This journal retracts the article "Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo ...Evaluation" ....
Piceatannol (PIC) is a naturally occurring polyphenolic stilbene, and it has pleiotropic pharmacological properties. Moreover, PIC has cytotoxic actions among various cancer cells. In this work, ...preparations of PIC-loaded bilosome-zein (PIC-BZ) were designed, formulated, and characterized, and the optimized PIC-BZ cytotoxic activities, measured as half maximal inhibitory concentration (IC
), against lung cancer cell line was investigated. Box-Behnken design was utilized in order to examine the effect of preparation factors on drug entrapment and particle size. PIC-BZ showed a spherical shape after optimization, and its particle size was determined as 157.45 ± 1.62 nm. Moreover, the efficiency of drug entrapment was found as 93.14 ± 2.15%. The cytotoxic activity evaluation revealed that the adjusted formulation, which is PIC-BZ formula, showed a substantially smaller IC
versus A549 cells. Cell cycle analysis showed accumulation of cells in the G2-M phase. Moreover, it showed in the sub-G1 phase, a rise of cell fraction suggestion apoptotic improving activity. Increased early and late phases of apoptosis were demonstrated by staining of cells with annexin V. Furthermore, the cellular caspase-3 protein expression was significantly raised by PIC-BZ. In addition, the wound healing experiment confirmed the results. To conclude, compared to pure PIC, PIC-BZ demonstrated a higher cell death-inducing activity against A549 cells.
Flibanserin (FLB) is a multifunctional serotonergic agent that was recently approved by the FDA for the oral treatment of premenopausal women with hypoactive sexual desire disorder. FLB is a ...centrally acting drug that has a low oral bioavailability of 33% owing to its exposure to the hepatic first-pass effect, as well as its pH-dependent solubility, which could be an obstacle hindering the drug dissolution and absorption via mucosal barriers. Thus, this work aimed at overcoming the aforementioned drawbacks and promoting the nose-to-brain delivery of FLB via the formulation of an intra-nasal in situ niosomal gel. The Box–Behnken design was employed to study the impact of Span® 85 concentration (X1), hydration time (X2), and pH of the hydrating buffer (X3) on the vesicle size and drug entrapment. The optimized formulation exhibited a spherical shape with a vesicular size of 46.35 nm and entrapment efficiency of 92.48%. The optimized FLB niosomes integrated into gellan gum-based in situ gel exhibited enhanced ex vivo permeation and improved plasma and brain concentrations after nasal administration in rats compared to raw FLB. These findings highlight the capability of the proposed intra-nasal FLB niosomal in situ gel to boost the drug bioavailability and to promote its direct delivery to the brain.
Prostate cancer (PCa) is becoming one of the most frequently occurring cancers among men and causes an even greater number of deaths. Due to the complexity of tumor masses, radiologists find it ...difficult to identify PCa accurately. Over the years, several PCa-detecting methods have been formulated, but these methods cannot identify cancer efficiently. Artificial Intelligence (AI) has both information technologies that simulate natural or biological phenomena and human intelligence in addressing issues. AI technologies have been broadly implemented in the healthcare domain, including 3D printing, disease diagnosis, health monitoring, hospital scheduling, clinical decision support, classification and prediction, and medical data analysis. These applications significantly boost the cost-effectiveness and accuracy of healthcare services. This article introduces an Archimedes Optimization Algorithm with Deep Learning-based Prostate Cancer Classification (AOADLB-P2C) model on MRI images. The presented AOADLB-P2C model examines MRI images for the identification of PCa. To accomplish this, the AOADLB-P2C model performs pre-processing in two stages: adaptive median filtering (AMF)-based noise removal and contrast enhancement. Additionally, the presented AOADLB-P2C model extracts features via a densely connected network (DenseNet-161) model with a root-mean-square propagation (RMSProp) optimizer. Finally, the presented AOADLB-P2C model classifies PCa using the AOA with a least-squares support vector machine (LS-SVM) method. The simulation values of the presented AOADLB-P2C model are tested using a benchmark MRI dataset. The comparative experimental results demonstrate the improvements of the AOADLB-P2C model over other recent approaches.
The serum concentrations of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies are directly correlate in the induction and diagnosis of autoimmune thyroid disorders ...(AITDs). Therefore, the evaluation of serum anti-TPO and anti-TG antibodies in relation to thyroid function test parameters including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). This evaluation would be helpful in early diagnosis of abnormal thyroid function and associated autoimmune thyroid diseases. In this cross-sectional study, the serum anti-TPO, anti-TG, T3, T4 and TSH levels of 311 suspected patients of autoimmune thyroid disorders and 40 control subjects were evaluated. The data were presented as mean, ± standard deviations of the mean. Pearson correlation and chi-square tests were used to assess the correlation coefficients and significance in the contingency tables. The thyroid function test parameters in normal and AITDs suspected patients were significantly different in correlation to elevated serum levels of anti-TPO antibody. A significant association was detected between female gender and elevated levels of anti-TPO (P value = 0.047). A higher percentage of women showed elevated levels of anti-TG, but it was not statistically significant (P value= 0.107). The findings of the study reveal a strong correlation between thyroid function test and thyroid antibodies levels, elaborating the clinical importance of thyroid antibodies in clinical examination and follow-up of patients with autoimmune thyroid disorders.
The therapeutic effectiveness of anticancer drugs with a selective target for the nucleus of cancer cells may be improved by experimental approaches. In this regard, the formulation of anticancer ...drugs is considered one of the best ways to improve their effectiveness in targeting cancerous tissues. To enhance the anticancer activity of 2-methoxy-estradiol (2 ME) for breast cancer, 2-methoxyestradiol loaded alpha lipoic acid nanoparticles have been formulated. The prepared formula was observed to be spherical with a nanometer-scale and low PDI size (.234). The entrapment efficiency of the 2ME-ALA NPs was 87.32 ± 2.21% with > 85% release of 2 ME within 24 h. There was a 1.2-fold increase in apoptosis and a 3.46-fold increase in necrosis of the MCF-7 cells when incubated with 2ME-ALA NPs when compared to control cells. This increased apoptosis was also associated with increased ROS and increased p53 expression in 2ME-ALA NPs treated cells compared to the raw-2 ME group. Evaluation of cell-cycle data showed a substantial arrest of the G2-M phase of the MCF-7 cells when incubated with 2ME-ALA NPs. At the same time, a dramatically increased number of pre-G1 cells showed the increased apoptotic potential of the 2 ME when administered via the proposed formulation. In the end, the differential upregulation of caspase-3, p53, and ROS in MCF-7 cells established the superiority of the 2ME-ALA-Ms approach in targeting breast cancer. In summary, these results demonstrate that 2ME-ALA NPs are an efficient delivery tool for controlling the growth of breast cancer cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Statins, including simvastatin (SMV), are commonly used for the control of hyperlipidaemia and have also proven therapeutic and preventative effects in cardiovascular diseases. Besides that, there is ...an emerging interest in their use as antineoplastic drugs as demonstrated by different studies showing their cytotoxic activity against different cancer cells. In this study, SMV-loaded emulsomes (SMV-EMLs) were formulated and evaluated for their cytotoxic activity in MCF-7 breast cancer cells. The emulsomes were prepared using a modified thin-film hydration technique. A Box–Behnken model was used to investigate the impact of formulation conditions on vesicle size and drug entrapment. The optimized formulation showed a spherical shape with a vesicle size of 112.42 ± 2.1 nm and an entrapment efficiency of 94.34 ± 1.11%. Assessment of cytotoxic activities indicated that the optimized SMV-EMLs formula exhibited significantly lower half maximal inhibitory concentration (IC50) against MCF-7 cells. Cell cycle analysis indicated the accumulation of cells in the G2-M phase as well as increased cell fraction in the pre-G1 phase, suggesting an enhancement of anti-apoptotic activity of SMV. The staining of cells with Annex V revealed an increase in early and late apoptosis, in line with the increased cellular content of caspase-3 and Bax. In addition, the mitochondrial membrane potential (MMP) was significantly decreased. In conclusion, SMV-EMLs demonstrated superior cell death-inducing activity against MCF-7 cells compared to pure SMV. This is mediated, at least in part, by enhanced pro-apoptotic activity and MMP modulation of SMV.
Diabetic nephropathy is a significant medical condition that arises from elevated blood sugar levels associated with both type I and type II diabetes. Recent research has indicated that ellagic acid ...(EA), either alone or in combination with other medications, can provide anti-diabetic benefits. This study aimed to explore the effects of EA and EA nanoformulations (EN) on nephropathy induced by type II diabetes in rats, while also investigating the underlying mechanisms at play. To induce type II diabetes, rats were fed a high-fat diet for four weeks, followed by a single intraperitoneal dose of streptozotocin (35 mg/kg), and continued on the high-fat diet for an additional four weeks. Diabetic rats were then treated with Metformin (M), EA, EN, EA + M, or EN + M for four weeks. The findings revealed that treatment with EN and the combination of M led to significant reductions in serum urea and creatinine levels, indicating an improvement in renal function. Additionally, EN and/or M effectively mitigated lipid peroxidation (LPO) levels in the affected kidneys, reduced fasting serum glucose, and lowered C-reactive protein (CRP) levels. Moreover, EN and/or M demonstrated the ability to prevent diabetes-induced histological alterations in the kidney glomeruli and tubules, as well as reduce collagen mesangial matrix formation. The presence of caspase 3, an apoptotic mediator, was significantly reduced in the kidneys of diabetic rats treated with EN and/or M. In conclusion, EN and/or M have the potential to prevent nephropathy induced by type II diabetes by enhancing glycemic control, reducing oxidative stress and inflammation, and scavenging free radicals, all of which contribute to apoptotic changes in kidney tissue.
The immunosuppressant cyclosporine A (CSA) has been linked to serious renal toxic effects. Although 2-methoxyestradiol (2ME) possesses a wide range of pharmacological abilities, it suffers poor ...bioavailability after oral administration. The purpose of this study was to evaluate the potential of 2ME loaded D-ɑ-tocopheryl polyethylene glycol succinate (TPGS) micelles to prevent CSA-induced nephrotoxicity in rats. A 2ME-TPGS was prepared and showed particle size of 44.3 ± 3.5 nm with good entrapment efficiency and spherical structures. Male Wistar rats were divided into 5 groups, namely: Control, Vehicle, CSA, CSA + 2ME-Raw, and CSA + 2ME-Nano. CSA was injected daily at a SC dose of 20 mg/kg. Both 2ME-Raw and 2ME-Nano were given daily at oral doses of 5 mg/kg. Treatments continued for three successive weeks. 2ME-TPGS exerted significant protective effects against CSA nephrotoxicity. This was evidenced in ameliorating deterioration of renal functions, attenuation of pathological changes in kidney tissues, exerting significant anti-fibrotic, antioxidant, and anti-inflammatory effects together with significant anti-apoptotic effects. Western blot analyses showed both 2ME-Raw and 2ME-Nano significantly inhibited protein expression of TGF-β1 and phospho-ERK (p-ERK). It was observed that 2ME-TPGS, in almost all experiments, exerted superior protective effects as compared with 2ME-Raw. In conclusion, 2ME loaded in a TPGS nanocarrier possesses significant protective activities against CSA-induced kidney injury in rats. This is attributable to 2ME anti-fibrotic, antioxidant, anti-inflammatory, and anti-apoptotic activities which are mediated at least partly by inhibition of TGF-β1/p-ERK axis.
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