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Background: Endomyocardial fibrosis is a grim disease. It is the most common restrictive cardiomyopathy worldwide, but the exact etiology and pathogenesis both remain unknown. Endomyocardial fibrosis is recurrently associated with chronic eosinophilia and probable dietary, environmental, and infectious factors, which contribute not only to the onset of the disease (an inflammatory process) but also to its progression and maintenance (endomyocardial damage and scar formation). The trademark of the disease is the fibrotic obliteration of the affected ventricle. The combination of such processes produces focal or diffuse endocardial thickening and fibrosis, which leads to restrictive physiology. Endomyocardial fibrosis affects the apices of the right and the left ventricle in around 50% of cases and most often extends to the posterior leaflet of the mitral valve. Sometimes it involves the papillary muscle and chordae tendineae, causing atrioventricular valve dysfunction. The fibrosis does not affect extracardiac organs. This cardiomyopathy is most recurrent in tropical areas of the world. Case presentation: A 67-year-old Black male with past medical history of schistosomiasis infection in childhood presented with progressive dyspnea, lower extremity edema, and weakness for 2 years. He was diagnosed with endomyocardial fibrosis. The echocardiogram showed an increased thickness in the septum (17 mm) and free left ventricular wall (15 mm), obliteration of the left ventricular apex and inflow tract, and mitral valve regurgitation. Cardiac magnetic resonance imaging revealed apical left ventricle wall thickening with left ventricular apical obliteration associated with enlargement of the respective atrium. Delayed enhancement imaging showed endomyocardium enhancement involving left ventricular apex, mitral valve regurgitation due to annulus dilation, and a thrombus at left ventricular apex. He underwent open heart surgery with mitral valve replacement, endocardial decortication, endomyocardiectomy, and two-vessel coronary artery bypass grafting as preoperative coronary angiogram showed mild right coronary artery and proximal left anterior descending artery severe lesions. Postoperative course was uncomplicated, and he was discharged successfully from the hospital. Six months after surgery, he was New York Heart Association functional class I. Conclusion: The purpose of this case report is to illustrate the aspects of endomyocardial fibrosis by reporting a case of this entity. In conclusion, progress in imaging techniques and treatment in a reference institution for cardiac diseases contribute to earlier diagnosis and survival in patients with endomyocardial fibrosis. [ABSTRACT FROM AUTHOR]

Nitrite is an important food additive for cured meats; however, high nitrite levels pose adverse health effects to humans. Hence, monitoring nitrite concentration is critical to comply with limits imposed by regulatory agencies. Laser-induced graphene (LIG) has proven to be a scalable manufacturing alternative to produce high-performance electrochemical transducers for sensors. Herein, we expand upon initial LIG studies by fabricating hydrophilic and hydrophobic LIG that are subsequently converted into ion-selective sensors to monitor nitrite in food samples with comparable performance to the standard photometric method (Griess method). The hydrophobic LIG resulted in an ion-selective electrode with improved potential stability due partly to a decrease in the water layer between the electrode and the nitrite poly(vinyl) chloride-based ion-selective membrane. These resultant nitrite ion-selective sensors displayed Nernstian response behavior with a sensitivity of 59.5 mV dec−1, a detection limit of 0.3 ± 0.1 mg L-1 (mean ± standard deviation), and a broad linear sensing range from 10−5 to 10−1 M, which was significantly larger than currently published nitrite methods. Nitrite levels were determined directly in food extract samples of sausage, ham, and bacon for 5 min. These sensor metrics are significant as regulatory agencies limit nitrite levels up to 200 mg L-1 in finished products to reduce the potential formation of nitrosamine (carcinogenic compound). These results demonstrate the versatility of LIG as a platform for ion-selective-LIG sensors and simple, efficient, and scalable electrochemical sensing in general while demonstrating a promising alternative to monitor nitrite levels in food products ensuring regulatory compliance. [ABSTRACT FROM AUTHOR]

Current solid-contact ion-selective electrodes (ISEs) suffer from signal-to-noise drift and short lifespans partly due to water uptake and the development of an aqueous layer between the transducer and ion-selective membrane. To address these challenges, we report on a nitrate ISE based on hydrophobic laser-induced graphene (LIG) coated with a poly(vinyl) chloride–based nitrate selective membrane. The hydrophobic LIG was created using a polyimide substrate and a double lasing process under ambient conditions (air at 23.0 ± 1.0 °C) that resulted in a static water contact angle of 135.5 ± 0.7° (mean ± standard deviation) in wettability testing. The LIG–ISE displayed a Nernstian response of − 58.17 ± 4.21 mV dec−1 and a limit-of-detection (LOD) of 6.01 ± 1.44 µM. Constant current chronopotentiometry and a water layer test were used to evaluate the potential (emf) signal stability with similar performance to previously published work with graphene-based ISEs. Using a portable potentiostat, the sensor displayed comparable (p > 0.05) results to a US Environmental Protection Agency (EPA)–accepted analytical method when analyzing water samples collected from two lakes in Ames, IA. The sensors were stored in surface water samples for 5 weeks and displayed nonsignificant difference in performance (LOD and sensitivity). These results, combined with a rapid and low-cost fabrication technique, make the development of hydrophobic LIG–ISEs appealing for a wide range of long-term in situ surface water quality applications. [ABSTRACT FROM AUTHOR]

Bariatric surgery (BS) is the most effective therapy for severe obesity, which improves several comorbidities (such as diabetes, hypertension, dyslipidemia, among others) and results in marked weight loss. Despite these consensual beneficial effects, sleeve gastrectomy and Roux-en-Y gastric bypass (the two main bariatric techniques) have also been associated with changes in bone metabolism and progressive bone loss. The objective of this literature review is to examine the impact of bariatric surgery on bone and its main metabolic links, and to analyze the latest findings regarding the risk of fracture among patients submitted to bariatric surgery. [ABSTRACT FROM AUTHOR]

Extensive research into green technologies is driven by the worldwide push for eco‐friendly materials and energy solutions. The focus is on synergies that prioritize sustainability and environmental benefits. This study explores the potential of abundant, non‐toxic, and sustainable resources such as paper, lignin‐enriched paper, and cork for producing laser‐induced graphene (LIG) supercapacitor electrodes with improved capacitance. A single‐step methodology using a CO2 laser system is developed for fabricating these electrodes under ambient conditions, providing an environmentally friendly alternative to conventional carbon sources. The resulting green micro‐supercapacitors (MSCs) achieve impressive areal capacitance (≈7–10 mF cm−2) and power and energy densities (≈4 μW cm‐2 and ≈0.77 µWh cm−2 at 0.01 mA cm−2). Stability tests conducted over 5000 charge–discharge cycles demonstrate a capacitance retention of ≈80–85%, highlighting the device durability. These LIG‐based devices offer versatility, allowing voltage output adjustment through stacked and sandwich MSCs configurations (parallel or series), suitable for various large‐scale applications. This study demonstrates that it is possible to create high‐quality energy storage devices based on biodegradable materials. This development can lead to progress in renewable energy and off‐grid technology, as well as a reduction in electronic waste. [ABSTRACT FROM AUTHOR]

Given the increasing incidence of obesity, bariatric procedures are gaining attention during the past decades, being one of the most effective methods of long-term weight loss. Nutritional optic neuropathy (NON) following bariatric surgeries is a rare but devastating complication caused by a complete lack or inadequate supply of nutrients for the normal function of nerve fibers. We report a case of bilateral anterior NON after a Single Anastomosis Duodenoileal Bypass with Sleeve Gastrectomy, and present a review of the literature about neuro-ophthalmic complications associated with these procedures. Bariatric surgery may constitute an established risk factor for NON and both patient and physician have to be aware of the importance of closely monitoring vitamin depletions and neurologic and visual symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Catecholamines (CA) play a major role in metabolism and immune response. Recent reports showing adipose tissue can synthetize CA enlighten new roles for these amines in obesity. This study aimed to evaluate the expression of both tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) and CA content along preadipocytes differentiation, under normal and obesigenic conditions. Methods: 8–9 week-old male C57BL/6 mice were divided in two groups: one fed with a high-fat diet (HFD) and other with a standard diet (SD) for 20 weeks. Afterwards, both TH and PNMT expression, localization, and CA content in adipocytes, were evaluated. Results: qPCR results showed no changes for TH and PNMT expression during the differentiation process for visceral and subcutaneous preadipocytes from mice fed with SD. Comparing to SD, HFD increased TH gene expression of subcutaneous preadipocytes and PNMT gene expression of both visceral preadipocytes and adipocytes. HPLC-ED analyses revealed HFD increased visceral adipocytes noradrenaline intracellular content comparing with preadipocytes (p = 0.037). When compared with SD, HFD raised and decreased noradrenaline content, respectively, in visceral adipocytes (p = 0.004) and subcutaneous preadipocytes (p = 0.001). Along the differentiation process, HFD increased visceral adrenaline intracellular content comparing with SD (p < 0.001). HFD increased visceral comparing to subcutaneous adrenaline content for both preadipocytes (p = 0.004) and adipocytes (p = 0.001). Conclusions: TH and PNMT expression in adipose tissue is differently modulated in visceral and subcutaneous adipose depots, and seems to depend on diet. Differences observed in visceral adipose CA handling in HFD-fed mice might uncover novel pharmacological/nutritional strategies against obesity and cardiovascular risk. [ABSTRACT FROM AUTHOR]

Nile tilapia (Oreochromis niloticus) is a freshwater phytoplanktivorous fish species reported to accumulate and tolerate large amounts of cyanotoxins such as microcystins (MCs). The present study aimed to investigate molecular responses to the acute exposure of Nile tilapia to the Microcystin-LA analogue (MC-LA). Thus, the specimens were sublethally exposed to 1000 μg kg−1 of MC-LA for 12, 24, 48, and 96 h. Gene expression of PP1, PP2A, GST, GPX and actin was analyzed by quantitative PCR. The protein abundance profile of PP2A was determined by immunoblotting, while the integrity of its biological function was assessed by a phosphatase enzymatic assay. PP2A activity was significantly and strongly reduced by MC-LA. A resulting feedback mechanism significantly increased PP2A gene expression and protein abundance in all assessed times. However, a recovery of that phosphatase activity was not observed. In this study, the observed increase in GPX gene expression was the only response that could be directly related to the unknown factors associated to the fish survival to such high dose exposure. • Tilapia survived to MC-LA high dose, even presenting a strong inhibition of PP2A. • PP2A inhibition leads to an increase in the transcription and translation of this protein. • GPX mRNA increasing could be related to the fish survival to such high dose exposure. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most frequent oral malignant neoplasia. As consequence of OSCC treatment, oral mucositis (OM) is one of the most common adverse effects of OSCC treatment. Currently, there is no consensus for OM treatment. The purpose of the current study was to test the combination of red and infrared low-level laser therapy (LLLT) for OM treatment. Primary culture of human fibroblast was performed to identify LLLT dose. After laboratory tests, a two-arm parallel, single-blind, controlled study was conducted. The two arms were group 1, both 660- and 808-nm wavelengths (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2), and group 2, only 660-nm wavelength (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2). Both treatments were performed twice a week. Group 1 presented a reduction of mucositis grade in comparison to group 2. Group 1 also presented reduction of analgesics prescription. But no significant differences between groups 1 and 2 were observed according to the pain scale. In conclusion, the current study demonstrated that a combination of red and infrared at a higher dose (300 J/cm2) reduced both oral mucositis grade and analgesics prescription. The effects of the combination of RT and LLLT are unclear and need more studies. [ABSTRACT FROM AUTHOR]

Sjögren’s syndrome (SS) is an autoimmune disease most commonly characterized by ocular and oral dryness. Despite the high prevalence of SS, generation and perpetuation of this disease is still unclear in many aspects. Inflammation, nonetheless, seems to play a central role in this pathology especially in the form of Th-1, Th-2 and Th-17 cytokines release within different aspects, concentrations and connections involved in the maintenance of the syndrome. Moreover, the chronically created pro-inflammatory environment appears to promote glandular atrophy and irreparable architectural modifications. The establishment of germinal centers (GC) in SS are considered the main reason for the 16-times increased probability of lymphoproliferative disease development in these patients. SS is also interconnected with numerous others auto-inflammatory and autoimmune diseases, many of them representing the first clear sign of a dysregulated immune system. Despite the recent advances, treatment options are still insufficient. This overview aims to better elucidate this local and systemic disease, which can be of vital use not only for SS but also to other rheumatic pathological conditions. [ABSTRACT FROM PUBLISHER]

Considered a public health problem, suicide is increasing worldwide. It is a complex problem for which there is no single cause or reason, and so that prevention ise effective it is necessary that health professionals understand the issue and know how to recognize suicidal behavior. In this regard it was drawn to analyze the scientific production of Brazilian nursing on suicide and attempted suicide in the period from 2005 to 2015. Integrative review with thematic analysis. There was an increase in publications about suicide, suicide attempt and adolescents. Men commit more suicide and women are more prevalent in attempts. Hanging, poisoning and firearms are the most used means of suicide and the suicide attempts. It was concluded that there is an urgent need to work to prevent suicide based on publications, since the same address not only the suicide's profile but alsothe methods used in suicide and suicide attempts. [ABSTRACT FROM AUTHOR]

Obesity remains nowadays one of the main threats to human health, being a problem of worldwide proportions. It is characterized by augmented storage of fatty acids in an enlarged adipose tissue. This process is possible thanks to a rich capillary network, supported by a mechanism that has also a crucial role on cancer: angiogenesis. Given that several studies point obesity as a risk factor for cancer development, angiogenesis may be approached as the missed link between these two pathologies. Understanding the different pathways behind angiogenesis becomes essential to break this link by developing new anti-angiogenic therapies or improving the actual ones. In the first phase, this paper will focus the structural and cellular changes that adipose tissue suffers in obesity. Then, the main pro-angiogenic players will be reviewed, taking into account the pathways that explain their putative role in obesity–cancer link. Finally, the clinical implications of the presented mechanisms will also be regarded, being the main focus on the anti-angiogenic therapies. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a severe mental disorder poorly elucidated from the etiopathogenesis prism. Recently, several micro- and macro-vascular abnormalities have been consistently implicated in SZ's pathophysiology. Since angiogenesis is involved in several biological functions and is a fundamental process in vascular formation and angioregulation, it can provide a framework in which some etiological factors and susceptibility genes for SZ can be linked together. We performed a comprehensive non-systematic review of the literature to explore the possible link between SZ and angiogenesis from a vascular perspective, taking into account new insights from genetic, molecular, neurochemical, animal, and neuroimaging functional studies. Recent molecular and neuroimaging studies indicate that angiogenesis could be involved in SZ etiopathogenesis through its role in neurogenesis during neurodevelopment, or by angiomodulation of cerebral blood flow (CBF). Furthermore, it has been hypothesized that the epidemiological finding of lesser predisposition of SZ patients to certain types of cancer could be derived by a putative interplay between SZ pathophysiology and angiogenesis. While it is yet unclear how a complex multivariate interplay between angiogenic factors, neurotrophins, dopamine and other neurotransmitters, brain angiogenic inhibitor molecules (BAI1–3) and patterns of regional blood flow may yield to a biological effect, the importance of further investigation and considering them as potential therapeutic targets for SZ is highlighted. [ABSTRACT FROM AUTHOR]

Excessive UV radiation exposure is harmful to skin cells since sunburn is accompanied by oxidative burst, leading to a rapid increase in skin cancer. However, the insufficient UV photoprotection of approved sunscreens and the negative impact of their compositions on ecosystems and human health makes the utility of sunscreen a questionable recommendation. Therefore, discovering UV filters with significant antioxidant activity and improved topical performance and photostability is an urgent need. Recently, the use of nanosized natural molecules incorporated in sunscreens has been a scientific hot topic, as it has been suggested that they provide a synergistic effect with synthetic UV filters, improving overall SPF and antioxidant activity, higher retention on the epidermis, and less toxicity. The aim of this review was to verify the usefulness of sunscreens incorporating flavonoid-loaded nanoparticles. A literature review was performed, where original and review articles published in the last 6 years were analyzed. Formulations containing nanosized flavonoids with improved UVA photoprotection and safer toxicological profiles, associated or not with synthetic filters, are promising sunscreens and more clinical investigation must be performed to validate these findings. [ABSTRACT FROM AUTHOR]

Abstract: Cancer prevalence and risk in schizophrenia (SZ) patients, as well as their implicated molecular pathways, is a debate that has become increasingly appreciated, despite lacking evidence. Since angiogenesis is imbalanced in both conditions, a non-systematic review of the existing literature using the PubMed database was performed to summarize current knowledge and to elucidate hypothesis regarding the reduced incidence of cancer in SZ, exploring possible angiogenesis biology aspects that can be interrelated both with SZ and cancer. Some lines of evidence based in epidemiology, genetic, molecular and biochemical studies suggest a putative interplay between SZ pathophysiology and angiogenesis, involving different molecular pathways and also influencing cancer biology. Studying angiogenesis in SZ and its implications to cancer is an unexplored field that could provide more insightful knowledge regarding its pathophysiology and promote the development of treatment applications. [Copyright &y& Elsevier]

Cyanobacteria are commonly-occurring contaminants of surface waters worldwide. Microcystins, potent hepatotoxins, are among the best characterized cyanotoxins. During November, 2001, a group of 44 hemodialysis patients were exposed to microcystins via contaminated dialysate. Serum microcystin concentrations were quantified with enzyme-linked immunosorbent assay which measures free serum microcystin LR equivalents (ME). We describe serum ME concentrations and biochemical outcomes among a subset of patients during 8 weeks following exposure. Thirteen patients were included; 6 were males, patients’ median age was 45 years (range 16–80), one was seropositive for hepatitis B surface antigen. The median serum ME concentration was 0.33 ng/mL (range: <0.16–0.96). One hundred thirty nine blood samples were collected following exposure. Patients’ biochemical outcomes varied, but overall indicated a mixed liver injury. Linear regression evaluated each patient’s weekly mean biochemical outcome with their maximum serum ME concentration; a measure of the extrinsic pathway of clotting function, prothrombin time, was negatively and significantly associated with serum ME concentrations. This group of exposed patients’ biochemical outcomes display evidence of a mixed liver injury temporally associated with microcystin exposure. Interpretation of biochemical outcomes are complicated by the study population’s underlying chronic disease status. It is clear that dialysis patients are a distinct ‘at risk’ group for cyanotoxin exposures due to direct intravenous exposure to dialysate prepared from surface drinking water supplies. Careful monitoring and treatment of water supplies used to prepare dialysate is required to prevent future cyanotoxin exposure events. [ABSTRACT FROM AUTHOR]

Abstract: Diabetes mellitus (DM) is a chronic metabolic disease characterized by the presence of hyperglycemia, which can lead to many complications over time. These complications, such as nephropathy, retinopathy, neuropathy, impaired wound healing and accelerated atherosclerosis, are implicated with a large number of cellular and subcellular changes on vessels. In agreement, evidence indicates that in retinopathy, nephropathy and atherosclerotic plaque, there is excessive angiogenesis, whereas in wound healing and myocardial perfusion, blood vessel growth is impaired. Despite the awareness of this angiogenic paradox, many questions remain unanswered. This review aims at highlighting the different microvascular and macrovascular complications that are often concurrent in diabetic patients. A revision of the recent findings published in the literature regarding the angiogenic paradox will be performed. Apparently, endothelial dysfunction, as well as molecules such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) play a major role in diabetic vascular complications. Specific tissues with impaired angiogenesis exhibit microenvironment features, such as increased PAI-1/uPA ratio and decreased blood flow, whereas TGFbeta increases extracellular matrix deposition, preventing the vascularization process. In addition, the monocytes/macrophages are important in endothelium activation for arteriogenesis and its arteriogenic response is reduced, leading to impaired collateral artery growth. Moreover, molecular mechanisms involved will be addressed, including abnormalities in growth factor, cytokines and metabolic derangements. [Copyright &y& Elsevier]

Abstract: Diabetes-induced metabolic derangements promote endothelial malfunction, contributing to erectile dysfunction (ED). However, it remains unclear which angiogenic molecular mechanisms are deregulated in diabetic corpus cavernosum (CC). We investigated early and late alterations in cavernosal angiogenic gene expression associated to diabetes. Angiogenic changes were assessed in penile tissue of streptozotocin-induced Wistar rats, in an early (2-week) and established stage (8-week) of diabetes. Differentially expressed genes were identified by microarrays and expression data validated by quantitative real-time PCR (qrt-PCR). At protein level, quantitative immunohistochemistry confirmed the arrays data and dual immunofluorescence for selected alterations and α-smooth muscle actin (α-SMA) identified the cellular location of target proteins. The selected differentially expressed genes were also evaluated in human non-diabetic and diabetic CC by quantitative immunolabeling. At 2-week diabetes there was no differential gene expression between non-diabetic and diabetic CC. At 8-week, 10 genes were found down-regulated in diabetics. The results were validated by qrt-PCR for the insulin-like growth factor-1 (Igf1) and the natriuretic peptide receptor-1 (Npr1) genes. Dual immunofluorescence for IGF-1/ α-SMA showed predominant localization of IGF-1 in SM. NPR-1 expression was diffuse and mostly present in trabecular fibroblasts and SM. Quantitative immunostaining confirmed the decreased expression of both proteins in diabetic tissues. Concordantly, we detected a significant reduction in IGF-1 and NPR-1 protein expressions in human diabetic samples. Microarray analysis identified 10 angiogenic-related molecules deregulated in CC of established diabetes. Among them, IGF-1 and NPR-1 were significantly down-regulated and might result in preventive/therapeutic targets for ED management. [Copyright &y& Elsevier]

Erectile dysfunction (ED) is a common problem in aged men; however, the molecular events involved in aging ED remain unclear. To better characterize the effects of aging in the penis, we evaluated cavernosal tissue remodeling capability and the downstream activation of the intracellular signaling mediator mitogen-activated protein p42/44 kinase (p42/44 MAPK). We used male Wistar rats, which were divided in groups of 2, 6, 12, 18, and 24 months old. Penile tissues were harvested and processed for protein isolation and immunohistochemical analysis. Cavernosal viability was assessed by TUNEL assay, and proliferation was analyzed by immunohistochemical detection of proliferating cell nuclear antigen (PCNA). Immunolocalization of the activated form of p42/44 MAPK was evaluated by immunofluorescence, and changes in its phosphorylation status were quantified by western blotting. p42/44 phosphorylation profile was also assessed in situ in human young and elderly cavernosal samples. With the advancement of age, experimental cavernosal tissue remodeling was affected by an age-dependent unbalance between the rate of apoptosis and proliferation, in all erectile components. Moreover, this turnover alteration was accompanied by significant modifications in the activation profile of the downstream effector p42/44 MAPK. In the youngest corporeal samples, p42/44 was mostly activated at perivascular sites, potentially mediating cell survival/proliferation. However, in elderly experimental erectile tissue, p42/44 phosphorylation shifted to trabecular fibroblasts, indicating a potential role in extracellular matrix (ECM) production. More importantly, the same differential pattern of p42/44 activation was observed in human young and aged cavernosal fragments, suggesting a distinct function of this protein with aging. We provided evidence for the first time that with the advancement of age, there is a differential activation of p42/44 MAPK in cavernosal tissue, which may promote ECM expansion and fibrosis, therefore compromising erectile function in the elderly. [ABSTRACT FROM AUTHOR]

Abstract: We have previously identified the expression of an estradiol (E2)-related molecule by Schistosoma haematobium total antigen (Sh). We now show that this molecule has an antagonistic effect of estradiol in vitro. Our results are consistent with the existence of an estrogenic molecule that antagonizes the activity of estradiol. We found evidence for this molecule as we identified and characterized by mass spectrometry new estrogenic molecules previously unknown, present in schistosome worm extracts and sera of Schistosoma-infected individuals. We also show that Sh is able to interact in vitro with estrogen receptor (ER), explaining how host endocrine system can favor the establishment of schistosomes. These findings highlight the exploitation of the host endocrine system by schistosomes and represent an additional regulatory component of schistosome development that defines a novel paradigm enabling host–parasite interactions. The identification of these molecules opens new ways for the development of alternative drugs to treat schistosomiasis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Obesity is an important component of the metabolic syndrome in constituting a risk factor for cardiovascular disease, diabetes, and cancer. Estrogens influence lipid accumulation in adipocytes, acting indirectly or directly on adipose tissue. In this study we aimed to investigate the influence of red wine ingestion on the expression of aromatase (estrogen synthase) in adipose tissue. Methods: Red wine or ethanol solution, in the concentration found in red wine, was provided to Wistar rats as the sole drinking fluid for 8 wk. Food and drink intakes and body weight were monitored throughout treatment and adipocyte size and aromatase expression in the adipose tissue were determined at the end of the experimental period. Results: Red wine and ethanol increased aromatase expression in the adipose tissue and red wine decreased adipocyte size (P < 0.05). In addition, animals treated with red wine or ethanol had significantly lower weight gain than controls, despite a similar energy intake. Conclusion: Thus, the ingestion of red wine may alter the production of estrogens by adipose tissue, body weight gain, and adipocyte size. Some of these red wine effects are attributable to ethanol. This relation among estrogen availability, adipocyte biology, and weight gain is most interesting and deserves further study because it may lead to new strategies to reduce metabolic syndrome incidence. [Copyright &y& Elsevier]

Introduction. Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum. Aim. To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status. Methods. Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT). Main Outcome Measures. Establish an index of ACD and correlate those results with patient clinical data. Results. Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 ± 0.44 (mean apoptotic cells/tissue area mm2 ± standard error). The diabetic group showed an increased ACD of 23.82 ± 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI. Conclusions. We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI. Costa C, Soares R, Castela Â, Adães S, Hastert V, Vendeira P, and Virag R. Increased endothelial apoptotic cell density in human diabetic erectile tissue—Comparison with clinical data. J Sex Med 2009;6:826–835. [ABSTRACT FROM AUTHOR]

Abstract: Toxic cyanobacteria blooms in drinking water supplies have been an increasing public health concern all over the world. Human populations can be exposed to microcystins, an important family of cyanotoxins, mainly by oral ingestion. However, inhalation from recreational water and hemodialysis can represent other routes. This study investigated changes in respiratory mechanics, histology, protein phosphatase (PP) 1 and 2A activity and microcystin in lung of adult mice injected intraperitoneally (i.p.) with microcystin-LR. Thirty-six mice were divided into control (CTRL) and test (CYANO) groups. CTRL group received an i.p. injection of saline and the CYANO group received 40μg MCYST-LR/kg i.p. After 2 and 8h, and 1, 2 and 4 days after toxin injection, six mice from each group were sampled for analyses. Resistive and viscoelastic pressures, static and dynamic elastances augmented at 2h in CYANO and so remained until day 4. Alveolar collapse and inflammatory cell infiltration were found 2h after the injection, reaching peak values at 8h. However, no microcystin or inhibition of PPases could be detected in mice lungs. In conclusion, MCYST-LR led to a rapid increase in lung impedance and an inflammatory response with interstitial edema and inflammatory cell recruitment in mice. [Copyright &y& Elsevier]

In order to understand accumulation and depuration of microcystins (MCYSTs) in Tilapia rendalli, three experiments with juveniles were done. The experiments simulated the fish diet during a Microcystis aeruginosa bloom in three different situations. In the first one each fish received daily, during 15 days, fish food plus toxic cells of M. aeruginosa (20.4μg MCYSTs fish-1 day-1). In the following 15 days they were fed without toxic cells. In the second experiment, fish were fed only with toxic cells during 28 days (14.6μg MCYSTs fish-1 day-1) and in the third experiment, during 42 days, fish were fed with fish food plus toxic cells (29.2μg MCYSTs fish-1 day-1) previously disrupted (to simulate a senescent bloom). MCYSTs analyses were done by enzyme-linked immunosorbent assay (ELISA) in liver and muscle samples in all experiments and in faeces in the first one (only in the depuration period). The results demonstrated different profiles of MCYSTs accumulation in liver and muscle of T. rendalli. Comparing the experiments, the highest MCYSTs accumulation in the liver (2.8μgg-1) occurred in the second one, where fish had only toxic cells as feeding source. In the first experiment, the highest MCYSTs accumulation in liver (0.6μg MCYSTs g-1) was observed during the accumulation period, while in muscle, interestingly, the highest concentration (0.05μg MCYSTs g-1) occurred in the depuration period. In this same period, it was also observed elimination of toxins through faeces. The second and third experiments showed almost the same average concentrations in tissues although fish have received more MCYSTs in third one. With respect to implications of the fish comsumption, MCYSTs accumulation in muscle of T. rendalli in all three experiments reached concentrations that would represent an intake of these toxins above the tolerable limit for humans and these results confirmed our previous observations from a field study. In conclusion, in this study it was observed that T. rendalli is able to accumulate MCYSTs and the availability of other feeding sources, besides toxic cells, probably interferes with the accumulation rate. Therefore, the occurrence of toxic cyanobacterial blooms produncing MCYSTs in aquaculture ponds could represent a risk to the quality of fish to the consumers. [Copyright &y& Elsevier]

Costa C, Soares R, Schmitt F. Angiogenesis: now and then. APMIS 2004;112:402–12.Angiogenesis or new blood vessel formation plays an essential role during embryogenesis, adult vascular remodeling and in several pathological disorders, as in tumor development. Although sprouting of blood vessels is the principal angiogenic mechanism, additional ones, such as the recruitment of bone marrow-derived cells, have recently been described. These processes are controlled by several molecules, although members of the VEGF family of angiogenic factors and its receptors seem to be the main mediators. Initially, VEGF receptors were described as endothelial specific; however, further studies have reported their presence in several types of cells of non-endothelial origin, such as tumor cells. This VEGF receptor altered expression has suggested an angiogenesis-independent growth advantage mechanism on certain types of cancers by the generation of autocrine loops. A possible role in tumorigenesis and a potential novel target in cancer therapy have been hypothesized. Detection of other receptors and molecules considered to be angiogenic players has also been observed on tumor cells. Currently, their clinical significance as well as their potential as therapeutic targets for the treatment of certain cancers is being evaluated, having in mind the future development of promising mechanism-based therapies. The aspects mentioned above are the main focus of this review, which aims to throw light on recent findings respecting angiogenesis and novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Suggests that estrogen can mediate endothelial proliferation and differentiation and evaluates the effect of one anti-estrogenic agent ICI 182,780 in human umbilical vein endothelial cells. Decrease in cell viability and increase in apoptosis; Evaluation of gene expression profile of the ICI treated endothelial cells; Activation of apoptopic pathways in endothelial cells by impaired angiogenesis.

Abstract: Immunohistochemical analysis of the expression of transforming growth factor α (TGF-α) and its receptor, epidermal growth factor receptor (EGFR), was performed in a series of 86 invasive carcinomas of the breast. TGF-α immunostaining was observed in the majority of the cases (72.1%), both in epithelial cells and in adjacent stromal cells. EGFR was also present in tumors (34.2%) and in the endothelial cells (46.1% of the cases) near the tumors. A significant association was observed between TGF-α expression and angiogenesis evaluated by immunohistochemistry using an antibody against factor VIII-related antigen. No association was observed between TGF-α expression and other clinicopathologic features. In contrast, EGFR expression in the tumor was associated with features of poor prognosis, such as tumor size, histologic grade, lymph node status, estrogen receptor content, p53 expression, sialyl-Tn expression, and age. The presence of EGFR in endothelial cells was correlated to young patient age. We also observed an association of EGFR in endothelial cells and angiogenesis in tumors with a size of less than 2 cm. Inversely, in larger tumors, angiogenesis was only associated with tumor TGF-α expression. These results indicate that endothelial EGFR may play a role in the early steps of breast cancer angiogenesis. [ABSTRACT FROM AUTHOR]

It is well established that tumour cells undergo metabolic changes to acquire biological advantage over normal cells with activation of the glycolytic pathway, a process termed "Warburg effect". Enzyme isoforms are alternative enzymatic forms with the same function but with different biochemical or epigenetic features. Moreover, isoforms may have varying impacts on different metabolic pathways. We challenge ourselves to analyse the glycolytic and gluconeogenic enzymes and isoforms in breast cancer, a complex and heterogeneous pathology, associated with high incidence and mortality rates especially among women. We analysed epithelial and tumour cell lines by RT-PCR and compared values to a publicly available database for the expression profile of normal and tumour tissues (Gepia) of enzymes and enzymatic isoforms from glycolytic and gluconeogenic pathways. Additionally, GeneMANIA was used to evaluate interactions, pathways, and attributes of each glycolytic/gluconeogenic steps. The findings reveal that the enzymes and enzymatic isoforms expressed in cell culture were somewhat different from those in breast tissue. We propose that the tumor microenvironment plays a crucial role in the expression of glycolytic and gluconeogenic enzymes and isoforms in tumour cells. Nonetheless, they not only participate in glycolytic and gluconeogenic enzymatic activities but may also influence other pathways, such as the Pentose-Phosphate-Pathway, TCA cycle, as well as other carbohydrate, lipid, and amino acid metabolism. [Display omitted] • Enzymatic isoforms may have varying impacts on different metabolic pathways. • Enzymatic isoforms expressed differently in cell culture from breast cancer tissue. • Glycolysis and gluconeogenic enzymatic isoforms present a distinct expression. [ABSTRACT FROM AUTHOR]

The umbilical cord has been proved to be an easy-access, reliable, and useful source of mesenchymal stem cells (MSC) for clinical applications due to its primitive, immunomodulatory, non-immunogenic, secretory and paracrine, migratory, proliferative, and multipotent properties. This set of characteristics has recently attracted great research interest in the fields of nanotechnology and regenerative medicine and cellular therapy. Accumulating evidence supports a pronounced therapeutic potential of MSC in many different pathologies, from hematology to immunology, wound-healing, tissue regeneration, and oncology. Diabetes mellitus, branded the epidemic of the century, is considered a chronic metabolic disorder, representing a major burden for health system sustainability and an important public health challenge to modern societies. The available treatments for type 2 diabetes mellitus (T2DM) still rely mainly on combinations of oral antidiabetic agents with lifestyle and nutritional adjustments. Despite the continuous development of novel and better hypoglycemic drugs, their efficacy is limited in the installment and progression of silent T2DM complications. T2DM comorbidities and mortality rates still make it a serious, common, costly, and long-term manageable disease. Recently, experimental models, preclinical observations, and clinical studies have provided some insights and preliminary promising results using umbilical cord MSCs to treat and manage diabetes. This review focuses on the latest research and applications of human-derived umbilical cord MSC in the treatment and management of T2DM, exploring and systematizing the key effects of both umbilical cord MSC and its factor-rich secretome accordingly with the major complications associated to T2DM. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a complex pathology characterized by several features including molecular subtype (MS). Immunohistochemistry assays were used to investigate the expression of enzymes involved in glycolysis and gluconeogenesis. The analysis involved stratifying the data based on MS, body mass index (BMI), and the combination of BMI with MS (mBMI). This study revealed significant differences in the expression of three specific enzymes—pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP)—among tumor cells when stratified by MS and mBMI. Moreover, the expression levels of these enzymes were found to be closely related to hormonal receptor and HER2 status, as well as correlated pathological stage and histological grade. Obesity appeared to have an impact on these differences, particularly in the expression of PC. However, it was observed that these differences were not influenced by the presence of adipocyte deposition or inflammatory infiltration within the tumor microenvironment. Nevertheless, the expression of PCK and FBP was also influenced by the presence of obesity-related conditions such as diabetes, hypertension, and dyslipidemia. In summary, this study highlights the existence of distinct metabolic profiles for breast cancer based on its molecular subtypes, and how these profiles are affected by obesity and related health conditions. Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine. [ABSTRACT FROM AUTHOR]

Molecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line. [ABSTRACT FROM AUTHOR]

The occurrence of toxic blooms of cyanobacteria has been a matter of public health interest due to the cyanotoxins produced by these microorganisms. Cylindrospermopsin (CYN) is a cyanotoxin of particular concern due to its toxic effects on humans. This study investigated the removal and effects of CYN in ripened slow sand filters (SSFs) treating water from Paranoá Lake, Brasilia, Brazil. Four pilot-scale SSFs were ripened and operated for 74 days. Two contamination peaks with CYN were applied along the filtration run. The improvement of any of the evaluated water quality parameters was not affected by the presence of CYN in the raw water. The SSFs efficiently removed CYN, presenting concentrations lower than 0.8 µg/L in the filtered water. The microbiota of the SSFs were dominated by protozoa of the genus Euglypha and amoebas of the genera Arcella, Centropyxis, and Amoeba, together with some groups of rotifers. These microorganisms played a crucial role in removing total coliforms and E. coli. In addition, CYN was not identified as a determining factor in the microbiota composition. [ABSTRACT FROM AUTHOR]

Inflammation may play a significant role in Keratoconus (KC), but the relationship between inflammatory markers and choroidal thickness (CT) is unknown. The purpose of this study was to evaluate serum inflammatory markers and correlate them with the choroidal profile of KC patients and control subjects. Forty patients with KC and 26 age-matched control subjects were enrolled in a cross-sectional case–control study. Choroidal profile was studied with a Spectralis Heidelberg apparatus and venous blood samples were collected. Neutrophil/lymphocyte ratio (NLR), monocyte/HDL ratio (MHR), platelet/lymphocyte ratio (PLR) and systemic immune inflammation index (SII) were calculated. Serum inflammatory biomarkers IL-1, IL-6 and TNF-alfa were also analyzed. KC group presented thicker choroids in each evaluated point when compared to the control group (subfoveal CT 417.38 ± 79.79 vs 299.61 ± 76.13, p < 0.001 for all measured locations). Mean values of NLR, PLR and SII were significantly higher in patients with KC (NLR p = 0.001; PLR p = 0.042; SII p = 0.007). Although KC patients presented higher mean levels of MHR, IL-1, IL-6 and TNF-α than control group, no significant differences were achieved. Positive correlations were found between subfoveal CT and NLR and SII (0.408, p = 0.001 and 0.288, p = 0.019 respectively). The results presented are in favor of a relationship between the increased CT and inflammatory mechanisms in KC patients. The elevated serum inflammatory indices NLR, SII and PLR provide additional evidence of a role for systemic inflammation in the pathophysiology of KC. [ABSTRACT FROM AUTHOR]

Background In type 2 diabetes, insulin resistance is observed, and β-cells are incapable of responding to glycemia demands, leading to hyperglycemia. Although the nature of β-cells dysfunction in this disease is not fully understood, a link between the induction of pancreatic β-cell premature senescence and its metabolic implications has been proposed. This study aimed to understand the relationship between diabetes and pancreatic senescence, particularly at the beginning of the disease. Methods C57Bl/6 J mice were fed two different diets, a normal diet and a high-fat diet, for 16 weeks. Pancreatic histomorphology analysis, insulin quantification, inflammation parameters, and senescence biomarkers for the experimental animals were assessed at weeks 12 and 16. Results The results proved that diabetes onset occurred at week 16 in the High Fat Diet group, supported by glycaemia, weight and blood lipid levels. Increased β-cells size and number accompanied by increased insulin expression were observed. Also, an inflammatory status of the diabetic group was noted by increased levels of systemic IL-1β and increased pancreatic fibrosis. Finally, the expression of galactosidase-beta 1 (GLB1) was significantly increased in pancreatic β-cells. Conclusion The study findings indicate that senescence, as revealed by an increase in GLB1 expression, is a key factor in the initial stage of diabetes. [ABSTRACT FROM AUTHOR]

Objective: The effect of diabetes on adhesive capsulitis (AC) and its impact on the outcomes of ultrasound (US)-guided hydrodistension of the glenohumeral joint are still unclear. We aimed to identify predictors of US-guided hydrodistension outcomes, while assessing the performance of the method in diabetic compared to non-diabetic patients. Materials and methods: A total of 135 patients with AC who underwent US-guided hydrodistension were prospectively included. Demographics and factors linked to chronic inflammation and diabetes were recorded and patients were followed-up for 6 months. Functionality and pain were evaluated with the Disabilities of the Arm, Shoulder and Hand (DASH) and the Visual Analogue Scale (VAS) score. Statistical analysis was performed with Mann–Whitney U test, linear, and binary logistic regression. Results: Diabetes was identified in 25/135 patients (18.5%). Diabetic patients had worse DASH and VAS score at presentation (P < 0.0001) and presented with a higher grade of AC (P < 0.0001) and lower range of motion (P < 0.01) compared to non-diabetics. Higher DASH (P = 0.025) and VAS scores (P = 0.039) at presentation were linked to worse functionality at 6 months. Presence and duration of diabetes, and the number of hydrodistension repeats, correlated with worse VAS and DASH scores at 6 months. The number of procedure repeats was the only independent predictor of complete pain resolution at 6 months (OR 0.418, P = 003). Conclusion: Diabetes is linked to more severe AC at presentation and worse outcomes in patients undergoing US-guided hydrodistension. In resistant cases, repeating the intervention is independently linked to worse outcomes for at least 6 months post-intervention. [ABSTRACT FROM AUTHOR]

Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. During infection, eggs are deposited in the bladder causing an intense inflammatory reaction. Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions. A growing amount of evidence points to angiogenesis playing a key role in schistosomiasis-associated bladder cancer. Thus, identifying biomarkers of this process plays an important role in the study of cancer. Here, we review recent findings on the role of angiogenesis in bladder cancer and the growth factors that induce and assist in their development, particularly SCC of the bladder associated to urogenital schistosomiasis. [ABSTRACT FROM AUTHOR]

The Pantanal is a hotspot for arbovirus studies in South America. Various medically important flaviviruses and alphaviruses have been reported in domestic and wild animals in the region. To expand the knowledge of local arbovirus circulation, a serosurvey for 14 Brazilian orthobunyaviruses was conducted with equines, sheep and free-ranging caimans. Sera were tested for specific viral antibodies using plaque-reduction neutralization test (PRNT). Monotypic reactions were detected for Maguari, Xingu, Apeu, Guaroa, Murutucu, Oriboca, Oropouche and Nepuyo viruses. Despite the low titers for most of the orthobunyaviruses tested, the detection of monotypic reactions for eight orthobunyaviruses suggests the Pantanal as a region of great orthobunyavirus diversity. The present data, in conjunction with previous studies that detected a high diversity of other arboviruses, ratify the Pantanal as an important natural reservoir for sylvatic and medically important arboviruses in Brazil. [ABSTRACT FROM AUTHOR]

BACKGROUND: Breast cancer (BC) and obesity are two closely associated pathologies with increasing incidence and mortality rates. Bilateral Breast Cancer (BBC) displays a low incidence rate within BC and obesity represents a major risk factor. OBJECTIVE: The aim of this study is to analyzed BBC clinicopathological features distribution and determine the potential influence of obesity in BBC in these same features and overall survival. METHODS: Clinicopathological information was obtained from 42 cases of women with BBC diagnosed in IPO-Porto. To evaluate the frequency distribution of the clinicopathological data, a chi-square goodness of fit test was performed for BBC cases. A chi-square test of independence was applied for BMI stratification. Cox regression was performed for overall survival. Statistical significance was set at p-value < 0.05. RESULTS: Distribution of BBC clinicopathological features was found to be statistically significant in family history (p-value < 0.001), BBC type (p-value < 0.001), stage (p-value = 0.005), differentiation grade (p-value < 0.001), receptor expression (p-value < 0.001) and histological type (p-value = 0.031). In comparison to the statistical expected results, we observed an increased cases of absence of family history and less cases of metachronous BBC. Histological types between tumours of BBC were mostly concordant. All cases presented concordant receptor expression. Analysis stratified by BMI revealed that obese women were diagnosed later, although without statistical significance. All obese women presented poor differentiation grade (n = 6). Overweight patients display a tendency to a better overall survival with lower tumour stages and lower differentiation grades. CONCLUSIONS: Our results reveal the same receptor expression between contralateral tumours. Also, most tumours share the same histological type. When stratified by BMI, we observed a tendency for overweight women to have improved overall survival. [ABSTRACT FROM AUTHOR]

The unfoldase ClpC1 is one of the most exciting drug targets against tuberculosis. This AAA+ unfoldase works in cooperation with the ClpP1P2 protease and is the target of at least four natural product antibiotics: cyclomarin, ecumicin, lassomycin, and rufomycin. Although these molecules are promising starting points for drug development, their mechanisms of action remain largely unknown. Taking advantage of a middle domain mutant, we determined the first structure of Mycobacterium tuberculosis ClpC1 in its apo, cyclomarin-, and ecumicin-bound states via cryo-EM. The obtained structure displays features observed in other members of the AAA+ family and provides a map for further drug development. While the apo and cyclomarin-bound structures are indistinguishable and have N-terminal domains that are invisible in their respective EM maps, around half of the ecumicin-bound ClpC1 particles display three of their six N-terminal domains in an extended conformation. Our structural observations suggest a mechanism where ecumicin functions by mimicking substrate binding, leading to ATPase activation and changes in protein degradation profile. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor concerning triggering transcription growth factor-beta and notch signalling cross-talk.

This study aimed to determine the effect of three widely used radiopharmaceuticals with intestinal excretion on selected relevant bacteria that are part of the human gut microbiota, using an ex vivo approach. Fecal samples obtained from healthy volunteers were analyzed. Each sample was divided into four smaller aliquots. One served as the non-irradiated control. The other three were homogenized with three radiopharmaceutical solutions ([131I]NaI, [99mTc]NaTcO4, and [223Ra]RaCl2). Relative quantification of each taxa was determined by the 2−ΔΔC method, using the ribosomal gene 16S as an internal control (primers 534/385). Twelve fecal samples were analysed: three controls and nine irradiated. Our experiment showed fold changes in all analyzed taxa with all radiopharmaceuticals, but results were more significant with I-131, ranging from 1.87–83.58; whereas no relevant differences were found with Tc-99m and Ra-223, ranging from 0.98–1.58 and 0.83–1.97, respectively. This study corroborates limited existing research on how ionizing radiation changes the gut microbiota composition, providing novel data regarding the ex vivo effect of radiopharmaceuticals. Our findings justify the need for future larger scale projects. [ABSTRACT FROM AUTHOR]

Presents the abstract of the article 'BRCA1 Mutation Analysis in a Portuguese Population with Early-Onset Breast and/or Ovarian Cancer,' by Raquel Soares, Ronald van Eijk, Aureliano Dias, M ò nica Botelho, Carla Costa, Isabel Amendoeira, Carlos Lopes, Peter Devilee and Fernando Schmitt.

Chronic wounds are one of the most frequent complications that are associated with diabetes mellitus. The overproduction of reactive oxygen species (ROS) is a key factor in the delayed healing of a chronic wound. In the present work, we develop a novel in situ-forming silk sericin-based hydrogel (SSH) that is produced by a simple methodology using horseradish peroxidase (HRP) crosslinking as an advanced dressing for wound healing. The antioxidant and angiogenic effects were assessed in vitro and in vivo after in situ application using an excisional wound-healing model in a genetically-induced diabetic db/db mice and though the chick embryo choriollantoic membrane (CAM) assay, respectively. Wounds in diabetic db/db mice that were treated with SSH closed with reduced granulation tissue, decreased wound edge distance, and wound thickness, when compared to Tegaderm, a dressing that is commonly used in the clinic. The hydrogel also promoted a deposition of collagen fibers with smaller diameter which may have had a boost effect in re-epithelialization. SSH treatment slightly induced two important endogenous antioxidant defenses, superoxide dismutase and catalase. A CAM assay made it possible to observe that SSH led to an increase in the number of newly formed vessels without inducing an inflammatory reaction. The present hydrogel may result in a multi-purpose technology with angiogenic, antioxidant, and anti-inflammatory properties, while advancing efficient and organized tissue regeneration. [ABSTRACT FROM AUTHOR]

Early-life consumption of high-fat and sugar-rich foods is recognized as a major contributor for the onset of metabolic dysfunction and its related disorders, including diabetes and nonalcoholic fatty liver disease. The lifelong impact of early unhealthy eating habits that start at younger ages remains unclear. Therefore, to better understand the effects of diet, it is essential to evaluate the structural and functional changes induced in metabolic organs and potential mechanisms underlying those changes. To investigate the long-term effects of eating habits, young male rats were exposed to high-sugar and high-energy diets. After 14 weeks, body composition was assessed, and histopathological changes were analyzed in the liver and adipose tissue. Serum biochemical parameters were also determined. Expression of inflammatory markers in the liver was evaluated by immunohistochemistry. Our results revealed that serum levels of glucose, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), and lipid profile were increased in rats red high-sugar and high-energy diets. Histopathological alterations were observed, including abnormal hepatocyte organization and lipid droplet accumulation in the liver, and abnormal structure of adipocytes. In both unhealthy diet groups, hepatic expression of Toll-like receptor 4 (TLR4), cyclooxygenase 2 (COX-2), and E-selectin were increased, as well as a biomarker of oxidative stress. Together, our data demonstrated that unhealthy diets induced functional and structural changes in the metabolic organs, suggesting that proinflammatory and oxidative stress mechanisms trigger the hepatic alterations and metabolic dysfunction. [ABSTRACT FROM AUTHOR]

During the pathophysiological course of type 2 diabetes (T2D), several metabolic imbalances occur. There is increasing evidence that metabolic dysfunction far precedes clinical manifestations. Thus, knowing and understanding metabolic imbalances is crucial to unraveling new strategies and molecules (biomarkers) for the early-stage prediction of the disease's non-clinical phase. Lifestyle interventions must be made with considerable involvement of clinicians, and it should be considered that not all patients will respond in the same manner. Individuals with a high risk of diabetic progression will present compensatory metabolic mechanisms, translated into metabolic biomarkers that will therefore show potential predictive value to differentiate between progressors/non-progressors in T2D. Specific novel biomarkers are being proposed to entrap prediabetes and target progressors to achieve better outcomes. This study provides a review of the latest relevant biomarkers in prediabetes. A search for articles published between 2011 and 2021 was conducted; duplicates were removed, and inclusion criteria were applied. From the 29 studies considered, a survey of the most cited (relevant) biomarkers was conducted and further discussed in the two main identified fields: metabolomics, and miRNA studies. [ABSTRACT FROM AUTHOR]

Background and aims: Glucose homeostasis is a critical cornerstone in both health and disease. It is described to be regulated by the balance of insulin and glucagon secretion but, this bi-hormonal perspective is long overdue since glucose homeostasis is now known to be a multi-hormonal process. Metabolic syndrome (MetS) is a cluster of metabolic features that includes impaired glucose metabolism and obesity. Obesity promotes a low chronic inflammation state due to the release of bioactive molecules like cytokines, ultimately contributing to cardiovascular disease, diabetes, and cancer. The gastrointestinal tract (GIT), namely the stomach and intestine, has a vital role not only in the food uptake and absorption but also in the production of incretin hormones, such as GLP-1. We aim to evaluate the GLP-1 receptor (GLP-1R) in the GIT of a MetS animal model and to assess whether it correlates with inflammatory levels. Material and method: The expression of GLP-1R and interleukin-6 (IL-6) was evaluated in the stomach and intestine of mice subjected to normal diet (ND) and high fat diet (HFD) by immunohistochemistry. Results: We observed that HFD fed animals presented lower levels of GLP-1R in the stomach and intestine when compared with animals fed with ND. Concomitantly, these mice expressed increased levels of IL-6. Conclusions: GLP-1R expression is inversely correlated with the expression of the pro-inflammatory cytokine IL-6. [ABSTRACT FROM AUTHOR]

Abstract: The acute poisoning of chronic renal patients during hemodialysis sessions in 1996 in Caruaru City (Pernambuco State, Brazil) stimulated an intensive search for the cause of this severe complication. This search culminated in the identification of microcystins (MC), hepatotoxic cyclic heptapeptides produced by cyanobacteria, as the causative agents. More than ten years later, additional research data provides us with a better understanding of the factors related to cyanobacterial bloom occurrence and production of MC in Brazil and other South American countries. The contamination of water bodies and formation of toxic blooms remains a very serious concern, especially in countries in which surface water is used as the main source for human consumption. The purpose of this review is to highlight the discoveries of the past 15 years that have brought South American researchers to their current level of understanding of toxic cyanobacteria species and that have contributed to their knowledge of factors related to MC production, mechanisms of action and consequences for human health and the environment. [ABSTRACT FROM AUTHOR]