Triple-negative breast cancer (TNBC) presents unique challenges in diagnosis and treatment. Resveratrol exhibits potential as a therapeutic intervention against TNBC by regulating various pathways ...such as the PI3K/AKT, RAS/RAF/ERK, PKCδ, and AMPK, leading to apoptosis through ROS-mediated CHOP activationand the expression of DR4 and DR5. However, the clinical efficacy of resveratrol is limited due to its poor biopharmaceutical characteristics and low bioavailability at the tumor site. Nanotechnology offers a promising approach to improving the biopharmaceutical characteristics of resveratrol to achieve clinical efficacy in different cancers. The small dimension (<200 nm) of nanotechnology-mediated drug delivery system is helpful to improve the bioavailability, internalization into the TNBC cell, ligand-specific targeted delivery of loaded resveratrol to tumor site including reversal of MDR (multi-drug resistance) condition.
This manuscript provides a comprehensive discussion on the structure-activity relationship (SAR), underlying anticancer mechanism, evidence of anticancer activity in in-vitro/in-vivo investigations, and the significance of nanotechnology-mediated delivery of resveratrol in TNBC.
Advanced nano-formulations of resveratrol such as oxidized mesoporous carbon nanoparticles, macrophage-derived vesicular system, functionalized gold nanoparticles, etc. have increased the accumulation of loaded therapeutics at the tumor-site, and avoid off-target drug release. In conclusion, nano-resveratrol as a strategy may provide improved tumor-specific image-guided treatment options for TNBC utilizing theranostic approach.
There are concerns within the regulatory and research communities regarding the health impact associated with consumer exposure to silver nanoparticles (AgNPs). This study evaluated particulate and ...ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (2 mM sodium citrate (CIT) or water). At termination, complete necropsies were conducted, histopathology, hematology, serum chemistry, micronuclei, and reproductive system analyses were performed, and silver accumulations and distributions were determined. Rats exposed to AgNP did not show significant changes in body weights or intakes of feed and water relative to controls, and blood, reproductive system, and genetic tests were similar to controls. Differences in the distributional pattern and morphology of silver deposits were observed by TEM: AgNP appeared predominantly within cells, while AgOAc had an affinity for extracellular membranes. Significant dose-dependent and AgNP size-dependent accumulations were detected in tissues by ICP-MS. In addition, sex differences in silver accumulations were noted for a number of tissues and organs, with accumulations being significantly higher in female rats, especially in the kidney, liver, jejunum, and colon.
The infection caused by the hepatitis C virus (HCV) is a significant global health concern. The prevailing genotype of HCV in Egypt is 4a, commonly referred to as GT‐4a. A significant proportion ...exceeding 50% of patients infected with HCV experience extrahepatic manifestations (EHMs), encompassing a diverse range of clinical presentations. These manifestations, including essential mixed cryoglobulinemia (MC), can serve as initial and solitary indicators of the disease. The complete understanding of the pathogenesis of EHM remains unclear, with autoimmune phenomena being recognized as the primary causative factor. In this study, we examined the predictive significance of T‐cell subpopulations in relation to the occurrence and prognosis of cryoglobulinemia in HCV patients. A total of 450 CHC genotype four treatment naïve patients were enrolled in this analytic cross‐sectional study after thorough clinical, laboratory, and radiological examinations. All patients underwent laboratory investigations, including testing for cryoglobulin antibodies and measurements of CD4 and CD8 levels; two groups were described according to their test results: Group 1 consists of patients who have tested positive for cryoglobulin antibodies and Group 2 consists of patients who have tested negative for cryoglobulin antibodies. The exclusion criteria encompassed individuals with HIV infection or chronic HBV infection. Additionally, pelvi‐abdominal ultrasonography was performed. Our study included 450 treatment naïve CHC patients (59% male, mean age 50.8 years). The patients were categorized according to their cryoglobulin antibodys test results into two groups: group A, CHC patients with cryoglobulin antibodies (Abs) negative (364 patients), and group B, CHC patients with cryoglobulin Ab positive (86 patients). Group B demonstrated a higher average age, elevated international normalized ratio, more prolonged duration of HCV infection, lower albumin, higher alanine aminotransferase, higher aspartate aminotransferase, higher bilirubin, lower CD8, lower CD4, and lower CD4:CD8 ratio. In contrast, 27 out of 86 (31.40%) patients in group B had symptoms; 85.8% had purpura and arthralgia, 74.3% had paresthesias, 86.7% had weakness, and 12.2% had non‐Hodgkin's lymphoma. The levels of CD4 and CD8 were found to be decreased in chronic HCV patients with MC. T‐cell subpopulation serves as a reliable indicator for assessing the prevalence and prognosis of MC in individuals with genotype 4 chronic hepatitis C. However, additional research is needed to further understand the development and spread of various emerging infectious diseases. Nevertheless, it is noteworthy that a critical threshold may exist beyond which EHM reaches a point of no return.
The aim of the Council for the Accreditation of Educator Preparation (CAEP) is to assure excellence in teacher preparation by focusing on quality and continuous improvement through peer review and ...outcomes-based accreditation. This paper draws conclusions and recommendations from the literature on the challenges facing Saudi education preparation providers (EPPs) in achieving CAEP standards. The researcher explored the accreditation system in Saudi Higher Education, and the challenges that EPPs face on the way to becoming accredited by the CAEP. The study of current issues for Saudi EPPs will help teacher educators become better prepared to meet the CAEP standards and to provide more effective teacher education for students. Each CAEP standard is briefly identified and followed by a discussion of related challenges in Saudi higher education that might influence EPPs' abilities to meet the standard. Recommendations and solutions are offered in each instance. By way of conclusion, three priority areas for improvement are identified: faculty involvement and development; strategies for quality assurance; and strategy for curriculum improvement.
Toxicological study of aqueous-methanol solvent fraction of methanol extract of Dacryodes edulis leaves.
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•Toxicity of aqueous-methanol solvent fraction of methanol extract of ...Dacryodes edulis leaves was evaluated.•The oral median lethal dose (LD50) was greater than 5000 mg/kgbw –practically non-toxic.•Erythrocytic indices – RBC, HB, HCT – were significantly decreased.•No renal or liver toxicity observed on treating (200−600 mg/kgbw) for 28- days.•Mitotic depression and chromosomal aberrations were observed in the Allium cepa model.
Dacryodes edulis (G. Don) H.J. Lam) is the most popular species under the genus Dacryodes. It is well known for its nutritional and ethno-medicinal uses in South-eastern and South-western Nigeria. This study was aimed to evaluate the toxicity of the aqueous-methanol fraction of crude methanol extract of Dacryodes edulis leaves (AMDE). The test rats were randomized to groups of single oral treatment of AMDE (10−5000 mg/kgbw) for the acute toxicity study. They were monitored for obvious signs of behavioural change and mortality. For the subacute toxicity study, the rats were randomized to three daily treatment groups (of 200, 400 and 600 mg/kgbw of AMDE) for 28 days. The fourth group (control) received 2.5 %v/v DMSO. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluation. The histopathology of the livers and kidneys were assessed using the excised organs. The cytotoxicity and genotoxicity of AMDE were also evaluated using Allium cepa model. The result showed that acute administration of AMDE, up to a dose of 5000 mg/kgbw did not result in mortality of the test rats. The observed median lethal dose (LD50) was greater than 5000 mg/kgbw. The subacute oral administration of AMDE for 28 days showed no significant (p > 0.05) effect on liver function, kidney function indices, organ - body weight ratio, but significantly (p < 0.05) decreased erythrocytic indices: red blood cells, haematocrit, and haemoglobin at 600 mg/kgbw. The Allium cepa assay revealed a non-significant reduction in mitotic index and low chromosomal aberrations of the treated groups. In conclusion, the aqueous-methanol solvent fraction of methanol extract of Dacryodes edulis leaves, AMDE is relatively safe. However, there are strong indications that it may contain compounds that are cytotoxic and reduces erythrocytic indices including red blood cells at high doses. Thus, adequate care should be taken in dosing and administering the extract to avert anaemic condition.
Shear Failure of RC Dapped-End Beams Aswin, Muhammad; Mohammed, Bashar S.; Liew, M. S. ...
Advances in materials science and engineering,
01/2015, Letnik:
2015
Journal Article
Recenzirano
Odprti dostop
Reinforced concrete dapped-end beams (RC-DEBs) are mainly used for precast element construction. RC-DEBs generally are recessed at their end parts and supported by columns, cantilevers, inverted ...T-beams, or corbels. The geometric discontinuity of dapped-end beams evokes a severe stress concentration at reentrant corners that may lead to shear failure. Therefore, stress analysis is required at the reentrant vicinity for design requirement of these beams. Four large-scale RC-DEBs specimens were prepared, cast, and tested up to failure. Three parameters were investigated: amount of nib reinforcements, main flexural reinforcements, and concrete type at the dapped-end area. Finite element analysis using Vec2 was also conducted to predict the behavior of RC-DEBs. It has been found that highest stresses concentration factors occur at the reentrant corners and its vicinity. By using engineered cementitious composite (ECC) in the dapped-end area, the failure load has increased by 51.9%, while the increment in the failure load was 62.2% and 46.7% as the amount of nib reinforcement and main flexural reinforcement increased, respectively. In addition, Vec2 analysis has been found to provide better accuracy for predicting the failure load of RC-DEBs compared to other analysis approaches.
This paper presents entropy generation analysis for stagnation point flow in a porous medium over a permeable stretching surface with heat generation/absorption and convective boundary condition. We ...have used Von Kantian transformations to transform the governing equations into ordinary differential equations. Thevelocity, temperature and concentration profiles obtained using the Homotopy Analysis Method. The HAM is a valid mathematical tool for most of non-linear problems in science and engineering. Finally we have computed the entropy generation number. The effect of the Prandtl number, Brinkman number, Reynolds number, suction/injection parameter, Biot number, Lewis number, Brownian motion parameter, thermophoresisparameterand constant parameters on velocity, concentration and temperature profiles are analyzed. Moreover the influences of the Reynolds number and Brinkman number on the entropy generation are presented. The entropy generation number increases with increasing the Brinkman and Reynolds number.
COVID-19 has been frequently demonstrated to be associated with anosmia. Calcium cations are a mainstay in the transmission of odor. One of their documented effects is feedback inhibition. Thus, it ...has been advocated that reducing the free intranasal calcium cations using topical chelators such as pentasodium diethylenetriamine pentaacetate (DTPA) could lead to restoration of the olfactory function in patients with post-COVID-19 anosmia.
This is a randomized controlled trial that investigated the effect of DTPA on post-COVID-19 anosmia. A total of 66 adult patients who had confirmed COVID-19 with associated anosmia that continued beyond three months of being negative for SARS-CoV-2 infection. The included patients were randomly allocated to the control group that received 0.9 % sodium chloride-containing nasal spray or the interventional group that received 2 % DTPA-containing nasal spray at a 1:1 ratio. Before treatment and 30 days post-treatment, the patients' olfactory function was evaluated using Sniffin' Sticks, and quantitative estimation of the calcium cations in the nasal mucus was done using a carbon paste ion-selective electrode test.
Patients in the DTPA-treated group significantly improved compared to the control group in recovery from functional anosmia to hyposmia. Additionally, they showed a significant post-treatment reduction in the calcium concentration compared to the control group.
This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.
•Reports demonstrated a relationship between anosmia and COVID-19•Olfactory dysfunction causes an increase in intracellular calcium concentration.•Pentasodium diethylenetriamine pentaacetate (DTPA) can decrease the concentration of calcium in the nasal secretion.•Intranasal DTPA could be effective in treating anosmia.
Diabetes is a metabolic disorder with a highly complex, multifaceted and intricate etiologies and thus may require management options that proffers multimodal mechanism of action. This present study ...evaluated the antidiabetic and antioxidant potential of the methanolic extract/fractions of leaves of
The antidiabetic potential was evaluated and using STZ-induced diabetic Wistar rat model (
) and inhibition of α-amylase and α-glucosidase activity (
). Antioxidant activity was assessed
by free radical scavenging and reducing power assays and
via monitoring SOD and CAT activities; GSH and MDA levels.
The total phenolic content (221.0±3.0 mg catechol/g of sample) and tannins (146.0±4.0 mg tannic acid/g of sample) of the crude extract; and flavonoid of the aqueous-methanol fraction (216.0.0±1.0 mg of rutin/g of sample) were found to be significantly higher relative to others. The crude extract and the aqueous-methanol fraction exhibited a significantly (p<0.05) higher percentage reduction in fasting blood glucose and a concomitant increase in serum insulin level relative to the diabetic control group. The highest radical scavenging activity and reducing power were observed in the aqueous-methanol fraction. The aqueous-methanol solvent fraction also significantly reversed the alterations in oxidative stress markers occasioned by the diabetic condition.
In conclusion, the result of the present study has demonstrated evidently that extracts of
leaves ameliorates hyperglycemia and the associated oxidative stress in STZ-induced rats.
The present study evaluated the antidiabetic and antioxidant potential of the methanolic extract/solvent fractions of the leaves of Dacryodes edulis using a streptozotocin (STZ)-induced diabetic ...Albino Wistar rat model. The fasting blood glucose/insulin levels and inhibition of α-amylase and α-glucosidase were determined. Antioxidant activity was assessed in vitro by 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, superoxide scavenging, reducing power, and total antioxidant capacity assays and in vivo by monitoring catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and reduced glutathione (GSH) and malondialdehyde (MDA) levels. The aqueous-methanol fraction exhibited the highest and significant (P < .05) reduction in fasting blood glucose (FBG; 54.03%) with a concomitant inhibition of α-amylase and α-glucosidase activities. The ethyl acetate fraction also exhibited a significant (P < .05) reduction in FBG and an increase in insulin levels in the treated diabetic Wistar rats. A significantly (P < .05) higher reducing power and radical scavenging activity was observed in the aqueous-methanol and ethyl acetate fractions. The aqueous-methanol and ethyl acetate fractions also significantly (P < .05) reversed the alterations in oxidative stress markers (GSH, MDA, CAT, and SOD) observed in the diabetic control group. In conclusion, the study demonstrated that the methanol extract of Dacryodes edulis ameliorates hyperglycemia and the associated oxidative stress in STZ-induced diabetic Wistar rats. These observed activities are largely due to the compounds that partitions into the aqueous-methanol (55:45) solvent fraction. This provides scientific evidence for the use of this plant extract in folk medicine and also a baseline data for its further characterization. Further work should be carried out to characterize the aqueous-methanol solvent fractions for the active compounds.
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