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This study was conducted to evaluate the effects of thyme, ginger, and their nano-particles, as alternatives to antibiotic growth promotors (AGP), on productive performance, carcass traits, meat quality and gut health of broiler chickens. A total of 270 one-day-old broiler chicks were randomly distributed into 6 groups, each consisting of 3 replicates (n = 15 chicks/replicate). The birds in group 1 were fed the control diet which contained neither antibiotic growth promotors nor phytogenic feed additives (PFA). Birds in group 2 were fed diets containing 0.05% of AGP (Bacitracin methylene disalicylate). Chicks in group 3 and 4 were fed diets supplemented with 1.0% of thyme and ginger, respectively, whereas birds in group 5 and 6 were offered diets including 0.10% of nano-thyme and nano-ginger, respectively. The experiment lasted for 35 days. It was found that thyme and ginger with their nano-products, like the antibiotic, improved the body weight, weight gain and feed conversion rate of birds. The effect of ginger and nano-ginger on body weight and weight gain was greater than other treatments. During the overall feeding period, the feed cost of production was the highest in antibiotic group, but was the lowest in ginger and nano-ginger treatments. There was no effect of dietary treatments on carcass yield or organs weight except bursa of Fabricius and abdominal fat. Thyme, ginger and their nano-composites increased the weight of bursa and reduced the abdominal fat amount. The phytogenic additives and their nano-particles improved the colour, water holding capacity, and flavor of meat. Moreover, these additives reduced the total intestinal bacterial count as well as the total aerobic mesophilic count of meat. The effect of PFA and their nano-particles on the bacterial count was similar to that of antibiotic. In conclusion, thyme and ginger with their nano- particles can be considered as promising agents in feeding of broilers to improve the growth performance, gut health and meat quality. Moreover, these additives can be used as alternatives to AGP to overcome its health hazards and the high cost. The nanotechnology of herbal plants enables them to be added in smaller amounts in poultry diets with producing the same effect of raw ingredients, and this could be due to the higher bioavailability.
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Ração Animal , Galinhas , Dieta , Carne , Nanopartículas , Thymus (Planta) , Zingiber officinale , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/microbiologia , Zingiber officinale/química , Thymus (Planta)/química , Ração Animal/análise , Dieta/veterinária , Carne/normas , Nanopartículas/administração & dosagem , Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , MasculinoRESUMO
This study was conducted to evaluate the effects of Spirulina platensis in Nile tilapia diets on growth performance, blood hematological and biochemical parameters, immunological status, and intestinal histomorphometry. A total of 228 fish were randomly allocated into four groups with triplicates (19 fish per replicate). The first group was fed the control diet, which contained no Spirulina supplementation. The other three groups were fed diets containing graded levels of powdered Spirulina: 2.5%, 5.0%, and 10.0% in the second, third, and fourth group, respectively. S. platensis was added to the diets partially substituting the fish meal content. The experiment lasted for 8 weeks. The results showed that dietary Spirulina supplementation improved (P < 0.05) the body weight and length, weight gain, specific growth rate, condition factor, and feed conversion efficiency. Moreover, Spirulina increased significantly (P < 0.05) the hemoglobin, PCV, RBCs, and WBCs count. Also, it increased the lymphocytes, eosinophils, IgM level, lysozyme activity, and phagocytic activity in the blood. Additionally, the Spirulina raised (P < 0.05) the serum albumin level but reduced (P < 0.05) the creatinine and urea levels. The addition of Spirulina increased (P < 0.05) the height and width of intestinal villi and the lymphocytes and goblet cells count in the intestine. The obtained results were increased by increasing the inclusion level of Spirulina, especially for body weight and length, weight gain, FCR, phagocytic activity, and intestinal parameters. In conclusion, supplementing S. platensis can improve the growth performance of fish. Moreover, it can stimulate the immunity of fish through increasing the level of immunological blood indicators (IgM, lysozyme, phagocytic activity, lymphocytes, and eosinophils) as well as the local intestinal immunity (lymphocytes and goblet cells). So, it can be recommended to use S. platensis in fish diets not only to improve the growth performance but also to enhance the immune status.
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Ciclídeos , Suplementos Nutricionais , Animais , Muramidase/metabolismo , Dieta/veterinária , Peso Corporal , Aumento de Peso , Imunoglobulina M , Ração Animal/análiseRESUMO
This study was conducted to evaluate the effect of using protease in diets of Nile tilapia on growth performance, water quality, blood parameters and intestinal morphology. The cost of these diets and their return on fish performance was calculated. A total of 360 fish were randomly allocated into four groups with triplicates (30 fish per replicate). Four diets were formulated; two controls (without protease supplementation) and two experimental diets (supplemented with protease). The first control diet contained the normal protein requirement (30% CP; control +ve), while the second control had a low protein content (29% CP; control -ve). The third diet was supplemented with protease at a dose of 500 g/ton, and its CP content was reduced to 29.0%, by reducing the fish meal content. The fourth diet contained the same CP level as the first control (30%) and supplemented with 250 g protease per ton feed. The experiment lasted for 14 weeks. The results showed that body weight and length, weight gain, specific growth rate, feed intake and feed conversion efficiency in the control -ve group (low CP) supplemented with protease were similar (p > 0.05) to that of the control +ve with normal CP content. However, these performance parameters were lower (p < 0.05) in fish fed low CP diet without protease supplementation. Providing protease to the control +ve diet improved all measured performance indices. The ammonia and nitrite concentrations of the water were reduced (p < 0.05) in control -ve and protease-supplemented groups. The height and width of intestinal villi were increased (p < 0.05) in fish fed diets containing protease. The inclusion of protease reduced the diet cost and also the feed cost of fish weight gain. In conclusion, supplementation of protease can improve the productive performance of fish, spare dietary protein and produce economical diets. Moreover, it can help in improving the water quality of fish via lowering the ammonia and nitrite contents, or through increasing the degradation of dietary protein.
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Ciclídeos , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Peptídeo Hidrolases/farmacologia , Qualidade da ÁguaRESUMO
This study was conducted to evaluate the dietary effects of chromium methionine (Cr-Meth) chelate on growth performance, oxidative stress parameters, blood biochemistry, and carcass traits of broiler chickens. An experiment was conducted on 34,000 1-day-old straight-run broiler chicks (Indian River; 42.0 ± 0.03) at a commercial farm. The chicks were divided randomly into 3 groups; the first group contained 17,000 birds, which used as a control, whereas the second and third groups consisted of 7000 and 10,000 birds, respectively, with 5 replicates per group. A completely randomized design was used. The birds were fed the experimental diets containing graded levels of Cr-Meth chelate: 0 (control), 50, and 100 g/ton. This compound consisted of chromium (0.4%) chelated with methionine, and it supply the diets with 200 and 400 ppb Cr for the used levels of 50 and 100 g/ton feed, respectively. Growth performance indices (body weight, body weight gain, feed intake, and feed conversion ratio) were measured throughout the experiment. At the end of experiment, 10 birds per treatment were slaughtered, and the carcass yield with relative weight of the internal organs was determined. Also, blood samples were taken and analyzed for glutathione peroxidase activity, malondialdehyde, ALT, AST, total protein, albumin, glucose, urea, creatinine, triglycerides, and total cholesterol. It was found that Cr-Meth improved the body weight, weight gain, feed intake, and feed conversion ratio of broilers. Moreover, it reduced the mortality rate of birds. The chelated chromium can alleviate the oxidative status of birds by increasing the plasma glutathione peroxidase activity and reducing the serum malondialdehyde level. It was observed that the effects of 100 g/ton Cr-Meth chelate on performance indices, mortality rate, and oxidative stress parameters were better than that of 50 g/ton inclusion rate. Supplementation of Cr-Meth increased the total protein level, but reduced the glucose, total cholesterol, and triglyceride concentrations in the blood serum. In addition, it increased the carcass yield and reduced the abdominal fat percentage of the birds' carcass. Therefore, chromium can be included in diets of broilers at a rate of 200 to 400 ppb, and the higher concentration was more effective than the lower one. So, it can be recommended to use Cr-Meth chelate in broiler diets at 100 g/ton to improve the productive performance and reduce the oxidative stress of birds.
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Galinhas , Metionina , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Peso Corporal , Colesterol , Cromo , Dieta/veterinária , Suplementos Nutricionais , Glucose/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo , Triglicerídeos , Aumento de PesoRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is an international public health emergency with major disruptions and devastating health consequences resulting from the associated cytokine storm syndrome. The aim of our research was to assess the inflammatory biomarkers and risk factors associated with severity of (COVID-19) patients. METHODS: A cross-sectional study was conducted and included 150 Egyptian patients with COVID-19. Patients were classified into mild, moderate, and severe according to the clinical and CT chest findings. Blood samples were collected from patients for laboratory assessment of inflammatory biomarkers. RESULTS: Our results showed significant negative correlation between oxygen saturation percent and serum levels of inflammatory markers. The correlations were statistically significant with IL-6, CRP, ferritin, LDH, and D-dimer which can be used as sensitive biomarkers for assessment of the risk of severity of infection in COVID 19 patients. CONCLUSIONS: The study revealed that the risk factors associated with severity of COVID 19 infection included older age, male gender, presence of underlying chronic disease, and increased levels of inflammatory biomarkers: CRP, LDH, ferritin, IL-6, and D-dimer.
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COVID-19 , Citocinas , Idoso , Biomarcadores , Estudos de Coortes , Estudos Transversais , Egito , Humanos , Masculino , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
This study was carried out to evaluate the effect of essential oils or saponins alone or in combination on productive performance, intestinal morphology, and digestive enzymes' activity in broilers. Four hundred one-day-old male broiler chickens were randomly assigned to four treatments, each with 5 replicates. The birds were fed experimental diets contained either no phytogenic feed additives (control) or were supplemented with 25.0 mg/kg of an essential oil blend from star anise, rosemary, thyme and oregano (essential oils); 46.0 mg/kg of a Quillaja saponin blend (saponins); or a combination of both phytogenic preparations (essential oils plus saponins). The experiment lasted for 42 days. Body weight, feed intake and weight gain were recorded weekly, and the feed conversion ratio was calculated, throughout the experiment. Intestinal morphology and digestive enzymes' activity were determined at the end of the experiment. It was found that the body weight was increased by all dietary supplements at the end of the experiment. There was no change in performance parameters among the treatments during the starter period. At the grower period and the overall experiment, the weight gain of birds was higher in all supplemented groups compared to the control, but the feed conversion was better in the essential oils with saponins treatment. Supplementation of essential oils or saponins alone or in combination increased the villus height and the villus/crypt ratio of the intestine. There was an increase in trypsin, chymotrypsin and elastase activities in the essential oils plus saponins group only. The obtained results indicate that the phytogenic feed additives, especially essential oils with saponins, can be considered as new promising agents in promoting the growth performance of broilers. The effect could be related to its improving impact in intestinal development and increasing the protease enzymes' activity, resulting in increased protein digestibility and absorption of dietary nutrients.
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Óleos Voláteis , Saponinas , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas , Dieta/veterinária , Suplementos Nutricionais , Intestinos , Masculino , Óleos Voláteis/farmacologia , Saponinas/farmacologiaRESUMO
This study was conducted to evaluate the effects of green fodders, fresh Sesbania sesban, and reed grass, on growth performance, blood metabolites, and meat quality of growing lambs. Twenty-one male Farafra lambs (19.0 ± 1.87 kg body weight) were randomly distributed into three groups, each with seven animals. The first group was fed on 60% concentrates and 40% fresh alfalfa, and served as a control. The second and third groups were fed also on 60% concentrates plus 40% fresh Sesbania sesban and reed grass, respectively. Lambs were fed the diets until reaching the target slaughter weight of about 50.0 kg, which was obtained after a period of 215 days. Five lambs from each group were randomly selected and slaughtered at the end of the experiment. Slaughter body weight, carcass traits weight, and dressing percentage were estimated. Chemical composition and physical properties of longissimus dorsi muscle, from the animals' right side, were determined. It was found that no significant (P > 0.05) differences among groups in body weight, average daily gain, feed conversion rate, hot carcass, dressing percentage, and carcass components were observed. The forage intake of Sesbania and alfalfa tended to be higher than that of reed forage. There were no significant (P > 0.05) differences in the blood parameters among the treatments, except the urea level which was higher in Sesbania sesban group than the reed one. However, the serum urea concentration in Sesbania and reed groups was similar to that of alfalfa. Sesbania sesban and reed forages decreased (P < 0.05) the eye muscle area and shear force in lambs when compared to the control group. The longissimus dorsi muscle of the Sesbania and reed treatments was found to be numerically higher in the moisture and lower in the fat and collagen contents than the alfalfa group. Most of meat and fat color parameters were improved by feeding of Sesbania and reed forages. In conclusion, Sesbania sesban or reed grass, as unconventional forage sources, can be used as alternatives of the commonly used alfalfa feed. Moreover, these sources could enhance the meat quality of lambs and increasing the tenderness with accepted meat and fat color. So, it can be recommended to use Sesbania or reed grass forages in diets of sheep, to overcome the rising in the price or shortage in the availability of traditional green fodders.
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Sesbania , Ração Animal/análise , Animais , Composição Corporal , Dieta/veterinária , Masculino , Carne , Poaceae , OvinosRESUMO
BACKGROUND: Understanding cellular responses via signal transduction is a core focus in systems biology. Tools to automatically reconstruct signaling pathways from protein-protein interactions (PPIs) can help biologists generate testable hypotheses about signaling. However, automatic reconstruction of signaling pathways suffers from many interactions with the same confidence score leading to many equally good candidates. Further, some reconstructions are biologically misleading due to ignoring protein localization information. RESULTS: We propose LocPL, a method to improve the automatic reconstruction of signaling pathways from PPIs by incorporating information about protein localization in the reconstructions. The method relies on a dynamic program to ensure that the proteins in a reconstruction are localized in cellular compartments that are consistent with signal transduction from the membrane to the nucleus. LocPL and existing reconstruction algorithms are applied to two PPI networks and assessed using both global and local definitions of accuracy. LocPL produces more accurate and biologically meaningful reconstructions on a versatile set of signaling pathways. CONCLUSION: LocPL is a powerful tool to automatically reconstruct signaling pathways from PPIs that leverages cellular localization information about proteins. The underlying dynamic program and signaling model are flexible enough to study cellular signaling under different settings of signaling flow across the cellular compartments.
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Biologia Computacional/métodos , Proteínas/metabolismo , Transdução de Sinais , Algoritmos , Automação , Humanos , Ligação Proteica , Mapeamento de Interação de Proteínas , Transporte ProteicoRESUMO
OBJECTIVE: This study was conducted to investigate the effects of probiotic, prebiotic and synbiotic with and without feed restriction on broilers performance, blood parameters, carcass characteristics, and feed cost of production from 1 to 56 days of age. METHODS: Two hundred and forty unsexed one day-old chicks of Arbor Acres breed were used. Two trials, I and II, were conducted, with 120 birds in both. Each trial was divided into 4 equal groups. The birds in trial I were fed ad libitum throughout the experiment, while the chicks in trial II were fed ad libitum during the first week of age, then subjected to 5 hours/d of feed restriction from the beginning of the second week up to the end of the experiment. In both trials, the birds in group 1 were fed on a control diet while the other groups were given the same control diet supplemented either with a probiotic in group 2, prebiotic in group 3, or synbiotic in group 4. RESULTS: It was found that chicks fed diets supplemented with probiotic, prebiotic and synbiotic (with and without feed restriction) exhibited higher body weight and feed efficiency than chicks fed the control diets. The feed additives in both trials did not affect hemoglobin, serum total protein, albumin, globulin, glucose, and total cholesterol, except the packed cell volume which was increased in the additive treatments with restriction at the end of the experiment. Moreover, the dietary treatments did not influence the carcass yield. However, the relative weights of liver, gizzard and proventriculus, small intestine and bursa of fabricius were found to be increased. The additives decreased the visible fat in the carcass, with more decreasing effect in the additive groups with restriction. The lowest feed cost per kg of weight gain was observed in the birds fed diets supplemented with synbiotic, probiotic and prebiotic. Feed restriction improved the feed conversion ratio, economic return, but decreased the feed intake, serum total cholesterol and visible fat in comparison with non-restricted groups. CONCLUSION: The biological feed additives could be routinely added to broiler diets, especially when a feed restriction program is followed. Finally, it can be recommended to restrict feed, and add probiotic or synbiotic to increase weight, improve feed conversion rate and reduce feed cost of production.
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We report the synthesis of an amphiphilic triblock copolymer composed of a hydrophilic poly(ethylene glycol) (PEG) block, a central poly(acrylic acid) (PAA) block, and a hydrophobic poly(methyl methacrylate) (PMMA) block using atom transfer radical polymerization technique. We examined the self-assembly of PEG-b-PAA-b-PMMA copolymers in aqueous solutions forming nanosized micelles and their ability to encapsulate hydrophobic guest molecules such as Nile Red (NR) dye and cabazitaxel (CTX, an anticancer drug). We used 2,2ß'-(propane-2,2-diylbis(oxy))-diethanamine to react with the carboxylic acid groups of the central PAA block forming acid-labile, shell cross-linked micelles (SCLM). We investigated the loading efficiency and release of different guest molecules from non-cross-linked micelles (NSCLM) and shell cross-linked micelles (SCLM) prepared by reacting 50% (SCLM-50) and 100% (SCLM-100) of the carboxylic acid groups in the PAA in physiologic (pH 7.4) and acidic (pH 5.0) buffer solutions as a function of time. We examined the uptake of NR-loaded NSCLM, SCLM-50, and SCLM-100 micelles into PC-3 and C4-2B prostate cancer cells and the effect of different micelle compositions on membrane fluidity of both cell lines. We also investigated the effect of CTX-loaded NSCLM, SCLM-50, and SCLM-100 micelles on the viability of PC-3 and C4-2B cancer cells compared to free CTX as a function of drug concentration. Results show that PEG-b-PAA-b-PMMA polymers form micelles at concentrations ≥11 µg/mL with an average size of 40-50 nm. CTX was encapsulated in PEG-b-PAA-b-PMMA micelles with 55% loading efficiency in NSCLM. In vitro release studies showed that 30% and 85% of the loaded CTX was released from SCLM-50 micelles in physiologic (pH 7.4) and acidic (pH 5.0) buffer solutions over 30 h, confirming micelles' sensitivity to solution pH. Results show uptake of NSCLM and SCLM into prostate cancer cells delivering their chemotherapeutic cargo, which triggered efficient cancer cell death. PEG-b-PAA-b-PMMA micelles were not hemolytic and did not cause platelet aggregation, which indicate their biocompatibility.
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Micelas , Taxoides/administração & dosagem , Taxoides/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Concentração de Íons de Hidrogênio , Macrófagos/metabolismo , Masculino , Neoplasias da Próstata/metabolismo , Taxoides/efeitos adversosRESUMO
Eculizumab is a biologic medication used for the treatment of complement-related disorders including anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. It targets C5 complement, preventing its cleavage into active terminal components. Thus, vaccination against encapsulated organisms is advised before starting this treatment. C5 also has a critical role against Cryptococcus neoformans infection. Here, we present a case of a 34-year-old man with a history of myasthenia gravis who was treated with prednisone and azathioprine in addition to eculizumab that was added to his regimen about a year ago, and who came to the hospital with headache, and was found to have Cryptococcus meningitis with disseminated cryptococcosis. The patient was negative for human immunodeficiency virus. He was treated with antifungal medications, and his condition improved. Although rarely reported, it is important to have a low threshold for diagnosis of cryptococcosis in patients on eculizumab given its complement inhibition mechanism of action.
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This study introduces a novel approach for the separation of indacrinone (IC) enantiomers, crucial in treating edema, hypertension, and hyperuricemia. A cationic biopolymer from furan-2-ylmethylhydrazine-cellulose (FUH-CE), derived from cyanoethyl cellulose (CEC), serving as a substrate in molecular imprinting. A key innovation is the use of the Diels-Alder reaction for efficient cross-linking with bis(maleimido)ethane (BME). This chemical strategy resulted in molecularly imprinted microparticles with high selectivity for the S-IC enantiomer, which can be eluted by adjusting the solution's pH. Extensive characterization confirmed the chemical modifications and selective binding efficacy of these biopolymers. Utilizing separation columns, our method achieved an impressive chiral resolution of (±)-IC, with an enantiomeric excess (ee) of 95 % for R-IC during the loading phase and 97 % for S-IC during elution. Under optimized conditions, the biopolymer demonstrated a maximum binding capacity of 131 mg/g at pH 6. This advanced approach represents a significant advancement in chiral separation technology, offering a robust and efficient technique for the selective isolation of enantiomers. This method not only enhances potential targeted therapeutic applications but also provides a scalable solution for industrial chiral separations.
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Celulose , Reação de Cicloadição , Furanos , Impressão Molecular , Furanos/química , Celulose/química , Celulose/análogos & derivados , Estereoisomerismo , Impressão Molecular/métodos , Cátions/química , Concentração de Íons de HidrogênioRESUMO
Introduction: Liver cancer, particularly Hepatocellular carcinoma (HCC), remains a significant global health concern due to its high prevalence and heterogeneous nature. Despite the existence of approved drugs for HCC treatment, the scarcity of predictive biomarkers limits their effective utilization. Integrating diverse data types to revolutionize drug response prediction, ultimately enabling personalized HCC management. Method: In this study, we developed multiple supervised machine learning models to predict treatment response. These models utilized classifiers such as logistic regression (LR), k-nearest neighbors (kNN), neural networks (NN), support vector machines (SVM), and random forests (RF) using a comprehensive set of molecular, biochemical, and immunohistochemical features as targets of three drugs: Pantoprazole, Cyanidin 3-glycoside (Cyan), and Hesperidin. A set of performance metrics for the complete and reduced models were reported including accuracy, precision, recall (sensitivity), specificity, and the Matthews Correlation Coefficient (MCC). Results and Discussion: Notably, (NN) achieved the best prediction accuracy where the combined model using molecular and biochemical features exhibited exceptional predictive power, achieving solid accuracy of 0.9693 ∓ 0.0105 and average area under the ROC curve (AUC) of 0.94 ∓ 0.06 coming from three cross-validation iterations. Also, found seven molecular features, seven biochemical features, and one immunohistochemistry feature as promising biomarkers of treatment response. This comprehensive method has the potential to significantly advance personalized HCC therapy by allowing for more precise drug response estimation and assisting in the identification of effective treatment strategies.
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Introduction: Pulmonary fibrosis (PF) and tissue remodeling can greatly impair pulmonary function and often lead to fatal outcomes. Methodology: In the present study, we explored a novel molecular interplay of long noncoding (Lnc) RNA CBR3-AS1/ miRNA-29/ FIZZ1 axis in moderating the inflammatory processes, immunological responses, and oxidative stress pathways in bleomycin (BLM)-induced lung fibrosis. Furthermore, we investigated the pharmacological potential of Trimetazidine (TMZ) in ameliorating lung fibrosis. Results: Our results revealed that the BLM-treated group exhibited a significant upregulation in the expression of epigenetic regulators, lncRNA CBR3-AS1 and FIZZ1, compared to the control group (P<0.0001), along with the downregulation of miRNA-29 expression. Furthermore, Correlation analysis showed a significant positive association between lnc CBR3-AS1 and FIZZ1 (R=0.7723, p<0.05) and a significant negative association between miRNA-29 and FIZZ1 (R=-0.7535, p<0.05), suggesting lnc CBR3-AS1 as an epigenetic regulator of FIZZ1 in lung fibrosis. BLM treatment significantly increased the expression of Notch, Jagged1, Smad3, TGFB1, and hydroxyproline. Interestingly, the administration of TMZ demonstrated the ability to attenuate the deterioration effects caused by BLM treatment, as indicated by biochemical and histological analyses. Our investigations revealed that the therapeutic potential of TMZ as an antifibrotic drug could be ascribed to its ability to directly target the epigenetic regulators lncRNA CBR3-AS1/ miRNA-29/ FIZZ1, which in turn resulted in the mitigation of lung fibrosis. Histological and immunohistochemical analyses further validated the potential antifibrotic effects of TMZ by mitigating the structural damage associated with fibrosis. Discussion: Taken together, our study showed for the first time the interplay between epigenetic lncRNAs CBR3-AS1 and miRNA-29 in lung fibrosis and demonstrated that FIZZ1 could be a downregulatory gene for lncRNA CBR3-AS1 and miRNA-29. Our key findings demonstrate that TMZ significantly reduces the expression of fibrotic, oxidative stress, immunomodulatory, and inflammatory markers, along with epigenetic regulators associated with lung fibrosis. This validates its potential as an effective antifibrotic agent by targeting the CBR3-AS1/miRNA-29/FIZZ1 axis.
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Bleomicina , MicroRNAs , Fibrose Pulmonar , RNA Longo não Codificante , Trimetazidina , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Animais , Camundongos , Trimetazidina/farmacologia , Masculino , Camundongos Endogâmicos C57BLRESUMO
Type 1 diabetes stem-cell-based treatment approach is among the leading therapeutic strategies for treating cardiac damage owing to the stem cells' regeneration capabilities. Mesenchymal stem cells derived from adipose tissue (AD-MSCs) have shown great potential in treating diabetic cardiomyopathy (DCM). Herein, we explored the antioxidant-supporting role of N, N'-diphenyl-1,4-phenylenediamine (DPPD) in enhancing the MSCs' therapeutic role in alleviating DCM complications in heart tissues of type 1 diabetic rats. Six male albinos Wistar rat groups have been designed into the control group, DPPD (250 mg/kg, i.p.) group, diabetic-untreated group, and three diabetic rat groups treated with either AD-MSCs (1 × 106 cell/rat, i.v.) or DPPD or both. Interestingly, all three treated diabetic groups exhibited a significant decrease in serum glucose, HbA1c, heart dysfunction markers (lactate dehydrogenase and CK-MP) levels, and lipid profile fractions (except for HDL-C), as well as some cardiac oxidative stress (OS) levels (MDA, AGEs, XO, and ROS). On the contrary, serum insulin, C-peptide, and various cardiac antioxidant levels (GSH, GST, CAT, SOD, TAC, and HO-1), beside viable cardiac cells (G0/G1%), were markedly elevated compared with the diabetic untreated group. In support of these findings, the histological assay reflected a marked enhancement in the cardiac tissues of all diabetic-treated groups, with obvious excellency of the AD-MSCs + DPPD diabetic-treated group. Such results strongly suggested the great therapeutic potentiality of either DPPD or AD-MSCs single injection in enhancing the cardiac function of diabetic rats, with a great noted enhancement superiority of DPPD and AD-MSCs coadministration.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Cardiomiopatias Diabéticas , Ratos Wistar , Animais , Cardiomiopatias Diabéticas/terapia , Masculino , Ratos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/terapia , Fenilenodiaminas/farmacologia , Fenilenodiaminas/administração & dosagem , Tecido Adiposo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Estresse Oxidativo/efeitos dos fármacosRESUMO
Accessory tricuspid valve (ATV) is a rare cardiac anomaly often associated with other complex cardiac disorders, most commonly tetralogy of Fallot (TOF) and ventricular septal defect (VSD), but it can also be an isolated entity. It is usually diagnosed in childhood. It can be asymptomatic and get diagnosed incidentally, but it can also lead to cardiac complications such as right ventricular outflow obstruction (RVOTO) or tricuspid valve regurgitation. Here, we present the case of a 23-year-old woman with an isolated ATV diagnosed on an echocardiogram without symptoms after a physical exam noted a murmur, with a subsequent echocardiogram showing moderate to severe tricuspid valve regurgitation. A literature review was also performed. Only a small number of ATV cases have been reported, most of them diagnosed in childhood and associated with other congenital cardiac anomalies. Most of the cases necessitated surgical intervention, with a portion resulting in fatalities. It is important to understand the diagnosis and morphology of the ATV due to its association with dangerous complications to guide the management of this entity. It is also important to conduct further research to understand the inheritance of this pathology and develop screening and prevention plans.
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[This corrects the article DOI: 10.7759/cureus.43907.].
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Since the first report of the organoselenium compound, ebselen, as a potent inhibitor of the SARS-CoV-2 Mpro main protease by Z. Jin et al. (Nature, 2020), different OSe analogs have been developed and evaluated for their anti-COVID-19 activities. Herein, organoselenium-clubbed Schiff bases were synthesized in good yields (up to 87%) and characterized using different spectroscopic techniques. Their geometries were studied by DFT using the B3LYP/6-311 (d, p) approach. Ten FDA-approved drugs targeting COVID-19 were used as model pharmacophores to interpret the binding requirements of COVID-19 inhibitors. The antiviral efficiency of the novel organoselenium compounds was assessed by molecular docking against the 6LU7 protein to investigate their possible interactions. Our results showed that the COVID-19 primary protease bound to organoselenium ligands with high binding energy scores ranging from -8.19 to -7.33 Kcal/mol for 4c and 4a to -6.10 to -6.20 Kcal/mol for 6b and 6a. Furthermore, the docking data showed that 4c and 4a are good Mpro inhibitors. Moreover, the drug-likeness studies, including Lipinski's rule and ADMET properties, were also assessed. Interestingly, the organoselenium candidates manifested solid pharmacokinetic qualities in the ADMET studies. Overall, the results demonstrated that the organoselenium-based Schiff bases might serve as possible drugs for the COVID-19 epidemic.
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An effective electroanalytical method was developed for the quantitative evaluation of fenitrothion pesticide. The electrochemically modified carbon paste electrode CPE was constructed by applying a safranine layer on its surface. Safranine monomer is easily oxidized. So, a safranine layer was applied via electropolymerization using cyclic voltammetry in (2 × 10-5 M) safranine buffered solution with phosphate buffer BPS at pH.6, potential window (- 1.6: + 2 V), scan rate 100 mV/s. The morphology of the modified electrode was characterized using SEM images. The electropolymerization process was characterized by observing the gradual increases of the peak current with the subsequent scanning cycles. This modified CPE electrode showed an obvious sensitivity by cyclic voltammetry towards the cathodic peak of the fenitrothion nitro group at approximately - 0.73V with good sensitivity by enhancing it to be approximately 10 times more sensitive than on a bare carbon paste electrode CPE. The number of cycles was optimized for the electropolymerization process to be 12 cycles. Where, the peak current at - 0.73 V was gradually enhanced until 12 cycles when it is obviously decreased before slightly increasing again. The reproducibility of the modified electrode was ensured by repeating the sweep cycles using LSV for determining the fenitrothion at 5 µM where it was found that the peak current was unchanged for 10 sweeps before it starts to drop gradually. LSV voltammetry at previously optimized conditions of the potential window (- 0.4: - 1 V), sweep rate 100 mV/s, phosphate buffer at pH.6 was used for the quantitative studies. Where, the pHs of the determining medium were varied from pH 5.5 to pH 8 using phosphate buffer. It was observed that the most identified peak current was at pH.6 which is then decreased gradually until it completely disappeared at pH 8. The optimal accumulation time by adsorption of 140 s for the fenitrothion pesticide was confirmed in the range of (20 s-170 s). Where, the peak current was increased gradually with time up to 140 s then a plateau with a constant response was observed. The developed method showed an excellent linearity range of (1 µM:15 µM) with R2 parameter equal to 0.99906. LOD and LOQ were calculated to be 0.1 µM, and 0.34 µM respectively. Satisfactory levels have been reached for the calculated recovery, accuracy. Precision limits not exceed 1% for both repeatability and reproducibility measurements. F-value and t-value were measured for the suggested LSV method versus the standard HPLC method for the concentration of 8 µM fenitrothion and were found to be 1.482 and 0.123, respectively which didn't exceed the tabulated values. The ruggedness of the suggested method was examined toward deliberate safranine concentration variations in the concentration range of (0.01 mM-0.03 mM). Insignificant differences for the mean recovery at (98.33-98.93%) and precision at (1.39-2.6%) were observed. Hence, the reliability and validity of the developed LSV method were achieved and it was considered as rigid method.