matrix Nanocomposite (MMNC) materials based on titanium and boron, revealed their new properties in the nanoscale range. In situ nanocomposites, obtained through mechanical alloying and traditional powder metallurgy compaction and sintering, show obvious differences to their microstructural analogue. A unique microstructure connected with good mechanical properties reliant on the processing conditions favour the nanoscale range of results of the Ti-TiB in situ MMNC example. The data summarised in this work, support and extend the knowledge boundaries of the nanoscale size effect that influence not only the mechanical properties but also the studies on the cell viability and cytocompatibility. Prepared in the same bulk, in situ MMNC, based on titanium and boron, could be considered as a possible candidate for dental implants and other medical applications. The observed relations and research conclusions are transferable to the in situ MMNC material group. Aside from all the discussed relations, the increasing share of these composites in the ever-growing material markets, heavily depends on the attractiveness and a possible wider application of these composites as well as their operational simplicity presented in this work.

In vitro biocompatibility of titanium after plasma surface alloying with boron.

Recently, the effect of different sizes of precursor powders during surface plasma alloying modification on the properties of titanium surface was studied. In this work we show in vitro test results of the titanium (α-Ti) after plasma surface alloying with boron (B). Ti-B nanopowders with 2 and 10wt% B were deposited onto microcrystalline Ti substrate. The in vitro cytocompatibility of these biomaterials was evaluated and compared with a conventional microcrystalline Ti. During the studies, established cell line of human gingival fibroblasts and osteoblasts were cultured in the presence of tested materials, and its survival rate and proliferation activity were examined. For this purpose, MTT assay, flow cytometric and fluorescent microscopic evaluation were made. Biocompatibility tests carried out indicate that the Ti after plasma surface alloying with B could be a possible candidate for dental implants and other medicinal applications. Plasma alloying is a promising method for improving the properties of titanium, thus increasing the field of its applications.

Telomere length assessment in leukocytes presents potential diagnostic value in patients with breast cancer.

Telomere shortening is associated with cancer development, primarily through the induction of genomic instability. The majority of studies have indicated that individuals with shorter blood telomeres may be at a higher risk of developing various types of cancer. There is increasing evidence that the study of the alterations in telomere length may improve cancer prognosis. The aim of the present study was to verify the use of telomere length parameters in the diagnostics of breast cancer stage. Telomere length was analyzed in the blood leukocytes of 52 patients with breast cancer relative to 47 control subjects using quantitative polymerase chain reaction. The effects of stage, grade, estrogen receptor, progesterone receptor and human epidermal growth factor 2 (HER2) status were assessed. The current study demonstrated that the average telomeric sequence length was significantly shorter in leukocytes from individuals diagnosed with a more severe stage of breast cancer (T2N1M0) than in leukocytes in the early stages of the disease (T1N0M0) (P=0.0207). Furthermore, the data indicated that telomeres in leukocytes derived from patients with HER2+ breast cancer were significantly longer compared with those with the HER2- type (P=0.0347). These results suggest that the assessment of telomeres in blood leukocytes may, at least partially, correspond with breast cancer staging and HER2 receptor status.

Zapotin (5,6,2',6'-tetramethoxyflavone) Modulates the Crosstalk Between Autophagy and Apoptosis Pathways in Cancer Cells with Overexpressed Constitutively Active PKCϵ.

Autophagy is important in the regulation of survival and death signaling pathways in cancer. PKCϵ revealed high transforming potential and the ability to increase cell migration, invasion, and metastasis. Zapotin (5,6,2',6'-tetramethoxyflavone), a natural flavonoid, showed chemopreventive and anticancer properties. Previously, we reported that downmodulation of induced PKCϵ level by zapotin was associated with decreased migration and increased apoptosis in HeLa cell line containing doxycycline-inducible constitutively active PKCϵ (PKCϵA/E, Ala(159) → Glu). Depending on the genetic and environmental content of cells, autophagy may either precede apoptosis or occur simultaneously. The purpose of this study was to assess the effect of zapotin on autophagy. Increasing concentration of zapotin (from 7.5 µM to 30 µM) caused an inhibition of the formation of autophagosomes and a decline in microtubule-associated protein 1 light chain 3 (LC3) protein levels. The gene expression level of major negative regulator of autophagy was noticeably increased. Moreover, the expression of the pivotal autophagy genes was decreased. These changes were accompanied by alternation in autophagy-related protein levels. In conclusion, our results implied that both the antiautophagic and the proapoptosis effect of zapotin in HeLaPKCϵA/E cells are associated with the protein kinase C epsilon signaling pathway and lead to programmed cell death.

Telomere shortening in Down syndrome patients--when does it start?

Down syndrome (DS) is one of the most common aneuploidy. In general population, its prevalence is 1:600-1:800 live births. It is caused by a trisomy of chromosome 21. DS is phenotypically manifested by premature aging, upward slant to the eyes, epicanthus, flattened face, and poor muscle tone. In addition to physical changes, this syndrome is characterized by early onset of diseases specific to old age, such as Alzheimer's disease, vision and hearing problems, and precocious menopause. Since DS symptoms include premature aging, the shortening of telomeres might be one of the markers of cellular aging. Consequently, the aim of the study was to determine the length of the telomeres in leukocytes from the blood of juvenile patients with DS (n=68) compared to an age-matched control group (n=56) and also to determine the diagnostic or predictive value for this parameter. We show that, for the first time, in juveniles, the average relative telomere length in studied subjects is significantly longer than in the control group (50.46 vs. 40.56, respectively arbitrary units [AU]; p=0.0026). The results provide interesting basis for further research to determine the causes and consequences of telomere maintaining and the dynamics of this process in patients with DS.

Telomerase modulation in therapeutic approach.

Telomerase is a specialized enzymatic complex responsible for the synthesis of telomeric repeats 5'-TTAGGG-3' localized at the ends of eukaryotic chromosomes. This mechanism prevents shortening of telomeres after each cell division. The enzyme is detected in about 85% of human tumors, but it is not expressed in normal cells or its expression is significantly lower. Consequently, it provides the cancer cells immortality. Thus, since showing cancer cell specificity (to a certain extent), the enzyme became a target for an adjuvant cancer therapy. So far, in vitro studies and preclinical studies seem to be promising. This work focuses on the pathways and mechanisms that are targeted in order to eliminate telomerase with consequence of cancer cell death. The anti-telomerase strategy may be beneficial especially in the context of sensitization of tumor cell to chemotherapeutic agents. We also indicate potential side effects and consequences of telomerase downregulation that should be considered when anti-telomerase strategy is undertaken. Alternatively, we also emphasize potential useful application of telomerase induction.