Up-regulation of inflammatory, oxidative stress, and apoptotic mediators via inflammatory, oxidative stress, and apoptosis-associated pathways in bovine endometritis.

Endometritis is the inflammation of the endothelial lining of the uterine lumen and is multifactorial in etiology. Escherichia (E.) coli is a Gram-negative bacteria, generally considered as a primary causative agent for bovine endometritis. Bovine endometritis is characterized by the activation of Toll-like receptors (TLRs) by E. coli, which in turn triggers inflammation, oxidative stress, and apoptosis. The objective of this study was to investigate the gene expression of inflammatory, oxidative stress, and apoptotic markers related to endometritis in the uteri of cows. Twenty uterine tissues were collected from the abattoir. Histologically, congestion, edema, hyperemia, and hemorrhagic lesions with massive infiltration of neutrophil and cell necrosis were detected markedly (P < 0.05) in infected uterine samples. Additionally, we identify E. coli using the ybbW gene (177 base pairs; E. coli-specific gene) from infected uterine samples. Moreover, qPCR and western blot results indicated that TLR2, TLR4, proinflammatory mediators, and apoptosis-mediated genes upregulated except Bcl-2, which is antiapoptotic, and there were downregulations of oxidative stress-related genes in the infected uterine tissue. The results of our study suggested that different gene expression regimes related to the immune system reflex were activated in infected uteri. This research gives a novel understanding of active immunological response in bovine endometritis.

Biochemical properties of sheep colostrum and its potential benefits for lamb survival: a review.

Colostrum is the initial secretion of the mammary glands following parturition, which offers main food, protection, and biological active substances for the new born. The most threatening episode of neonate's life is the initial two weeks after birth. This period is associated with high neonatal mortality and morbidity. These worthwhile losses lead to a poor prolificacy rate, low profitability, and ultimately poor performance in animal production. Hence, both diseases and mortality cause valuable losses in terms of production and economic losses. The survival of neonate is correlated with their immune status and passive immune transfer (PIT). Colostrum provides the primary source of nutrition and immunity (PIT) that protects neonates against infections. It must be given as soon as possible after birth since its immunoglobulins are absorbed within the first 16-27 hours after birth, ideally within 2-4 hours. As a result, immunoglobulin (PIT) is the most important component of distressing infectious immunity, and a passable concentration of immunoglobulin in the blood of newborn lambs is linked to their health and survival rate. In this review, we summarized the importance of colostrum in early life and its association with neonatal lamb's survival, profitability and productivity of sheep farming.

Safranal inhibits NLRP3 inflammasome activation by preventing ASC oligomerization.

NLRP3 inflammasome is involved in several chronic inflammatory diseases. The inflammatory effect of the NLRP3 inflammasome is executed through IL-1ß and IL-18. Therefore, IL-1ß is one of the primary targets in chronic inflammatory conditions. However, current treatment regimens are dependent on anti- IL-1ß biologicals. The therapies targeting IL-1ß through inhibition of NLRP3 inflammasome are thus being actively explored. We identified safranal, a small molecule responsible for the essence of saffron as a potential inhibitor of the NLRP3 inflammasome. Safranal significantly suppressed the release of IL-1ß from ATP stimulated J774A.1 and bone marrow-derived macrophages (BMDMs) by regulating CASP1 and CASP8 dependent cleavage of pro-IL-1ß. Safranal markedly suppressed the expression of NLRP3 and its ATPase activity. Safranal treatment enhanced the expression of NRF2, whereas, si-RNA mediated silencing of Nrf2 abrogated the anti-NLRP3 effect of safranal. Furthermore, safranal inhibited ASC oligomerization and formation of ASC specks. Safranal also displayed anti-NLRP3 activity in multiple mice models. Treatment of animals with safranal reduced the production of IL-1ß in ATP elicited peritoneal inflammation, MSU induced air pouch inflammation, and MSU injected foot paw edema in mice. Thus, our data projects safranal as a potential preclinical drug candidate against NLRP3 inflammasome triggered chronic inflammation.

Discovery of benzo[cd]indol-2-one and benzylidene-thiazolidine-2,4-dione as new classes of NLRP3 inflammasome inhibitors via ER-ß structure based virtual screening.

The structure-guided virtual screening (VS) has proved to be successful strategy in identification of new scaffolds for biological targets. The overactivity of NLRP3 inflammasome has been implicated in variety of inflammatory diseases including Alzheimer's disease. The up-regulation of estrogen-receptor ß (ER-ß) activity has been directly linked with inhibition of NLRP3 inflammasome activity. In the present study, we report discovery of new NLRP3 inflammasome inhibitors via ER-ß crystal structure (PDB: 5TOA) guided virtual screening of 20,000 compound library. For experimental validation, top 10 ligands were selected based on structure novelty, docking score, prime MMGB/SA binding affinity and interaction pattern analysis. Amongst the tested compounds, three thiazolidin-4-ones IIIM-1268, IIIM-1269 and IIIM-1270 and benzo[cd]indol-2-one IIIM-1266 have shown 73, 69, 75 and 77% suppression of IL-1ß release in mouse macrophages (J774A.1 cells) at 10 µM. Benzylidene-thiazolidine-2,4-diones IIIM-1268 and IIIM-1270 inhibited IL-1ß release with IC50 of 2.3 and 3.5 µM and also significantly decreased the protein expression level of mature form of IL-1ß in western-blot analysis. IIIM-1266 and IIIM-1270 displayed bidentate H-bonding with Arg 346 and Glu 305 residues in the active site of ER-ß; and they also strongly occupied the ADP-binding site of NLRP3 protein. The results presented herein, indicate that ER-ß guided VS can be successfully used to identify new NLRP3 inflammasome inhibitors, which may have potential in the development of novel anti-Alzheimer agents.

A quantitative and qualitative analysis of the COVID-19 pandemic model.

Global efforts around the world are focused on to discuss several health care strategies for minimizing the impact of the new coronavirus (COVID-19) on the community. As it is clear that this virus becomes a public health threat and spreading easily among individuals. Mathematical models with computational simulations are effective tools that help global efforts to estimate key transmission parameters and further improvements for controlling this disease. This is an infectious disease and can be modeled as a system of non-linear differential equations with reaction rates. This work reviews and develops some suggested models for the COVID-19 that can address important questions about global health care and suggest important notes. Then, we suggest an updated model that includes a system of differential equations with transmission parameters. Some key computational simulations and sensitivity analysis are investigated. Also, the local sensitivities for each model state concerning the model parameters are computed using three different techniques: non-normalizations, half normalizations, and full normalizations. Results based on the computational simulations show that the model dynamics are significantly changed for different key model parameters. Interestingly, we identify that transition rates between asymptomatic infected with both reported and unreported symptomatic infected individuals are very sensitive parameters concerning model variables in spreading this disease. This helps international efforts to reduce the number of infected individuals from the disease and to prevent the propagation of new coronavirus more widely on the community. Another novelty of this paper is the identification of the critical model parameters, which makes it easy to be used by biologists with less knowledge of mathematical modeling and also facilitates the improvement of the model for future development theoretically and practically.

Redox regulation of type-I inositol trisphosphate receptors in intact mammalian cells.

A sensitization of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release is associated with oxidative stress in multiple cell types. These effects are thought to be mediated by alterations in the redox state of critical thiols in the IP3R, but this has not been directly demonstrated in intact cells. Here, we utilized a combination of gel-shift assays with MPEG-maleimides and LC-MS/MS to monitor the redox state of recombinant IP3R1 expressed in HEK293 cells. We found that under basal conditions, ∼5 of the 60 cysteines are oxidized in IP3R1. Cell treatment with 50 µm thimerosal altered gel shifts, indicating oxidation of ∼20 cysteines. By contrast, the shifts induced by 0.5 mm H2O2 or other oxidants were much smaller. Monitoring of biotin-maleimide attachment to IP3R1 by LC-MS/MS with 71% coverage of the receptor sequence revealed modification of two cytosolic (Cys-292 and Cys-1415) and two intraluminal cysteines (Cys-2496 and Cys-2533) under basal conditions. The thimerosal treatment modified an additional eleven cysteines, but only three (Cys-206, Cys-767, and Cys-1459) were consistently oxidized in multiple experiments. H2O2 also oxidized Cys-206 and additionally oxidized two residues not modified by thimerosal (Cys-214 and Cys-1397). Potentiation of IP3R channel function by oxidants was measured with cysteine variants transfected into a HEK293 IP3R triple-knockout cell line, indicating that the functionally relevant redox-sensitive cysteines are predominantly clustered within the N-terminal suppressor domain of IP3R. To our knowledge, this study is the first that has used proteomic methods to assess the redox state of individual thiols in IP3R in intact cells.

Human Placenta Expresses α2-Adrenergic Receptors and May Be Implicated in Pathogenesis of Preeclampsia and Fetal Growth Restriction.

α2-Adrenergic receptors (α2ARs) are G-protein-coupled receptors involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. We examined placental expression and function of α2AR subtypes in women with severe preeclampsia (sPE) with and without intrauterine growth restriction (IUGR). Placental biopsies were analyzed from 52 women with i) sPE (n = 8); ii) sPE + IUGR (n = 9); iii) idiopathic IUGR (n = 8); iv) idiopathic preterm birth (n = 16); and v) healthy term controls (n = 11). Expression of α2AR subtypes (α2A, α2B, α2C) and phospho-ERK1/2 (receptor activation marker) was investigated by immunohistochemistry and/or quantitative real-time RT-PCR. The effects of α2CAR knockdown on syncytialization (syncytin-1 and -2) and ß-human chorionic gonadotropin secretion were examined in BeWo cells stimulated with forskolin. The effects of α2AR agonist UK 14,304 and specific α2CAR antagonist were tested, using a trophoblast migration assay. All three α2ARs were expressed and functionally active in human placenta with site-specific localization. Highest α2BAR and α2CAR mRNA expression was identified in sPE + IUGR. α2CAR knockdown increased expression of syncytin-1 and -2 but decreased secretion of ß-human chorionic gonadotropin. UK 14,304 impaired trophoblast migration. The observed α2AR expression pattern suggests different function for each subtype. α2CAR modulates trophoblast syncytialization and migration and may carry pathogenic role in sPE + IUGR.

Discovery of Quinazolin-4(3 H)-ones as NLRP3 Inflammasome Inhibitors: Computational Design, Metal-Free Synthesis, and in Vitro Biological Evaluation.

NLRP3 inflammasome is an important therapeutic target for a number of human diseases. Herein, computationally designed series of quinazolin-4(3 H)-ones were synthesized using iodine-catalyzed coupling of arylalkynes (or styrenes) with O-aminobenzamides. The key event in this transformation involves the oxidative cleavage of the C-C triple/double bond and the release of formaldehyde. The reaction relies on the C-N bond formation along with the C-C bond cleavage under metal-free conditions. The nitro-substituted quinazolin-4(3 H)-one 2k inhibited NLRP3 inflammasome (IC50 5 µM) via the suppression of IL-1ß release from ATP-stimulated J774A.1 cells.

Alterations in VASP phosphorylation and profilin1 and cofilin1 expression in hyperoxic lung injury and BPD.

BACKGROUND: Hyperoxia is a frequently employed therapy for prematurely born infants, induces lung injury and contributes to development of bronchopulmonary dysplasia (BPD). BPD is characterized by decreased cellular proliferation, cellular migration, and failure of injury repair systems. Actin binding proteins (ABPs) such as VASP, cofilin1, and profilin1 regulate cell proliferation and migration via modulation of actin dynamics. Lung mesenchymal stem cells (L-MSCs) initiate repair processes by proliferating, migrating, and localizing to sites of injury. These processes have not been extensively explored in hyperoxia induced lung injury and repair. METHODS: ABPs and CD146+ L-MSCs were analyzed by immunofluorescence in human lung autopsy tissues from infants with and without BPD and by western blot in lung tissue homogenates obtained from our murine model of newborn hyperoxic lung injury. RESULTS: Decreased F-actin content, ratio of VASPpS157/VASPpS239, and profilin 1 expression were observed in human lung tissues but this same pattern was not observed in lungs from hyperoxia-exposed newborn mice. Increases in cofilin1 expression were observed in both human and mouse tissues at 7d indicating a dysregulation in actin dynamics which may be related to altered growth. CD146 levels were elevated in human and newborn mice tissues (7d). CONCLUSION: Altered phosphorylation of VASP and expression of profilin 1 and cofilin 1 in human tissues indicate that the pathophysiology of BPD involves dysregulation of actin binding proteins. Lack of similar changes in a mouse model of hyperoxia exposure imply that disruption in actin binding protein expression may be linked to interventions or morbidities other than hyperoxia alone.

Effect of ambient management interventions on the production and physiological performance of lactating Sahiwal cattle during hot dry summer.

During summer season, increase in the environmental temperature in the subtropical regions of Pakistan is negatively affecting the performance of dairy animals. The study objective was to determine the effect of ambient management (90 days) on productive and physiological performance of lactating Sahiwal cows during hot dry summer season. Fifteen lactating cows during the early lactation stage, having similar parity (3), daily milk production (6.2 l), were randomly allocated to three treatments, 5 cows each, i.e., (1) kept under roof shade only, (2) provision of fans along with roof shade, and (3) provision of roof shade, fans, and sprinklers designated as S, SF, and SFS, respectively. The fans were of 360-rpm capacity and showers were on for 40 min after every 90-min interval from 9:00 to 21:00 h. THI values were 81.1 ± 0.7, 80.5 ± 0.7, and 77.7 ± 0.4 under S, SF, and SFS treatments, respectively. Cows were milked twice daily. Respiration rate (RR) and rectal temperature (RT) data were collected at 14:00 h on daily basis. The daily milk production was significantly higher in cows under SF (7.9 ± 1 kg) followed by SFS (6.9 ± 1.2 kg) and S (6.1 ± 0.9 kg) treatments. The mean RT (101.0 ± 0.04 °F) was significantly lower in cows under SFS than that on SF and S treatments and similarly mean RR was also lower (21.2 breaths/min) in cows under SFS followed by SF and S treatments. It is concluded that milk production and physiological performance in Sahiwal cows can be improved by fan-assisted ventilation during hot dry summer in subtropical regions.

DHA suppresses chronic apoptosis in the lung caused by perinatal inflammation.

We have previously shown that an adverse perinatal environment significantly alters lung growth and development and results in persistently altered cardiopulmonary physiology in adulthood. Our model of maternal LPS treatment followed by 14 days of neonatal hyperoxia exposure causes severe pulmonary disease characterized by permanent decreases in alveolarization and diffuse interstitial fibrosis. The current investigations tested the hypothesis that dysregulation of Notch signaling pathways contributes to the permanently altered lung phenotype in our model and that the improvements we have observed previously with maternal docosahexaenoic acid (DHA) supplementation are mediated through normalization of Notch-related protein expression. Results indicated that inflammation (IL-6 levels) and oxidation (F2a-isoprostanes) persisted through 8 wk of life in mice exposed to LPS/O2 perinatally. These changes were attenuated by maternal DHA supplementation. Modest but inconsistent differences were observed in Notch-pathway proteins Jagged 1, DLL 1, PEN2, and presenilin-2. We detected substantial increases in markers of apoptosis including PARP-1, APAF-1, caspase-9, BCL2, and HMGB1, and these increases were attenuated in mice that were nursed by DHA-supplemented dams during the perinatal period. Although Notch signaling is not significantly altered at 8 wk of age in mice with perinatal exposure to LPS/O2, our findings indicate that persistent apoptosis continues to occur at 8 wk of age. We speculate that ongoing apoptosis may contribute to persistently altered lung development and may further enhance susceptibility to additional pulmonary disease. Finally, we found that maternal DHA supplementation prevented sustained inflammation, oxidation, and apoptosis in our model.

Role of SM22 in the differential regulation of phasic vs. tonic smooth muscle.

Preliminary proteomics studies between tonic vs. phasic smooth muscles identified three distinct protein spots identified to be those of transgelin (SM22). The latter was found to be distinctly downregulated in the internal anal sphincter (IAS) vs. rectal smooth muscle (RSM) SMC. The major focus of the present studies was to examine the differential molecular control mechanisms by SM22 in the functionality of truly tonic smooth muscle of the IAS vs. the adjoining phasic smooth muscle of the RSM. We monitored SMC lengths before and after incubation with pFLAG-SM22 (for SM22 overexpression), and SM22 small-interfering RNA. pFLAG-SM22 caused concentration-dependent and significantly greater relaxation in the IAS vs. the RSM SMCs. Conversely, temporary silencing of SM22 caused contraction in both types of the SMCs. Further studies revealed a significant reverse relationship between the levels of SM22 phosphorylation and the amount of SM22-actin binding in the IAS and RSM SMC. Data showed higher phospho-SM22 levels and decreased SM22-actin binding in the IAS, and reverse to be the case in the RSM SMCs. Experiments determining the mechanism for SM22 phosphorylation in these smooth muscles revealed that Y-27632 (Rho kinase inhibitor) but not Gö-6850 (protein kinase C inhibitor) caused concentration-dependent decreased phosphorylation of SM22. We speculate that SM22 plays an important role in the regulation of basal tone via Rho kinase-induced phosphorylation of SM22.

Habb-e-Asgand, polyherbal Unani formulation, protects liver and antioxidative enzymes against paracetamol induced hepatotoxicity.

Abstract Context: Habb-e-Asgand, a polyherbal Homeopathy/Unani drug from Hamdard Wakf Laboratory, India, used in arthritis, gout and joint pain, is a mixture of many herbal medicinal plants. Scientific attempts to test and validate its efficacy are meager. Objective: To evaluate the hepatoprotective and antioxidative potential of Habb-e-Asgand against paracetamol toxicity. Materials and methods: Swiss albino male mice (n = 5/group) were treated with Habb-e-Asgand (250 mg/kg, body weight (b.w.) in normal saline orally for 14 days followed by a single dose of paracetamol (400 mg/kg b.w./normal saline) intraperitoneally 24 h before euthanization. We estimated liver function (LFTs) using diagnostic kits, while antioxidant enzymes, cytochrome P450 (CYP) and lipid peroxidation (LPO) were measured using spectrophotometric methods. Results: Paracetamol alone induced LFTs enzymes significantly (p < 0.05 and p < 0.01, 0.001), serum glutamate pyruvate transaminase (SGPT, ∼70%), serum glutamate oxaloacetate transaminase (SGOT, ∼20%), alkaline phosphatase (ALP, ∼20%), total bilirubin (∼30%), CYP activity (∼50%) and LPO (∼45%), while it significantly inhibited the activity of antioxidant enzymes glutathione reductase (GR, ∼35%), glutathione peroxidase (GPx, ∼40%), glutathione S-tranferase (GST, ∼16%), catalase (CAT, ∼84%) and glutathione (GSH, ∼30%) contents. Habb-e-Asgand alone and in combination of paracetamol significantly (p < 0.05, 0.01, 0.001) decreased LFT levels (20-25%), CYP activity (∼45%) and LPO level (∼25%), while it induced antioxidant enzyme activity (GR, ∼15%; GPx, ∼17%; GST, ∼20% and CAT, ∼60%). Discussion: Paracetamol metabolites may be mediating production of reactive oxidant species (ROS) and liver injury, which are attenuated by Habb-e-Asgand antioxidant constituents. Conclusion: Habb-e-Asgand may be used as a prophylaxis for ROS related liver injury.

Therapeutic administration of Luteolin protects against Escherichia coli-derived Lipopolysaccharide-triggered inflammatory response and oxidative injury.

Endometritis reduces reproductive effectiveness and leads to significant financial losses in the dairy sector. Luteolin is a natural phyto-flavonoid compound with many biological activities. However, the therapeutic effect of Luteolin against lipopolysaccharides (LPS)-induced endometritis has not yet been explored. A total of eighty female Kunming mice were randomly assigned into four treatment groups (n = 20). Following a successful initiation of the endometritis model by LPS, Luteolin was intraperitoneally administered three times, at six-hour intervals between each injection in the Luteolin groups. The histopathological findings revealed that Luteolin significantly alleviated uterine injury induced by LPS. Moreover, Luteolin suppressed the synthesis of pro-inflammatory mediators [interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α] while promoting the synthesis of an anti-inflammatory mediator (IL-10) altered by LPS. Furthermore, Luteolin significantly mitigated the LPS-induced oxidative stress by scavenging malondialdehyde (MDA) and reactive oxygen species (ROS), accumulation and boosting the capacity of antioxidant enzyme activities such as superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (Gpx1) in the uterine tissue of mice. Additionally, injection of Luteolin markedly increased the expression of Toll-like receptors (TLR) 4 both at mRNA and protein levels under LPS stimulation. Western blotting and ELISA findings demonstrated that Luteolin suppressed the activation of the NF-κB pathway in response to LPS exposure in the uterine tissue of mice. Notably, Luteolin enhanced the anti-oxidant defense system by activating the Nrf2 signaling pathway under LPS exposure in the uterine tissue of mice. Conclusively, our findings demonstrated that Luteolin effectively alleviated LPS-induced endometritis via modulation of TLR4-associated Nrf2 and NF-κB signaling pathways.

Melting heat transfer analysis in magnetized bioconvection flow of sutterby nanoliquid conveying gyrotactic microorganisms.

In biotechnology and biosensors bioconvection along with microorganisms play a important role. This article communicates a theoretic numerical analysis concerning the bioconvective Sutterby nanofluid flow over a stretchable wedge surface. Bioconvection is a remarkable occurrence of undercurrents fluid that is produced owing to the turning of microbes. It is considered for hydrodynamics unsteadiness and forms classified in interruption of inclined swimming microbes. Bioconvection is perceived practically in many uses for example pharmaceutical products, bio sensing applications, biomedical, bio-micro systems, biotechnology advancements and refining of mathematical models. Additionally, unsteady parameter influences are taken into account. Furthermore, no mass flux as well as heat sink/source consequences are measured in existing analysis. The similarity transformation are established for the non-linear PDEs of microorganism's field, nanofluid concentration, energy, momentum and mass for bioconvection flow of Sutterby nanofluid. Then, altered non-linear ODEs are resolved by utilizing the bvp4c technique. Moreover, nanofluids are declining in thermal and concentration fields and the greater number of Peclet number declines the field of microorganisms. Acquired numerical data displays that temperature field of nanofluid increases for more thermophoretic and unsteady parameters.

Comparative Antihyperglycemic and Antihyperlipidemic Effects of Lawsone Methyl Ether and Lawsone in Nicotinamide-Streptozotocin-Induced Diabetic Rats.

Our previous study uncovered potent inhibitory effects of two naphthoquinones from Impatiens balsamina, namely lawsone methyl ether (2-methoxy-1,4-naphthoquinone, LME) and lawsone (2-hydroxy-1,4-naphthoquinone), against α-glucosidase. This gave us the insight to compare the hypoglycemic and hypolipidemic effects of LME and lawsone in high-fat/high-fructose-diet- and nicotinamide-streptozotocin-induced diabetic rats for 28 days. LME and lawsone at the doses of 15, 30, and 45 mg/kg, respectively, produced a substantial and dose-dependent reduction in the levels of fasting blood glucose (FBG), HbA1c, and food/water intake while boosting the insulin levels and body weights of diabetic rats. Additionally, the levels of total cholesterol (TC), triglycerides (TGs), high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), aspartate transaminase (AST), alanine transaminase (ALT), creatinine, and blood urea nitrogen (BUN) in diabetic rats were significantly normalized by LME and lawsone, without affecting the normal rats. LME at a dose of 45 mg/kg exhibited the most potent antihyperglycemic and antihyperlipidemic effects, which were significantly comparable to glibenclamide but higher than those of lawsone. Furthermore, the toxicity evaluation indicated that both naphthoquinones were entirely safe for use in rodent models at doses ≤ 50 mg/kg. Therefore, the remarkable antihyperglycemic and antihyperlipidemic potentials of LME make it a promising option for future drug development.

Combinatorial Effect of Arsenic and Herbal Compounds in Telomerase-Mediated Apoptosis Induction in Liver Cancer.

Tumour illness and its resistance against existing anticancer therapies pose a serious health concern globally despite the progressive advancement of therapeutic options. The prevailing treatment of HCC using numerous antitumor agents has inflated long-lived complete remissions, but a percentage of individuals still die due to disease recurrence, indicating a need for further exploration of possible anti-tumour regimes. We aim to boost the effectiveness of the HCC treatment by conducting current investigations evaluating the effect of arsenic trioxide (ATO) with different herbal compounds like quercetin and aloe-emodin against liver tumour via inhibition of telomerase, a pro-cancer enzyme. The anticancer activity of ATO with herbal compounds was investigated in human control liver cell line (Wrl-68) and cancer liver cell line (HepG2) at different time intervals. Viability and cytotoxicity in response to combinatorial drugs were assessed in vitro by trypan blue dye exclusion assay and MTT and WST assay. Apoptosis was analysed by annexin V/PI assay, and the expression of telomerase and apoptosis-regulating proteins was evaluated by immunoblotting and qRT-PCR. Arsenic trioxide in combination with quercetin and aloe-emodin reduced cell viability in cancerous cells compared to normal cells by inducing apoptosis, downregulating telomerase and Bcl-2 (anti-apoptotic protein) and upregulating the expression of Bax (pro-apoptotic protein). ATO exhibited significant anticancer effects due to the synergistic effects of quercetin and aloe-emodin in liver tumour cells. The current study data collectively suggest that a successful inhibition of cancer growth by the combination of ATO and tested herbal medicines against liver tumour growth is via the inhibition of telomerase activity.

Innovation modeling and simulation of thermal convective on cross nanofluid flow over exponentially stretchable surface.

This work reported to investigate convective flow of non-Newtonian fluid effect on an exponentially stretchable surface. Effect of nanoparticle is considered in heat and mass equation. The transformation technique utilized on dimensionless equations is converted to non-dimensionless equations are solved thought numerical approach Bvp4c. Influence of approatiate analysis of velocities, heat and mass transport are scrutinized through figures. Furthermore, the comparative analysis of drag forces, Nusselt number and Sherwood number are evaluated over and done with tabulated values. It is give details that the temperature field strengthens with intensification in thermophoresis and random diffusions. Similarly, rises in thermophoresis effect parameter both temperature and concentration profile increasing.

Ameliorative Effects of Luteolin and Activated Charcoal on Growth Performance, Immunity Function, and Antioxidant Capacity in Broiler Chickens Exposed to Deoxynivalenol.

Deoxynivalenol (DON, Vomitoxin) is a threatening mycotoxin that mainly produces oxidative stress and leads to hepatotoxicity in poultry. Antioxidant dietary supplements dramatically boost immunity, safeguarding animals from DON poisoning. Luteolin (LUT) is an active plant-derived compound that poses influential antioxidants. This study explored the effectiveness of LUT in combination with activated charcoal (AC) in detoxifying DON in broilers. The 180 one-day broiler chickens were allocated into five different groups having six replicates in each group, provided with ad libitum feed during the trial period (28 days) as follows: in the control group, basal diet (feed with no supplementation of LUT, AC or DON); in group 2, a basal diet added with 10 mg/kg DON from contaminated culture (DON); in group 3, a basal diet augmented by 350 mg/kg LUT and DON 10 mg/kg (DON + LUT); in group 4, a basal diet supplemented by DON 10 mg/kg + AC 200 mg/kg (DON + AC); and in group 5, a basal diet supplemented by 10 mg/kg DON + 350 mg/kg LUT + 200 mg/kg AC (DON + LUT + AC). Concerning the control group, the DON-treated broilers demonstrated a significant decrease in growth performance (p < 0.05) and serum immunoglobulin (p < 0.05) contents, negatively changing the serum biochemical contents and enzymatic activities and an increase in histopathological liver lesions. Furthermore, DON substantially increased (p < 0.05) malondialdehyde (MDA) concentration and decreased total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the serum and liver. The intake of AC and LUT to the DON-contaminated diet decreased DON residue in the liver and potentially reduced the adverse effects of DON. Considering the results, supplementation of LUT with mycotoxin adsorbent has protective effects against mycotoxicosis caused by DON. It could be helpful for the development of novel treatments to combat liver diseases in poultry birds. Our findings may provide important information for applying LUT and AC in poultry production.

Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers.

BACKGROUND: Suppressor of fused (SuFu) is a tumor-suppressor gene that regulates hedgehog signaling. Its involvement in some malignancies is broadly accepted. However, its association with colorectal cancer (CRC) pathogenesis is not clear. Likewise, no study has clearly associated blood-based inflammatory biomarkers with cancer diagnosis/prognosis as yet. AIM: Our goal was to look at SuFu expression levels in CRC patients and its relationship with other clinicopathological factors. Additionally, we looked into the function of a few blood-based biomarkers in CRC and whether or not a combined strategy at the genetic and clinical levels can be applied in CRC. METHODS: The investigation included 98 histopathologically confirmed CRC samples and adjacent normal tissues (controls). A colonoscopy was followed by a targeted biopsy for each suspected colon cancer patient. A CT scan and MRI were also performed on every patient with rectal cancer. Real-time polymerase chain reaction and immunohistochemistry (IHC) were used for assessment. A Beckman Coulter DxH900 was used to examine blood parameters. A Beckman Coulter DxI800 was used to identify pretreatment carcinoma embryonic antigens (CEA) and carbohydrate antigens (CA 19-9) in CRC patients. RESULTS: The expression of SuFu was associated with gender, education, passive smoking, tumor grade, perineural invasion (PNI), lymph node metastasis (LNM), node status, stage, vital status, and recurrence (p < 0.05). In the combined analysis, the areas under the curve produced by the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW) were the greatest (AUCRDW+PLR+NLR = 0.91, 95% CI: 0.86-0.93, p < 0.05). Furthermore, the most severe pathological features were linked to RDW, PLR, NLR, and HPR. SuFu expression, node status, LNM, PNI, and stage all had significant correlations with OS and DFS rates in IHC-based univariate survival analysis (p < 0.05). According to the Cox regression, CA-19.9 had a strong independent predictive link with 3-year DFS (p < 0.05). CONCLUSION: In CRC, SuFu was downregulated both transcriptionally and translationally, was primarily nucleo-cytoplasmic, and was expressed less in high-grade tumors. In addition, SuFu was linked to a poor overall and disease-free survival rate. It may be possible to use SuFu as a therapeutic target for CRC in the future. However, SuFu expression had no effect on RDW, PLR, NLR, or HPR serum levels.