Effects of Calendula officinalis extract on liver histopathology, lipid profile, and oxidative stress in rats submitted to a diet rich in cholesterol and carbohydrates.

PURPOSE: To evaluate the modulatory properties of Calendula officinalis L. (Asteraceae) (C. officinalis) extract on cafeteria diet-fed rats. METHODS: A cafeteria diet was administered ad libitum for 45 days to induce dyslipidemia. Then, the rats were treated with the formulations containing C. officinalis in the doses of 50, 100, and 150 mg/kg or only with the vehicle formulation; the control group received a commercial ration. RESULTS: The cafeteria diet decreased glutathione S-transferase activity and high-density lipoprotein plasmatic levels and damaged the hepatic architecture. The C. officinalis extract was able to reduce lipid infiltration in liver tissue and to modulate oxidative stress and lipid profile markers. CONCLUSIONS: The correlations between the variables suggest a pathological connection between oxidative stress markers and serum lipid profile.

Seminal quality comparison of first and second cryopreserved ejaculates of Alpine kid goats by flow cytometry.

Discarding the first ejaculate is recommended as an alternative for improving seminal quality after long sexual resting, especially when semen should be used for cryopreservation. However, when the males are not in sexual resting the necessity to discarding the first ejaculate is still unknown. Therefore, this study aimed to compare by flow cytometry the quality of the first and second ejaculates. Ten kids and uniform goats between 5 and 6 months of age were used in a completely randomized design. Semen collection was carried out every 4 days, until a total of five ejaculates per animal in each treatment was completed. The fresh and frozen semen collected were processed and analyzed using macroscopic and microscopic parameters, resistance test, hypo-osmotic medium test, and flow cytometry (FC). The FC parameters were production of reactive oxygen species, plasma and acrosomal membrane integrity, and lipid peroxidation of the plasma membrane. The ejaculates did not differ for the resistance test, the reactivity in the hypo-osmotic medium and for the macroscopic and microscopic seminal parameters, except for sperm volume and concentration. The first ejaculate had a higher percentage of minor and total defects. None of the FC parameters analyzed differed between the first and second ejaculates. The first and second ejaculates demonstrated similar seminal qualities, so for Alpine kid goats without a sexual resting period, discarding the first ejaculate it is not recommended.

Effects of Calendula officinalis extract on liver histopathology, lipid profile, and oxidative stress in rats submitted to a diet rich in cholesterol and carbohydrates

ABSTRACT Purpose: To evaluate the modulatory properties of Calendula officinalis L. (Asteraceae) (C. officinalis) extract on cafeteria diet-fed rats. Methods: A cafeteria diet was administered ad libitum for 45 days to induce dyslipidemia. Then, the rats were treated with the formulations containing C. officinalis in the doses of 50, 100, and 150 mg/kg or only with the vehicle formulation; the control group received a commercial ration. Results: The cafeteria diet decreased glutathione S-transferase activity and high-density lipoprotein plasmatic levels and damaged the hepatic architecture. The C. officinalis extract was able to reduce lipid infiltration in liver tissue and to modulate oxidative stress and lipid profile markers. Conclusions: The correlations between the variables suggest a pathological connection between oxidative stress markers and serum lipid profile.

Bioética e medicina personalizada no envelhecimento: explorando complexidades / Bioethics and concierge medicine in aging: exploring complexities / Bioética y medicina personalizada en el envejecimiento: explorar las complejidades

Resumo A medicina personalizada surgiu como uma abordagem promissora para fornecer tratamentos exclusivos e personalizados para doenças usando ferramentas genômicas. No campo dos estudos do envelhecimento, a medicina personalizada tem grande potencial para transformar o tratamento e a prevenção de doenças associadas à idade e relacionadas à nutrigenômica e à farmacogenômica. No entanto, o uso de dados genômicos na medicina personalizada levanta preocupações bioéticas significativas, incluindo questões como privacidade, consentimento, equidade e potencial uso indevido de dados genômicos para fins discriminatórios. Portanto, é crucial considerar cuidadosamente os aspectos biomédicos, sociais e éticos da medicina personalizada no contexto de condições relacionadas à idade. Esta revisão tem o objetivo de explorar os principais aspectos da medicina personalizada concernentes a doenças relacionadas à idade nos dados farmacogenômicos e nutrigenômicos, abordando as preocupações bioéticas envolvidas no uso desses dados.

Abstract Concierge medicine emerged as a promising approach to offer exclusive and personalized treatments using genomic tools. In aging studies, concierge medicine has the potential to transform the treatment and prevention of age-associated and related diseases through pharmacogenetics and nutrigenomics; however, its use of genomic data raises important bioethical concerns, including privacy, consent, equity issues and potential misuse of these data for discriminatory purposes. Hence, careful consideration should be given to the biomedical, social, and ethical aspects of concierge medicine in aging contexts. Our review explores the main aspects of age-related pharmacogenetics and nutrigenomics data in concierge medicine, discussing the bioethical concerns involved in its use.

Resumen La medicina personalizada surgió como un enfoque prometedor con el fin de proporcionar tratamientos únicos y personalizados a enfermedades utilizando herramientas genómicas. En los estudios de envejecimiento, la medicina personalizada puede transformar el tratamiento y la prevención de enfermedades asociadas a la edad y relacionadas con la nutrigenómica y la farmacogenómica. Sin embargo, el uso de datos genómicos en medicina personalizada plantea importantes preocupaciones bioéticas, incluidos temas como la privacidad, el consentimiento, la equidad y el posible uso indebido de los datos genómicos con fines discriminatorios. Así, es fundamental ponderar cuidadosamente los aspectos biomédicos, sociales y éticos de la medicina personalizada en el contexto de las afecciones relacionadas con la edad. Esta revisión pretende explorar los principales aspectos de la medicina personalizada sobre las enfermedades relacionadas con la edad en los datos farmacogenómicos y nutrigenómicos al abordar las preocupaciones bioéticas involucradas en el uso de estos datos.

Systems biology and OMIC data integration to understand gastrointestinal cancers.

Gastrointestinal (GI) cancers are a set of diverse diseases affecting many parts/ organs. The five most frequent GI cancer types are esophageal, gastric cancer (GC), liver cancer, pancreatic cancer, and colorectal cancer (CRC); together, they give rise to 5 million new cases and cause the death of 3.5 million people annually. We provide information about molecular changes crucial to tumorigenesis and the behavior and prognosis. During the formation of cancer cells, the genomic changes are microsatellite instability with multiple chromosomal arrangements in GC and CRC. The genomically stable subtype is observed in GC and pancreatic cancer. Besides these genomic subtypes, CRC has epigenetic modification (hypermethylation) associated with a poor prognosis. The pathway information highlights the functions shared by GI cancers such as apoptosis; focal adhesion; and the p21-activated kinase, phosphoinositide 3-kinase/Akt, transforming growth factor beta, and Toll-like receptor signaling pathways. These pathways show survival, cell proliferation, and cell motility. In addition, the immune response and inflammation are also essential elements in the shared functions. We also retrieved information on protein-protein interaction from the STRING database, and found that proteins Akt1, catenin beta 1 (CTNNB1), E1A binding protein P300, tumor protein p53 (TP53), and TP53 binding protein 1 (TP53BP1) are central nodes in the network. The protein expression of these genes is associated with overall survival in some GI cancers. The low TP53BP1 expression in CRC, high EP300 expression in esophageal cancer, and increased expression of Akt1/TP53 or low CTNNB1 expression in GC are associated with a poor prognosis. The Kaplan Meier plotter database also confirmed the association between expression of the five central genes and GC survival rates. In conclusion, GI cancers are very diverse at the molecular level. However, the shared mutations and protein pathways might be used to understand better and reveal diagnostic/prognostic or drug targets.

Heterologous Expression, Purification, and Immunomodulatory Effects of Recombinant Lipoprotein GUDIV-103 Isolated from Ureaplasma diversum.

Ureaplasma diversum is a bacterial pathogen that infects cattle and can cause severe inflammation of the genital and reproductive systems. Lipid-associated membrane proteins (LAMPs), including GUDIV-103, are the main virulence factors in this bacterium. In this study, we heterologously expressed recombinant GUDIV-103 (rGUDIV-103) in Escherichia coli, purified it, and evaluated its immunological reactivity and immunomodulatory effects in bovine peripheral blood mononuclear cells (PBMCs). Samples from rabbits inoculated with purified rGUDIV-103 were analysed using indirect enzyme-linked immunosorbent assay and dot blotting to confirm polyclonal antibody production and assess kinetics, respectively. The expression of this lipoprotein in field isolates was confirmed via Western blotting with anti-rGUDIV-103 serum and hydrophobic or hydrophilic proteins from 42 U. diversum strains. Moreover, the antibodies produced against the U. diversum ATCC 49783 strain recognised rGUDIV-103. The mitogenic potential of rGUDIV-103 was evaluated using a lymphoproliferation assay in 5(6)-carboxyfluorescein diacetate succinimidyl ester−labelled bovine PBMCs, where it induced lymphocyte proliferation. Quantitative polymerase chain reaction analysis revealed that the expression of interleukin-1ß, toll-like receptor (TLR)-α, TLR2, TLR4, inducible nitric oxide synthase, and caspase-3−encoding genes increased more in rGUDIV-103−treated PBMCs than in untreated cells (p < 0.05). Treating PBMCs with rGUDIV-103 increased nitric oxide and hydrogen peroxide levels. The antigenic and immunogenic properties of rGUDIV-103 suggested its suitability for immunobiological application.

Citral modulates human monocyte responses to Staphylococcus aureus infection.

Staphylococcus aureus is a Gram-positive bacterium that is considered an important human pathogen. Due to its virulence and ability to acquire mechanisms of resistance to antibiotics, the clinical severity of S. aureus infection is driven by inflammatory responses to the bacteria. Thus, the present study aimed to investigate the modulating role of citral in inflammation caused by S. aureus infection. For this, we used an isolate obtained from a nasal swab sample of a healthy child attending a day-care centre in Vitória da Conquista, Bahia, Brazil. The role of citral in modulating immunological factors against S. aureus infection was evaluated by isolating and cultivating human peripheral blood mononuclear cells. The monocytes were treated with 4%, 2%, and 1% citral before and after inoculation with S. aureus. The cells were analysed by immunophenotyping of monocyte cell surface molecules (CD54, CD282, CD80, HLA-DR, and CD86) and cytokine dosage (IL-1ß, IL-6, IL-10, IL-12p70, IL-23, IFN-γ, TGF-ß, and TNF-α), and evaluated for the expression of 84 genes related to innate and adaptive immune system responses. GraphPad Prism software and variables with P values < 0.05, were used for statistical analysis. Our data demonstrated citral's action on the expression of surface markers involved in recognition, presentation, and migration, such as CD14, CD54, and CD80, in global negative regulation of inflammation with inhibitory effects on NF-κB, JNK/p38, and IFN pathways. Consequently, IL-1ß, IL-6, IL-12p70, IL-23, IFN-γ, and TNF-α cytokine expression was reduced in groups treated with citral and groups treated with citral at 4%, 2%, and 1% and infected, and levels of anti-inflammatory cytokines such as IL-10 were increased. Furthermore, citral could be used as a supporting anti-inflammatory agent against infections caused by S. aureus. There are no data correlating citral, S. aureus, and the markers analysed here; thus, our study addresses this gap in the literature.

Citral modulates virulence factors in methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for high morbidity and mortality rates. Citral has been studied in the pharmaceutical industry and has shown antimicrobial activity. This study aimed to analyze the antimicrobial activity of citral in inhibiting biofilm formation and modulating virulence genes, with the ultimate goal of finding a strategy for treating infections caused by MRSA strains. Citral showed antimicrobial activity against MRSA isolates with minimum inhibitory concentration (MIC) values between 5 mg/mL (0.5%) and 40 mg/mL (4%), and minimum bactericidal concentration (MBC) values between 10 mg/mL (1%) and 40 mg/mL (4%). The sub-inhibitory dose was 2.5 mg/mL (0.25%). Citral, in an antibiogram, modulated synergistically, antagonistically, or indifferent to the different antibiotics tested. Prior to evaluating the antibiofilm effects of citral, we classified the bacteria according to their biofilm production capacity. Citral showed greater efficacy in the initial stage, and there was a significant reduction in biofilm formation compared to the mature biofilm. qPCR was used to assess the modulation of virulence factor genes, and icaA underexpression was observed in isolates 20 and 48. For icaD, seg, and sei, an increase was observed in the expression of ATCC 33,591. No significant differences were found for eta and etb. Citral could be used as a supplement to conventional antibiotics for MRSA infections.

Hallmarks of Aging in Macrophages: Consequences to Skin Inflammaging.

The skin is our largest organ and the outermost protective barrier. Its aging reflects both intrinsic and extrinsic processes resulting from the constant insults it is exposed to. Aging in the skin is accompanied by specific epigenetic modifications, accumulation of senescent cells, reduced cellular proliferation/tissue renewal, altered extracellular matrix, and a proinflammatory environment favoring undesirable conditions, including disease onset. Macrophages (Mφ) are the most abundant immune cell type in the skin and comprise a group of heterogeneous and plastic cells that are key for skin homeostasis and host defense. However, they have also been implicated in orchestrating chronic inflammation during aging. Since Mφ are related to innate and adaptive immunity, it is possible that age-modified skin Mφ promote adaptive immunity exacerbation and exhaustion, favoring the emergence of proinflammatory pathologies, such as skin cancer. In this review, we will highlight recent findings pertaining to the effects of aging hallmarks over Mφ, supporting the recognition of such cell types as a driving force in skin inflammaging and age-related diseases. We will also present recent research targeting Mφ as potential therapeutic interventions in inflammatory skin disorders and cancer.

Can maintenance intake reduce production costs without compromising the reproductive performance in bucks?

Excessive intake of nutrients can result in decreases in the reproductive efficiency of goat bucks and increase production costs in goat e nterprises. In this study, the aim was to compare the reproductive features of young bucks fed diets for maintenance of growth or were fed ad libitum. Ten bucks were used (n = 5/group), with a completely randomized design. Blood and semen were collected from each animal every 2 weeks for nine collections. Semen was frozen and later analyzed using flow cytometry to compare reactive oxygen species, plasma membrane integrity, acrosome integrity, and membrane lipid peroxidation. Body condition score, sexual behavior, testicular biometry and histomorphometry of the testis, as well as oxidative enzymes and carbonylated proteins, were also evaluated. Animals fed ad libitum had a greater body condition score (3.32 + 0.08 × 2.88 + 0.05), sperm volume (0.68 + 0.04 × 0.52 + 0.03 mL), and testis circumference (25.2 + 0.21 × 24.5 + 0.24 cm) and volume (121 + 5.83 × 107 + 4.38 cm³, left testicle; 116 + 5.26 × 100 + 3.75 cm³, right testicle). Ejaculates of the bucks fed diets to maintain growth rate had a larger number of minor and total sperm morphology defects. There were no differences in testosterone concentrations and sexual behavior. In conclusion, there can be feeding for growth rate maintenance instead of ad libitum feeding, for the reduction in production costs of young bucks without compromising semen quality and reproductive functions.

PDAC-ANN: an artificial neural network to predict pancreatic ductal adenocarcinoma based on gene expression.

BACKGROUND: Although the pancreatic ductal adenocarcinoma (PDAC) presents high mortality and metastatic potential, there is a lack of effective therapies and a low survival rate for this disease. This PDAC scenario urges new strategies for diagnosis, drug targets, and treatment. METHODS: We performed a gene expression microarray meta-analysis of the tumor against normal tissues in order to identify differentially expressed genes (DEG) shared among all datasets, named core-genes (CG). We confirmed the CG protein expression in pancreatic tissue through The Human Protein Atlas. It was selected five genes with the highest area under the curve (AUC) among these proteins with expression confirmed in the tumor group to train an artificial neural network (ANN) to classify samples. RESULTS: This microarray included 461 tumor and 187 normal samples. We identified a CG composed of 40 genes, 39 upregulated, and one downregulated. The upregulated CG included proteins and extracellular matrix receptors linked to actin cytoskeleton reorganization. With the Human Protein Atlas, we verified that fourteen genes of the CG are translated, with high or medium expression in most of the pancreatic tumor samples. To train our ANN, we selected the best genes (AHNAK2, KRT19, LAMB3, LAMC2, and S100P) to classify the samples based on AUC using mRNA expression. The network classified tumor samples with an f1-score of 0.83 for the normal samples and 0.88 for the PDAC samples, with an average of 0.86. The PDAC-ANN could classify the test samples with a sensitivity of 87.6 and specificity of 83.1. CONCLUSION: The gene expression meta-analysis and confirmation of the protein expression allow us to select five genes highly expressed PDAC samples. We could build a python script to classify the samples based on RNA expression. This software can be useful in the PDAC diagnosis.

Photodynamic therapy controls of Staphylococcus aureus intradermal infection in mice.

Infections caused by Staphylococcus aureus lead to skin infections, as well as soft tissues and bone infections. Given the communal resistance to antibiotics developed by strains of this bacterium, photodynamic therapy emerges as a promising alternative treatment to control and cure infections. Females of the Balb/C mice were infected with 108 CFU of methicillin-resistant S. aureus (MRSA) and divided into four distinct groups: P-L- (negative control group), P+L- (group exposed only to curcumin), P-L+ (group exposed only to LED incidence of 450 nm, 75 mW/cm2, and 54 J/cm2 for 10 min), and P+L+ (group exposed to curcumin followed by 10 min of LED irradiation) (n = 24). The mice were euthanized 48 and 72 h after infection, and biologic materials were collected for analysis of the bacterial load, peripheral blood leukocyte counts, and draining lymph nodes cell counts. The normalization of data was checked and the ANOVA test was applied. The bacterial load in the draining lymph node of P+L+ group was lower when compared to the control groups 72 h post infection (p < 0.0001), indicating that the LED incidence associated with curcumin controls of the staphylococci intradermal infection. The number of the total lymph node cells shows to be lower than control groups in the two availed times (p < 0.01). The histological analysis and the counting of white blood cells did not show differences among cells in the blood and in the tissue of infection. This is the first report showing that photodynamic therapy may be effective against MRSA infection in a murine model of intradermal infection.

Identification of Long Noncoding RNAs Deregulated in Papillary Thyroid Cancer and Correlated with BRAFV600E Mutation by Bioinformatics Integrative Analysis.

Papillary Thyroid Cancer (PTC) is an endocrine malignancy in which BRAFV600E oncogenic mutation induces the most aggressive phenotype. In this way, considering that lncRNAs are arising as key players in oncogenesis, it is of high interest the identification of BRAFV600E-associated long noncoding RNAs, which can provide possible candidates for secondary mechanisms of BRAF-induced malignancy in PTC. In this study, we identified differentially expressed lncRNAs correlated with BRAFV600E in PTC and, also, extended the cohort of paired normal and PTC samples to more accurately identify differentially expressed lncRNAs between these conditions. Indirectly validated targets of the differentially expressed lncRNAs in PTC compared to matched normal samples demonstrated an involvement in surface receptors responsible for signal transduction and cell adhesion, as well as, regulation of cell death, proliferation and apoptosis. Targets of BRAFV600E-correlated lncRNAs are mainly involved in calcium signaling pathway, ECM-receptor interaction and MAPK pathway. In summary, our study provides candidate lncRNAs that can be either used for future studies related to diagnosis/prognosis or as targets for PTC management.