A Novel Spectrofluorimetric Determination of Antazoline and Xylometazoline in their Ophthalmic Formulation; Green Approach and Evaluation.

A green developed spectrofluorimetric method has been applied for Antazoline (ANT) and Xylometazoline (XLO) determination in both pharmaceutical formulation and pure form. The developed method is synchronous spectrofluorimetry coupled with the second derivative mathematical tool for the determination of antazoline and xylometazoline in their dosage form. The developed method depends on reacting the cited drugs with dansyl chloride, a suitable derivatizing agent, to generate highly fluorescent derivatives. The products formed were measured at emission wavelengths; 703.0 and 712.0 nm after being excited at wavelengths; 350.0 and 355.0 nm for antazoline and xylometazoline, respectively. Synchronous spectrofluorimetry coupled with second derivative mathematical tool was developed and optimized using fluorescence data manager software generating second derivative peak amplitudes at 556.5 nm for antazoline and 598.0 nm for xylometazoline. Linear responses have been represented over a wide range of concentration 0.5-12.0 µg/mL for antazoline and 0.1-10.0 µg/mL for xylometazoline, correspondingly. Method validation was successfully applied. Additionally, statistical comparison of developed method with official ones has been carried out where no significant difference was found. Evaluation of the method's greenness was proven using several assessment tools. Indeed, the method developed is found to be precise, sensitive, and discriminating to assess the cited drugs for regular analysis.

Unlocking the secrets: exploring the influence of the aryl hydrocarbon receptor and microbiome on cancer development.

Gut microbiota regulates various aspects of human physiology by producing metabolites, metabolizing enzymes, and toxins. Many studies have linked microbiota with human health and altered microbiome configurations with the occurrence of several diseases, including cancer. Accumulating evidence suggests that the microbiome can influence the initiation and progression of several cancers. Moreover, some microbiotas of the gut and oral cavity have been reported to infect tumors, initiate metastasis, and promote the spread of cancer to distant organs, thereby influencing the clinical outcome of cancer patients. The gut microbiome has recently been reported to interact with environmental factors such as diet and exposure to environmental toxicants. Exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) induces a shift in the gut microbiome metabolic pathways, favoring a proinflammatory microenvironment. In addition, other studies have also correlated cancer incidence with exposure to PAHs. PAHs are known to induce organ carcinogenesis through activating a ligand-activated transcriptional factor termed the aryl hydrocarbon receptor (AhR), which metabolizes PAHs to highly reactive carcinogenic intermediates. However, the crosstalk between AhR and the microbiome in mediating carcinogenesis is poorly reviewed. This review aims to discuss the role of exposure to environmental pollutants and activation of AhR on microbiome-associated cancer progression and explore the underlying molecular mechanisms involved in cancer development.

A novel green spectrofluorimetric method for simultaneous determination of antazoline and tetryzoline in their ophthalmic formulation.

A novel spectrofluorimetric method has been developed for determination of antazoline (ANT) and tetryzoline (TET) in their pharmaceutical formulation. A combined application of synchronous spectrofluorimetry and second derivative mathematical treatment was developed. The proposed method depends on reacting the cited drugs with dansyl chloride (DNS-Cl) being a suitable derivatizing agent generating highly fluorescent derivatives measured at emission wavelengths of 703.0 and 642.0 nm after excitation wavelengths of 350.0 and 320.0 nm for ANT and TET, respectively. The joint use of synchronous spectrofluorimetry with second derivative mathematical treatment is for the first time to be developed and optimized in aid of using fluorescence data manager software generating second derivative peak amplitudes at 556.5 nm for ANT and 516.7 nm for TET. Linear responses have been represented over a wide range of concentration (0.5-12.0 µg/mL for ANT and 0.5-10.0 µg/mL for TET). Additionally, statistical comparison of the developed method with the official ones has been carried out where no significant difference was found. Additionally, greenness profile assessment was accomplished by means of four metric tools. Indeed, the method developed is found to be precise, sensitive, and discriminating to assess the cited drugs for regular analysis.

Curriculum, competency development, and assessment methods of MSc and PhD pharmacy programs: a scoping review.

BACKGROUND/OBJECTIVES: We aim to systematically review and evaluate the current landscape of postgraduate pharmacy education to a) identify current evidence, best practices, challenges, recommendations, and solutions; and b) develop a framework to optimize postgraduate pharmacy programs. METHODS: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Electronic databases, including PubMed, Scopus, EMBASE, ProQuest, Web of Science, and Google Scholar were utilized. The search covered studies published from January 2011 to September 2023. Following the principles of Arksey and O'Malley's framework, data charting and extraction were performed using a pre-designed data collection tool, followed by the synthesis and grouping of studies based on common themes. RESULTS: Of the 5542 articles found, the review included 36 eligible ones focusing on pharmacy postgraduate education (PhD and MSc), grouped into three themes: 1) courses and curriculum; 2) training and skills development; 3) assessment and mentorship methods. Utilized methodologies included descriptive analyses, questionnaires, surveys, trials, and focus groups/interviews. The studies underscored the need for competency-based curricula with regular evaluations, career planning, and diverse course offerings. Identified key skills and competencies in the studies included soft skills, communication, research, desperate skills (e.g., leadership and management), and critical thinking. The studies also emphasized the value of comprehensive evaluation and peer review methods. Challenges included balancing academic and real-world requirements, training, limited resources, time constraints, and faculty workload. CONCLUSION: Evidence-based suggestions to improve postgraduate pharmacy education include the implementation of practice-oriented courses, value of tailored/or comprehensive assessments, focus on real-world skills, effectiveness of advanced teaching methods, and mentorship role. The proposed framework can guide program enhancement and highlight the need to improve programs holistically, entailing the three themes.

Regulation of the aryl hydrocarbon receptor in cancer and cancer stem cells of gynecological malignancies: An update on signaling pathways.

Gynecological malignancies are a female type of cancers that affects the reproductive system. Cancer metastasis or recurrence mediated by cellular invasiveness occurs at advanced stages of cancer progression. Cancer Stem Cells (CSCs) enrichment in tumors leads to chemoresistance, which results in cancer mortality. Exposure to environmental pollutants such as polycyclic aromatic hydrocarbons is associated with an increased the risk of CSC enrichment in gynecological cancers. One of the important pathways that mediates the metabolism and bioactivation of these environmental chemicals is the transcription factor, aryl hydrocarbon receptor (AhR). The present review explores the molecular mechanisms regulating the crosstalk and interaction of the AhR with cancer-related signaling pathways, such as apoptosis, epithelial-mesenchymal transition, immune checkpoints, and G-protein-coupled receptors in several gynecological malignancies such as ovarian, uterine, endometrial, and cervical cancers. The review also discusses the potential of targeting the AhR pathway as a novel chemotherapy for gynecological cancers.

Evaluation of hazards of electronic -cigarette's liquid refill on testes of mice, complemented by histopathological and chromatographic analysis.

Electronic-cigarettes (e-cigarettes) are devices designed to become an alternative to classic cigarettes. Vaping of e-cigarettes and their recharge liquid have become extremely popular among the adolescents; however, its safety is not well established. Evaluation of the components of e-cigarette liquid and their potential effects on testis of adult male mice. This aim will be fulfilled by histological, ultrastructural, and immunohistochemical analysis of mice testis biopsies. Twenty mice were allocated into two groups of equal size. The control group was given regular saline, whereas the treated group was given e-liquid (contains 3 mg of nicotine/kg of body weight) both groups daily intraperitoneally injected for 3 weeks. Analysis of e-liquid by Gas Chromatography-Mass Spectrometric GC/MS demonstrated nicotine, phenol, vanillin, aldehydes, and pyrethroid insecticide. Evaluation of oxidative stress parameters revealed significant reduction of SOD and GPx. Histological results revealed a significant reduction in the height of seminiferous tubules, sloughing of spermatogenic cells, most cells being dark and pyknotic, and thickening of the interstitium with accumulation of PAS positive exudate. Most spermatogenic cells showed degenerative changes as rarefied cytoplasm, ill-defined electron-dense nuclei, and elongated spermatid showed deformity of ectoplasmic specialization. Immunohistochemical studies revealed a significant increase in caspase-3 positive cells and a significant reduction of area % of E-cadherin. The analysis of an available E-liquid demonstrated potentially harmful chemicals that are not shown in the labeling of the product. E-liquid appears to impair anti-oxidant defense and cause degenerative changes in the body and disruption of blood testes barrier BTB. So, e-cigarettes cannot be regarded as a non-harmful smoking replacement.

Testing efficacy of the nicotine protection of the substantia nigra pars compacta in a rat Parkinson disease model. Ultrastructure study.

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) with subsequent motor manifestations. This study aimed to assess the ameliorative effects of nicotine, in rotenone-induced PD rat model. Thirty adult male Albino Wistar rats were divided into three equal groups. Group I received an injection of normal saline. Group II received subcutaneous injection of rotenone at a dose of 1.5 mg/kg every other day. Group III received rotenone in the same previous dose and nicotine at a dose of 1.5 mg/kg daily. After 11 days of treatment, body weight (BW) and rat motor behavior were estimated. Specimens from the midbrain were processed for light and electron microscopy. The expression of tyrosine hydroxylase (TH), α-synuclein, and GFAP was examined. Serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA), and striatal levels of dopamine (DA) were analyzed. Group III revealed a significant improvement in BW and motor activity. Nicotine upregulated the expression of TH, downregulated the expression of α-synuclein and GFAP. The levels of MDA and TAC were improved but were still far from those of the control. Striatal DA levels increased. Nicotine activated the neurons and glial cells. The vascular endothelium, however, did not elicit improvement. Although nicotine ameliorated the loss of the dopaminergic neurons and motor deficit, it did not show improvement of vascular endothelium. It is still necessary to examine nicotin's ability to maintain the dopaminergic neurons in a good functioning state.

The Novel Potential Therapeutic Utility of Montelukast in Alleviating Autistic Behavior Induced by Early Postnatal Administration of Thimerosal in Mice.

BACKGROUND AND AIM: Thimerosal (THIM) is a mercury-containing preservative widely used in many biological and medical products including many vaccines. It has been accused of being a possible etiological factor for some neurodevelopmental disorders such as autistic spectrum disorders (ASDs). In our study, the potential therapeutic effect of montelukast, a leukotriene receptor antagonist used to treat seasonal allergies and asthma, on THIM mice model (ASDs model) was examined. METHODOLOGY: Newborn mice were randomly distributed into three groups: (Group 1) Control (Cont.) group received saline injections. (Group 2) THIM-treated (THIM) group received THIM intramuscular (IM) at a dose of 3000 µg Hg/kg on postnatal days 7, 9, 11, and 15. (Group 3) Montelukast-treated (Monte) group received THIM followed by montelukast sodium (10 mg/kg/day) intraperitoneal (IP) for 3 weeks. Mice were evaluated for growth development, social interactions, anxiety, locomotor activity, and cognitive function. Brain histopathology, alpha 7 nicotinic acetylcholine receptors (α7nAChRs), nuclear factor kappa B p65 (NF-κB p65), apoptotic factor (Bax), and brain injury markers were evaluated as well. RESULTS: THIIM significantly impaired social activity and growth development. Montelukast mitigated THIM-induced social deficit probably through α7nAChRs upregulation, NF-κB p65, Bax, and brain injury markers downregulation, thus suppressing THIM-induced neuronal toxicity and inflammation. CONCLUSION: Neonatal exposure to THIM can induce growth retardation and abnormal social interactions similar to those observed in ASDs. Some of these abnormalities could be ameliorated by montelukast via upregulation of α7nAChRs that inhibited NF-κB activation and significant suppression of neuronal injury and the associated apoptosis.

Tramadol administration induced hippocampal cells apoptosis, astrogliosis, and microgliosis in juvenile and adult male mice, histological and immunohistochemical study.

Tramadol is a common analgesic, frequently used for relieving moderate or severe pain and widely used to delay ejaculation. However, repeated large doses have several adverse effects, especially on the brain tissue. So, this study was designed to assess the potentially deleterious effects of chronic administration of tramadol on principal fields of the hippocampus in adult and juvenile male albino mice. Thirty swiss male albino mice were divided equally into three groups: Group Ia (control adult) 3 months old, Group Ib (control juvenile) 3-week postnatal mice, Group II (tramadol treated adult mice) and Group III (tramadol treated juvenile mice). Both treated groups received tramadol tablets dissolved in water in a dose of 40mg/kg for 1 month by gastric tube. Tramadol treated groups showed degenerative changes in dentate gyrus (DG) granule cells, pyramidal neurons of CA1and CA3 fields in the form of electron-dense or rarified cytoplasm, dilated rER and mitochondrial changes. Additionally, immunohistochemical results revealed significantly increased in caspase 3 positive cells in different hippocampal principal fields. Astrogliosis and microgliosis were proved by the increased immunoreactivity of astrocytes to glial fibrillary acidic protein (GFAP) and microglia to CD68. Morphometric findings showed a significant reduction of both surface area of granule and pyramidal cells, and in thickness of DG, CA1, CA3 layers. Moreover, most of these morphological changes were aggravated in the juvenile-treated group. So, it can be concluded that tramadol abuse can induce an altered morphological change on the principal fields of the hippocampus in adult and juvenile mice.

Protective effect of tetrahydrobiopterin on hepatic and renal damage after acute cadmium exposure in male rats.

Cadmium (Cd) has been recognized as one of the most important environmental and industrial pollutants. This study investigated the impact of acute exposure to Cd on oxidative stress and the inflammatory marker interleukin-6 (IL-6) in the plasma of rats and the histological picture of liver and kidney, as well as to examine the potential protective effect of tetrahydrobiopterin (BH4). METHODS: Rats were divided into control group, Cd group that received a single intraperitoneal (i.p.) dose of 4 mg/kg b.w. of CdCl2 and BH4+ Cd group that received a single dose of BH4 (20 mg/kg, i.p.) and subsequently exposed to a single dose of Cd 24 h after the BH4 treatment. RESULTS: Cd increased the plasma levels of hepatic enzymes (ALT and AST), urea, creatinine, malondialdehyde (MDA), and IL-6 and decreased the superoxide dismutase (SOD) activity. Also, it induced histopathological alterations in the liver with severe degeneration, especially in centrilobular zones. Renal tubular epithelium showed vacuolated cytoplasm and dense nuclei. VEGF expression was mild. Ultrastuctural changes were seen in some renal tubules. The nuclei appeared distorted with electron dense chromatin. Mitochondria with destructed cristae were observed. BH4 pretreatment had protective effects, since it significantly reduced the levels of IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Improvement of histopathological alterations was observed in Cd-groups. The nuclei were vesicular euchromatic, intact mitochondria and normal appearance of the filtration membrane. Moderate expression of VEGF was noted. CONCLUSION: This study has provided clear evidence for the protective efficacy of BH4 against experimental Cd toxicity.

Rat hippocampal CA3 neuronal injury induced by limb ischemia/reperfusion: A possible restorative effect of alpha lipoic acid.

Limb ischemia reperfusion (I/R) injury is associated with serious local and systemic effects. Reperfusion may augment tissue injury in excess of that produced by ischemia alone. The hippocampus has been reported to be vulnerable to I/R injury. Alpha lipoic acid (ALA) is an endogenous antioxidant with a powerful antioxidative, anti-inflammatory, and antiapoptotic properties. We studied the probable restorative effect of ALA on limb I/R-induced structural damage of rat hippocampus. Forty adult male albino rats were divided equally into four groups: group I (sham); group II (I/R-1 day) has undergone bilateral femoral arteries occlusion (3 h), then reperfusion for 1 day; group III (I/R-7 days) has undergone reperfusion for seven days; group IV (I/R-ALA) has undergone I/R as group III and received an intraperitoneal injection of ALA (100 mg/kg) for 7 days. I/R groups revealed degenerative changes in the pyramidal neuronal perikarya of CA3 field in the form of dark-stained cytoplasm, dilated RER cisternae, mitochondrial alterations, and dense bodies' accumulation. Their dendrites showed disorganized microtubules. Astrogliosis is featured by an increased number and increased immunoreactivity of astrocytes for glial fibrillary acid protein. Morphometric data revealed significant reduction of light neurons, surface area of neurons, and thickness of the CA3 layer. Most blood capillaries exhibited narrow lumen and irregular basal lamina. ALA ameliorated the neuronal damage. Pyramidal neurons revealed preservation of normal structure. Significant increase in the thickness of pyramidal layer in CA3 field and surface area and number of light neurons was observed but astrogliosis persisted. Limb I/R had a deleterious remote effect on the hippocampus aggravated with longer period of reperfusion. This work may encourage the use of ALA in the critical clinical settings with I/R injury.

Consecutive high-performance removal of Cu2+ metal ions and Deltamethrin using multifunctional pyrolysis cuttlebone/cotton fabric nanocomposite.

A simple technique was developed for the modification of cotton materials that is inexpensive, environmentally friendly, and very effective. Waste Cotton fabrics (WCFs) are loaded with propolis extract (PE) for Cu2+ removal. Then, Cu2+ underwent a pyrolysis process with modified cuttlebone (CB) at 900 °C for 5 h. The surface of the prepared materials was characterized using X-ray diffraction (XRD), scanning electron microscopy with energy-dispersive X-ray (SEM-EDX), Fourier transform infrared (FTIR), BET, particle sizes, thermogravimetric analysis (TGA) and zeta potential analysis. The Cu2+ metal ions from an aqueous solution were removed using WCFs/PE, and DLM was subsequently removed using pyro WCFs/PE/Cu/CB. The as-prepared NPs exhibited the face-centered cubic structure of WCFs/PE/Cu/CB with crystallite sizes ranging from 386.70 to 653.10 nm. FTIR spectra revealed that CB was present on the surface of the resulting WCFs/PE/Cu. SEM revealed the dispersion of a uniformly flower-like morphology over a large area. Sorption studies were performed based on parameters that included pH, dose, contact time, and initial concentration. The adsorption isotherm and the kinetic studies of the DLM adsorption process were applied at a pH of 5.0 and a temperature of 25 °C using several isotherms and kinetic models. The results revealed qmax (20.51 mg/g) with R2 = 0.97, the Langmuir isotherm that best matches the experimental data. Hence, the Langmuir isotherm suggests that it is the model that best describes sorption on homogenous surfaces or surface-supporting sites with various affinities. The correlation coefficient R2, χ2, adjusted correlation coefficient, and error functions like root mean square (RMSE), normalized root mean square error (NRMES), and mean absolute error (MAE) were used to evaluate the best-fit models to the experimental adsorption data. Moreover, cost estimation for the prepared adsorbent WCFs/PE/Cu showed that it costs approximately 3 USD/g, which is a cheap adsorbent compared to other similar adsorbents reported in the literature. The examined WCFs/PE have significant applicability potential for Cu2+-laden wastewater treatment due to their superior Cu2+ metal ions adsorption capability and reusability. The cytotoxicity and safety study showed that at higher concentrations, it resulted in much less cell viability. Additionally, the removal efficiency of Cu2+ metal ions from synthetic, realistic industrial wastewater using WCFs/PE reached up to 96.29 %, demonstrating good adsorption capability. Thus, there is a huge possibility of accomplishing this and performing well. This study paves the way for the reuse and valorization of selected adsorbents following circular economy principles. Two green metrics were applied, the Analytical Eco-scale and the Analytical GREEnness Calculator (AGREE).

The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways.

In colorectal cancer (CRC), aberrations in KRAS are associated with aggressive tumorigenesis and an overall low survival rate because of chemoresistance and adverse effects. Ergo, complementary, and integrative medicines are being considered for CRC treatment. Among which is the use of natural chalcones that are known to exhibit anti-tumor activities in KRAS mutant CRC subtypes treatment regimens. Consequently, we examine the effect of two novel compounds (DK13 and DK14) having chalcones with nitrogen mustard moiety on CRC cell lines (HCT-116 and LoVo) with KRAS mutation. These compounds were synthesized in our lab and previously reported to exhibit potent activity against breast cancer cells. Our data revealed that DK13 and DK14 treatment suppress cell growth, disturb the progression of cell cycle, and trigger apoptosis in CRC cell lines. Besides, treatment with both compounds impedes cell invasion and colony formation in both cell lines as compared to 5-FU; this is accompanied by up and down regulations of E-cadherin and Vimentin, respectively. At the molecular level, both compounds deregulate the expression and phosphorylation of ß-catenin, Akt and mTOR, which are the main likely molecular mechanisms underlying these biological occurrences. Our findings present DK13 and DK14 as novel chemotherapies against CRC, through ß-catenin/Akt/mTOR signaling pathways.

Phe354Leu polymorphism of the liver kinase B1 gene as a prognostic factor in adult egyptian patients with acute myeloid leukemia.

Background: The human liver kinase B1 (LKB1) gene is a significant tumor suppressor widely expressed in all fetal and adult tissues. Despite its established role in solid tumors, the biological and clinical implications of LKB1 gene alterations in hematological malignancies have not been sufficiently recognized. Aim: This study aimed to determine the frequency of the LKB1 Phe354Leu polymorphism in adult Egyptian patients with cytogenetically normal AML (CN-AML), evaluate its clinical prognostic significance, and investigate its effect on the therapeutic outcome and patient survival. Methods: Direct sequencing of amplified exon eight of the LKB1 gene was performed to detect the Phe354Leu polymorphism in 72 adult de novo CN-AML patients. Results: The LKB1 Phe354Leu polymorphism was detected in 16.7% of patients and associated with younger age and lower hemoglobin levels (p < 0.001). Patients in the mutated group had significantly higher total leukocytic count and bone marrow blasts (p = 0.001 and p < 0.001, respectively). The most common FAB subtypes in mutated patients were M4 and M2. The relapse rate was significantly higher in the mutated group (p = 0.004). There was a significant association between the FLT3-ITD polymorphism and LKB1 F354L (p < 0.001). The mutated group had shorter overall survival (p = 0.003). In multivariate analysis, the Phe354Leu polymorphism was a significant independent prognostic variable for the overall and disease-free survival of the studied patients (p = 0.049). Conclusion: The LKB1 Phe354Leu polymorphism was diagnosed at younger ages in Egyptian CN-AML patients and represented a poor independent prognostic factor in CN-AML. Patients who carried this polymorphism had shorter overall survival and more frequent relapses. Our findings may provide insight into the design of therapeutic targets, and molecular testing of the LKB1 gene is recommended for proper risk stratification of CN-AML patients.

Exquisite integration of quality-by-design and green analytical approaches for simultaneous determination of xylometazoline and antazoline in eye drops and rabbit aqueous humor, application to stability study.

This work implements a stability indicating HPLC method developed to simultaneously determine xylometazoline (XYLO) and antazoline (ANT) in their binary mixture, rabbit aqueous humor and cited drug's degradates by applying analytical quality-by-design (AQbD) combined with green analytical chemistry (GAC) experiment for the first time. This integration was designed to maximize efficiency and minimize environmental impacts, as well as energy and solvent consumption. Analytical quality-by-design was applied to achieve our aim starting with evaluation of quality risk and scouting analysis, tracked via five parameters chromatographic screening using Placket-Burman design namely: pH, temperature, organic solvent percentage, flow rate, and wavelength detection. Recognizing the critical method parameters was done followed by optimization employing central composite design and Derringer's desirability toward assess optimum conditions that attained best resolution with satisfactory peak symmetry with short run time. Optimal chromatographic separation was attained by means of an XBridge® C18 (4.6 × 250 mm, 5 µm) column through isocratic elution using a mobile phase consists of phosphate buffer (pH 3.0): ethanol (60:40, by volume) at a 1.6 mL/min flow rate and 230.0 nm UV detection. Linearity acquired over a concentration range of 1.0-100.0 µg/mL and 0.5-100.0 µg/mL for XYLO and ANT, respectively. Furthermore, imperiling cited drugs' stock solutions to stress various conditions and satisfactory peaks of degradation products were obtained indicating that cited drugs are vulnerable to oxidative degradation and basic hydrolysis. Degradates' structures were elucidated using mass spectrometry. Applying various assessment tools; namely: analytical greenness (AGREE), green analytical procedure index (GAPI), analytical eco-scale, and national environmental method index (NEMI), Greenness method's evaluation was applied and proved to be green. In fact, the developed method is established to be perceptive, accurate, and selective to assess cited drugs for routine analysis.

Novel solid-contact ion-selective electrode based on a polyaniline transducer layer for determination of alcaftadine in biological fluid.

Fabrication of a novel ion selective electrode for determining alcaftadine was achieved. The glassy carbon electrode (GCE) was utilized as a substrate in fabrication of an electrochemical sensor containing polyaniline (PANI) as an ion-to-electron transducer layer. A PVC polymeric matrix and nitrophenyl-octyl-ether were employed in designing the ion-sensing membrane (ISM). Potential stability was improved and minimization of electrical signal drift was achieved for inhibition of water layer formation at the electrode interface. Potential stability was achieved by inclusion of PANI between the electronic substrate and the ion-sensing membrane. The sensor's performance was evaluated following IUPAC recommendations. The sensor dynamic linear range was from 1.0 × 10-2 to 1.0 × 10-6 mol L-1 and it had a 6.3 × 10-7 mol L-1 detection limit. The selectivity and capabilities of the formed alcaftadine sensor were tested in the presence of its pharmaceutical formulation excipients as well as its degradation products. Additionally, the sensor was capable of quantifying the studied drug in a rabbit aqueous humor. Method's greenness profile was evaluated by the means of Analytical Greenness (AGREE) metric assessment tool.

Spectrophotometric platform windows' exploitation for the green determination of Alcaftadine in presence of its oxidative degradation product.

This study presents the determination of Alcaftadine (ALF) in its oxidative degradation product presence by applying comprehensive study comparative of four different green stability indicating spectrophotometric approaches through successful exploitation of different spectrophotometric platform windows. Window I; based on absorption spectrum zero order data manipulation using the newly developed extended absorbance difference (EAD). Window II; based on derivative spectra by second order derivative (D2) data manipulation. Window III; based on ratio spectra applying constant multiplication (CM) and absorptivity centering via factorized ratio difference spectrum (ACT-FSRΔP) methods data manipulation. Finally, window IV; based on derivative of ratio spectrum by virtue of first derivative of ratio spectral (DD1) method data manipulation. Calibration curves construction were over linearity range; 1.0-14.0 µg/mL for ALF. The proposed methods accuracy, precision, and linearity range were determined and validated as per ICH guidelines. Moreover, they were able to analyze ALF in raw form, dosage form and in existence of its oxidative degradation product. Statistical comparisons were done between the proposed methods and the reported one showing no significant difference concerning accuracy and precision. Furthermore, greenness profile assessment was accomplished by means of four metric tools; namely: analytical greenness (AGREE), green analytical procedure index (GAPI), analytical eco-scale, and national environmental method index (NEMI).

Green TLC-Densitometric Method for Simultaneous Determination of Antazoline and Tetryzoline: Application to Pharmaceutical Formulation and Rabbit Aqueous Humor.

Ophthalmic pharmaceutical preparation containing antazoline (ANT) and tetryzoline (TET) is prescribed widely as an over the counter medication for allergic conjunctivitis treatment. Development of a selective, simple and environmentally friendly thin-layer chromatographic method established to determine both ANT and TET in their pure forms, pharmaceutical formulation and spiked aqueous humor samples. By using silica gel plates and means of a developing system consists of ethyl acetate:ethanol (5:5, by volume), the studied drugs separation was achieved, and scanning was carried out at 220.0 nm for the separated bands with a 0.2-18.0 µg/band concentration range for each of ANT and TET. Standard addition technique application was carried out to determine the proposed method validity. Statistical comparison was made between the proposed method and the official methods ANT and TET showing no significant difference concerning accuracy and precision. Furthermore, greenness profile assessment was accomplished by means of four metric tools, namely, analytical greenness, green analytical procedure index, analytical eco-scale and national environmental method index.Highlights.

Naproxen as a potential candidate for promoting rivastigmine anti-Alzheimer activity against aluminum chloride-prompted Alzheimer's-like disease in rats; neurogenesis and apoptosis modulation as a possible underlying mechanism.

BACKGROUND AND AIM: Alzheimer's disease (AD) is one of the leading causes of dependence and disability among the elderly worldwide. The traditional anti-Alzheimer medication, rivastigmine, one of the cholinesterase inhibitors (ChEIs), fails to achieve a definitive cure. We tested the hypothesis that naproxen administration to the rivastigmine-treated aluminum chloride (AlCl3) Alzheimer's rat model could provide an additive neuroprotective effect compared to rivastigmine alone. MATERIALS AND METHODS: The studied groups were control (Cont), AlCl3 treated (Al), rivastigmine treated (RIVA), naproxen treated (Napro), and combined rivastigmine and naproxen treated (RIVA + Napro). Rats' memory, spatial learning, and cognitive behavior were assessed followed by evaluation of hippocampal acetylcholinesterase (AChE) activity. Hippocampal and cerebellar histopathology were thoroughly examined. Activated caspase-3 and the neuroepithelial stem cells marker; nestin expressions were immunohistochemically assayed. RESULTS: AD rats displayed significantly impaired memory and cognitive function, augmented hippocampal AChE activity; massive neurodegeneration associated with enhanced astrogliosis, apoptosis, and impaired neurogenesis. Except for the enhancement of neurogenesis and suppression of apoptosis, the combination therapy had no additional neuroprotective benefit over rivastigmine-only therapy. CONCLUSION: Naproxen's efficacy was established by its ability to function at the cellular level, improved neurogenesis, and decreased, apoptosis without having an additional mitigating impact on cognitive impairment in rivastigmine-treated AD rats.

Elaeagnus angustifolia Plant Extract Induces Apoptosis via P53 and Signal Transducer and Activator of Transcription 3 Signaling Pathways in Triple-Negative Breast Cancer Cells.

Elaeagnus angustifolia (EA) is used as an alternative medicine in the Middle East to manage numerous human diseases. We recently reported that EA flower extract inhibits cell proliferation and invasion of human oral and HER2-positive breast cancer cells. Nevertheless, the outcome of EA extract on triple-negative breast cancer (TNBC) cells has not been explored yet. We herein investigate the effect of the aqueous EA extract (100 and 200 µl/ml) on two TNBC cell lines (MDA-MB-231 and MDA-MB-436) for 48 h and explore its underlying molecular pathways. Our data revealed that EA extract suppresses cell proliferation by approximately 50% and alters cell-cycle progression of these two cancer cell lines. Additionally, EA extract induces cell apoptosis by 40-50%, accompanied by the upregulation of pro-apoptotic markers (Bax and cleaved caspase-8) and downregulation of the anti-apoptotic marker, Bcl-2. Moreover, EA extract inhibits colony formation compared to their matched control. More significantly, the molecular pathway analysis of EA-treated cells revealed that EA extract enhances p53 expression, while inhibiting the expression of total and phosphorylated Signal Transducer and Activator Of Transcription 3 (STAT3) in both cell lines, suggesting p53 and STAT3 are the main key players behind the biological events provoked by the extract in TNBC cells. Our findings implicate that EA flower extract may possess an important potential as an anticancer drug against TNBC.