The role of fibrosis in cardiomyopathies: An opportunity to develop novel biomarkers of disease activity.

Cardiomyopathies encompass a spectrum of heart disorders with diverse causes and presentations. Fibrosis stands out as a shared hallmark among various cardiomyopathies, reflecting a common thread in their pathogenesis. This prevalent fibrotic response is intricately linked to the consequences of dysregulated extracellular matrix (ECM) remodeling, emphasizing its significance in the development and progression the disease. This review explores the ECM involvement in various cardiomyopathies and its impact on myocardial stiffness and fibrosis. Additionally, we discuss the potential of ECM fragments as early diagnosis, prognosis, and risk stratification. Biomarkers deriving from turnover of collagens and other ECM proteins hold promise in clinical applications. We outline current clinical management, future directions, and the potential for personalized ECM-targeted therapies with specific focus on microRNAs. In summary, this review examines the role of the fibrosis in cardiomyopathies, highlighting the potential of ECM-derived biomarkers in improving disease management with implications for precision medicine.

Dual roles of myocardial mitochondrial AKT on diabetic cardiomyopathy and whole body metabolism.

BACKGROUND: The PI3K/AKT pathway transduces the majority of the metabolic actions of insulin. In addition to cytosolic targets, insulin-stimulated phospho-AKT also translocates to mitochondria in the myocardium. Mouse models of diabetes exhibit impaired mitochondrial AKT signaling but the implications of this on cardiac structure and function is unknown. We hypothesized that loss of mitochondrial AKT signaling is a critical step in cardiomyopathy and reduces cardiac oxidative phosphorylation. METHODS: To focus our investigation on the pathophysiological consequences of this mitochondrial signaling pathway, we generated transgenic mouse models of cardiac-specific, mitochondria-targeting, dominant negative AKT1 (CAMDAKT) and constitutively active AKT1 expression (CAMCAKT). Myocardial structure and function were examined using echocardiography, histology, and biochemical assays. We further investigated the underlying effects of mitochondrial AKT1 on mitochondrial structure and function, its interaction with ATP synthase, and explored in vivo metabolism beyond the heart. RESULTS: Upon induction of dominant negative mitochondrial AKT1, CAMDAKT mice developed cardiac fibrosis accompanied by left ventricular hypertrophy and dysfunction. Cardiac mitochondrial oxidative phosphorylation efficiency and ATP content were reduced, mitochondrial cristae structure was lost, and ATP synthase structure was compromised. Conversely, CAMCAKT mice were protected against development of diabetic cardiomyopathy when challenged with a high calorie diet. Activation of mitochondrial AKT1 protected cardiac function and increased fatty acid uptake in myocardium. In addition, total energy expenditure was increased in CAMCAKT mice, accompanied by reduced adiposity and reduced development of fatty liver. CONCLUSION: CAMDAKT mice modeled the effects of impaired mitochondrial signaling which occurs in the diabetic myocardium. Disruption of this pathway is a key step in the development of cardiomyopathy. Activation of mitochondrial AKT1 in CAMCAKT had a protective role against diabetic cardiomyopathy as well as improved metabolism beyond the heart.

The lipolysis inhibitor acipimox reverses the cardiac phenotype induced by electronic cigarettes.

Electronic cigarettes (e-cigarettes) are a prevalent alternative to conventional nicotine cigarettes among smokers and people who have never smoked. Increased concentrations of serum free fatty acids (FFAs) are crucial in generating lipotoxicity. We studied the effects of acipimox, an antilipolytic drug, on e-cigarette-induced cardiac dysfunction. C57BL/6J wild-type mice on high fat diet were treated with saline, e-cigarette with 2.4% nicotine [e-cigarette (2.4%)], and e-cigarette (2.4%) plus acipimox for 12 weeks. Fractional shortening and ejection fraction were diminished in mice exposed to e-cigarettes (2.4%) compared with saline and acipimox-treated mice. Mice exposed to e-cigarette (2.4%) had increased circulating levels of inflammatory cytokines and FFAs, which were diminished by acipimox. Gene Set Enrichment Analysis revealed that e-cigarette (2.4%)-treated mice had gene expression changes in the G2/M DNA damage checkpoint pathway that was normalized by acipimox. Accordingly, we showed that acipimox suppressed the nuclear localization of phospho-p53 induced by e-cigarette (2.4%). Additionally, e-cigarette (2.4%) increased the apurinic/apyrimidinic sites, a marker of oxidative DNA damage which was normalized by acipimox. Mice exposed to e-cigarette (2.4%) had increased cardiac Heme oxygenase 1 protein levels and 4-hydroxynonenal (4-HNE). These markers of oxidative stress were decreased by acipimox. Therefore, inhibiting lipolysis with acipimox normalizes the physiological changes induced by e-cigarettes and the associated increase in inflammatory cytokines, oxidative stress, and DNA damage.

Perfil de riesgo cardiovascular en mujeres de tres entornos de la Provincia de Tucumán - Argentina / Cardiovascular risk profile in women from three different areas of the Province of Tucumán, Argentina

RESUMEN Introducción : El rol del entorno sobre la salud en la población femenina de Tucumán está poco estudiado. El objetivo del presente trabajo fue evaluar el perfil de riesgo cardiovascular de mujeres de los entornos rural, periurbano y urbano de la provincia de Tucumán (Argentina). Material y métodos : Se efectuó un estudio analítico transversal en 3 grupos de mujeres de Tucumán: rural (n=125), periurbano (n= 50) y urbano (n=112). Resultados : La presión arterial (PA) fue menor en el grupo rural; el grupo urbano presentó mayor frecuencia cardíaca y menor circunferencia de cuello. El 29,7% de las mujeres presentaron sobrepeso y el 42,4% obesidad, sin diferencia significativa entre los 3 grupos. La circunferencia de cuello estuvo aumentada en el 62% de las mujeres del grupo rural, 79% del periurbano y 41% del urbano (p<0,001). El grupo urbano presentó más frecuentemente tabaquismo. En los grupos urbano y periurbano fue mayor la proporción de mujeres con estudios superiores (p <0,001). El nivel educativo se correlacionó positivamente con la frecuencia cardíaca. Conclusiones : Independientemente del entorno las mujeres de Tucumán presentan sobrepeso u obesidad asociados a otros factores de riesgo para enfermedad cardiovascular. Ello debe ser tenido en cuenta para la elaboración de políticas y la toma de conductas a fin de mejorar su pronóstico.

ABSTRACT Background : The role of the environment on female population health in Tucumán has been little studied. This study aimed to evaluate the cardiovascular risk profile in women from rural, peri-urban and urban areas in the province of Tucumán (Argentina) and to analyse their differences. Methods : An analytical cross-sectional study was conducted in 3 groups of women from Tucumán: rural (n = 125), peri-urban (n = 50) and urban (n = 112). Results : Blood pressure (BP) was lower in the rural group; the urban group showed higher heart rate and smaller neck cir cumference. Of the studied women, 29.7% were overweight and 42.4% obese, and no significant differences were found in the 3 groups. Increased neck circumference was observed in 62% of women in the rural group, 79% in the peri-urban group and 41% in the urban group (p <0.001). Smoking was more frequent in the urban group. In the urban and peri-urban groups, the proportion of women with higher education level was greater (p <0.001). Education level was positively correlated with heart rate. Conclusion : Regardless of the environment, women from Tucumán are overweight or obese and have other risk factors for cardiovascular disease. This should be considered when planning policies and making decisions in order to improve their prognosis.

Agronomic Evaluation and Chemical Characterization of Lavandula latifolia Medik. under the Semiarid Conditions of the Spanish Southeast.

Lavandula latifolia is one of the main rainfed crops of aromatic and medicinal plants produced in Spain. As a global concern, the agronomic productivity of this aromatic crop is also threatened by the consequences of imminent climate change. On this basis, the study of the agronomic production of two drought-tolerant ecotypes, after three years of cultivations practices, constitutes the main objective of the present study. For this trial, clones of the two pre-selected ecotypes, along with clones from two commercial plants (control), were grown in an experimental plot. The main results confirmed an increase in biomass and essential oil production with plant age. The essential oil chemotype defined by 1,8-cineol, linalool, and camphor was maintained over time, but a decrease in 1,8-cineol in the benefit of linalool was detected. In the phenolic profile, 14 components were identified, with salvianic acid and a rosmarinic acid derivate being the main compounds quantified. These phenolic extracts showed potent in vitro antioxidant capacity, and after the second year of cultivation practices, both phenolic compounds and antioxidant capacity remained stable. Thus, under semiarid conditions, L. latifolia drought-tolerant ecotypes reach a good level of production after the second year of crop establishment.

Synthesis and Expression of a Targeted, Ferritin-Based Tracer for PET Imaging of Kidney Glomeruli.

Cationic ferritin (CF) has been developed as a multimodal, targeted imaging tracer to directly detect and map nephrons in the kidney in vivo. Direct detection of functional nephrons provides a unique, sensitive biomarker to predict or monitor kidney disease progression. CF has been developed to map functional nephron number from magnetic resonance imaging (MRI) or positron emission tomography (PET). Previous preclinical imaging studies have used non-human-derived ferritin and commercial formulations that must still be developed for translation to clinical use. Here we describe the reproducible formulation of CF (either derived from horse or from human recombinant ferritin) optimized for intravenous injection and radiolabeling by PET. The human recombinant heteropolymer ferritin is spontaneously assembled in liquid culture (Escherichia coli, E. coli) and modified to form human recombinant cationic ferritin (HrCF) to mitigate potential immunologic reactions for use in humans.

Bacterial benz(a)anthracene catabolic networks in contaminated soils and their modulation by other co-occurring HMW-PAHs.

Polycyclic aromatic hydrocarbons (PAHs) are major environmental pollutants in a number of point source contaminated sites, where they are found embedded in complex mixtures containing different polyaromatic compounds. The application of bioremediation technologies is often constrained by unpredictable end-point concentrations enriched in recalcitrant high molecular weight (HMW)-PAHs. The aim of this study was to elucidate the microbial populations and potential interactions involved in the biodegradation of benz(a)anthracene (BaA) in PAH-contaminated soils. The combination of DNA stable isotope probing (DNA-SIP) and shotgun metagenomics of 13C-labeled DNA identified a member of the recently described genus Immundisolibacter as the key BaA-degrading population. Analysis of the corresponding metagenome assembled genome (MAG) revealed a highly conserved and unique genetic organization in this genus, including novel aromatic ring-hydroxylating dioxygenases (RHD). The influence of other HMW-PAHs on BaA degradation was ascertained in soil microcosms spiked with BaA and fluoranthene (FT), pyrene (PY) or chrysene (CHY) in binary mixtures. The co-occurrence of PAHs resulted in a significant delay in the removal of PAHs that were more resistant to biodegradation, and this delay was associated with relevant microbial interactions. Members of Immundisolibacter, associated with the biodegradation of BaA and CHY, were outcompeted by Sphingobium and Mycobacterium, triggered by the presence of FT and PY, respectively. Our findings highlight that interacting microbial populations modulate the fate of PAHs during the biodegradation of contaminant mixtures in soils.

Structural Diversity among Edwardsiellaceae Core Oligosaccharides.

The Edwardsiella genus presents five different pathogenic species: Edwardsiella tarda, E. anguillarum, E. piscicida, E. hoshinae and E. ictaluri. These species cause infections mainly in fish, but they can also infect reptiles, birds or humans. Lipopolysaccharide (endotoxin) plays an important role in the pathogenesis of these bacteria. For the first time, the chemical structure and genomics of the lipopolysaccharide (LPS) core oligosaccharides of E. piscicida, E. anguillarum, E. hoshinae and E. ictaluri were studied. The complete gene assignments for all core biosynthesis gene functions were acquired. The structure of core oligosaccharides was investigated by ¹H and 13C nuclear magnetic resonance (NMR) spectroscopy. The structures of E. piscicida and E. anguillarum core oligosaccharides show the presence of →3,4)-L-glycero-α-D-manno-Hepp, two terminal ß-D-Glcp, →2,3,7)-L-glycero-α-D-manno-Hepp, →7)-L-glycero-α-D-manno-Hepp, terminal α-D-GlcpN, two →4)-α-D-GalpA, → 3)-α-D-GlcpNAc, terminal ß-D-Galp and →5-substituted Kdo. E. hoshinare core oligosaccharide shows only one terminal ß-D-Glcp, and instead of terminal ß-D-Galp a terminal α-D-GlcpNAc. E. ictaluri core oligosaccharide shows only one terminal ß-D-Glcp, one →4)-α-D-GalpA and do not have terminal α-D-GlcpN (see complementary figure).

Revalorisation of Sage (Salvia lavandulifolia Vahl) By-Product Extracts as a Source of Polyphenol Antioxidants for Novel Jelly Candies.

Sage (Salvia lavandulifolia Vahl) aqueous extracts (SE) obtained from distillation by-products were assessed as antioxidants for nutritionally enhanced jelly candies. Two experimental SEs with a different content of phenolic acids and flavonoids were tested: (i) SE38 (37.6 mg/g) and (ii) SE70 (69.8 mg/g), with salvianic and rosmarinic acids as main polyphenols, respectively. Flavour alteration, stability of sage polyphenols, physical quality traits and antioxidant capacity (AC) were studied in strawberry candies formulated without sugars and enriched with SEs at 0.25, 0.50 and 0.75 g/kg. Despite their different quantitative composition, SE38 and SE70 provided similar antioxidant properties, which were dose dependent. Salvianic and rosmarinic acids were stable without degrading to candy processing (up to 80 °C), keeping their antioxidant potential. There were no relevant differences in flavour or physical traits (pH, °Brix and CIELab colour) between untreated and SE-enriched strawberry candies. The addition of 0.75 g SE/kg resulted in relevant increases of candy AC: (i) from 30 to 38 mg GAE/100 g (total phenolics); (ii) from 10 to 17 mg TE/100 g (DPPH• radical scavenging assay); (iii) from 5 to 13 mg TE/100 g (ABTS·+ radical scavenging assay); (iv) from 84 to 163 µmol Fe2+/100 g (FRAP capacity) and (v) from to 75 to 83% (inhibition of deoxyribose damage). Sage distillation by-products can be revalorised as a source of natural antioxidants to produce healthier candies.

Multi-Omic Profiling of a Newly Isolated Oxy-PAH Degrading Specialist from PAH-Contaminated Soil Reveals Bacterial Mechanisms to Mitigate the Risk Posed by Polar Transformation Products.

Polar biotransformation products have been identified as causative agents for the eventual increase in genotoxicity observed after the bioremediation of PAH-contaminated soils. Their further biodegradation has been described under certain biostimulation conditions; however, the underlying microorganisms and mechanisms remain to be elucidated. 9,10-Anthraquinone (ANTQ), a transformation product from anthracene (ANT), is the most commonly detected oxygenated PAH (oxy-PAH) in contaminated soils. Sand-in-liquid microcosms inoculated with creosote-contaminated soil revealed the existence of a specialized ANTQ degrading community, and Sphingobium sp. AntQ-1 was isolated for its ability to grow on this oxy-PAH. Combining the metabolomic, genomic, and transcriptomic analyses of strain AntQ-1, we comprehensively reconstructed the ANTQ biodegradation pathway. Novel mechanisms for polyaromatic compound degradation were revealed, involving the cleavage of the central ring catalyzed by Baeyer-Villiger monooxygenases (BVMO). Abundance of strain AntQ-1 16S rRNA and its BVMO genes in the sand-in-liquid microcosms correlated with maximum ANTQ biodegradation rates, supporting the environmental relevance of this mechanism. Our results demonstrate the existence of highly specialized microbial communities in contaminated soils responsible for processing oxy-PAHs accumulated by primary degraders. Also, they underscore the key role that BVMO may play as a detoxification mechanism to mitigate the risk posed by oxy-PAH formation during bioremediation of PAH-contaminated soils.

Oregano Essential Oil and Purple Garlic Powder Effects on Intestinal Health, Microbiota Indicators and Antimicrobial Resistance as Feed Additives in Weaning Piglets.

Finding alternatives to zinc oxide is a pressing issue for the pig production sector. We studied the impact of the bioactive components degradation of oregano essential oil (OEO) and purple garlic powder (PGP) during storage in silos, their effect on the morphometry of the jejunum and ileum and the cecal microbiota as intestinal health indicators in piglets during the post-weaning period. We also monitored antimicrobial resistance in the commensal indicator E. coli. Histological parameters and intestinal microbiota were measured in 140 piglets weaned at 21 days of age. Seven dietary treatments were used: a negative control group (basal diet), a positive control group with ZnO (3000 mg/kg of food), two groups with OEO at 0.4% and 1.2%, respectively, two groups with PGP 0.4% and 2%, respectively, and a group with OEO with 1.2% combined with PGP with 2%. Each group of piglets received the treatment for seven weeks, from weaning, before samples were taken. Antibiotic resistance profiles were measured in 81 E. coli strains. On this occasion, only the control groups, ZnO, OEO 1.2%, PGP 2% and OEO 1.2% + PGP 2% were used, and the samples were obtained from the cecal content. A progressive loss of the bioactive components of OEO and PGP was observed during the 34 days of storage (p < 0.05). PGP 2%, OEO 1.2% and their combination showed results similar to ZnO (p > 0.05), or superior in the study of intestinal morphometry and the values of E. coli and Lactobacillus. All categories showed high levels of resistance. Only the strains isolated from the OEO 1.2% group did not show resistance to colistin and presented the lowest resistance values. In general, high doses of the additives studied showed the best results, obtaining levels like or higher than those offered by ZnO.

Polyphenolic Profile of Tunisian Thyme (Thymbra capitata L.) Post-Distilled Residues: Evaluation of Total Phenolic Content and Phenolic Compounds and Their Contribution to Antioxidant Activity.

During the last decade there has been growing interest in the formulation of new cosmetic, food and pharmaceutical products containing natural compounds with antioxidant activity and other beneficial properties. Aromatic and medicinal plants have always been the major source of bioactive compounds, especially, wild thyme (Thymbra capitata L.), which has been used since ancient times for its valuable health benefits that could be attributed to the richness of polyphenolic compounds. This study was undertaken with the following aims: to estimate the total polyphenolic content (TPC); to evaluate the antioxidant activity; to identify and quantify the phenolic compounds of post-distilled residues of Tunisian thyme, and their contribution to the antioxidant activity. The TPC, as determined by the Folin−Ciocalteu method, was found to reach the values of 126.7 and 107.84 mg gallic acid equivalent/g plant dry weight (mg GAE/g PDW). The antioxidant activity, which is assessed by DPPH and FRAP assays, reached the values of 42.97−45.64 µg/mL and 42.22−50.21 mMFe2+/mg PDW, respectively. HPLC analysis revealed the presence of fourteen polyphenolic compounds, of which diosmin and rosmarinic acid were found to be the most abundant (24.26 to 33.80 and 22.0.1 to 26.29 mg/g PDW, respectively). An important correlation was found between the antioxidant activity and several identified phenolic compounds (p < 0.05). The findings revealed that thyme post-distilled residues have an effective natural antioxidant potential due to their high concentration of bioactive molecules, and they appear to be useful in the pharmaceutical, cosmetic, and food industries, with beneficial effects on human health. Therefore, supplementing a balanced diet with herbs may have beneficial health effects.

Electronic Cigarette Use and the Risk of Cardiovascular Diseases.

Electronic cigarettes or e-cigarettes are the most frequently used tobacco product among adolescents. Despite the widespread use of e-cigarettes and the known detrimental cardiac consequences of nicotine, the effects of e-cigarettes on the cardiovascular system are not well-known. Several in vitro and in vivo studies delineating the mechanisms of the impact of e-cigarettes on the cardiovascular system have been published. These include mechanisms associated with nicotine or other components of the aerosol or thermal degradation products of e-cigarettes. The increased hyperlipidemia, sympathetic dominance, endothelial dysfunction, DNA damage, and macrophage activation are prominent effects of e-cigarettes. Additionally, oxidative stress and inflammation are unifying mechanisms at many levels of the cardiovascular impairment induced by e-cigarette exposure. This review outlines the contribution of e-cigarettes in the development of cardiovascular diseases and their molecular underpinnings.

Treatment of Wound Infections in a Mouse Model Using Zn2+-Releasing Phage Bound to Gold Nanorods.

Infections caused by drug-resistant bacteria, particularly Gram-negative organisms, are increasingly difficult to treat using antibiotics. A potential alternative is "phage therapy", in which phages infect and lyse the bacterial host. However, phage therapy poses serious drawbacks and safety concerns, such as the risk of genetic transduction of antibiotic resistance genes, inconsistent pharmacokinetics, and unknown evolutionary potential. In contrast, metallic nanoparticles possess precise, tunable properties, including efficient conversion of electronic excitation into heat. In this work, we demonstrate that engineered phage-nanomaterial conjugates that target the Gram-negative pathogen Pseudomonas aeruginosa are highly effective as a treatment of infected wounds in mice. Photothermal heating, performed as a single treatment (15 min) or as two treatments on consecutive days, rapidly reduced the bacterial load and released Zn2+ to promote wound healing. The phage-nanomaterial treatment was significantly more effective than systemic standard-of-care antibiotics, with a >10× greater reduction in bacterial load and ∼3× faster healing as measured by wound size reduction when compared to fluoroquinolone treatment. Notably, the phage-nanomaterial was also effective against a P. aeruginosa strain resistant to polymyxins, a last-line antibiotic therapy. Unlike these antibiotics, the phage-nanomaterial showed no detectable toxicity or systemic effects in mice, consistent with the short duration and localized nature of phage-nanomaterial treatment. Our results demonstrate that phage therapy controlled by inorganic nanomaterials can be a safe and effective antimicrobial strategy in vivo.

Extraction and Encapsulation of Phenolic Compounds of Tunisian Rosemary (Rosmarinus officinalis L.) Extracts in Silk Fibroin Nanoparticles.

Rosemary (Rosmarinus officinalis L.) is known to be an effective potential source of natural antioxidants which confer benefits to human health. Their bioactive properties are mainly due to phenolic compounds but these molecules are highly vulnerable to oxidants, light, heat, pH, water and enzymatic activities. Therefore, the stability and shelf life of phenolic compounds should be increased by being protected from chemical and physical damage by means of encapsulation prior to application. Encapsulation is becoming increasingly important in the pharmaceutical, food, cosmetics, textile, personal care, chemical, biotechnology, and medicinal industries due to its potential for stabilization and delivery of delicate and precious bioactive compounds. The aim of the present work was to describe the polyphenolic profile of Tunisian Rosemary, collected from two different bioclimatic areas, and further loading in silk fibroin nanoparticles. The loaded nanoparticles were characterized in terms of morphology, size, polydispersity, Z-potential, secondary structure of the protein, encapsulation efficiency, loading content, and antioxidant activity. On one hand, HPLC analysis revealed the presence of 18 polyphenolic compounds of whichcarnosic acid and carnosol were found to be the most abundant compounds (46.3 to 76.4 and 22.4 to 43.5 mg of compound per gram of dry plant weight (mg/g DPW) respectively), Total phenolic content (TPC) ranged from 85.8 to 137.3 mg of gallic acid equivalent (GAE)/g DPW in post-distilled rosemary extracts andantioxidant activity reached the values of 5.9 to 8.3 µmol of ascorbic acid equivalent (AAE)/g DPW). On the other hand loaded nanoparticles were almost spherical and presented nanometric size and negative Z-potential. Although the encapsulation efficiency in silk fibroin nanoparticles and the drug loading content were low in the conditions of the assay, the encapsulated polyphenols retained near 85% of the radical scavenging activity against DPPH· after 24 h. of incubation at 37 °C. The results showed that post-distilled rosemary residues had an effective potential as natural antioxidants due to their significant antioxidant activity and seemed to be useful in both pharmaceutical and food industries with beneficial properties that might confer benefits to human health and these silk fibroin nanoparticles loaded with rosemary extracts are thus a promising combination for several applications in food technology or nanomedicine.

Performance evaluation of ceramic pot filters combined with adsorption processes for the removal of heavy metals and phenolic compounds.

It has been demonstrated that the ceramic pot filters (CPFs) with impregnated colloidal silver are efficient for the removal of turbidity and pathogens for household water treatment. This investigation evaluated the efficiency of two filter models for the removal of chemical contaminants (Hg, Pb, As and phenolic compounds) during 175 days. The first model is a traditional CPF impregnated with colloidal silver and the second consists of the ceramic silver-impregnated pot plus a post-filtration column with granular activated carbon and zeolite (CPF + GAC-Z). The results of the CPF showed average efficiencies of 91.5% (Hg), 92% (Pb), 50.2% (As) and 78.7% (phenols). The CPF + GAC-Z showed similar efficiencies for the removal of heavy metals (92.5% Hg, 98.1% Pb and 52.3% As) and a considerably higher efficiency for the removal of phenols (96.4%). The As concentration of the filtered water in both systems was higher than the regulatory limit. The ceramic pot was responsible for the highest removal of chemical compounds. It can be concluded that the traditional CPF is a viable option for water supply treatment at the household level for the removal of chemical contaminants. The efficiency of this filter can be improved with the post-filtration column mainly for the removal of organic constituents.

Antimicrobial Resistance of Campylobacter jejuni, Escherichia coli and Enterococcus faecalis Commensal Isolates from Laying Hen Farms in Spain.

Antimicrobial resistance (AMR) is a global threat for human and animal health. Few studies have been carried out in laying hens. We evaluated the antimicrobial susceptibility of commensal Campylobacter jejuni, Escherichia coli, and Enterococcus faecalis isolates in Spanish laying hens in 2018. The Minimum Inhibitory Concentration (MIC) was used to identify any AMR of the studied isolates by means of a broth microdilution method. C. jejuni was highly resistant to the B category antimicrobials, and 52% of the isolates were susceptible to all the antimicrobials tested. E. coli showed medium and high percentages of resistance to the B and A antibiotic categories, respectively, and 33.33% of the isolates were susceptible to all antimicrobials. The E. faecalis resistance to A category antimicrobials was variable, and 4.62% of the isolates were susceptible to all antimicrobials. In our work, novel data on AMR in laying hen commensal isolates in Spain is provided, and the AMR levels differ from those reported for poultry in the EU. A high resistance to key drugs for human medicine was found, representing a public health risk.

A small molecule inhibitor of the chloride channel TMEM16A blocks vascular smooth muscle contraction and lowers blood pressure in spontaneously hypertensive rats.

Hypertension is a major cause of cardiovascular morbidity and mortality, despite the availability of antihypertensive drugs with different targets and mechanisms of action. Here, we provide evidence that pharmacological inhibition of TMEM16A (ANO1), a calcium-activated chloride channel expressed in vascular smooth muscle cells, blocks calcium-activated chloride currents and contraction in vascular smooth muscle in vitro and decreases blood pressure in spontaneously hypertensive rats. The acylaminocycloalkylthiophene TMinh-23 fully inhibited calcium-activated TMEM16A chloride current with nanomolar potency in Fischer rat thyroid cells expressing TMEM16A, and in primary cultures of rat vascular smooth muscle cells. TMinh-23 reduced vasoconstriction caused by the thromboxane mimetic U46619 in mesenteric resistance arteries of wild-type and spontaneously hypertensive rats, with a greater inhibition in spontaneously hypertensive rats. Blood pressure measurements by tail-cuff and telemetry showed up to a 45-mmHg reduction in systolic blood pressure lasting for four-six hours in spontaneously hypertensive rats after a single dose of TMinh-23. A minimal effect on blood pressure was seen in wild-type rats or mice treated with TMinh-23. Five-day twice daily treatment of spontaneously hypertensive rats with TMinh-23 produced sustained reductions of 20-25 mmHg in daily mean systolic and diastolic blood pressure. TMinh-23 action was reversible, with blood pressure returning to baseline in spontaneously hypertensive rats by three days after treatment discontinuation. Thus, our studies provide validation for TMEM16A as a target for antihypertensive therapy and demonstrate the efficacy of TMinh-23 as an antihypertensive with a novel mechanism of action.

Targeted Genetic Reduction of Mutant Huntingtin Lessens Cardiac Pathology in the BACHD Mouse Model of Huntington's Disease.

Individuals affected by Huntington's disease (HD) present with progressive degeneration that results in a wide range of symptoms, including cardiovascular (CV) dysfunction. The huntingtin gene (HTT) and its product are ubiquitously expressed, hence, the cardiomyopathy could also be driven by defects caused by its mutated form (mHTT) in the cardiomyocytes themselves. In the present study, we sought to determine the contribution of the mHTT expressed in the cardiomyocytes to CV symptoms. We utilized the BACHD mouse model, which exhibits many of the HD core symptoms, including CV dysfunction. This model allows the targeted genetic reduction of mHTT expression in the cardiomyocytes while maintaining the expression of the mHTT in the rest of the body. The BACHD line was crossed with a line of mice in which the expression of Cre recombinase is driven by the cardiac-specific alpha myosin-heavy chain (Myh6) promoter. The offspring of this cross (BMYO mice) exhibited a dramatic reduction in mHTT in the heart but not in the striatum. The BMYO mice were evaluated at 6 months old, as at this age, the BACHD line displays a strong CV phenotype. Echocardiogram measurements found improvement in the ejection fraction in the BMYO line compared to the BACHD, while hypertrophy was observed in both mutant lines. Next, we examined the expression of genes known to be upregulated during pathological cardiac hypertrophy. As measured by qPCR, the BMYO hearts exhibited significantly less expression of collagen1a as well as Gata4, and brain natriuretic peptide compared to the BACHD. Fibrosis in the hearts assessed by Masson's trichrome stain and the protein levels of fibronectin were reduced in the BMYO hearts compared to BACHD. Finally, we examined the performance of the mice on CV-sensitive motor tasks. Both the overall activity levels and grip strength were improved in the BMYO mice. Therefore, we conclude that the reduction of mHtt expression in the heart benefits CV function in the BACHD model, and suggest that cardiomyopathy should be considered in the treatment strategies for HD.