X-ray induced ultrafast charge transfer in thiophene-based conjugated polymers controlled by core-hole clock spectroscopy.

We explore ultrafast charge transfer (CT) resonantly induced by hard X-ray radiation in organic thiophene-based polymers at the sulfur K-edge. A combination of core-hole clock spectroscopy with real-time propagation time-dependent density functional theory simulations gives an insight into the electron dynamics underlying the CT process. Our method provides control over CT by a selective excitation of a specific resonance in the sulfur atom with monochromatic X-ray radiation. Our combined experimental and theoretical investigation establishes that the dominant mechanism of CT in polymer powders and films consists of electron delocalisation along the polymer chain occurring on the low-femtosecond time scale.

Comparison of Sepsis-1, 2 and 3 for Predicting Mortality in Septic Patients of a Middle-Income Country: A Retrospective Observational Cohort Study.

INTRODUCTION: The diagnosis of sepsis is based on expert consensus and does not yet have a "gold standard." With the aim of improving and standardizing diagnostic methods, there have already been three major consensuses on the subject. However, there are still few studies in middle-income countries comparing the methods. This study describes the characteristics of patients diagnosed with sepsis and evaluates and compares the performance of Sepsis-1, 2, and 3 criteria in predicting 28 days, and in-hospital mortality. PATIENTS AND METHODS: A retrospective observational cohort study was conducted in the intensive care unit of a tertiary hospital. All admissions between January 1, 2018, and December 31, 2019, were reviewed. Patients diagnosed with sepsis were included. RESULTS: During the study period, 653 patients diagnosed with sepsis (by any of the studied criteria) were included in the study. The 28 days mortality rate was 45.8%, and the in-hospital mortality rate was 59.7%. We observed that 72.1% of patients met the minimum criteria for diagnosing sepsis according to the three protocols, and this group also had the highest mortality rate. Age and comorbidities such as cancer and liver cirrhosis were significantly associated with in-hospital mortality. The most common microorganisms were Escherichia coli, Klebsiella spp., and Staphylococcus spp. CONCLUSIONS: The study found that most patients met the diagnostic criteria for sepsis using the three methods. Sepsis-2 showed greater sensitivity to predict mortality, while Sequential Organ Failure Assessment showed low accuracy, but was the only significant one. Furthermore, quick Sequential Organ Failure Assessment (qSOFA) had the highest specificity for mortality. Overall, these findings suggest that, although all three methods contribute to the diagnosis and prognosis of sepsis, Sepsis-2 is particularly sensitive in predicting mortality. Sepsis-3 shows some accuracy but requires improvement, and qSOFA exhibits the highest specificity. More research is needed to improve predictive capabilities and patient outcomes.

Leishmania (Sauroleishmania) tarentolae versus pathogenic species: comparative evaluation of protease activity, glycoconjugates, resistance to complement and metabolome composition.

BACKGROUND: Leishmania tarentolae is a non-pathogenic species found in lizards representing an important model for Leishmania biology. However, several aspects of this Sauroleishmania remain unknown to explain its low level of virulence. OBJECTIVES: We reported several aspects of L. tarentolae biology including glycoconjugates, proteolytic activities and metabolome composition in comparison to pathogenic species (Leishmania amazonensis, Leishmania braziliensis, Leishmania infantum and Leishmania major). METHODS: Parasites were cultured for extraction and purification of lipophosphoglycan (LPG), immunofluorescence probing with anti-gp63 and resistance against complement. Parasite extracts were also tested for proteases activity and metabolome composition. FINDINGS: Leishmania tarentolae does not express LPG on its surface. It expresses gp63 at lower levels compared to pathogenic species and, is highly sensitive to complement-mediated lysis. This species also lacks intracellular/extracellular activities of proteolytic enzymes. It has metabolic differences with pathogenic species, exhibiting a lower abundance of metabolites including ABC transporters, biosynthesis of unsaturated fatty acids and steroids, TCA cycle, glycine/serine/threonine metabolism, glyoxylate/dicarboxylate metabolism and pentose-phosphate pathways. MAIN CONCLUSIONS: The non-pathogenic phenotype of L. tarentolae is associated with alterations in several biochemical and molecular features. This reinforces the need of comparative studies between pathogenic and non-pathogenic species to elucidate the molecular mechanisms of virulence during host-parasite interactions.

Increased hippocampal CREB phosphorylation after retrieval of remote contextual fear memories in Carioca high-conditioned freezing rats.

The participation of the hippocampal formation in consolidation and reconsolidation of contextual fear memories has been widely recognized and known to be dependent on the activation of the cAMP response element (CRE) binding protein (CREB) pathway. Recent findings have challenged the prevailing view that over time contextual fear memories migrate to neocortical circuits and no longer require the hippocampus for retrieval of remote fearful memories. It has also recently been found that this brain structure is important for the maintenance and recall of remote fear memories associated with aversive events, a common trait in stress-related disorders such as generalized anxiety disorder (GAD), major depression, and post-traumatic stress disorder. In view of these findings, here we examined the putative role of CREB in the hippocampus of an animal model of GAD during the retrieval of remote contextual fear memories. Specifically, we evaluated CREB phosphorylation in the hippocampus of male Carioca High- and Low-conditioned Freezing rats (CHF and CLF, respectively) upon re-exposure of animals to contextual cues associated to footshocks weeks after fear conditioning. Age-matched male rats from a randomized crossbreeding population served as controls (CTL). Adrenal catecholamine levels were also measured as a biological marker of stress response. Seven weeks after contextual fear conditioning, half of the sample of CHF (n = 9), CLF (n = 10) and CTL (n = 10) rats were randomly assigned to return to the same context chamber where footshocks were previously administrated (Context condition), while the remaining animals were individually placed in standard housing cages (Control condition). Western blot results indicated that pCREB levels were significantly increased in the hippocampus of CHF rats for both Context and Control conditions when compared to the other experimental groups. CHF rats in the Context condition also exhibited significant more freezing than that observed for both CLF and CTL rats. Lastly, CHF animals in the Context condition displayed significantly higher adrenal catecholamine levels than those in the Control condition, whereas no differences in catecholamine levels were observed between Context and Control conditions for CLF and CTL rats. These findings are discussed from a perspective in which the hippocampus plays a role in the maintenance and recall of remote contextual fear memories via the CREB pathway.

A scoping review on hyposalivation associated with systemic conditions: the role of physical stimulation in the treatment approaches.

BACKGROUND: Several systemic conditions can result in distinct degrees of salivary gland damage and consequent hypofunction. The development of successful management schemes is highly challenging due to the complexity of saliva. This study aimed to systematically map the literature on the physical stimulation of salivary glands for hyposalivation management and the response of individuals according to different systemic conditions causing salivary impairment. METHODS: A systematic search in the literature was performed. Two reviewers independently selected clinical trials, randomized or not, that used physical stimulation to treat hyposalivation caused by systemic conditions. Studies evaluating healthy subjects without hyposalivation were included as controls. Single-arm clinical studies or case series were also included for protocol mapping (PRISMA extension for scoping reviews). RESULTS: Out of 24 included studies, 10 evaluated healthy subjects, from which 9 tested transcutaneous electrical nerve stimulation (TENS) and 1 tested acupuncture and electroacupuncture. Fourteen studies evaluated individuals with hyposalivation: 6 applied TENS, 6 applied low-level laser therapy (LLLT), and 2 applied acupuncture, carried out in post-chemotherapy, medication use, postmenopausal women, hemodialysis patients, smokers, diabetics, Sjögren's syndrome (SS). All showed increased salivation after treatment, except for two LLLT studies in individuals with SS. CONCLUSIONS: Among the different patient groups, individuals with Sjögren's syndrome (SS) exhibited the poorest responses, while those with medication-induced hyposalivation demonstrated the most favorable treatment outcomes, independently of the management strategy for saliva stimulation. It means that physical stimulation of salivary glands holds promise as an alternative for managing hyposalivation in cases of reversible gland damage. However, to make informed decisions in current practice, it is necessary to conduct new well-designed randomized clinical trials with appropriate methodologies.

Circulating microparticles from subjects with active pulmonary tuberculosis infection modulate immune response.

Microparticles (MPs) which circulate within the plasma are elevated in patients with active pulmonary tuberculosis infection. Circulating MPs isolated from the plasma of patients with active pulmonary tuberculosis infection modulate the cytokine production of immune cells in vitro.

Serum 25-hydroxyvitamin D and cancer-related fatigue: associations and effects on depression, anxiety, functional capacity and health-related quality of Life in breast cancer survivors during adjuvant endocrine therapy.

BACKGROUND: The adjuvant treatment with Aromatase Inhibitor (AI) is considered standard of care for postmenopausal breast cancer (BC) women with hormone receptor-positive (HR +), however, it often causes adverse effects such as cancer-related fatigue (CRF). The high prevalence of vitamin D deficiency in postmenopausal women who start adjuvant AI supports the hypothesis that hypovitaminosis D would be one of the biological explanations for toxicity of AI. This study aimed to identify the relationship between 25-hydroxyvitamin D [25(OH)D] and CRF, and to analyze their associations and effects on depression, anxiety, functional disability, muscle/joint aches and HRQL. METHODS: This prospective study included 89 postmenopausal women diagnosed with HR + early BC in adjuvant endocrine therapy with AI. Anthropometric and body composition assessments were performed, as well as dietary assessments by application of 24-h dietary recall, at three time points, totaling 24 months of follow-up. The women completed the Cervantes Scale (CS), Hospital Anxiety and Depression Scale (HADS) and Health Assessment Questionnaire (HAQ). The CRF was determined from the Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F). The serum 25(OH)D was determined by electrochemiluminescence, with cut-off point above 75 nmol/L adopted as sufficiency. Generalized Linear Model (GLzM) and Generalized Mixed Model (GMM) analysis were used. RESULTS: At baseline, 36% (n = 32) of the women presented CRF and 39.3% (n = 35) had 25(OH)D below 75 nmol/L. None of the women reached the Estimated Average Requirements (EAR) of vitamin D. The causality between 25(OH)D and CRF was not significant. Longitudinally, lower levels of 25(OH)D had a negative effect on anxiety (p = 0.020), Menopause and Health (p = 0.033) and Vasomotor scores (p = 0.007). Also, the CRF had a negative effect on anxiety (p = 0.028); depression (p = 0.027); functional disability (p = 0.022); HRQL (p = 0.007); Menopause and Health (p = 0.042), Psychological (p = 0.008) and Couple Relations (p = 0.008) domains; and on Health (p = 0.019) and Aging (p = 0.036) subdomains. Vasomotor subdomain (ß = -2.279, p = 0.045) and muscle/joint aches (ß = -0.779, p = 0.013) were significant with CRF only at baseline. CONCLUSIONS: This study found negative effect of body adiposity on CRF. Still, the clinical relevance of 25(OH)D and CRF is highlighted, especially that of CRF, considering the consistent impact on several adverse effects reported by BC survivors during adjuvant endocrine therapy.

Decreasing Attacks and Improving Quality of Life through a Systematic Management Program for Patients with Hereditary Angioedema.

INTRODUCTION: Prevention of attacks is a major goal in management of patients with hereditary angioedema (HAE). We aimed to investigate the effects of a systematic intervention for HAE patients. METHODS: Thirty-three patients with HAE with C1-inhibitor deficiency, belonging to a single family, participated in a management program coordinated by an allergist/immunologist. Angioedema attacks before intervention were ascertained by interviews and emergency room charts and recorded prospectively by patients or caregivers after enrollment. Mean number of attacks/month was compared at 12 months preintervention and 8 and 14 months within intervention. Patient-reported outcome instruments were used to assess quality of life, including HAE Quality of Life (HAE-QoL) questionnaire, psychological conditions, and work impairment, at baseline and 8 and 14 months within intervention. Data were stored in REDCap platform and analyzed by adjusted Bayesian models of double Poisson regression. RESULTS: Mean number of attacks/month significantly decreased (95% credible interval [CrI] excluding 0) from 1.15 preintervention to 0.25 and 0.23, 8 and 14 months within intervention, with mean decreases of -0.89 (95% CrI: -1.21 to -0.58) and -0.92 (95% CrI: -1.22 to -0.60), respectively. HAE-QoL scores showed mean total increases of 15.2 (95% CrI: 1.23-29.77) and 26 (95% CrI: 14.56-39.02) at 8 and 14 months within the study, as compared to baseline, revealing marked improvement in quality of life. Significant increase in role-emotional and reduction of depression, stress, and anxiety were observed at 14 months. CONCLUSION: A systematic approach integrating HAE-specific care with effective handling of psychological issues decreased the number of attacks and improved quality of life, targets for best practice in HAE.

Fructose-1,6-bisphosphate induces generation of reactive oxygen species and activation of p53-dependent cell death in human endometrial cancer cells.

Fructose-1,6-bisphosphate (F1,6BP), an intermediate of the glycolytic pathway, has been found to play a promising anticancer effect; nevertheless, the mechanisms involved remain poorly understood. The present study aimed to evaluate the effect and mechanisms of F1,6BP in a human endometrial cancer cell line (Ishikawa). F1,6BP showed an antiproliferative and non-cytotoxic effect on endometrial cancer cells. These effects are related to the increase in reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). These harmful stimuli trigger the upregulation of the expression of pro-apoptotic genes (p53 and Bax), leading to the reduction of cell proliferation through inducing programmed cell death by apoptosis. Furthermore, F1,6BP-treated cells had the formation of autophagosomes induced, as well as a decrease in their proliferative capacity after withdrawing the treatment. Our results demonstrate that F1,6BP acts as an anticancer agent through the generation of mitochondrial instability, loss of cell function, and p53-dependent cell death. Thus, F1,6BP proves to be a potential molecule for use in the treatment against endometrial cancer.

Mindfulness-based intervention for college faculties and students in Brazil.

Background: Teacher and students' stress has been a challenge in education. An approach to stress reduction is mindfulness training. The Mindfulness-based stress reduction (MBSR) has been used to improve the condition of individuals with various health outcomes. The aim of this study was to examine whether MBSR may improve depression, well-being, and perceived stress of Brazilian college faculty and students. Methods: MBSR was performed with college faculty and students from Centro Universitario de Belo Horizonte (UniBH). Participants answered questionnaires (Psychological General Well-Being Index, Perceived Stress Scale, and Beck Depression Index) at the beginning and end of the intervention. A control group of teachers also answered the questionnaires but did not participate in the MBSR intervention. Statistical analyses were performed using paired Student's t-test (P < 0.05 significance). Results: The MBSR intervention positively impacted all conditions measured in the questionnaires in faculty and students who attended the intervention. Faculty and students in the control group had shown conditions being maintained or worsened. Discussion: The MBSR was effective as faculty and students from the experimental group exhibited improvement in general well-being, depression levels, and perceived stress after attending the intervention.

Immune-pineal axis protects rat lungs exposed to polluted air.

Environmental pollution in the form of particulate matter <2.5 µm (PM2.5 ) is a major risk factor for diseases such as lung cancer, chronic respiratory infections, and major cardiovascular diseases. Our goal was to show that PM2.5 eliciting a proinflammatory response activates the immune-pineal axis, reducing the pineal synthesis and increasing the extrapineal synthesis of melatonin. Herein, we report that the exposure of rats to polluted air for 6 hours reduced nocturnal plasma melatonin levels and increased lung melatonin levels. Melatonin synthesis in the lung reduced lipid peroxidation and increased PM2.5 engulfment and cell viability by activating high-affinity melatonin receptors. Diesel exhaust particles (DEPs) promoted the synthesis of melatonin in a cultured cell line (RAW 264.7 cells) and rat alveolar macrophages via the expression of the gene encoding for AANAT through a mechanism dependent on activation of the NFκB pathway. Expression of the genes encoding AANAT, MT1, and MT2 was negatively correlated with cellular necroptosis, as disclosed by analysis of Gene Expression Omnibus (GEO) microarray data from the human alveolar macrophages of nonsmoking subjects. The enrichment score for antioxidant genes obtained from lung gene expression data (GTEx) was significantly correlated with the levels of AANAT and MT1 but not the MT2 melatonin receptor. Collectively, these data provide a systemic and mechanistic rationale for coordination of the pineal and extrapineal synthesis of melatonin by a standard damage-associated stimulus, which activates the immune-pineal axis and provides a new framework for understanding the effects of air pollution on lung diseases.

Solitary fibrous tumour of the oral cavity: An update.

BACKGROUND: Solitary fibrous tumour is an unusual neoplasm of the oral cavity that is sometimes not clinically distinguishable from other lesions. The purpose of the present study was to review the clinical, microscopic and molecular aspects of malignant and benign solitary fibrous tumour of the oral cavity currently available in literature. METHODS: For our review, an electronic search was performed using PubMed, Scopus, Ovid/MedLine, Web of science and ProQuest Dissertations and Theses Global database. RESULTS: A total of 74 publications reporting 150 cases were included. Oral solitary fibrous tumours are most frequently described as submucosal, well-circumscribed, asymptomatic nodule, more prevalent in females in their fourth to fifth decades of life. Buccal mucosa is the most commonly affected site by the benign tumour variant, whereas the tongue is the most common location affected by the malignant form of the neoplasm. Most of the lesions were treated by conservative surgery. One recurrent malignant tumour and one metastasis are reported. CONCLUSION: Asymptomatic normal-coloured submucosal nodules located in the buccal mucosa and tongue in adult patients are suggestive of oral solitary fibrous tumour, but only a careful microscopic examination can differentiate benign from malignant variants and the use of immunohistochemistry (CD34, Bcl-2, CD99 and STAT6), and cytogenetic studies (NAB2-STAT6) contribute significantly to confirm the diagnosis of solitary fibrous tumour in difficult cases.

Cell-derived microparticles and von Willebrand factor in Brazilian renal transplant recipients.

AIM: This study was aimed at investigating platelet-derived microparticles (PMP), endothelium cell-derived microparticles (EMP) and von Willebrand factor (VWF) according to renal function and time post-transplant. We found this study relevant because unusual biomarkers seem to be a promising tool to evaluate chronic renal disease and post-transplant monitoring. METHODS: Ninety-one renal transplant recipients (RTx) were allocated into groups according to creatinine plasma levels (C1 < 1.4 and C2 ≥ 1.4 mg/dL), estimated glomerular filtration rates (R1 < 60 and R2 ≥ 60 mL/min per 1.73 m2 ) and time post-transplant (T1: 3-24; T2: 25-60; T3: 61-120; and T4 > 120 months). EMP and PMP levels were assessed by flow cytometry and VWF levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: Platelet-derived microparticle levels were higher in C1 group compared with C2 (P = 0.00). According to diameter, small PMP and EMP (≤0.7 µm) were also higher in C1 group, all values of P less than 0.05. T1 and T2 groups have shown high EMP levels and a predominance of big microparticle (>0.7 µm) compared with T4 group, all values of P less than 0.05. Higher VWF levels were observed among RTx with creatinine ≥1.4 mg/dL compared with other RTx, P = 0.01. CONCLUSION: The results showed that PMP, EMP and VWF are promising markers to evaluate endothelial function in RTx. These biomarkers could play a major role in monitoring patients after renal transplant.

Tacrine derivatives stimulate human glioma SF295 cell death and alter important proteins related to disease development: An old drug for new targets.

Glioblastoma is the most common and aggressive glioma, characterized by brain invasion capability. Being very resistant to the current therapies, since even under treatment, surgery, and chemotherapy with temozolomide (TMZ), patients achieve a median survival of one year. In the search for more effective therapies, new molecules have been designed. For nervous system cancers, molecules able to cross the blood-brain barrier are handled with priority. Accordingly, tacrine was chosen for this study and the inclusion of spiro-heterocyclic rings was done in its structure resulting in new compounds. Cytotoxic activity of tacrine derivatives was assayed using glioblastoma cell line (SF295) as well as analyzing cell death mechanism. Increased caspases activities were observed, confirming apoptosis as cell death type. Some derivatives also increased reactive oxygen species formation and decreased the mitochondrial membrane potential. Moreover, compounds acted on several glioblastoma-related proteins including p53, HLA-DR, beta-catenin, Iba-1, MAP2c, Olig-2, and IDH1. Therefore, tacrine derivatives presented promising results for the development of new glioblastoma therapy, particularly to treat those patients resistant to TMZ.

Proresolving Actions of Synthetic and Natural Protease Inhibitors Are Mediated by Annexin A1.

Annexin A1 (AnxA1) is a glucocorticoid-regulated protein endowed with anti-inflammatory and proresolving properties. Intact AnxA1 is a 37-kDa protein that may be cleaved in vivo at the N-terminal region by neutrophil proteases including elastase and proteinase-3, generating the 33-kDa isoform that is largely inactive. In this study, we investigated the dynamics of AnxA1 expression and the effects of synthetic (sivelestat [SIV]; Eglin) and natural (secretory leukocyte protease inhibitor [SLPI]; Elafin) protease inhibitors on the resolution of LPS-induced inflammation. During the settings of LPS inflammation AnxA1 cleavage associated closely with the peak of neutrophil and elastase expression and activity. SLPI expression increased during resolving phase of the pleurisy. Therapeutic treatment of LPS-challenge mice with recombinant human SLPI or Elafin accelerated resolution, an effect associated with increased numbers of apoptotic neutrophils in the pleural exudates, inhibition of elastase, and modulation of the survival-controlling proteins NF-κB and Mcl-1. Similar effects were observed with SIV, which dose-dependently inhibited neutrophil elastase and shortened resolution intervals. Mechanistically, SIV-induced resolution was caspase-dependent, associated to increased levels of intact AnxA1 and decreased expression of NF-κB and Mcl-1. The proresolving effect of antiproteases was also observed in a model of monosodium urate crystals-induced inflammation. SIV skewed macrophages toward resolving phenotypes and enhanced efferocytosis of apoptotic neutrophils. A neutralizing antiserum against AnxA1 and a nonselective antagonist of AnxA1 receptor abolished the accelerated resolution promoted by SIV. Collectively, these results show that elastase inhibition not only inhibits inflammation but actually promotes resolution, and this response is mediated by protection of endogenous intact AnxA1 with ensuing augmentation of neutrophil apoptosis.

Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review.

Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. This endocrinopathy is associated with many metabolic disorders such as dyslipidemia and insulin resistance, with increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular complications. Inflammation is likely to play an important role in the promoting these metabolic imbalances, while prothrombotic and pro-oxidative mechanisms further contribute to the cardiovascular risk of these patients. The etiology of PCOS is still not fully understood, but there is evidence of genetic and environmental components. This review aims to discuss some molecular pathways associated with PCOS that could contribute to the better understanding about this syndrome. Recent evidence suggests that intrauterine exposure of female mice to an excess of anti-Müllerian hormone may induce PCOS features in their post-natal life. High cytokine levels and cytokine gene polymorphisms also appear to be associated with the pathophysiology of PCOS. Furthermore, high levels of microparticles may contribute to the altered hemostasis and enhanced inflammation in PCOS. All these mechanisms may be relevant to clarify some aspects of PCOS pathogenesis and inspire new strategies to prevent the syndrome as well as treat its symptoms and mitigate the risk of long-term complications.

Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis.

OBJECTIVE AND DESIGN: Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues. MATERIALS AND METHODS: Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 106 cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR. RESULTS: We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group. CONCLUSIONS: In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.

Fructose-1,6-bisphosphate reverts iron-induced phenotype of hepatic stellate cells by chelating ferrous ions.

Hepatic fibrosis is an extracellular matrix deposition by hepatic stellate cells (HSC). Fibrosis can be caused by iron, which will lead to hydroxyl radical production and cell damage. Fructose-1,6-bisphosphate (FBP) has been shown to deliver therapeutic effects in many pathological situations. In this work, we aimed to test the effects of FBP in HSC cell line, GRX, exposed to an excess of iron (Fe). The Fe-treatment increased cell proliferation and FBP reversed this effect, which was not due to increased necrosis, apoptosis or changes in cell cycle. Oil Red-O staining showed that FBP successfully increased lipid content and lead GRX cells to present characteristics of quiescent HSC. Fe-treatment decreased PPAR-γ expression and increased Col-1 expression. Both effects were reversed by FBP which also decreased TGF-ß1 levels in comparison to both control and Fe groups. FBP, also, did not present scavenger activity in the DPPH assay. The treatment with FBP resulted in decreased proliferation rate, Col-1 expression and TGF-ß1 release by HSC cells. Furthermore, activated PPAR-γ and increased lipid droplets induce cells to become quiescent, which is a key event to reversion of hepatic fibrosis. FBP also chelates iron showing potential to improve Cell redox state.

Substituents' effect in electron attachment to epigenetic modifications of cytosine.

Epigenetic modifications of cytosine have been found to influence differently in many processes in biological systems. In order to investigate the differences in electron attachment to different epigenetic modifications of cytosine, we reported the A″ component of the integral cross section of electron scattering by cytosine (C) and its epigenetic modifications 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Our results were obtained with the Schwinger multichannel method with pseudopotentials in the static-exchange (SE) and static-exchange plus polarization (SEP) approximations. In addition to the scattering results, we present electron attachment energies obtained through an empirical scaling relation for the five molecules. We observed three π* resonances for C, 5mC, and 5hmC and four for 5fC and 5caC, in both SE and SEP approximations. The cross sections show that the π* resonances of 5mC and 5hmC are located at higher energies than the resonances of C, while the resonances of 5fC and 5caC are located at lower energies. In order to investigate this shift in the resonances' positions, we analyzed the π* lowest-lying orbitals and the electronic density over the molecules. Using the inductive and mesomeric effects, we were able to analyze the influence of each substituent over the molecule and on the resonances' positions.

Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome.

PURPOSE: The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin. METHODS: We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS-13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers. RESULTS: Total MPs levels were lower in treated patients (59.58 ± 28.43 MPs/µL) when compared to untreated group (97.32 ± 59.42; p = 0.033). Plasma levels of TFMPs were also significantly lower in the group of patients who used metformin (1.10 ± 0.94 MPs/µL) when compared to untreated patients (2.20 ± 1.42 MPs/µL) (p = 0.003). CONCLUSIONS: Considering that metformin reduced the levels of total MPs and TFMPs, our results suggest that this mechanism could be involved in the antithrombotic metformin effect, corroborating with the indication of this drug in the PCOS treatment.