Disparate effects of sclerostin deletion on alveolar bone and cellular cementum in mice.

BACKGROUND: Cellular cementum (CC) includes cementocytes, cells suspected to regulate CC formation or resorption as osteocytes do in bone. Sclerostin (SOST) is a secreted negative regulator of Wnt/ß-catenin signaling expressed by osteocytes and cementocytes. Osteocyte SOST expression reduces bone formation. We investigated the functional importance of SOST in CC compared with alveolar bone (AB) using a Sost knockout (Sost-/-) mouse model to better understand the role of cementocytes in CC. METHODS: Mandibles and femurs of Sost-/- and wild-type (WT) mice were analyzed at 42 and 120 days postnatal (dpn). Maxillary first molars were bilaterally extracted at 42 dpn and both AB healing (maxillary molar sockets) and CC apposition (mandibular first molars) were examined at 21 days post-procedure. Analyses included micro-computed tomography, histology, and immunohistochemistry. RESULTS: Femur cortical and trabecular bone and mandibular bone volumes were similarly increased in Sost-/- versus WT mice at 42 and/or 120 dpn. In contrast to previous reports, CC was not increased by Sost-/- at either age. We conducted challenge experiments on AB and CC to explore tissue-specific responses. Post-extraction AB healing was improved by Sost deletion. In contrast, experimentally-induced apposition in molars failed to stimulate increased CC formation in Sost-/- versus WT mice. Wnt pathway markers AXIN2 and DKK1, which were increased in Sost-/- versus WT AB osteocytes, were unchanged in cementocytes. CONCLUSIONS: These data indicate CC is less responsive than AB to SOST deletion. Within the study limitations, these results do not support cementocytes as critical for directing increased CC formation. PLAIN LANGUAGE SUMMARY: Sclerostin is a protein known to inhibit bone formation, and removing sclerostin leads to more bone formation. Cementum is the thin layer that covers the surface of the tooth's root. Previous studies suggest that inhibiting sclerostin can similarly increase the amount of cementum. We wanted to compare the response of cementum and bone when sclerostin is absent to understand similarities and differences between these two tissues. In this study, we removed the Sost gene (the gene which produces sclerostin) in mice. We found that mice without sclerostin have more bone in their legs and jaws. Moreover, mice without sclerostin also healed better after tooth removal compared with normal mice. Surprisingly, unlike previous studies, we found that the amount of cementum was not different in mice without sclerostin compared with normal mice. Additionally, we challenged the cementum by taking out the opposing tooth to cause the first mandibular molar to move up by building more cementum. Even with this challenge, we found no difference in the amount of cementum in mice lacking sclerostin compared with normal mice. Therefore, we conclude here that cementum is less sensitive to the absence of sclerostin compared with bone.

Urea intercalated encapsulated microalgae composite hydrogels for slow-release fertilizers.

In agriculture, hydrogels can be addressed for effective operation of water and controlled-release fertilizers. Hydrogels have a significant ability for retaining water and improving nutrient availability in soil, enhancing plant growth while reducing water and fertilizer usage. This work aimed to prepare a hydrogel composite based on microalgae and biopolymers including chitosan and starch for use as a soil conditioner. The hydrogel composite was characterized by FTIR, XRD, and SEM. All hydrogel properties were studied including swelling degree, biodegradability, water-holding capacity, water retention, and re-swelling capacity in soil and water. The urea fertilizer loading and releasing behavior of the prepared hydrogels were investigated. The results revealed that the range of the maximal urea loading was between 99 and 440%, and the kinetics of loading was fitted with Freundlich model. The urea release % exhibited 78-95%, after 30 days, and the kinetics of release was fitted with zero-order, Higuchi, and Korsmeyer-Peppas models. Furthermore, the prepared hydrogels obtained a significant water-holding capacity, after blending soil (50 g) with small amount of hydrogels (1 g), the capacity increased in the range of 99.4-101.5%. In sum, the prepared hydrogels have the potential to be applied as a soil conditioner.

Cardioprotective Potential of Moringa Oleifera Leaf Extract Loaded Niosomes Nanoparticles - Against Doxorubicin Toxicity In Rats.

INTRODUCTION: Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are still a major clinical issue. Plant extracts have shown cardioprotective effects and reduced the risk of cardiovascular diseases. METHOD: The current study is intended to explore the cardioprotective effect of ethanolic Moringa oleifera extracts (MOE) leaves loaded into niosomes (MOE-NIO) against DOXinduced cardiotoxicity in rats. MOE niosomes nanoparticles (NIO-NPs) were prepared and characterized by TEM. Seventy male Wistar rats were randomly divided into seven groups: control, NIO, DOX, DOX+MOE, DOX+MOE-NIO, MOE+DOX, and MOE-NIO+DOX. DOX (4 mg/kg, IP) was injected once per week for 4 weeks with daily administration of MOE or MOENIO (250 mg/kg, PO) for 4 weeks; in the sixth and seventh groups, MOE or MOE-NIO (250 mg/kg, PO) was administered one week before DOX injection. Various parameters were assessed in serum and cardiac tissue. Pre and co-treatment with MOE-NIO have mitigated the cardiotoxicity induced by DOX as indicated by serum aspartate aminotransferase (AST), creatine kinase - MB(CK-MB) and lactate dehydrogenase (LDH), cardiac Troponin 1(cTn1) and lipid profile. MOE-NIO also alleviated lipid peroxidation (MDA), nitrosative status (NO), and inflammatory markers levels; myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α) obtained in DOX-treated animals. Additionally, ameliorated effects have been recorded in glutathione content and superoxide dismutase activity. MOE-NIO effectively neutralized the DOXupregulated nuclear factor kappa B (NF-kB) and p38 mitogen-activated protein kinases (p38 MAPK), and DOX-downregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in the heart. RESULTS: It is concluded that pre and co-treatment with MOE-NIO could protect the heart against DOX-induced cardiotoxicity by suppressing numerous pathways including oxidative stress, inflammation, and apoptosis and by the elevation of tissue antioxidant status. CONCLUSION: Thus, it may be reasonable to suggest that pre and co-treatment with MOE-NIO can provide a potential cardioprotective effect when doxorubicin is used in the management of carcinoma.

Chemical synthesis and super capacitance performance of novel CuO@Cu4O3/rGO/PANI nanocomposite electrode.

Copper oxide-based nanocomposites are promising electrode materials for high-performance supercapacitors due to their unique properties that aid electrolyte access and ion diffusion to the electrode surface. Herein, a facile and low-cost synthesis in situ strategy based on co-precipitation and incorporation processes of reduced graphene oxide (rGO), followed by in situ oxidative polymerization of aniline monomer has been reported. CuO@Cu4O3/rGO/PANI nanocomposite revealed the good distribution of CuO@Cu4O3 and rGO within the polymer matrix which allows improved electron transport and ion diffusion process. Galvanostatic charge-discharge (GCD) results displayed a higher specific capacitance value of 508 F g-1 for CuO@Cu4O3/rGO/PANI at 1.0 A g-1 in comparison to the pure CuO@Cu4O3 278 F g-1. CuO@Cu4O3/rGO/PANI displays an energy density of 23.95 W h kg-1 and power density of 374 W kg-1 at the current density of 1 A g-1 which is 1.8 times higher than that of CuO@Cu4O3 (13.125 W h kg-1) at the same current density. The retention of the electrode was 93% of its initial capacitance up to 5000 cycles at a scan rate of 100 mV s-1. The higher capacitance of the CuO@Cu4O3/rGO/PANI electrode was credited to the formation of a fibrous network structure and rapid ion diffusion paths through the nanocomposite matrix that resulted in enhanced surface-dependent electrochemical properties.

Green synthesis of zinc oxide/Allium sativum nano-composite and its efficacy against murine cryptosporidiosis.

Cryptosporidiosis is a global health problem threats life of immunocompromised patients. Allium sativum (A. sativum) is one of the therapeutic options for cryptosporidiosis. This study develops green synthesized ZnO-NPs based on A. sativum extract, and assesses its therapeutic application in treating experimental cryptosporidiosis in immunosuppressed mice. FTIR, scanning electron microscopy, and zeta analyzer were used for characterization of bio ZnO-NPs. The morphology of prepared materials appeared as sponge with many pores on the whole surface that allows the feasibility of bio ZnO-NPs for different biological activities. Its structural analysis was highly stabilized with negative charge surface which indicated for well distribution into the parasite matrix. Twenty-five immunosuppressed Cryptosporidium parvum infected mice, classified into 5 groups were sacrificed at 21th day after infection with evaluation of parasitological, histopathological, oxidative, and proinflammatory biomarkers. Treated mice groups with 50 and 100 mg/kg of AS/ZnO-NPs showed a highly significant decline (79.9% and 83.23%, respectively) in the total number of expelled oocysts. Both doses revealed actual amelioration of the intestinal, hepatic, and pulmonary histopathological lesions. They also significantly produced an increase in GSH values and improved the changes in NO and MDA levels, and showed high anti-inflammatory properties. This study is the first to report green synthesis of ZnO/A. sativum nano-composite as an effective therapy in treating cryptosporidiosis which gave better results than using A. sativum alone. It provides an economical and environment-friendly approach towards novel delivery synthesis for antiparasitic applications. RESEARCH HIGHLIGHTS: Green synthesis of ZnO-NPs was developed using A. sativum extract. The morphology of prepared ZnO-NPs appeared as sponge with many pores on SEM The study evaluates its therapeutic efficacy against murine cryptosporidiosis The green synthesized ZnO-NPs significantly reduced percent of oocyst shedding, improved the pathological changes, and showed high antioxidant and anti-inflammatory potentials.

The renoprotective activity of amikacin-gamma-amino butyric acid-chitosan nanoparticles: a comparative study.

The development of nanoparticles (NPs) with active components with upgraded stability, and prolonged release helps in enhanced tissue regeneration. In addition, NPs are feasible strategy to boost antibiotic effectiveness and reduce drug side effects. Our study focuses on the use of amikacin (AMK) and gamma amino butyric acid (GABA) unloaded combinations or loaded on chitosan nanoparticles (CSNPs) for kidney protection. The AMK-GABA-CSNPs were prepared with the ionic gelation method, the morphology was studied using transmission electron microscopy (TEM), zetasizer and the Fourier transform-infrared spectroscopy (FT-IR) spectrum of the synthesized NPs was observed. The average size of AMK-GABA-CSNPs was 77.5 ± 16.5 nm. Zeta potential was + 38.94 ± 2.65 mV. AMK-GABA-CSNPs revealed significant in vitro antioxidant, anti-coagulation, non-hemolytic properties and good cell compatibility. To compare the effects of the unloaded AMK-GABA combination and AMK-GABA-CSNPs on the renal tissue, 42 healthy Sprague-Dawley rats were divided into seven groups. G1: normal control (NC), normal saline; G2: low-dose nephrotoxic group (LDN), AMK (20 mg/kg/day; i.p.); G3: unloaded AMK (20 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.); G4: AMK-GABA-CSNPs (20 mg/kg/day; i.p.); G5: high-dose nephrotoxic group (HDN), AMK (30 mg/kg/day; i.p.); G6: unloaded AMK (30 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.) and G7: AMK-GABA-CSNPs (30 mg/kg/day; i.p.). The results showed that AMK-GABA-CSNPs formulation is superior to unloaded AMK-GABA combination as it ameliorated kidney functions, oxidative stress and displayed a significant homeostatic role via suppression of inflammatory cytokines of Th1, Th2 and Th17 types. Hence, AMK-GABA-CSNPs could afford a potential nano-based therapeutic formula for the management of AMK-nephrotoxicity.

Novel Bis(2-cyanoacrylamide) Linked to Sulphamethoxazole: Synthesis, DNA Interaction, Anticancer, ADMET, Molecular Docking, and DFT Studies.

In the light of advancement and potential extensive use of medication design and therapy, new bis(cyanoacrylamides) incorporating sulphamethoxazole derivatives (7 a-7 f) were synthesized and confirmed by different spectral tools. In vitro anticancer activity towards different human cancer cells (HCT116, MDA-MB-231 and A549) was assessed using MTT assay. Among all derivatives, 4C- and 6C-spacer derivatives (7 e and 7 f) had the most potent growth inhibitory activities against HCT116 cells with IC50 values of 39.7 and 28.5 µM, respectively. 7 e and 7 f induced apoptosis and suppressed migration of HCT116 cells. These compounds also induced a significant increase in caspase-3 and CDH1 activities, and a downregulation of Bcl2 using ELISA. pBR322 DNA cleavage activities of cyanoacrylamides were determined using agarose gel electrophoresis. Furthermore, 7 e and 7 f showed good DNA and BSA binding affinities using different spectroscopic techniques. Furthermore, molecular docking for 7 e and 7 f was performed to anticipate their binding capabilities toward various proteins (Bcl2, CDH1 and BSA). The docking results were well correlated with those of experimental results. Additionally, density functional theory and ADMET study were performed to evaluate the molecular and pharmacokinetic features of 7 e and 7 f, respectively. Thus, this work reveals promising antitumor lead compounds that merit future research and activity enhancement.

TGFßR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling.

Transforming growth factor (TGF)-ß and toll-like receptors (TLRs) have been shown to independently modulate the proliferation of hepatocellular carcinoma (HCC). Since a direct cross-talk between these two signalling pathways in HCC has not been clearly described before, we aimed here to explore the possibility of such interaction. A human HCC tissue array (n = 20 vs. four control samples), human HCC samples (n = 10) and steatohepatitis-driven murine HCC samples (control, NASH and HCC; n = 6/group) were immunostained for TGFßR1, pSMAD2, TRAF6, IRAK1 and PCNA. The results were confirmed by immunoblotting. Effects of constant activation of the SMAD pathway by constitutive expression of ALK5 or knockdown of mediators of TLR signalling, IRAK1 and MyD88, on HCC proliferation, were investigated in the HCC cell line (HUH-7) after treatment with TGFß1 cytokine or TGFßR1 kinase inhibitor (LY2157299) using PCNA and MTS assay. TGFßR1 expression is decreased in human and murine HCC and associated with downregulated pSMAD2, but increased IRAK1, TRAF6 and PCNA staining. TGFßR1 kinase inhibition abolished the cytostatic effects of TGFß1 and led to the induction of IRAK1, pIRAK1 and elevated mRNA levels of TLR-9. Overexpression of ALK5 and knockdown of MyD88 or IRAK1 augmented the cytostatic effects of TGFß1 on HUH-7. In another epithelial HCC cell line, that is, HepG2, TGFßR1 kinase inhibitor similarly elevated cellular proliferation. There is a balance between the canonical SMAD-driven tumour-suppressing arm and the non-canonical tumour-promoting arm of TGFß signalling. Disruption of this balance, by inhibition of the canonical pathway, induces HCC proliferation through TLR signalling.

The anti-staphylococcal fusidic acid as an efflux pump inhibitor combined with fluconazole against vaginal candidiasis in mouse model.

BACKGROUND: Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC). OBJECTIVES: This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates. METHODS: The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis. RESULTS: Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue. CONCLUSION: The current findings highlight FA's potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.

New pyrrolidine-carboxamide derivatives as dual antiproliferative EGFR/CDK2 inhibitors.

Cancer is one of the leading causes of mortality worldwide, making it a public health concern. A novel series of pyrrolidine-carboxamide derivatives 7a-q were developed and examined in a cell viability assay utilizing a human mammary gland epithelial cell line (MCF-10A), where all the compounds exhibited no cytotoxic effects and more than 85% cell viability at a concentration of 50 µM. Antiproliferative activity was evaluated in vitro against four panels of cancer cell lines A-549, MCF-7, Panc-1, and HT-29. Compounds 7e, 7g, 7k, 7n, and 7o were the most active as antiproliferative agents capable of triggering apoptosis. Compound 7g was the most potent of all the derivatives, with a mean IC50 of 0.90 µM compared to IC50 of 1.10 µM for doxorubicin. Compound 7g inhibited A-549 (epithelial cancer cell line), MCF-7 (breast cancer cell line), and HT-29 (colon cancer cell line) more efficiently than doxorubicin. EGFR inhibitory assay results of 7e, 7g, 7k, 7n, and 7o demonstrated that the tested compounds inhibited EGFR with IC50 values ranging from 87 to 107 nM in comparison with the reference drug erlotinib (IC50 = 80 nM). 7e, 7g, 7k, 7n, and 7o inhibited CDK2 efficiently in comparison to the reference dinaciclib (IC50 = 20 nM), with IC50 values ranging from 15 to 31 nM. The results of inhibitory activity assay against different CDK isoforms revealed that the tested compounds had preferential inhibitory activity against the CDK2 isoform.

Users' experience with health-related content on YouTube: an exploratory study.

BACKGROUND: This study focuses on health-related content (HRC) on YouTube and addresses the issue of misinformation on this platform. While previous research centered on content evaluations by experts, this study takes a user-centered approach and aims to explore users' experiences with and perceptions of HRC videos and to establish links between these perceptions and some socio-demographic characteristics including age, gender, profession, and educational level. METHODS: A quantitative research design was used in the study. 3,000 YouTube users responded to a 35-item anonymous questionnaire to collect information about the content they watch toward decision-making, their perceptions of the usefulness and bias of this content, what they identify as quality indicators for HRC, and what they recommend to improve the quality of such content on YouTube. The data were analyzed using descriptive statistics, frequency, and correlation analyses. RESULTS: The results reveal that 87.6 percent (n=2630) of the participants watch HRC on YouTube, and 84.7 percent (n=2542) make decisions based on what they watch. Exercise and bodybuilding videos are the most popular, with over half of the participants watching them. 40 percent of the users watch YouTube videos to decide whether to consult a doctor or adopt specific health-related practices. In contrast to evaluations by experts in previous studies, most respondents perceive HRC videos on YouTube as useful and do not find connections between video quality and surface features like the number of views and likes. Weak or no correlations were observed between the perceived usefulness of HRC videos and age, gender, profession, or educational level. Participants' recommendations for enhancing HRC quality align with previous research findings. CONCLUSIONS: Users turn to YouTube not only for health information but also as a decision-making tool. Combined with their generally positive attitudes towards content quality on this platform, this can have significant consequences for their health. Follow-up studies are needed to get more insights into decision-making behaviors and how users assess their decisions in retrospect.

DiaNet v2 deep learning based method for diabetes diagnosis using retinal images.

Diabetes mellitus (DM) is a prevalent chronic metabolic disorder linked to increased morbidity and mortality. With a significant portion of cases remaining undiagnosed, particularly in the Middle East North Africa (MENA) region, more accurate and accessible diagnostic methods are essential. Current diagnostic tests like fasting plasma glucose (FPG), oral glucose tolerance tests (OGTT), random plasma glucose (RPG), and hemoglobin A1c (HbA1c) have limitations, leading to misclassifications and discomfort for patients. The aim of this study is to enhance diabetes diagnosis accuracy by developing an improved predictive model using retinal images from the Qatari population, addressing the limitations of current diagnostic methods. This study explores an alternative approach involving retinal images, building upon the DiaNet model, the first deep learning model for diabetes detection based solely on retinal images. The newly proposed DiaNet v2 model is developed using a large dataset from Qatar Biobank (QBB) and Hamad Medical Corporation (HMC) covering wide range of pathologies in the the retinal images. Utilizing the most extensive collection of retinal images from the 5545 participants (2540 diabetic patients and 3005 control), DiaNet v2 is developed for diabetes diagnosis. DiaNet v2 achieves an impressive accuracy of over 92%, 93% sensitivity, and 91% specificity in distinguishing diabetic patients from the control group. Given the high prevalence of diabetes and the limitations of existing diagnostic methods in clinical setup, this study proposes an innovative solution. By leveraging a comprehensive retinal image dataset and applying advanced deep learning techniques, DiaNet v2 demonstrates a remarkable accuracy in diabetes diagnosis. This approach has the potential to revolutionize diabetes detection, providing a more accessible, non-invasive and accurate method for early intervention and treatment planning, particularly in regions with high diabetes rates like MENA.

Design, synthesis of novel chromene-based scaffolds targeting hepatocellular carcinoma: Cell cycle arrest, cytotoxic effect against resistant cancer cells, apoptosis induction, and c-Src inhibition.

New chromene derivatives were synthesized based on 4-(3,4-dimethoxy)-4H-chromene scaffold. All target compounds exhibited cytotoxic activity against HepG2 cells (IC50 = 2.40-141.22 µM). Chromens 5 and 9 showed superior cytotoxicity over staurosporine (IC50 = 18.27 µM) and vinblastine (IC50 = 5.20 µM). c-Src kinase inhibition assay of compounds 5 and 9 displayed the dominant c-Src inhibitory activity of 5 (IC50 = 0.184 µM) over 9 (IC50 = 0.288 µM). The safety of the most potent compound 5 against normal WI-38 cells was confirmed via its IC50 of 115.75 µM comparable with 5-FU (IC50 = 16.28 µM). Moreover, the promising chromene 5 displayed potent cytotoxicity against resistant HepG2 cells with IC50 of 26.03 µM comparable with 5-FU (IC50 = 42.68 µM). The most active chromene 5 arrested the HepG2 cell cycle at the S phase and induced a 29-fold increase in the total number of apoptotic cells indicating pre-G1 apoptosis. The ability of compound 5 to induce apoptosis was supported via elevation of caspase-3, caspase-7, caspase-9 and proapoptotic Bax protein levels in addition to downregulation of the antiapoptotic Bcl2 protein. Molecular docking studies of compound 5 showed good binding interaction pattern inside c-Src kinase enzyme active site.

New 1,2,3-triazole/1,2,4-triazole hybrids linked to oxime moiety as nitric oxide donor selective COX-2, aromatase, B-RAFV600E and EGFR inhibitors celecoxib analogs: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis and molecular modeling study.

A new series of bis-triazole 19a-l was synthesised for the purpose of being hybrid molecules with both anti-inflammatory and anti-cancer activities and assessed for cell cycle arrest, NO release. Compounds 19c, 19f, 19h, 19 l exhibited COX-2 selectivity indexes in the range of 18.48 to 49.38 compared to celecoxib S.I. = 21.10), inhibit MCF-7 with IC50 = 9-16 µM compared to tamoxifen (IC50 = 27.9 µM). and showed good inhibitory activity against HEP-3B with IC50 = 4.5-14 µM compared to sorafenib (IC50 = 3.5 µM) (HEP-3B). Moreover, derivatives 19e, 19j, 19k, 19 l inhibit HCT-116 with IC50 = 5.3-13.7 µM compared to 5-FU with IC50 = 4.8 µM (HCT-116). Compounds 19c, 19f, 19h, 19 l showed excellent inhibitory activity against A549 with IC50 = 3-4.5 µM compared to 5-FU with IC50 = 6 µM (A549). Compounds 19c, 19f, 19h, 19 l inhibit aromatase (IC50 of 22.40, 23.20, 22.70, 30.30 µM), EGFR (IC50 of 0.112, 0.205, 0.169 and 0.066 µM) and B-RAFV600E (IC50 of 0.09, 0.06, 0.07 and 0.05 µM).

Newly fabricated zinc oxide nanoparticles loaded materials for therapeutic nano delivery in experimental cryptosporidiosis.

Cryptosporidiosis is a global health problem that threatens the lives of immunocompromised patients. This study targets to fabricate and investigate the efficiency of zinc oxide nanoparticles (ZnO-NPs), nitazoxanide (NTZ)-loaded ZnO-NPs, and Allium sativum (A. sativum)-loaded ZnO-NPs in treating cryptosporidiosis. Further FTIR, SEM, XRD, and zeta analysis were used for the characterization of ZnO-NPs and loaded materials. The morphology of loaded materials for ZnO-NPs changed into wrapped layers and well-distributed homogenous particles, which had a direct effect on the oocyst wall. The charge surface of all particles had a negative sign, which indicated well distribution into the parasite matrix. For anti-cryptosporidiosis efficiency, thirty immunosuppressed Cryptosporidium parvum-infected mice, classified into six groups, were sacrificed on the 21st day after infection with an evaluation of parasitological, histopathological, and oxidative markers. It was detected that the highest reduction percent of Cryptosporidium oocyst shedding was (81.5%) in NTZ, followed by (71.1%) in A. sativum-loaded ZnO-NPs-treated groups. Also, treatment with A. sativum and NTZ-loaded ZnO-NPs revealed remarkable amelioration of the intestinal, hepatic, and pulmonary histopathological lesions. Furthermore, they significantly produced an increase in GSH values and improved the changes in NO and MDA levels. In conclusion, this study is the first to report ZnO-NPs as an effective therapy for treating cryptosporidiosis, especially when combined with other treatments that enhance their antioxidant activity. It provides an economical and environment-friendly approach to novel delivery synthesis for antiparasitic applications.

Effect of lactoferrin supplement on cadmium chloride induced toxicity to male rats: Toxicopathological, ultrastructural and immunological studies.

This study sought to determine whether lactoferrin supplementation could counteract the harm that cadmium (Cd) induced to the rats. The effect of Cd and lactoferrin were investigated in hematological, biochemical, histological, immunohistochemical expression and ultrastructural studies. After 30 days of treatment, rats exposed to Cd had significantly higher levels of Cd in their blood, more oxidized lipids, and less antioxidant capacity overall. Supplemental lactoferrin also significantly undoes that effect. Hematological and biochemical parameters changed along with the increase in blood Cd levels. The histological integrity of the liver, kidney, spleen, and (axillary, cervical, mesenteric and popliteal) lymph nodes that had been damaged by Cd exposure was also restored by lactoferrin supplementation. Moreover, the liver and spleen ultrastructure showed the same improvement. In addition, the spleen of Lf/Cd group showed less immunohistochemical expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in comparison to the Cd group. In conclusion, the current study showed that supplementing with lactoferrin improved immune response and restored biochemical and oxidative stability induced by Cd.

New pyrazolyl-thiazolidinone/thiazole derivatives as celecoxib/dasatinib analogues with selective COX-2, HER-2 and EGFR inhibitory effects: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis, molecular modelling and ADME studies.

Two new series of pyrazolyl-thiazolidinone/thiazole derivatives 16a-b and 18a-j were synthesised, merging the scaffolds of celecoxib and dasatinib. Compounds 16a, 16b and 18f inhibit COX-2 with S.I. 134.6, 26.08 and 42.13 respectively (celecoxib S.I. = 24.09). Compounds 16a, 16b, 18c, 18d and 18f inhibit MCF-7 with IC50 = 0.73-6.25 µM (dasatinib IC50 = 7.99 µM) and (doxorubicin IC50 = 3.1 µM) and inhibit A549 with IC50 = 1.64-14.3 µM (dasatinib IC50 = 11.8 µM and doxorubicin IC50 = 2.42 µM) with S.I. (F180/MCF7) of 33.15, 7.13, 18.72, 13.25 and 8.28 respectively higher than dasatinib (4.03) and doxorubicin (3.02) and S.I. (F180/A549) of 14.75, 12.96, 4.16, 7.07 and 18.88 respectively higher than that of dasatinib (S.I. = 2.72) and doxorubicin (S.I = 3.88). Derivatives 16a, 18c, 18d, 18f inhibit EGFR and HER-2 IC50 for EGFR of 0.043, 0.226, 0.388, 0.19 µM respectively and for HER-2 of 0.032, 0.144, 0.195, 0.201 µM respectively.

Effect of an educational program on pediatric nurses' knowledge, practice, and self-confidence about level of consciousness scales.

BACKGROUND: Nurses of pediatric acute critical care units routinely assess the Level of Consciousness (LOC). The precise, exact, and restriction-free evaluation tool aids pediatric nurses in LOC assessment and clinical decision-making. This study aimed to examine the effect of an educational program on pediatric nurses' knowledge, practice, and self-confidence about level of consciousness scales. METHODS: This pretest-post, single-group, quasi-experimental, double-site study included 49 pediatric nurses. The Glasgow Coma Scale (GCS)/Pediatric Glasgow Coma Scale (PGCS) and Pediatric Full Outline of UnResponsiveness Score Scale (PFSS) knowledge questionnaire and pediatric nurse practice checklist were developed and adopted. Self-reflection confidence statements were rated 1-5 (not confident-confident). RESULTS: The results of the study indicate that there were significant increases in knowledge, practice, and self-confidence after the intervention. The paired samples tests revealed that knowledge scores significantly increased from the pretest to the posttest for both GCS/PGCS (pretest mean:7.91, posttest mean:9.95) and PFSS (pretest mean:2.1, posttest mean:6.79). Practice scores also showed significant improvement for both GCS/PGCS (pretest mean: 4.12, post-test mean: 6.22) and PFSS (pretest mean: 2.46, post-test mean: 5.79). Furthermore, self-confidence significantly improved for GCS/PGCS (pretest mean:16.08, posttest mean:18.79) and PFSS (pretest mean:10.32, posttest mean:17.81). The statistical analyses supported the significance of these improvements (p < 0.001 for all except self-confidence in GCS/PGCS with p < 0.005). CONCLUSION: The educational program improved pediatric nurses' GCS/PGCS and PFSS knowledge, practice, and self-confidence. IMPLICATIONS TO PRACTICE: Effective teaching of pediatric nurses is required to address gaps in care practices and improve the use of the Consciousness Level Assessment Scales.

Incidental right renal agenesis in a 23-year-old patient: A case report.

Renal agenesis refers to the congenital absence or complete failure of development of one or both kidneys. It occurs when the kidneys fail to form during embryonic development. This case report describes the presentation of a 23-year-old male patient who experienced sporadic episodes of abdominal pain on the right side and occasional episodes of hematuria. Diagnostic investigations, including ultrasonography and magnetic resonance imaging scans, confirmed the diagnosis of right renal agenesis. The management of the patient in this case report involved close monitoring of renal function and regular follow-up visits. Initially, the patient was followed for a period of 3 months and based on the patient's clinical status and any associated risk factors, it was determined that a follow-up schedule of visits every 6 months is appropriate. This interval allows for ongoing assessment of renal function and facilitates early detection of any potential complications or changes in kidney health. This case highlights the importance of early diagnosis, comprehensive management, and long-term monitoring in individuals with renal agenesis.

Eobania vermiculata whole-body muscle extract-loaded chitosan nanoparticles enhanced skin regeneration and decreased pro-inflammatory cytokines in vivo.

BACKGROUND: Usually, wounds recover in four to six weeks. Wounds that take longer time than this to heal are referred to as chronic wounds. Impaired healing can be caused by several circumstances like hypoxia, microbial colonization, deficiency of blood flow, reperfusion damage, abnormal cellular reaction and deficiencies in collagen production. Treatment of wounds can be enhanced through systemic injection of the antibacterial drugs and/or other topical applications of medications. However, there are a number of disadvantages to these techniques, including the limited or insufficient medication penetration into the underlying skin tissue and the development of bacterial resistance with repeated antibiotic treatment. One of the more recent treatment options may involve using nanotherapeutics in combination with naturally occurring biological components, such as snail extracts (SE). In this investigation, chitosan nanoparticles (CS NPs) were loaded with an Eobania vermiculata whole-body muscle extract. The safety of the synthesized NPs was investigated in vitro to determine if these NPs might be utilized to treat full-skin induced wounds in vivo. RESULTS: SEM and TEM images showed uniformly distributed, spherical, smooth prepared CS NPs and snail extract-loaded chitosan nanoparticles (SE-CS NPs) with size ranges of 76-81 and 91-95 nm, respectively. The zeta potential of the synthesized SE-CS NPs was - 24.5 mV, while that of the CS NPs was 25 mV. SE-CS NPs showed a remarkable, in vitro, antioxidant, anti-inflammatory and antimicrobial activities. Successfully, SE-CS NPs (50 mg/kg) reduced the oxidative stress marker (malondialdehyde), reduced inflammation, increased the levels of the antioxidant enzymes (superoxide dismutase and glutathione), and assisted the healing of induced wounds. SE-CS NPs (50 mg/kg) can be recommended to treat induced wounds safely. SE was composed of a collection of several wound healing bioactive components [fatty acids, amino acids, minerals and vitamins) that were loaded on CS NPs. CONCLUSIONS: The nanostructure enabled bioactive SE components to pass through cell membranes and exhibit their antioxidant and anti-inflammatory actions, accelerating the healing process of wounds. Finally, it is advised to treat rats' wounds with SE-CS NPs.