Regulatory effect of Balanites aegyptiaca ethanol extract on oxidant/antioxidant status, inflammatory cytokines, and cell apoptosis gene expression in goat abomasum experimentally infected with Haemonchus Contortus.

This experiment aimed to assess the regulatory effects of treatment with Balanites aegyptiaca fruit ethanol extract (BA-EE) on oxidant/antioxidant status, anti-inflammatory cytokines, and cell apoptosis gene expression in the abomasum of Haemonchus contortus-infected goats. Twenty goat kids were assigned randomly to four equal groups: (G1) infected-untreated, (G2) uninfected-BA-EE-treated, (G3) infected-albendazole-treated, (G4) infected-BA-EE-treated. Each goat in (G1), (G3), and (G4) was orally infected with 10,000 infective third-stage larvae. In the fifth week postinfection, single doses of albendazole (5 mg/kg.BW) and BA-EE (9 g/kg.BW) were given orally. In the ninth week postinfection, the animals were slaughtered to obtain abomasum specimens. The following oxidant/antioxidant markers were determined: malondialdehyde (MDA), glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT). The mRNA gene expression of cytokines (IL-3, IL-6, IL-10, TNF-α) and cell apoptosis markers (Bax, Bcl-2) were estimated. (G1) showed significantly reduced GSH content and GST and SOD activities but a markedly increased MDA level. (G3) and (G4) revealed a markedly lower MDA level with pronouncedly elevated GSH, SOD, and GST levels. The antioxidant properties of BA-EE were superior to those of albendazole. The mRNA gene expressions of IL-3, IL-6, IL-10, TNF-α, and Bax-2 were upregulated in (G1) but downregulated in (G3) and (G4). Bcl-2 and Bcl-2/Bax ratio expression followed a reverse course in the infected and both treated groups. We conclude that BA-EE treatment has a protective role in the abomasum of H. contortus-infected goats. This could be attributed to its antioxidant properties and ability to reduce pro-inflammatory cytokines and cell apoptosis.

Beneficial effects of antioxidants in improving health conditions of sheep infected with foot-and-mouth disease.

The effect of multinutrient antioxidant treatment on sheep naturally infected with FMD virus was investigated in terms of general health conditions, serum proteins profile, and antioxidant/oxidant parameters. Twenty diseased sheep were divided into 4 equal groups (n = 5) and underwent certain therapeutic protocols for 8 weeks as follows: GI, infected not treated group; GII, infected and treated with the ideal and usual line of treatment against FMD virus infection; GIII, infected animals supplemented orally zinc methionine at a dose of 5 g/head/day and vitamin E with selenium-enriched yeast at the same dose level; GIV, infected animals received both the ideal treatment and antioxidants. The animals under experiment were clinically evaluated. Blood samples were obtained for the comet assay and biochemical examination at zero time and at the 8th week after treatment. Results revealed that DNA damage reduced in both GIII and GIV groups which received antioxidants. In the GI group, the activity of SOD and GPx and the level of total antioxidant capacity (TAC) markedly decreased. However, in both GIII and GIV groups treated with multinutrient antioxidants, GPx and TAC values significantly increased after treatment in comparison with the values of the same groups before treatment. After treatment with multinutrient antioxidants, α1-, ß-, and γ-globulins levels markedly increased in GII and GIII groups while α2-globulin level decreased. The improvement in healing of clinical signs and general health conditions was clear in the GIV group. Finally, FMD infection in sheep was found to be associated with oxidative stress. The use of antioxidants as therapeutic approaches recovers and improves general health conditions and performance of affected animals.

Novel wideband MIMO antennas that can cover the whole LTE spectrum in handsets and portable computers.

A dual resonant antenna configuration is developed for multistandard multifunction mobile handsets and portable computers. Only two wideband resonant antennas can cover most of the LTE spectrums in portable communication equipment. The bandwidth that can be covered by each antenna exceeds 70% without using any matching or tuning circuits, with efficiencies that reach 80%. Thus, a dual configuration of them is capable of covering up to 39 LTE (4G) bands besides the existing 2G and 3G bands. 2×2 MIMO configurations have been also developed for the two wideband antennas with a maximum isolation and a minimum correlation coefficient between the primary and the diversity antennas.

Yield and Energy Modeling for Biochar and Bio-Oil Using Pyrolysis Temperature and Biomass Constituents.

Pyrolysis offers a sustainable and efficient approach to resource utilization and waste management, transforming organic materials into valuable products. The quality and distribution of the pyrolysis products highly depend on the constituents' properties and set process parameters. This research aims to investigate and model this dependency, offering decision-makers a tool to guide them when designing the process for a particular application. Experimental data on the pyrolysis of various types of feedstocks processed at a wide range of pyrolysis temperatures (350-650 °C) are utilized to develop the prediction models. Four variables are modeled: the yield and energy content for both the biochar and bio-oil as a function of the pyrolysis temperature and feedstock characteristics. The models developed had very good prediction power with the coefficient of determination above 90%. The results highlight the advantages of food waste (leftover) as a suitable feedstock to produce biochar at the pyrolysis temperature within the range of 450-550 °C. Furthermore, the biofuels produced from food waste are found to be of good quality, with the bio-oil exceptionally high in energy content (HHV = 34.6 MJ/kg), which is almost 80% of that of diesel. The developed models provide a tool for predicting the biofuel yield and quality based on the feedstock selection and process temperature.

Fluid based sandwich panel core structure for blast load mitigation.

Researchers have extensively explored various approaches to enhance the blast resistance of structures, concentrating on optimizing structural designs and employing a wide range of materials. This research investigates the impact of incorporating water as a fluid within the core of tubular sandwich panels on blast mitigation effectiveness. The study systematically analyzes various panel configurations by altering key design parameters: the thickness of the face sheets, spacing between the core elements, and proportion of fluid within the core. These variables are scrutinized through metrics such as elastic strain energy, the amount of work applied externally, and the movement of the panel. Utilizing finite element analysis, 27 distinct numerical experiments were conducted to gather data. The findings demonstrate that panels with a water-filled core exhibit superior blast resistance compared to their non-fluid counterparts. Specifically, panels with completely filled cores showed the lowest levels of panel displacement and external work, whereas those with half-filled cores recorded the highest elastic strain energy. Furthermore, regression analysis revealed that plate thickness predominantly influences panel displacement and external work, whereas the fluid volume fraction within the core most significantly affects elastic strain energy. This study contributes to the understanding of fluid-structure interactions in blast-resistant design, offering valuable insights for optimizing structural defenses against blast impacts.

Alirocumab boosts antioxidant status and halts inflammation in rat model of sepsis-induced nephrotoxicity via modulation of Nrf2/HO-1, PCSK9/HMGB1/NF-ᴋB/NLRP3 and Fractalkine/CX3CR1 hubs.

Acute kidney injury (AKI) is a devastating consequence of sepsis, accompanied by high mortality rates. It was suggested that inflammatory pathways are closely linked to the pathogenesis of lipopolysaccharide (LPS)-induced AKI. Inflammatory signaling, including PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-κB, NLRP3/caspase-1 and Fractalkine/CX3CR1 are considered major forerunners in this link. Alirocumab, PCSK9 inhibitor, with remarkable anti-inflammatory features. Accordingly, this study aimed to elucidate the antibacterial effect of alirocumab against E. coli in vitro. Additionally, evaluation of the potential nephroprotective effects of alirocumab against LPS-induced AKI in rats, highlighting the potential underlying mechanisms involved in these beneficial actions. Thirty-six adult male Wistar rats were assorted into three groups (n=12). Group I; was a normal control group, whereas sepsis-mediated AKI was induced in groups II and III through single-dose intraperitoneal injection of LPS on day 16. In group III, animals were given alirocumab. The results revealed that LPS-induced AKI was mitigated by alirocumab, evidenced by amelioration in renal function tests (creatinine, cystatin C, KIM-1, and NGAL); oxidative stress biomarkers (Nrf2, HO-1, TAC, and MDA); apoptotic markers and renal histopathological findings. Besides, alirocumab pronouncedly hindered LPS-mediated inflammatory response, confirmed by diminishing HMGB1, TNF-α, IL-1ß, and caspase-1 contents; the gene expression of PCSK9, RAGE, NF-ᴋB and Fractalkine/CX3CR1, along with mRNA expression of TLR4, MYD88, and NLRP3. Regarding the antibacterial actions, results showed that alirocumab displayed potential anti-bacterial activity against pathogenic gram-negative E. coli. In conclusion, alirocumab elicited nephroprotective activities against LPS-induced AKI via modulation of Nrf2/HO-1, PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-ᴋB/NLRP3/Caspase-1, Fractalkine/CX3R1 and apoptotic axes.

The potential role of Tirzepatide as adjuvant therapy in countering colistin-induced nephro and neurotoxicity in rats via modulation of PI3K/p-Akt/GSK3-ß/NF-kB p65 hub, shielding against oxidative and endoplasmic reticulum stress, and activation of p-CREB/BDNF/TrkB cascade.

Although colistin has a crucial antibacterial activity in treating multidrug-resistant gram-negative bacteria strains; it exhibited renal and neuronal toxicities rendering its use a challenge. Previous studies investigated the incretin hormones either glucose-dependent insulinotropic polypeptide (GIP) or glucagonlike peptide-1 (GLP-1) for their neuroprotective and nephroprotective effectiveness. The present study focused on investigating Tirzepatide (Tirze), a dual GLP-1/GIP agonist, as an adjuvant therapy in the colistin treatment protocol for attenuating its renal and neuronal complications. Rats were divided into; The normal control group, the colistin-treated group received colistin (300,000 IU/kg/day for 7 days; i.p.). The Tirze-treated group received Tirze (1.35 mg/kg on the 1,4,7thdays; s.c.) and daily colistin. Tirze effectively enhanced histopathological alterations, renal function parameters, and locomotor activity in rats. Tirze mechanistically acted via modulating various signaling axes evolved under the insult of phosphatidylinositol 3-kinases (PI3K)/phosphorylated protein kinase-B (p-Akt)/ glycogen synthase kinase (GSK)3-ß hub causing mitigation of nuclear factor (NF)-κB (NF-κB) / tumor necrosis factor-α (TNF-α), increment of nuclear factor erythroid 2-related factor 2 (Nrf2)/ glutathione (GSH), downregulation of ER stress-related biomarkers (activation transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP)), antiapoptotic effects coupling with reduction of glial fibrillary acidic protein (GFAP) immunoreactivity and enhancement of phosphorylated c-AMP response element-binding (p-CREB) / brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) neuroprotective pathway. Briefly, Tirze exerts a promising role as adjuvant therapy in the colistin treatment protocol for protection against colistin's nephro- and neurotoxicity according to its anti-inflammatory, antioxidant, and antiapoptotic impacts besides its ability to suppress ER stress-related biomarkers.

Speciation, phytoavailability, and accumulation of toxic elements and sulfur by humic acid-fertilized lemongrass and common sage in a sandy soil treated with heavy oil fly ash: A trial for management of power stations wastes.

Globally, power stations generate huge amounts of the hazardous waste heavy oil fly ash (HOFA), which is rich in Ni, V, Fe, S, and dumped into landfills. Thus, exploring new approaches for a safe recycling and sustainable management of HOFA is needed and of great environmental interest. The potential application of HOFA as an amendment to sandy soils has not been studied yet. This is the first research investigating the potentiality of using HOFA as a soil conditioner. To this end, we conducted a greenhouse experiment in order to investigate the impacts of HOFA addition (1.2, 2.4, 3.6 t ha-1) to sandy soil on the total and available content of nutrients (e.g., S, Fe, Mn, Cu, Zn) and toxic elements (TEs; e.g., Cd, Co, Cr, Ni, Pb, V) in the soil and their phytoextraction and translocation by lemongrass (Cymbopogon citratus) and common sage (Salvia officinalis). We also assessed the impact of humic acid (HA) foliar application (50 and 100 l ha-1) on the growth and elements accumulation by the two plants. The studied HOFA was acidic and highly enriched in S (43,268.0), V (3,527.0), Ni (1774.0), and Fe (15,159.0) (units in mg kg-1). The X-ray absorption near edge structure (XANES) data showed that V in HOFA was composed primarily of V(IV) sorbed onto goethite, V(V) sorbed onto humic substances, in the forms of V2O3, and VCl4. Addition of the lower doses of HOFA (1.2 and 2.4 t ha-1) did not change significantly soil pH, salinity, and the total and available elements content compared to the unamended soil. Although the elements content in the 3.6 t ha-1 HOFA-treated soil was significantly higher than the untreated, the total content of all elements (except for Ni) was lower than the maximum allowable concentrations in soils. HOFA addition, particularly in the highest dose (3.6 t ha-1), decreased significantly the growth and biomass of both plants. Common sage accumulated more elements than lemongrass; however, the elements content in the plants was lower than the critical concentrations for sensitive plants. The foliar application of humic acid enhanced significantly the plant growth and increased their tolerance to the HOFA-induced stress. We conclude that the addition of HOFA up to 2.4 t ha-1 in a single application as amendment to sandy soils is not likely to create any TE toxicity problems to plants, particularly if combined with a foliar application of humic acid; however, repeated additions of HOFA may induce toxicity. These findings should be verified under field conditions.

Apium extract alleviates indomethacin-induced gastric ulcers in rats via modulating the VEGF and IK-κB/NF-κB p65 signaling pathway: insights from in silico and in vivo investigations.

BACKGROUND: Gastric ulcers represent a worldwide health problem, characterized by erosions that affect the mucous membrane of the stomach and may even reach the muscular layer, leading to serious complications. Numerous natural products have been assessed as anti-ulcerogenic agents, and have been considered as new approaches for treatment or prevention of gastric ulcers. The present research investigated the preventive benefits of Apium graveolens L. (Apiaceae), known as celery, seed extract towards indomethacin-induced ulceration of the stomach in rats. METHODS: Metabolomic profiling, employing liquid chromatography coupled to high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), was implemented with the aim of investigating the chemical profile of the seeds. Histopathological analysis of gastric tissues, as well as assessment of numerous inflammatory cytokines and oxidative stress indicators, confirmed the in vivo evaluation. RESULTS: The prior treatment with A. graveolens seed extract resulted in a substantial reduction in the ulcer index when compared to the indomethacin group, indicating an improvement in stomach mucosal injury. Moreover, the gastroprotective effect was demonstrated through examination of the oxidative stress biomarkers which was significantly attenuated upon pre-treatment with A. graveolens seed extract. Vascular endothelial growth factor (VEGF), a fundamental angiogenic factor that stimulates angiogenesis, was markedly inhibited by indomethacin. A. graveolens seed extract restored this diminished level of VEGF. The dramatic reductions in NF-κB protein levels indicate a considerable attenuation of the indomethacin-induced IKκB/NF-κB p65 signaling cascade. These activities were also correlated to the tentatively featured secondary metabolites including, phenolic acids, coumarins and flavonoids, previously evidenced to exert potent anti-inflammatory and antioxidant activities. According to our network pharmacology study, the identified metabolites annotated 379 unique genes, among which only 17 genes were related to gastric ulcer. The PTGS2, MMP2 and PTGS1 were the top annotated genes related to gastric ulcer. The top biological pathway was the VEGF signaling pathway. CONCLUSION: A. graveolens seed extract possesses significant anti-ulcer activity, similar to famotidine, against gastric lesions induced by indomethacin in rats. It is worth highlighting that the extract overcomes the negative effects of conventional chemical anti-secretory drugs because it does not lower stomach acidity.

Medical prospects of cryptosporidiosis in vivo control using biofabricated nanoparticles loaded with Cinnamomum camphora extracts by Ulva fasciata.

Background and Aim: Global efforts are continuing to develop preparations against cryptosporidiosis. This study aimed to investigate the efficacy of biosynthesized Ulva fasciata loading Cinnamomum camphora oil extract on new zinc oxide nanoparticles (ZnONPs shorten to ZnNPs) and silver nanoparticles (AgNPs) as alternative treatments for Cryptosporidium parvum experimental infection in rats. Materials and Methods: Oil extract was characterized by gas chromatography-mass spectrometry, loaded by U. fasciata on ionic-based ZnO and NPs, and then characterized by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. Biosafety and toxicity were investigated by skin tests. A total of 105 C. parvum oocysts/rat were used (n = 81, 2-3 W, 80-120 g, 9 male rats/group). Oocysts shedding was counted for 21 d. Doses of each preparation in addition to reference drug were administered daily for 7 d, starting on post-infection (PI) day (3). Nitazoxanide (100 mg) was used as the reference drug. After 3 weeks, the rats were sacrificed for postmortem examination and histopathological examination. Two blood samples/rat/group were collected on the 21st day. Ethylenediaminetetraacetic acid blood samples were also used for analysis of biochemistry, hematology, immunology, micronucleus prevalence, and chromosomal abnormalities. Results: C. camphora leaves yielded 28.5 ± 0.3 g/kg oil and 20 phycocompounds were identified. Spherical and rod-shaped particles were detected at 10.47-30.98 nm and 18.83-38.39 nm, respectively. ZnNPs showed the earliest anti-cryptosporidiosis effect during 7-17 d PI. Other hematological, biochemical, immunological, histological, and genotoxicity parameters were significantly fruitful; hence, normalized pathological changes induced by infestation were observed in the NPs treatments groups against the infestation-free and Nitazoxanide treated group. Conclusion: C. camphora, U. fasciata, ZnNPs, and AgNPs have refluxed the pathological effects of infection as well as positively improved host physiological condition by its anticryptosporidial immunostimulant regenerative effects with sufficient ecofriendly properties to be proposed as an alternative to traditional drugs, especially in individuals with medical reactions against chemical commercial drugs.

Corona disease anxiety and health related behaviors: What happened to primgravida women post COVID-19?

Background: The COVID-19 pandemic has sparked psychological and behavioural changes among pregnant women across the globe and thereby might have a devastating impact on the fetal and neonatal outcomes. The dearth of information related to this significant topic can contribute to surge feelings of uneasiness and perinatal anxiety of primigravida women. Therefore, assessing and investigating the relationship between corona disease anxiety and health related behaviors among primigravida women post COVID-19, would provide an auxiliary template to the Ministry of health in the Middle East and North Africa (MENA) region to integrate this into their sustainable health agenda. Methods: A descriptive correlational research design was used in this study in which a convenient sample of 200 primigravida women completed a Corona disease anxiety scale (CDAS) and pregnant women's health- related behavior changes post COVID-19. Results: More than four fifth of the study subjects reported mild anxiety level (82%) and nearly three fifth of the studied primigravidas' reported fair level of health-related behaviors (59%). Also, a statistical significant correlation was found between the studied primigravidas' anxiety level and their health-related behavior including; healthy diet regimen, follow up visits, and protective personal measures (r = 0.273, P<0.001, r = 0.188, P<0.008, r = 0.242, P<0.001, r = 0.189, P<0.007, r = 0.407, P<0.001 and r = 0.309, P<0.001, respectively). Conclusion: Corona disease anxiety was proved to be the independent predictor of health- related behavior. Mental health screening of primigravida women at the outset of any public health emergency should be prompted.

CD4/CD8 Ratio could be predictor of burden hepatocellular carcinoma in Egyptian chronic hepatitis C after combined sofosbuvir and daclatasvir therapy.

Background: During the first years of the use of direct acting Hepatitis C antiviral drugs (DAAS), several studies reported a possible correlation between this new era of treatment and an increased risk of Hepatocellular carcinoma (HCC). Its development could possibly be favored by the changes in the immunological milieu and the different cellular behavior after eradication of HCV infection with them. For this reason, this study aimed to address the immunological effect of DAAS. Subject & methods: Prospective paired -sample design, carried out on 90 naïve chronically infected HCV patients before and after receiving a combination therapy of sofosbuvir; at a dose of 400 mg once daily and daclatasvir; at a dose of 60 mg once daily for 12 weeks and follow up for one year. immunological tests including: total T cell count, T helper cell count, T cytotoxic cell count and natural killer cell count in peripheral blood through (CD3, CD3/CD4, CD3/CD8 and CD56 respectively) by Fluorochrome monoclonal antibodies labelled with specific dyes through Multiparameter, FACSCanto ™ II flow cytometer (Becton Dickinson, USA). Result: Concerning the immunological changes, total T cells (CD3+), Natural killer cells showed non-significant decrease at end of therapy while significant decrease in T helper cells (CD3+CD4+) T cytotoxic cells (CD3+CD8+) compared to pre-treatment value. Long follow up revealed 26.6% developed focal HCC, in more addition, multivariate analysis show CD4/CD8 ratio could be predictor as well as sex for early development of HCC after combined DAAS therapy. Conclusion: HCV treatment by DAAS produces significant decrease in T helper, T cytotoxic cells in CHC patients at the end of therapy. 26.6% developed focal HCC with independent CD4/CD8 predictor for burden malignancy. Further large extended population study is needed for clarify this concern.

Infodemic Insights on Trust in a Health Emergency: A Narrative Deep-Dive.

Trust in authorities is important during health emergencies, and there are many factors that influence this. The infodemic has resulted in overwhelming amounts of information being shared on digital media during the COVID-19 pandemic, and this research looked at trust-related narratives during a one-year period. We identified three key findings related to trust and distrust narratives, and a country-level comparison showed less mistrust narratives in a country with a higher level of trust in government. Trust is a complex construct and the findings of this study present results that warrant further exploration.

Formoterol attenuated mitochondrial dysfunction in rotenone-induced Parkinson's disease in a rat model: Role of PINK-1/PARKIN and PI3K/Akt/CREB/BDNF/TrKB axis.

ß2-adrenoreceptors (ß2AR have been identified recently as regulators of the α-synuclein gene (SNCA), one of the key milieus endorsed in injury of dopamine neurons in Parkinson's disease (PD). Accumulation of α-synuclein leads to mitochondrial dysfunction via downregulation of mitophagy proteins (PINK-1 and PARKIN) and inhibition of mitochondria biogenesis (PGC-1α) along with an increase in the master inflammatory regulator NF-κB p65 production that provokes neurodegeneration and diminishes neuroprotective signaling pathway (PI3k/Akt/CREB/BDNF). Recently, formoterol exhibited a promising neuroprotective effect against neurodegenerative conditions associated with brain inflammation. Therefore, the present investigation aims to unveil the possible neuroprotective activity of formoterol, ß2AR agonist, against rotenone-induced PD in rats. Rats received rotenone (1.5 mg/kg; s.c.) every other day for 3 weeks and cured with formoterol (25 µg/kg/day; i.p.) 1 hr. after rotenone administration, starting from day 11. Formoterol treatment succeeded in upregulating ß2-adrenoreceptor expression in PD rats and preserving the function and integrity of dopaminergic neurons as witnessed by enhancement of muscular performance in tests, open field, grip strength-meter, and Rotarod, besides the increment in substantia nigra and striatal tyrosine hydroxylase immunoexpression. In parallel, formoterol boosted mitophagy by activation of PINK1 and PARKIN and preserved mitochondrial membrane potential. Additionally, formoterol stimulated the neuro-survival signaling axis via stimulation of PI3k/pS473-Akt/pS133-CREB/BDNF cascade to attenuate neuronal loss. Noteworthy formoterol reduces neuro-inflammatory status by decreasing NFκBp65 immunoexpression and TNF-α content. Finally, formoterol's potential as a stimulant therapy of mitophagy via the PINK1/PARKIN axis and regulation of mitochondrial biogenesis by increasing PGC-1α to maintain mitochondrial homeostasis along with stimulation of PI3k/Akt/CREB/BDNF axis.

Evaluation of novel pyrazol-4-yl pyridine derivatives possessing arylsulfonamide tethers as c-Jun N-terminal kinase (JNK) inhibitors in leukemia cells.

A series of 36 pyrazol-4-yl pyridine derivatives (8a-i, 9a-i, 10a-i, and 11a-i) was designed, synthesized, and evaluated for its antiproliferative activity over NCI-60 cancer cell line panel and inhibitory effect against JNK isoforms (JNK1, JNK2, and JNK3). All the synthesized compounds were tested against the NCI-60 cancer cell line panel. Compounds 11b, 11c, 11g, and 11i were selected to determine their GI50s and exerted a superior potency over the reference standard SP600125 against the tested cell lines. 11c showed a GI50 of 1.28 µM against K562 leukemic cells. Vero cells were used to assess 11c cytotoxicity compared to the tested cancer cells. The target compounds were tested against hJNK isoforms in which compound 11e exhibited the highest potency against JNK isoforms with IC50 values of 1.81, 12.7, and 10.5 nM against JNK1, JNK2, and JNK3, respectively. Kinase profiling of 11e showed higher JNK selectivity in 50 kinase panels. Compounds 11c and 11e showed cell population arrest at the G2/M phase, induced early apoptosis, and slightly inhibited beclin-1 production at higher concentrations in K562 leukemia cells relative to SP600125. NanoBRET assay of 11e showed intracellular JNK1 inhibition with an IC50 of 2.81 µM. Also, it inhibited CYP2D6 and 3A4 with different extent and its hERG activity showed little cardiac toxicity with an IC50 of 4.82 µM. hJNK3 was used as a template to generate the hJNK1 crystal structure to explore the binding mode of 11e (PDB ID: 8ENJ) with a resolution of 2.8 °A and showed a typical type I kinase inhibition against hJNK1. Binding energy scores showed that selectivity of 11e towards JNK1 could be attributed to additional hydrophobic interactions relative to JNK3.

FDTD analysis of a noninvasive hyperthermia system for brain tumors.

BACKGROUND: Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40-45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. METHODS: The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. RESULTS: The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. CONCLUSIONS: The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

Advances in diagnosis and control of anthelmintic resistant gastrointestinal helminths infecting ruminants.

Infection with gastrointestinal helminths is widely spread among ruminant causing severe losses and adversely affects the livestock husbandry. Synthetic chemotherapeutics have been utilized throughout years, as a means of combating helminthiasis. Anthelmintic resistance (AR) has a serious concern on livestock industry which, mainly arises as outcome of misuse, improper dosing and frequent utilization of the synthetic drugs.Various gastrointestinal helminths have the capability to survive the therapeutic dose of anthelmintics and become resistant to the major anthelmintic classes. Early diagnosis might delay or reduce the risk of AR. Conventional phenotyping methods were commonly used for detection of anthelmintic resistant helminths, but appeared to lack of sensitivity, especially when the frequency of resistant allele is very low. Several molecular assays were carried out to detect the AR with greater accuracy. Sustainable effective preventive and control measures for gastrointestinal helminths infection remain the corner stone to overcome AR. Rational use of anthelmintics with keeping unexposed proportion of worm populations, could have the potentiality to maintain and prolong the efficacy of anthelmintics. Several alternative anthelmintic treatments might offer valuable solutions either alone or adjunct to synthetic drugs to dilute the spread of resistance alleles among the helminths population. This article reviews current status of various diagnostic methods and control measures for anthelmintic resistant gastrointestinal helminths infecting ruminants and tries to present a practical protocol to avoid or delay the development of AR.

Cytokine modulation by etanercept ameliorates metabolic syndrome and its related complications induced in rats administered a high-fat high-fructose diet.

The aim of the present study was to investigate the effect of etanercept (ETA)-an anti-tumor necrosis factor α (TNF-α) monoclonal antibody-on metabolic disorders such as obesity, hypertension, dyslipidemia, and insulin resistance associated with the metabolic syndrome (MS). MS was induced in rats via high-fat high-fructose (HFHF) administration for 8 weeks. Rats were divided into three groups: negative control, HFHF model, and ETA-treated groups [HFHF + ETA (0.8 mg/kg/twice weekly, subcutaneously) administered in the last 4 weeks]. ETA effectively diminished the prominent features of MS via a significant reduction in the percent body weight gain along with the modulation of adipokine levels, resulting in a significant elevation of serum adiponectin consistent with TNF-α and serum leptin level normalization. Moreover, ETA enhanced dyslipidemia and the elevated blood pressure. ETA managed the prominent features of MS and its associated complications via the downregulation of the hepatic inflammatory pathway that induces nonalcoholic steatohepatitis (NASH)-from the expression of Toll-like receptor 4, nuclear factor kappa B, and TNF-α until that of transforming growth factor-in addition to significant improvements in glucose utilization, insulin sensitivity, and liver function parameter activity and histopathological examination. ETA was effective for the treatment of all prominent features of MS and its associated complications, such as type II diabetes mellitus and NASH.

Seroprevalence of nasal myiasis in camels determined by indirect enzyme-linked immunosorbent assay utilizing the most diagnostic Cephalopina titillator larval antigens.

Background and Aim: Nasal myiasis is a serious parasitic disease among camels caused by Cephalopina titillator larvae that negatively affect animal health and production globally. The diagnosis of the infestation relies on postmortem examination of the head region, which considers a cause impeding treatment of live animals and may be misdiagnosed as central nervous system disorders. This study aimed to identify the most diagnostic larval antigen with the capacity for monitoring C. titillator infestation, and to estimate the seroprevalence of nasal myiasis in camels in Egypt, using indirect enzyme-linked immunosorbent assay (ELISA). Materials and Methods: Three hundred and six male camels of Egyptian and Sudanese breeds, aged 2-5 years, were clinically evaluated for respiratory and/or nervous disorders in Cairo Governorate, Egypt. At the time of slaughter, blood samples were collected from all examined animals. The postmortem examination of 38 animals was conducted. Salivary glands, hemolymph, and somatic antigens were extracted from the second and third larval instars. Results: The results revealed that the salivary gland antigen was the most potent antigen in detecting C. titillator specific total IgG antibodies compared to haemolymph and crude somatic antigens. Using receiver-operating characteristic curves and area under the curve, the salivary gland antigen had a sensitivity of 91.67% and a specificity of 92.31%, respectively. It has the highest positive predictive value, 95.7%, and negative predictive value, 85.7%. However, using somatic and hemolymph antigens revealed a sensitivity of 79.17% and 70.83% and a specificity of 76.9% and 84.6%, respectively. There was complete concordance between ELISA results and autopsy findings (true positive). One hundred and forty out of 306 (45.8%) camel serum samples were found to contain C. titillator. Conclusion: This study demonstrated that salivary gland antigen is more effective than somatic and hemolymph antigens in accurately detecting nasal myiasis in camels. In addition, determining the seroprevalence of nasal myiasis with the salivary gland antigen through indirect ELISA revealed that it is a prevalent disease among camels in Egypt. Periodic surveillance of the C. titillator prevalence is necessary for effective management and control measures.

Three dimensional fluid structure interaction analysis of carotid artery models with different calcification patterns.

Carotid atherosclerosis treatments involve endovascular intervention. Predicting the mechanical behavior of carotid artery with calcified plaques can decrease the high risk for endovascular procedures. The aim of this research is to study the impact of morphological changes in calcification on the mechanical behavior of plaques. Fluid structure interaction simulations were applied to four 3D carotid artery models, with different calcification patterns, using the FEM. Results show that the magnitude and the spatial distribution of the circumferential strain is greatly affected by geometrical plaque morphology. The highest strain of 0.08 was observed for the diffused calcification with lipid model as compared to the strain in other plaque models (0.042, 0.031). The presence of a calcification region surrounding the lipid lowered the first principal stress value from 80KPa to 60KPa for the diffused calcification with lipid model. The morphological features of calcified plaques may play an important role in assessing plaque rupture and the choice of treatment plan.