ABSTRACT
Proteins secreted by tumoral cells (cancer secretomes) have been continuously associated with cancer development and progression processes. In this context, secreted proteins contribute to the signaling mechanisms related to tumor growth and spreading and studies on tumor secretomes provide valuable clues on putative tumor biomarkers. Although the in vitro identification of intracellular proteins in cancer secretome studies has usually been associated with contamination derived from cell lysis or fetal bovine serum, accumulated evidence reports on intracellular proteins with moonlighting functions in the extracellular environment. In this study, we performed a systematic reanalysis of public proteomics data regarding different cancer secretomes, aiming to identify intracellular proteins potentially secreted by tumor cells via unconventional secretion pathways. We found a similar repertoire of unconventionally secreted proteins, including the recurrent identification of nuclear proteins secreted by different cancer cells. In addition, in some cancer types, immunohistochemical data were in line with proteomics identifications and suggested that nuclear proteins might relocate from the nucleus to the cytoplasm. Both the presence of nuclear proteins and the likely unconventional secretion of such proteins may comprise biological signatures of malignant transformation in distinct cancer types and may be targeted for further analysis aiming at the prognostic/therapeutic value of such features.
Subject(s)
Neoplasms , Proteomics , Biomarkers, Tumor/metabolism , Computational Biology , Humans , Nuclear Proteins/metabolism , Proteome/metabolism , SecretomeABSTRACT
Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.
Subject(s)
Adaptation, Physiological , Heart Disease Risk Factors , Humans , Female , Pregnancy , Adult , Ventricular Function, Left , Cardiomegaly/physiopathology , Cardiomegaly/diagnostic imaging , Cardiomegaly/etiology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Pregnancy Complications, Cardiovascular/physiopathology , Pregnancy Complications, Cardiovascular/diagnostic imaging , Pregnancy Complications, Cardiovascular/blood , Stroke Volume , Pregnancy Trimester, Third , Diabetes, Gestational/physiopathology , Compliance , Pregnancy Trimester, First , Obesity/physiopathology , Obesity/complications , Risk FactorsABSTRACT
Adipose tissue dysfunction is a key mechanism that leads to adiposity-based chronic disease. This study aimed to investigate the reliability of the adiponectin/leptin ratio (AdipoQ/Lep) as an adipose tissue and metabolic function biomarker in adults with obesity, without diabetes. Data were collected from a clinical trial conducted in 28 adults with obesity (mean body mass index: 35.4 ± 3.7 kg/m2) (NCT02169778). With the use of a forward stepwise multiple linear regression model to explore the relationship between AdipoQ/Lep and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), it was observed that 48.6% of HOMA-IR variance was explained by triacylglycerols, AdipoQ/Lep, and waist-to-hip ratio (P < 0.001), AdipoQ/Lep being the strongest independent predictor (Beta = -0.449, P < 0.001). A lower AdipoQ/Lep was correlated with higher body mass index (Rs = -0.490, P < 0.001), body fat mass (Rs = -0.486, P < 0.001), waist-to-height ratio (Rs = -0.290, P = 0.037), and plasma resistin (Rs = -0.365, P = 0.009). These data highlight the central role of adipocyte dysfunction in the pathogenesis of insulin resistance and emphasize that AdipoQ/Lep may be a promising early marker of insulin resistance development in adults with obesity.NEW & NOTEWORTHY Adiponectin/leptin ratio, triacylglycerols, and waist-to-hip ratio explained almost half of HOMA-IR variance in the context of obesity. This study provides evidence to support adipose tissue dysfunction as a central feature of the pathophysiology of obesity and insulin resistance. Early identification of individuals at higher risk of developing metabolic complications through adipose tissue dysfunction assessment and the staging of obesity and its transient phenotypes can contribute to improve therapeutic decision-making.
Subject(s)
Insulin Resistance , Leptin , Humans , Leptin/metabolism , Adiponectin/metabolism , Insulin Resistance/physiology , Reproducibility of Results , Obesity/metabolism , Body Mass Index , TriglyceridesABSTRACT
Pregnant women with cardiovascular risk (CVR) factors are highly prone to develop cardiovascular disease later in life. Thus, recent guidelines suggest extending the follow-up period to 1 yr after delivery. We aimed to evaluate cardiovascular remodeling during pregnancy and determine which CVR factors and potential biomarkers predict postpartum cardiac and vascular reverse remodeling (RR). Our study included a prospective cohort of 76 healthy and 54 obese and/or hypertensive and/or with gestational diabetes pregnant women who underwent transthoracic echocardiography, pulse-wave velocity (PWV), and blood collection at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy as well as at the 1st/6th/12th mo after delivery. Generalized linear mixed-effects models was used to evaluate the extent of RR and its potential predictors. Pregnant women develop cardiac hypertrophy, as confirmed by a significant increase in left ventricular mass (LVM). Moreover, ventricular filling pressure (E/e') and atrial volume increased significantly during gestation. Significant regression of left ventricular (LV) volume, LVM, and filling pressures was observed as soon as 1 mo postpartum. The LV global longitudinal strain worsened slightly and recovered at 6 mo postpartum. PWV decreased significantly from 1T to 3T and normalized at 1 mo postpartum. We found that arterial hypertension, smoking habits, and obesity were independent predictors of increased LVM during pregnancy and postpartum. High C-reactive protein (CRP) and low ST2/IL33-receptor levels are potential circulatory biomarkers of worse LVM regression. Arterial hypertension, age, and gestational diabetes positively correlated with PWV. Altogether, our findings pinpoint arterial hypertension as a critical risk factor for worse RR and CRP, and ST2/IL33 receptors as potential biomarkers of postpartum hypertrophy reversal.NEW & NOTEWORTHY This study describes the impact of cardiovascular risk factors (CVR) in pregnancy-induced remodeling and postpartum reverse remodeling (up to 1 yr) by applying advanced statistic methods (multivariate generalized linear mixed-effects models) to a prospective cohort of pregnant women. Aiming to extrapolate to pathological conditions, this invaluable "human model" allowed us to demonstrate that arterial hypertension is a critical CVR for worse RR and that ST2/IL33-receptors and CRP are potential biomarkers of postpartum hypertrophy reversal.
Subject(s)
Cardiovascular Diseases , Diabetes, Gestational , Hypertension , Pregnancy , Female , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Prospective Studies , Interleukin-1 Receptor-Like 1 Protein , Interleukin-33 , Risk Factors , Postpartum Period , Obesity/complications , Obesity/diagnosis , Cardiomegaly , Biomarkers , Heart Disease Risk FactorsABSTRACT
Non-alcoholic fatty liver disease (NAFLD) affects around 25% of the worldwide population. Non-alcoholic steatohepatitis (NASH), the more progressive variant of NAFLD, is characterized by steatosis, cellular ballooning, lobular inflammation, and may culminate on hepatic stellate cell (HSC) activation, thus increasing the risk for fibrosis, cirrhosis, and HCC development. Conversely, the antifibrotic effects of sorafenib, an FDA-approved drug for HCC treatment, have been demonstrated in 2D cell cultures and animal models, but its mechanisms in a NAFLD-related microenvironment in vitro requires further investigation. Thus, a human 3D co-culture model of fatty hepatocytes and HSC was established by culturing hepatoma C3A cells, pre-treated with 1.32 mM oleic acid, with HSC LX-2 cells. The fatty C3A/LX-2 spheroids showed morphological and molecular hallmarks of altered lipid metabolism and steatosis-induced fibrogenesis, similarly to the human disease. Sorafenib (15 µM) for 72 hours reduced fatty spheroid viability, and upregulated the expression of lipid oxidation- and hydrolysis-related genes, CPT1 and LIPC, respectively. Sorafenib also inhibited steatosis-induced fibrogenesis by downregulating COL1A1, TGFB1, PDGF, and TIMP1 and by decreasing protein levels of IL-6, TGF-ß1, and TNF-α in fatty spheroids. The demonstration of the antifibrotic properties of sorafenib on steatosis-induced fibrogenesis in a 3D in vitro model of NAFLD supports its clinical use as a therapeutic agent for the treatment of NAFLD/NASH patients.
Subject(s)
Hepatic Stellate Cells/drug effects , Hepatocytes/drug effects , Liver Cirrhosis/prevention & control , Liver/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Sorafenib/pharmacology , Animals , Cell Line, Tumor , Cell Survival/drug effects , Coculture Techniques , Fibrosis , Hepatic Stellate Cells/pathology , Hepatocytes/pathology , Humans , Liver/metabolism , Liver/pathology , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Tissue Inhibitor of Metalloproteinase-1/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
Objective: The aim of this study was to compare the soft tissue changes and post-treatment status after complete fixed functional appliance non-extraction and maxillary premolar extraction treatment in patients with Class II division 1 malocclusion. Materials/methods: The sample consisted of 96 lateral cephalograms of 48 patients, divided into two groups. Group 1 consisted of 23 patients treated with fixed functional appliance associated with fixed appliances, with initial and final mean ages of 12.71 and 15.16 years, respectively, mean treatment time of 2.44 years and initial mean overjet of 6.83 mm. Group 2 comprised 25 patients treated with extraction of two maxillary premolars with initial and final mean ages of 13.05 and 15.74 years, respectively, mean treatment time of 2.67 years and initial mean overjet of 7.01 mm. t-Tests were used to compare treatment changes and the final cephalometric statuses between the groups. Results: According to the results, there was no inter-group difference regarding the soft tissue changes and post-treatment status. Limitations: The use of exclusively one type of fixed functional appliance in group 1 and performance of only one type of mechanics during space closure in group 2 were not always possible. Conclusion: Late pubertal patients with Class II division 1 malocclusion treated with fixed functional appliances associated with fixed appliances present similar soft tissue results as two-maxillary premolar extraction treatments.
Subject(s)
Bicuspid/surgery , Face/pathology , Malocclusion, Angle Class II/therapy , Orthodontic Appliances, Fixed , Tooth Extraction/methods , Adolescent , Cephalometry/methods , Child , Esthetics, Dental , Female , Humans , Male , Maxilla/surgery , Overbite/therapy , Retrospective Studies , Treatment OutcomeABSTRACT
The aim of this study was to compare smile attractiveness between one, three, and four premolar extraction protocols in patients with Class II division 1 subdivision malocclusions and to analyse the aesthetic influence of buccal and posterior corridor widths on smile attractiveness. The sample consisted of posed smile photographs obtained from 66 subjects, divided into three groups according to the treatment-extraction protocol. Group 1 was treated with one maxillary premolar extraction included 23 subjects, group 2 was treated with four premolar extractions included 23 subjects, and 20 patients in group 3 were treated with three premolar extractions. Buccal and posterior corridor widths of each photograph were measured in proportion to the smile width. To rate the posed smile photographs, panels of 70 orthodontists and 46 laypeople used a 10-point scale. There were no significant differences in smile attractiveness scores between the three groups and between orthodontists and laypeople. Also buccal and posterior corridor widths did not differ between the groups and they did not influence the aesthetic scores. It was concluded that smile attractiveness is similar in treatment protocols of one, three, and four premolar extractions and that widths of buccal and posterior corridors do not influence smile attractiveness in these groups.
Subject(s)
Bicuspid/surgery , Esthetics, Dental , Malocclusion, Angle Class I/surgery , Smiling , Tooth Extraction , Adolescent , Adult , Female , Humans , Male , Maxilla/surgery , PhotographyABSTRACT
ABSTRACTThe removal of organic matter and nitrogen from domestic sewage was evaluated using a system composed of two sequential reactors: an anaerobic reactor (ANR) with suspended sludge and an aerobic (AER) reactor with suspended and adhered sludge to polyurethane foams. Nitrogen removal consisted of AER operating at low dissolved oxygen (DO) concentrations; this favoured the simultaneous nitrification and denitrification (SND) process. The concentration of COD and N were 440 mgO2.L-1 and 37 mgTN.L-1, respectively. The operation was divided into three phases (P), lasting 51, 53, and 46 days, respectively. The initial DO concentrations applied in the AER were: 3.0 (PI) and 1.5 mg.L-1 (PII and PIII). In PIII, the AER effluent was recirculated to the ANR at a ratio of 0.25. Kinetic assays were performed to determine the nitrification and denitrification rates of the biomasses (ANR and AER in PIII). Changes in the microbial community were evaluated throughout phases PI to PIII by massive sequencing. In PIII, the best results obtained for chemical oxygen demand (COD) and total nitrogen (TN-N) removal efficiencies, were close to 94% and 65%, respectively. Under these conditions, system effluent concentrations below 30 mg COD.L-1 and 15 mg TN-N.L-1 were verified. The nitritation and nitration rates were 10.5 and 6.5 mg N.g VSS-1.h-1, while the denitrification via nitrite and nitrate were 6.8 and 5.8 mg N.g VSS-1.h-1, respectively. A mixotrophic community was prevalent, with Rhodococcus, Nitrosomonas, Pseudomnas, and Porphyromonas being dominant or co-dominant in most of the samples, confirming the SND process in the AER sludge.
ABSTRACT
The consumption of non-sugar sweeteners (NSS) has increased during pregnancy. The European Food Safety Agency suggested that steviol glycosides, such as Rebaudioside A (RebA), the major sweetener component of stevia, are safe for humans up to a dose of 4 mg/kg body weight/day. However, the World Health Organization recommended in 2023 the restraint of using NSS, including stevia, at any life stage, highlighting the need to study NSS safety in early periods of development. We aimed to study the mitochondrial and cardiometabolic effects of long-term RebA consumption during the reproductive stage of the life cycle. Female rats were exposed to RebA (4 mg steviol equivalents/kg body weight/day) in the drinking water from 4 weeks before mating until weaning. Morphometry, food and water consumption, glucose and lipid homeostasis, heart structure, function, and mitochondrial function were assessed. RebA showed an atrophic effect in the heart, decreasing cardiomyocyte cross-sectional area and myocardial fibrosis without repercussions on cardiac function. Mitochondrial and myofilamentary functions were not altered. Glucose tolerance and insulin sensitivity were not affected, but fasting glycemia and total plasma cholesterol decreased. This work suggests that this RebA dose is safe for female consumption during the reproductive stage, from a cardiometabolic perspective. However, studies on the effects of RebA exposure on the offspring are mandatory.
ABSTRACT
The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show long-term increased risk of cardiovascular disease and mortality is unknown. We aim to profile the urinary proteome in pregnant women with/without CV risk factors to identify proteins associated with postpartum RR. Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6 months postpartum. Shotgun HPLC-MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. An increase in arterial stiffness was documented from 3rd trimester to 6 months after delivery, being significantly elevated in women with CV risk factors. In addition, the presence of at least one CV risk factor was associated with worse LVM RR. We identified 6 and 11 proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system's activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Urinary proteome showed a predicting potential for identifying pregnant women with incomplete postpartum RR.
Subject(s)
Postpartum Period , Proteome , Ventricular Remodeling , Humans , Female , Pregnancy , Adult , Proteome/analysis , Postpartum Period/urine , Prospective Studies , Biomarkers/urine , Vascular Stiffness , Echocardiography , Risk FactorsABSTRACT
In addition to its highly aggressive nature and late diagnosis, hepatocellular carcinoma (HCC) does not respond effectively to available chemotherapeutic agents. The search is on for an ideal and effective compound with low cost and minimal side effects that can be used as an adjunct to chemotherapeutic regimens. One of the mechanisms involved in the pathology of HCC is the oxidative stress, which plays a critical role in tumor survival and dissemination. Our group has already demonstrated the antitumor potential of melatonin against HuH 7.5 cells. In the present study, we focused on the effects of melatonin on oxidative stress parameters and their consequences on cell metabolism. HuH 7.5 cells were treated with 2 and 4 mM of melatonin for 24 and 48 h. Oxidative stress biomarkers, antioxidant enzyme, mitochondrial membrane potential, formation of lipid bodies and autophagic vacuoles, cell cycle progression, cell death rate and ultrastructural cell alterations were evaluated. The treatment with melatonin increased oxidative stress biomarkers and reduced antioxidant enzyme activities of HuH 7.5 cells. Additionally, melatonin treatment damaged the mitochondrial membrane and increased lipid bodies and autophagic vacuole formation. Melatonin triggered cell cycle arrest and induced cell death by apoptosis. Our results indicate that the treatment of HuH 7.5 cells with melatonin impaired antioxidant defense systems, inhibited cell cycle progression, and caused metabolic stress, culminating in tumor cell death.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Melatonin , Humans , Carcinoma, Hepatocellular/pathology , Melatonin/pharmacology , Melatonin/therapeutic use , Antioxidants/therapeutic use , Liver Neoplasms/pathology , Oxidative Stress , Biomarkers/metabolism , ApoptosisABSTRACT
Heart failure (HF) is a debilitating disease with a significant clinical and economic impact worldwide. Multiple factors seem to increase the risk of developing HF, such as hypertension, obesity and diabetes. Since chronic inflammation plays a significant role in HF pathophysiology and gut dysbiosis is associated with low-grade chronic inflammation, the risk of cardiovascular diseases is likely modulated by the gut microbiome (GM). Considerable progress has been made in HF management. However, there is a need to find new strategies to reduce mortality and increase the quality of life, mainly of HFpEF patients, since its prevalence continues to rise. Recent studies validate that lifestyle changes, such as diet modulation, represent a potential therapeutic approach to improve several cardiometabolic diseases, although their effects on the GM and its indirect cardiac impact still warrant further research. Hence, in this paper, we aim to clarify the link between HF and the human microbiome.
Subject(s)
Heart Failure , Microbiota , Humans , Quality of Life , Stroke Volume , Diet , Inflammation , PrognosisABSTRACT
This study investigated the performance of a granular filtration system (GFS) composed of a rock filter (RF), a rapid sand filter (RSF), and an activated carbon filter (ACF), applied to the post-treatment of an anaerobic reactor effluent. Four filtration rates (FR) were applied to the GFS (in m3·m-2·d-1): 100-60-60, 100-90-90, 200-120-120, and 200-160-160, for RF-RSF-ACF, respectively. A clarified final effluent with low turbidity (~ 10 NTU), solids (~ 6.5 mg TSS.L-1), and organic matter content (~ 40 mg COD.L-1) was obtained when the GFS worked with FR up to 100-90-90 m3·m-2·d-1. For higher FR, the effluent quality was a little poorer. Principal component analysis showed when the RSF operated at 120 or 160 m3·m-2·d-1, it presented an effluent with higher turbidity which did not affect negatively the ACF performance. The hydraulic load limits in the RSF were reached in periods of 45, 30, and 24.5 h for the FR of 60, 120, and 160 m3·m-2·d-1, respectively, and head loss analysis depicted a more distributed solid retention through the sand depth with the lower FR. Thus, the results revealed that the RF-RSF-ACS system is a promising alternative for effluent polishing of anaerobic reactor, especially when the FR is set at 90 m3·m-2·d-1 or even higher.
Subject(s)
Waste Disposal, Fluid , Water Purification , Waste Disposal, Fluid/methods , Anaerobiosis , Charcoal , Filtration/methods , Water Purification/methodsABSTRACT
Early-life gut dysbiosis has been associated with an increased risk of inflammatory, metabolic, and immune diseases later in life. Data on gut microbiota changes in infants undergoing intestinal surgery requiring enterostomy are scarce. This prospective cohort study examined the enterostomy effluent of 29 infants who underwent intestinal surgery due to congenital malformations of the gastrointestinal tract, necrotizing enterocolitis, or spontaneous intestinal perforation. Initial effluent samples were collected immediately after surgery and final effluent samples were collected three weeks later. Gut microbiota composition was analysed using real-time PCR and 16S rRNA gene sequencing. Three weeks after surgery, an increase in total bacteria number (+21%, p = 0.026), a decrease in Staphylococcus (-21%, p = 0.002) and Candida spp. (-16%, p = 0.045), and an increase in Lactobacillus (+3%, p = 0.045) and in less abundant genera belonging to the Enterobacteriales family were found. An increase in alpha diversity (Shannon's and Simpson's indexes) and significant alterations in beta diversity were observed. A correlation of necrotizing enterocolitis with higher Staphylococcus abundance and higher alpha diversity was also observed. H2-blockers and/or proton pump inhibitor therapy were positively correlated with a higher total bacteria number. In conclusion, these results suggest that positive changes occur in the gut microbiota profile of infants three weeks after intestinal surgery.
ABSTRACT
AIMS: Hepatocellular Carcinoma (HCC) is a primary neoplasm derived from hepatocytes with low responsiveness and recurrent chemoresistance. Melatonin is an alternative agent that may be helpful in treating HCC. We aimed to study in HuH 7.5 cells whether melatonin treatment exerts antitumor effects and, if so, what cellular responses are induced and involved. MAIN METHODS: We evaluated the effects of melatonin on cell cytotoxicity and proliferation, colony formation, morphological and immunohistochemical aspects, and on glucose consumption and lactate release. KEY FINDINGS: Melatonin reduced cell motility and caused lamellar breakdown, membrane damage, and reduction in microvillus. Immunofluorescence analysis revealed that melatonin reduced TGF and N-cadherin expression, which was further associated with inhibition of epithelial-mesenchymal transition process. In relation to the Warburg-type metabolism, melatonin reduced glucose uptake and lactate production by modulating intracellular lactate dehydrogenase activity. SIGNIFICANCE: Our results indicate that melatonin can act upon pyruvate/lactate metabolism, preventing the Warburg effect, which may reflect in the cell architecture. We demonstrated the direct cytotoxic and antiproliferative effect of melatonin on the HuH 7.5 cell line, and suggest that melatonin is a promising candidate to be further tested as an adjuvant to antitumor drugs for HCC treatment.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Melatonin , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Melatonin/pharmacology , Melatonin/therapeutic use , Cell Line, Tumor , LactatesABSTRACT
Cobalt (Co), copper (Cu), manganese (Mn), molybdenum (Mo), and zinc (Zn) are essential trace elements (ETEs) and important cofactors for intermediary metabolism or redox balance. These ETEs are crucial during pregnancy, their role on specific pregnancy outcomes is largely unknown. This prospective study (#NCT04010708) aimed to assess urinary levels of these ETEs in pregnancy and to evaluate their association with pregnancy outcomes. First trimester pregnant women of Porto and Lisbon provided a random spot urine sample, and sociodemographic and lifestyle data. Clinical data were obtained from clinical records. Urinary ETEs were quantified by inductively coupled plasma mass spectrometry (ICP-MS). A total of 635 mother:child pairs were included. Having urinary Zn levels above the 50th percentile (P50) was an independent risk factor for pre-eclampsia (PE) (aOR [95% CI]: 5.350 [1.044-27.423], p = 0.044). Urinary Zn levels above the P50 decreased the risk of small for gestational age (SGA) birth head circumference (aOR [95% CI]: 0.315 [0.113-0.883], p = 0.028), but it increased the risk SGA length (aOR [95% CI]: 2.531 [1.057-6.062], p = 0.037). This study may provide valuable information for public health policies related to prenatal nutrition, while informing future efforts to de-fine urinary reference intervals for ETEs in pregnant women.
ABSTRACT
Citrus (genus Citrus L.) fruits are essential sources of bioactive compounds with antioxidant properties, such as flavonoids. These polyphenolic compounds are divided into subclasses, in which flavanones are the most prominent. Among them, naringenin and hesperidin are emerging compounds with anticancer potential, especially for breast cancer (BC). Several mechanisms have been proposed, including the modulation of epigenetics, estrogen signaling, induction of cell death via regulation of apoptotic signaling pathways, and inhibition of tumor invasion and metastasis. However, this information is sparse in the literature and needs to be brought together to provide an overview of how naringenin and hesperidin can serve as therapeutic tools for drug development and as a successful co-adjuvant strategy against BC. This review detailed such mechanisms in this context and highlighted how naringenin and hesperidin could interfere in BC carcinogenesis and be helpful as potential alternative therapeutic sources for breast cancer treatment.
ABSTRACT
Introduction: Empowerment lifestyle programs are needed to reduce the risk of hypertension. Our study compared the effectiveness of two empowerment-based approaches toward blood pressure (BP) reduction: salt reduction-specific program vs. healthy lifestyle general program. Methods: Three hundred and eleven adults (median age of 44 years, IQR 34-54 years) were randomly assigned to a salt reduction (n = 147) or a healthy lifestyle program (n = 164). The outcome measures were urinary sodium (Na+) and potassium (K+) excretion, systolic (SBP) and diastolic (DBP) blood pressure, weight, and waist circumference. Results: There were no significant differences in primary and secondary outcomes between the two program groups. When comparing each program to baseline, the program focused on salt reduction was effective in lowering BP following a 12-week intervention with a mean change of -2.5 mm Hg in SBP (95% CI, -4.1 to -0.8) and - 2.7 mm Hg in DBP (95% CI, -3.8 to -1.5) in the intention-to-treat (ITT) analysis. In the complete-case (CC) analysis, the mean change was -2.1 mm Hg in SBP (95% CI, -3.7 to -0.5) and - 2.3 mm Hg in DBP (95% CI, -3.4 to -1.1). This effect increases in subjects with high-normal BP or hypertension [SBP - 7.9 mm Hg (95% CI, -12.5 to -3.3); DBP - 7.3 mm Hg (95% CI, -10.2 to -4.4)]. The healthy lifestyle group also exhibited BP improvements after 12 weeks; however, the changes were less pronounced compared to the salt reduction group and were observed only for DBP [mean change of -1.5 mm Hg (95% CI, -2.6 to -0.4) in ITT analysis and - 1.4 mm Hg (95% CI, -2.4 to -0.3) in CC analysis, relative to baseline]. Overall, improvements in Na+/K+ ratio, weight, and Mediterranean diet adherence resulted in clinically significant SBP decreases. Importantly, BP reduction is attributed to improved dietary quality, rather than being solely linked to changes in the Na+/K+ ratio. Conclusion: Salt-focused programs are effective public health tools mainly in managing individuals at high risk of hypertension. Nevertheless, in general, empowerment-based approaches are important strategies for lowering BP, by promoting health literacy that culminates in adherence to the Mediterranean diet and weight reduction.
Subject(s)
Hypertension , Adult , Humans , Middle Aged , Blood Pressure , Hypertension/prevention & control , Sodium Chloride, Dietary , Outcome Assessment, Health CareABSTRACT
Intestinal alkaline phosphatase (IALP) has recently assumed a special relevance, being the subject of study in the prevention and treatment of certain diseases related to leaky gut. This brush border enzyme (ecto-enzyme) plays an important role in the maintenance of intestinal microbial homeostasis and intestinal barrier function through its ability to dephosphorylate lipopolysaccharide (LPS). This review addresses how IALP and intestinal barrier dysfunction may be implicated in the pathophysiology of specific diseases such as inflammatory bowel disease, necrotizing enterocolitis, and metabolic syndrome. The use of IALP as a possible biomarker to assess intestinal barrier function and strategies to modulate IALP activity are also discussed.
ABSTRACT
Gut microbiota modulation might constitute a mechanism mediating the effects of beer on health. In this randomized, double-blinded, two-arm parallel trial, 22 healthy men were recruited to drink 330 mL of nonalcoholic beer (0.0% v/v) or alcoholic beer (5.2% v/v) daily during a 4-week follow-up period. Blood and faecal samples were collected before and after the intervention period. Gut microbiota was analyzed by 16S rRNA gene sequencing. Drinking nonalcoholic or alcoholic beer daily for 4 weeks did not increase body weight and body fat mass and did not changed significantly serum cardiometabolic biomarkers. Nonalcoholic and alcoholic beer increased gut microbiota diversity which has been associated with positive health outcomes and tended to increase faecal alkaline phosphatase activity, a marker of intestinal barrier function. These results suggest the effects of beer on gut microbiota modulation are independent of alcohol and may be mediated by beer polyphenols.