Age-dependent development trends (models) of intestinal significant microbiota species and Eimeria oocysts in coccidia-challenged broiler chickens as affected by dietary encapsulated organic acids and anticoccidial drugs.

ABSTRACTThe study was conducted to investigate the effect of dietary encapsulated organic acids (EOAs) and anticoccidials on the age-dependent development trend of intestinal Lactobacillus, E. coli, coliforms, and Eimeria in Eimeria spp.-infected broiler chickens from reused litter. In total, 525 mixed-sex 1-day-old broiler chickens were used in an uninfected/un-supplemented control plus a 2 (no EOA or 0.1% EOA) × 3 (no anticoccidial, 0.05% maduramicin, and 0.02% diclazuril) factorial arrangement of treatments as a completely randomized design with five replicates of 15 chickens. Results indicated that the cubic model is the best model for explaining the development trends of the intestinal microbial population in uninfected and infected chickens (affected by the EOAs and anticoccidials). Based on the cubic models, the microbial populations had development trends with a decreasing slope from 1-day-old until the early or middle finisher period. EOAs and anticoccidials, especially their simultaneous usage, improved (P < 0.05) the linear and cubic models' slope (affected negatively by Eimeria infection). A polynomial model (order = 6) was determined as the best model for explaining the EOAs and anticoccidial effects on the trend of intestinal Eimeria oocysts in infected chickens. The infection peak (which happened at 25 days) was reduced by EOAs and anticoccidials, especially their simultaneous usage. In conclusion, cubic and polynomial (order = 6) regressions are the best models fitted for explaining the microbiota and Eimeria oocysts trends, respectively. EOAs and anticoccidials, especially their simultaneous usage, had beneficial effects on the microbiota and Eimeria development trends and gastrointestinal health in coccidia-infected broiler chickens. RESEARCH HIGHLIGHTSCubic regression is the best model for explaining intestinal microbiota development.Polynomial regression is the best model for intestinal Eimeria oocysts development.Age-development trends are affected by dietary encapsulated organic acids and anticoccidials.

Ferulic acid exerts a protective effect against cyclosporine-induced liver injury in rats via activation of the Nrf2/HO-1 signaling, suppression of oxidative stress, inflammatory response, and halting the apoptotic cell death.

Drug-induced liver injury is one of the main challenges that leads to the withdrawal of several drugs in the clinical setting. Cyclosporine is one of the drugs that its long-term administration exerts devastating effects on the hepatocytes. In the present study, we aimed to evaluate the effect of ferulic acid, a natural compound found in plants, on cyclosporine-mediated hepatotoxicity. Forty-eight male Wistar rats were treated with cyclosporine and/or ferulic acid to evaluate the function as well as the morphology of liver cells. We found that ferulic acid dose-dependently recovered the functional as well as histopathological parameters of liver cells, as revealed by the improvement of hepatocellular vacuolation, portal fibroplasia, and necrosis. Moreover, this phenolic compound was able to restore the balance of the redox system in cyclosporine-treated rats by activating the nuclear factor (NF) erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling axis. Of note, the protective effects of ferulic acid against cyclosporine-mediated liver toxicity were not restricted only to induction of the potential antioxidant property, as in the presence of this agent, the expression of pro-inflammatory cytokines such as NF-κB, tumor necrosis factor (TNF)-α, and interleukin-1ß was also diminished. Ferulic acid also shifted the equilibrium between the expression levels of proapoptotic to antiapoptotic proteins and thereby prevented the development of cyclosporine-induced liver injury. Overall, these findings highlighted that ferulic acid can reduce cyclosporine-induced liver injury due to its antioxidant properties.

Role of NF-κB/IL-1ß Pathway and Caspase 3 in Mediating the Hepatoprotective Effect of Rutin against Paraquat-Induced Liver Toxicity in Male Rats.

One of the most common bipyridinium herbicides that can lead to liver toxicity is paraquat. Rutin is a bioflavonoid with antioxidant, anti-inflammatory, anti-hepatotoxic, and antimicrobial properties. The effect of rutin on paraquat-induced liver toxicity was examined in this study. 48 male rats were divided into six groups: the control group was given a normal diet; the non-treated group was given paraquat; the positive control group was given paraquat, and silymarin and the treatment groups were given paraquat and rutin at doses of 25, 50, and 100 mg/kg. After fourteen days, the rats were anesthetized by xylazine-ketamine, and fasting blood samples were obtained from their hearts to measure alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), malondialdehyde (MDA), creatinine, lipid profile, antioxidant capacity, and carbonyl protein. The liver tissue was removed to measure the levels of catalase (CAT), superoxide dismutase (SOD), total protein, vitamin C, plus NF-κB, IL1ß, and caspase-3 gene expressions. Paraquat gavage in the untreated group (group 2) for 14 days in comparison with the control group induced a significant augmentation (p<0.05) in levels of lipid profile, AST, ALP, ALT, MDA, carbonyl protein, and also NF-κB, IL1ß, Caspase3 expressions. Treatment with rutin reduced the factors as mentioned above. Paraquat poisoning induced a substantial decline (p<0.05) in HDL content, FRAP level, CAT, and SOD activity of the liver compared to the control group. However, rutin oral treatment led to a substantial increase (p<0.05) in the level of these factors compared to the paraquat-only treated group. Based on the findings of the present study, it was found that rutin can be significantly effective in improving hepatotoxicity caused by paraquat.

Serum levels of IL-32 in patients with type 2 diabetes mellitus and its relationship with TNF-α and IL-6.

Type 2 diabetes mellitus (T2DM) is an important public health worldwide. The main underlying mechanism of T2DM is insulin resistance which is associated with chronic inflammation. Interleukin-32 (IL-32) is a pro-inflammatory cytokine which has been implicated in pro-inflammatory responses of several human diseases. Previous studies have reported higher levels of IL-32 in inflammatory disease and obesity. The present study aimed to evaluate the serum concentrations of IL-32 in patients with T2DM and its association with cardio-metabolic parameters. This study was undertaken on 93 patients with TDM and 74 healthy controls. T2DM was diagnosed based on ADA criteria. Serum levels of IL-32, adiponectin, TNF-α, and IL-6 were measured by ELISA technique. Our findings revealed independent elevated levels of IL-32 in T2DM group (1061 (841.9-1601) pg/mL) compared to the control (630.4 (331.1-830.9) pg/mL). Furthermore, it was associated with increased risk of T2DM incidence. IL-32 indicated a positive correlation with body mass index, fasting blood glucose, TNF-α, and IL-6 in patients with T2DM. Furthermore, linear regression showed independent association between IL-32 and IL-6 plus TNF-α in patients' group. The results of the present study revealed higher levels of IL-32 in T2DM patients which have been associated with inflammatory markers. These results suggest the possible role of IL-32 in chronic inflammation in patients with T2DM.

One-pot synthesis of thioxo-tetrahydropyrimidine derivatives as potent ß-glucuronidase inhibitor, biological evaluation, molecular docking and molecular dynamics studies.

A series of N,N-diethyl phenyl thioxo-tetrahydropyrimidine carboxamide have been synthesized and investigated for their ß-glucuronidase inhibitory activities. All molecules exhibited excellent inhibition with IC50 values ranging from 0.35 to 42.05 µM and found to be even more potent than the standard d-saccharic acid. Structure-activity relationship analysis indicated that the meta-aryl-substituted derivatives significantly influenced ß-glucuronidase inhibitory activities while the para-substitution counterpart outperforming moderate potency. The most potent compound in this series was 4g bearing thiophene motif with IC50 of 0.35 ± 0.09 µM. To verify the SAR, molecular docking and molecular dynamics studies were also performed.

Progesterone exerts antidepressant-like effect in a mouse model of maternal separation stress through mitigation of neuroinflammatory response and oxidative stress.

Context: Experiencing early-life adversity plays a key role in the development of mood disorders in adulthood. Experiencing adversities during early life period negatively affects brain development. Sex steroids such as progesterone affect the brain structure and functions and subsequently affects behaviour.Objective: We assess the antidepressant-like effect of progesterone in a mouse model of maternal separation (MS) stress, focussing on its anti-neuroinflammatory and antioxidative effects.Materials and methods: NMRI mice were treated with progesterone (10, 50, and 100 mg/kg, i.p., respectively) for 14 days. Valid behavioural tests including forced swimming test (FST), splash test and open field test (OFT) were used. Quantitative reverse transcription-PCR (qRT-PCR) was used for evaluation of genetic expression in the hippocampus. Antioxidant capacity was assessed by the FRAP method and the level of malondialdehide by TBA.Results: MS provoked depressive-like behaviour in mice. Treatment of MS mice with progesterone increased the grooming activity time in the splash test and decreased the immobility time in the FST. In addition, progesterone decreased the expression of inflammatory genes related to neuroinflammation (IL-1ß, TNF-α, TLR4 and NLRP3) as well as increased the antioxidant capacity and decreased the lipid peroxidation (MDA) in the hippocampus.Discussion and Conclusion: Administration of progesterone significantly mitigated the negative effects of MS on behaviours relevant to depressive-like behaviour as well as attenuated neuro-immune response and oxidative stress in the hippocampus of MS mice. In this context, we conclude that progesterone, at least partially, via attenuation of oxidative stress and neuroinflammation, exerts antidepressant-like effects.

Gallic acid mitigates diclofenac-induced liver toxicity by modulating oxidative stress and suppressing IL-1ß gene expression in male rats.

CONTEXT: Diclofenac (DIC) is an NSAID and consumption of this drug creates side effects such as liver injury. Gallic acid (GA), a natural component of many plants, is used as an antioxidant agent. OBJECTIVE: This study assesses the hepatoprotective effects of GA in the rat model of DIC-induced liver toxicity. MATERIALS AND METHODS: In this research, the male Wistar rats were separated into five groups (n = 6). Group 1, control, received normal saline (1 mL/kg bw, i.p.); Group 2 received DIC-only (50 mg/kg bw, i.p.); Groups 3, received DIC (50 mg/kg bw, i.p.) plus silymarin (100 mg/kg bw, po), groups 4 and 5 received DIC (50 mg/kg bw, i.p.) plus GA (50 and 100 mg/kg, po, respectively). RESULTS: The data demonstrated that the liver levels of the GSH, GPx, SOD, and CAT significantly reduced and the levels of the serum protein carbonyl, AST, ALP, ALT, total bilirubin, MDA, serum IL-1ß, and the liver IL-1ß gene expression were remarkably increased in the second group compared to control group. On the other hand, treatment with GA led to a significant elevation in GSH, GPx, SOD, CAT, and a significant decrease in protein carbonyl, AST, ALP, ALT, total bilirubin, MDA, serum IL-1ß, and gene expression of IL-1ß in comparison with the second group. Histological changes were also ameliorated by GA oral administration. Discussion and Conclusions: The data show that the oral administration of GA could alleviate the noxious effects of DIC on the antioxidant defense system and liver tissue.

Effects of N-acetyl cysteine on oxidative stress and TNF-α gene expression in diclofenac-induced hepatotoxicity in rats.

The consumption of non-steroidal anti-inflammatory drug, such as diclofenac, can lead to hepatotoxicity. In the present study, protective effect of N-acetyl cysteine (NAC) on diclofenac-induced hepatotoxicity was investigated. Thirty-two male rats were divided into four groups. Group 1 (control group) was treated with normal saline (1 ml/kg, i.p.) for 4 d. Group 2 (test without treatment) received diclofenac only (50 mg/kg, i.p.) for 4 d. Groups 3 and 4 received diclofenac (50 mg/kg, i.p.) plus NAC (150 mg/kg, p.o) and silymarin (100 mg/kg, p.o) for 4 d, respectively. At the end of experiment, serum glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), alkaline phosphatase (ALP), lipid profile, uric acid, protein carbonyl content, MDA, liver TNF-α, ferric-reducing antioxidant power, liver catalase, superoxide dismutase, vitamin C, and histopathological examination were done. In group 2, diclofenac caused a significant increase (p < .05) in the levels of serum ALP, GOT, GPT, TNF-α, uric acid, protein carbonyl content, MDA, and liver TNF-α gene expression as opposed to group 1. In treated groups with NAC and silymarin, a significant reduction (p < .05) was seen in all above mentioned parameters as well as improved liver histopathological changes compared with group 2. This study confirmed the protective effect of NAC on diclofenac-induced hepatotoxicity in rats due to not only reduces liver inflammatory cells, TNF-α, serum MDA, and PC but also through increases liver vitamin C, catalase, and superoxide dismutase activities.

Eigen value based loss function for training attractors in iterated autoencoders.

The way that the human brain handles the input variations has been one of the most interesting areas of research for neuroscientists. There are some evidences that the human brain acts like an attractor when trying to memorize or retrieve some information. Based on this fact, in this research, a new method is presented for creating attractors during training of an iterated autoencoder. In this method a new loss function is presented which decreases the absolute real of Eigen values while preserving the reconstruction error during training. A fully connected structure is chosen for constructing the iterated autoencoder in this research which mostly faces with local minima especially when they are deep. For getting through this issue, a layer-by-layer pre-training approach is taken to train the network. Using the evaluation on MNIST dataset, it is shown that the proposed model can retrieve 59.98% of test samples which shows a considerable improvement over Dense Associative Memory (DAM) when trained on 100 similar MNIST test samples. The performance of the proposed model is compared to overparameterized autoencoder (OAE) model which was recently presented and showed promising results in constructing associative memories. The results show that the proposed model outperforms OAE in terms of the number of attractors learned by the network in a similar number of network parameters. Finally, the performance of the proposed model is evaluated with corrupted version of training samples, revealing significant robustness when compared to the baseline autoencoder.

Factors that influence morningness-eveningness and daytime sleepiness: A cross-cultural comparison of Iranian and Brazilian adolescents.

As adolescents get older, they become more evening oriented and, because they are usually expected to wake early to attend school, they often present daytime sleepiness, which is associated with negative outcomes. It is still unclear if this is similar cross-culturally. Here, we studied morningness-eveningness and daytime sleepiness in early adolescence from two different developing nations (Brazil and Iran). A total sample of 697 Iranian and Brazilian early adolescents (9- to 15-year-old; 358 boys) from Tehran, Iran, and São Paulo, Brazil, varying in age and parental schooling (a proxy of socioeconomic status: SES) completed the Morningness-Eveningness Scale for Children (MESC) and the Pediatric Daytime Sleepiness Scale (PDSS) and reported their total sleep time on school nights. They also filled in the Pubertal Developmental Scale to determine their pubertal status. A negligible cross-cultural difference in morningness-eveningness was found, indicating that Brazilians showed a slight circadian-phase delay compared with Iranians throughout all tested ages. There was also seen a very slight increase in phase delay as early adolescents aged, indicative of more eveningness. However, there were no country differences in daytime sleepiness once total sleep time during school nights was controlled for, which was the only factor that affects PDSS scores.

Carvacrol Exerts Anti-Inflammatory, Anti-Oxidative Stress and Hepatoprotective Effects Against Diclofenac-Induced Liver Injury in Male Rats.

Background: Diclofenac (DIC) is an NSAID that can cause toxic effects in animals and humans and carvacrol (CAR) is a monoterpene compound that displays effective pharmacological and biological actions. The purpose of this work was to assess the influences of CAR on DIC-induced liver injury and oxidative stress in male rats. Methods: The male Wistar rats were segregated into four groups. Group 1, the control group; Group 2 received DIC-only (10 mg/kg BW, p.o); Group 3, received CAR-only (10 mg/kg BW, p.o), and group 4 received DIC plus CAR. The serum levels as well as the activity of several liver-associated markers, and oxidative and anti-oxidant compounds were tested. The expression of pro-inflammatory mediators was also studied using the qRT-PCR analysis. Results: Our results showed that DIC treatment was associated with the elevation in the serum levels of liver-related markers together with the increase in the serum and the hepatic levels of malondialdehyde (MDA) and protein carbonyl (PC). Moreover, DIC reduced the activity of the antioxidant system in the rats and increased lymphocyte infiltration into the hepatocytes. CAR; however, protected the hepatocytes from the toxic effects of DIC by enhancing the activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and Glutathione (GSH). By diminishing the expression of tumor necrosis factor (TNF)-α, CAR was also capable of preventing the inflammatory effects of DIC on liver cells. Conclusions: The findings of this study indicated that the administration of CAR could alleviate the noxious effects of DIC on the antioxidant defense system and liver tissue.

In vitro study of the differentiation of bone marrow stromal cells into cardiomyocyte-like cells.

Bone marrow multipotent stromal cells (BMSCs) have the ability to transdifferentiate into various cell types, including: osteoblasts, chondrocytes, adipocytes, neurons, and cardiomyocytes. This study aimed to differentiate the BMSCs into cardiomyocyte. BMSCs were exposed to 5-azacytidine for 24 h. Seven days after the induction of cell differentiation by 5-azacytidine, the cardiomyogenic cells were stained by fushin and binucleated cells were counted and compared with the neonate cardiomyocyte as positive control. In addition, immunofluorescence analysis and western blot were performed using the antibodies against α-actinin, desmin, troponin T, and ß-myosin heavy chain. Our results showed that there was no significant difference between the number of binucleated cells within the cardiomyogenic cell group and positive control group; however, a statistically significant difference was observed between both of these groups and undifferentiated cell group (P < 0.005). In addition, after 5-azacytidine treatment, BMSCs had a higher expression of cardiac-specific markers such as desmin, α-actinin, troponin T and ß-myosin heavy chain compared with the untreated groups (P < 0.005). We concluded that 5-azacytidine is an effective inducer for the differentiation of BMSCs into cardiomyocytes and could produce a population of binucleated cells, which express α-actinin, desmin, troponin T, and ß-myosin heavy chain, four markers of cardiomyocytes.

Anticoccidial and immunogenic effectivity of encapsulated organic acids and anticoccidial drugs in broilers infected with Eimeria spp.

The study was conducted to consider the anticoccidial and immunogenic effectivities of encapsulated organic acids and anticoccidial drugs in broilers reared on a reused litter infected with Eimeria spp. for simulating in-field exposure to avian coccidiosis. 525 mixed-sex one-day-old broiler chicks (Ross 308) were used in a 2 × 3 factorial experiment as a completely randomized design with seven experimental groups and five replicates of 15 chicks. The seven experimental groups were included: negative (uninfected; T1) and positive (infected; T2) control groups fed a diet without additive, and other infected groups (T3-T7) fed diets supplemented with 0.05% maduramicin, 0.02% diclazuril, 0.1% EOAs, 0.05% maduramicin and 0.1% EOAs, 0.02% diclazuril and 0.1% EOAs. During the experimental period, the evaluated parameters were European production efficiency factor (EPEF; at 22 days of age (d)), oocyst output per gram feces (OPG; at different ages), oocyst reduction rate (ORR; at 22-d), survival rate (SR; at 22-d), caecal lesion score (CLS at 22-d), sporulation percentage (SP; by in vitro anticoccidial tests), bloody diarrhea (BD; by scoring the bloody feces each morning from 13 to 31-d), immunity (humoral test at 28 and 35-d and cell-mediated test at 22-d), goblet cells analysis of the jejunum (GC; at 22-d) and anti-coccidiosis index (ACI; at 22-d). EOAs and anticoccidials, especially their simultaneous feeding improved (P < 0.05) broiler's EPEF, SR, OPG, ORR, SP, CLS, immunity and BD (scored). ACI was improved (P < 0.05) by EOAs more than anticoccidials (marked vs. moderate). The highest ACI was significantly observed in EOAs + diclazuril group. EOAs as a safe alternative had more intensive anticoccidial and immunogenic properties and increased the anticoccidial drugs' effectiveness, especially diclazuril in Eimeria spp-infected broilers.

An innovative inverse analysis based on the Bayesian inference for concrete material.

Nondestructive tests and evaluations are robust techniques for inspecting different attributes of concrete configuration. However, most nondestructive techniques focused on an aspect of concrete configuration based on comparison to other samples. In this paper, an innovative inverse analysis technique was developed to inspect different attributes of concrete configuration simultaneously. The methodology was based on the scattering feature of the ultrasonic waves during propagation in heterogeneous media. The transition matrix method was employed to determine the scattered wavefield. This method considers the shape of objects, unlike most other numerical methods. Furthermore, a novel algorithm was presented to establish a realistic space in three-dimensional for concrete. The Voronoi diagram and shrinking process established the framework of the algorithm. The inverse model conducted observation data from media to concrete configuration through the direct model. The inverse procedure extracted vast information from the medium. Statistical theory provided statistical inference based on Bayesian statistics for this procedure. The introduced inverse analysis technique then scrutinized the concrete specimens. For this aim, geopolymer concrete with different configurations was nominated as a sample of concrete material. In the end, the precision, accuracy, and validity of the inverse model solution were assayed in the light of statistics. The assessments demonstrated that the proposed method provided a comprehensive description of the overall concrete configuration.

Geriatric nutritional risk index in prediction of muscular strength of elderly patients undergoing hemodialysis.

PURPOSE: Geriatric nutritional risk index (GNRI) is one of the new tools to determine nutritional status in the elderly. This study assessed the association between GNRI and muscular strength through handgrip strength (HGS) in patients undergoing hemodialysis. METHODS: This cross-sectional analytical study assessed 110 hemodialysis patients at Guilan, North of Iran, (mean age of 70.3 ± 6.93), 57 men and 53 women through simple random sampling. Demographic characteristics, GNRI, and HGS of patients were determined. Data were analyzed using descriptive and inferential statistics, including independent t test, AVOVA, Pearson correlation, and linear multiple regression tests. RESULTS: The mean values of the GNRI and HGS were 93.90 ± 11.06 and 14.82 ± 3.72, respectively. Finally, it was identified that there is a direct and significant association between GNRI and HGS (p = 0.001, r = 0.734). Linear multiple regression showed that GNRI is an independent predictor of HGS (Adj.R2 = 0.67, ßGNRI = 8.13). CONCLUSION: GNRI can be used as a predictor of muscular strength in hemodialysis patients.