Sex Differences in Withdrawal-Induced Anxiety in Rats After Exposure to Tobacco Smoke.

Nicotine, a component of cigarettes, possesses strong reinforcing properties and improves cognitive function, which can lead to dependence. Upon cigarette smoking cessation, withdrawal symptoms occur and may cause an individual to relapse. Affective withdrawal symptoms, such as anxiety, is of great concern as studies have shown its ability to cause relapse in men and women. In this in vivo study, anxiety resulting from smoking cessation after 2-day smoke-free intervals per week for the duration of 4 weeks was investigated in 8 male and 8 female rats after their exposure to cigarette smoke compared to unexposed control rats (8 males and 8 female rats). The anxiety in rats during smoke-free intervals was investigated using an elevated plus-maze (EPM), open-field (OF), and light/dark test (LD). In all tests male rats exhibited significantly higher anxiety symptoms compared to female rats during nicotine withdrawal, despite control rats showing no differences. In the EPM, male rats spent less time in open arm as well having as lower number of crossings than female rats. As for the OFT, the amount of time spent in the center of the open field was also lower in male rats than female rats. In the LD test, the time spent in the light chamber and the latency (delay) to enter the dark chamber was lower in male rats compared to female rats. Our study showed that male rats show greater nicotine withdrawal effects, in terms of anxiety-like behavior than female rats.

Biological evaluation of combinations of tyrosine kinase inhibitors with Inecalcitol as novel treatments for human chronic myeloid leukemia.

Background: The use of tyrosine kinase inhibitors (TKIs) as a treatment for chronic myeloid leukemia (CML) has improved the natural history of the disease and increased the duration of survival. Tyrosine kinase inhibitors represent the success of target therapies that work on molecular targets, although some patients still have therapy failure. Vitamin D has antiproliferative, pro-apoptotic, and anti-angiogenic effects on cells, therefore it can be considered as a potential cancer preventative and treatment agent. Inecalcitol (TX-522) is the 14-epi-analogue of Calcitriol (1,25(OH)2-vitamin D3), and inhibits cancer cell proliferation more effectively than Calcitriol. This study was conducted to evaluate the antiproliferative and synergistic effects of the anticancer drugs Imatinib and Dasatinib in combinations with Inecalcitol on human chronic myeloid leukemia K-562 cells. Method: The growth inhibitory activities of Inecalcitol, Imatinib, Dasatinib, and different combinations of one of the two drugs (Imatinib and Dasatinib) with Inecalcitol, were determined in vitro using MTT assay against K-562 cell line. Results: Inecalcitol, Imatinib, and Dasatinib showed potent antiproliferative activities against K-562 cells with GI50 values of 5.6 µM, 0.327 µM, and 0.446 nM, respectively. Combinations of Imatinib or Dasatinib with different concentrations of Inecalcitol increased significantly the antiproliferative activities and potencies of both drugs (****p < 0.0001), with optimal GI50 values of 580 pM (Imatinib) and 0.51 pM (Dasatinib). Furthermore, the combination treatments showed synergistic interaction between the antileukemic drugs and Inecalcitol, with combination indices (CI) < 1. Conclusion: The study demonstrated that the human chronic myeloid leukemia K-562 cells were subjected to a synergistic growth inhibitory impact when antileukemic drugs (Imatinib or Dasatinib) were combined with Inecalcitol, therefore, it is recommended that these combinations be viewed as promising novel antileukemic medications and used in place of individual medications with lower dosages and negligible side effects in the treatment of CML.

Nanoencapsulated Curcumin Mitigates Liver Injury and Drug-Metabolizing Enzymes Induction in Diclofenac-Treated Mice.

Curcumin (CUR) is a natural product with known anti-inflammatory, antioxidant, and hepatoprotective properties. The aim of this study was to formulate CUR into a polymeric nanoparticle (NP) formulation and examine its potential hepatoprotective activity in an animal model of diclofenac (DIC)-induced hepatotoxicity. CUR was loaded into polymeric NPs composed of poly(ethylene glycol)-polycaprolactone (PEG-PCL). The optimal CUR NPs were evaluated against DIC-induced hepatotoxicity in mice, by studying the histopathological changes and gene expression of drug-metabolizing cyp450 (cyp2c29 and cyp2d9) and ugt (ugt2b1) genes in the livers of the animals. The optimal NPs were around 67 nm in diameter with more than 80% loading efficiency and sustained release. Histological findings of mice livers revealed that CUR NPs exhibited a superior hepatoprotective effect compared to free CUR, and both groups reduced DIC-mediated liver tissue injury. While treatment with DIC alone or with CUR and CUR NPs had no effect on cyp2c29 gene expression, cyp2d9 and ugt2b1 genes were upregulated in the DIC-treated group, and this effect was reversed by CUR both as a free drug and as CUR NPs. Our findings present a promising application for nanoencapsulated CUR in the treatment of nonsteroidal anti-inflammatory drugs-induced liver injury and the associated dysregulation in the expression of hepatic drug-metabolizing enzymes.

Effects of Beta Lactams on Behavioral Outcomes of Substance Use Disorders: A Meta-Analysis of Preclinical Studies.

INTRODUCTION: Preclinical studies demonstrated that beta-lactams have neuroprotective effects in conditions involving glutamate neuroexcitotoxicity, including substance use disorders (SUDs). This meta-analysis aims to analyze the existing evidences on the effects of beta-lactams as glutamate transporter 1 (GLT-1) upregulators in animal models of SUDs, identification of gaps in the literature, and setting the stage for potential translation into clinical phases. METHODS: Meta-analysis was conducted on preclinical studies retrieved systematically from MEDLINE and ScienceDirect databases. Abused substances were identified by refereeing to the National Institute on Drug Abuse (NIDA). The results were quantitatively described with a focus on the behavioral outcomes. Treatment effect sizes were described using standardized mean difference, and they were pooled using random effect model. I2-statistic was used to assess heterogeneity, and Funnel plot and Egger's test were used for assessment of publication bias. RESULTS: Literature search yielded a total of 71 studies that were eligible to be included in the analysis. Through these studies, the effects of beta-lactams were evaluated in animal models of nicotine, cannabis, amphetamines, synthetic cathinone, opioids, ethanol, and cocaine use disorders as well as steroids-related aggressive behaviors. Meta-analysis showed that treatments with beta-lactams consistently reduced the pooled undesired effects of the abused substances in several paradigms, including drug-self administration, conditioned place preference, drug seeking behaviors, hyperlocomotion, withdrawal syndromes, tolerance to analgesic effects, hyperalgesia, and hyperthermia. CONCLUSION: This meta-analysis revealed that enhancing GLT-1 expression in the brain through beta-lactams seemed to be a promising treatment approach in the context of substance use disorders, as indicated by results in animal models.

Investigating Carvedilol's Repurposing for the Treatment of Non-Small Cell Lung Cancer via Aldehyde Dehydrogenase Activity Modulation in the Presence of ß-Adrenergic Agonists.

Repurposing existing drugs appears to be a potential solution for addressing the challenges in the treatment of non-small cell lung cancer (NSCLC). ß-adrenoceptor antagonist drugs (ß-blockers) have tumor-inhibiting effects, making them promising candidates for potential NSCLC treatment. This study investigates the anticancer potential of a subset of ß-blockers in NSCLC cell lines; A549 and H1299. Additionally, it investigates the underlying mechanism behind ß-blockers' anticancer effect by influencing a potential novel target named aldehyde dehydrogenase (ALDH). The MTT assay assessed ß-blockers' cytotoxicity on both cell lines, while Western blot and NADH fluorescence assays evaluated their influence on ALDH protein expression and activity. Carvedilol (CAR) was the most effective blocker in reducing cell survival of A549 and H1299 with IC50 of 18 µM and 13.7 µM, respectively. Significantly, CAR led to a 50% reduction in ALDH expression and 80% decrease in ALDH activity in A549 cells, especially when combined with ß-agonists, in comparison to the control. This effect might be attributed to ß-agonist blockade or an alternative pathway. This novel finding adds to our understanding of CAR's multifaceted anticancer properties, implying that combining CAR with ß-agonists could be a useful strategy for lung cancer treatment.

Development and Comparative Evaluation of Ciprofloxacin Nanoemulsion-Loaded Bigels Prepared Using Different Ratios of Oleogel to Hydrogels.

Nanoemulsions and bigels are biphasic delivery systems that can be used for topical applications. The aim of this study was to incorporate an oil-in-water ciprofloxacin hydrochloride nanoemulsion (CIP.HCl NE) into two types of bigels, Type I (oleogel (OL)-in-hydrogel (WH)) and Type II (WH-in-OL) to enhance drug penetration into skin and treat topical bacterial infections. Bigels were prepared at various ratios of OL and WH (1:1, 1:2, and 1:4). Initially, CIP.HCl NE was prepared and characterized in terms of droplet size, zeta potential, polydispersity index, morphology, and thermodynamic and chemical stability. Then CIP.HCl NE was dispersed into the OL or WH phase of the bigel. The primary physical stability studies showed that Type I bigels were physically stable, showing no phase separation. Whereas Type II bigels were physically unstable, hence excluded from the study. Type I bigels were subjected to microstructural, rheological, in vitro release, antimicrobial, and stability studies. The microscopic images showed a highly structured bigel network with nanoemulsion droplets dispersed within the bigel network. Additionally, bigels exhibited pseudoplastic flow and viscoelastic properties. A complete drug release was achieved after 4-5 h. The in vitro and ex vivo antimicrobial studies revealed that bigels exhibited antimicrobial activity against different bacterial strains. Moreover, stability studies showed that the rheological properties and physical and chemical stability varied based on the bigel composition over three months. Therefore, the physicochemical and rheological properties, drug release rate, and antimicrobial activity of Type I bigels could be modified by altering the OL to WH ratio and the phase in which the nanoemulsion dispersed in.

Exhausted Grape Seed Residues as a Valuable Source of Antioxidant Molecules for the Formulation of Biocompatible Cosmetic Scrubs.

Grape seed of Obeidi, a white Lebanese autochthonous variety, was previously tested in different studies as a valuable source of bioactive molecules such as polyphenols, oils, and proteins by means of extraction procedures for the development of cosmetic and therapeutic products. However, an un-valorized, exhausted grape seed residue remains as "secondary waste" after the extraction processes. In this study, the exhausted seeds have been further exploited to produce cosmetic scrubs capable of releasing antioxidant molecules during the exfoliation process, in accordance with the principles of the circular economy and going toward a zero-waste process. The deep characterization of the exhausted seeds confirmed the presence of antioxidant phenolic molecules including gallic acid, catechins and protocatechuic acid (0.13, 0.126, and 0.089 mg/g of dry matter DM), and a high phenolic content (11.85 mg gallic acid equivalents (GAE)/g of dry matter (DM)). Moreover, these residues were shown to possess a sandy texture (Hausner ratio (HR): 1.154, Carr index (CI): 0.133, and angle of repose: 31.62 (°) degrees), similar to commercial natural exfoliants. In this respect, exhausted Obeidi grape seed residues were incorporated at increasing concentrations (0.5, 1, 1.5, and 2% w/w) in a cosmetic scrub, and stored for 5 weeks at 4, 25, and 50 °C for stability testing. All tested scrub formulations exhibited good spreadability with a spread diameter of 3.6-4.7 cm and excellent physical stability, as no phase separation or color change were observed after four cycles of heat shock at 4 and 50 °C. Finally, an in vivo skin irritation test showed that the scrub enriched with 1.5% of exhausted Obeidi grape seed residues was the most promising formulation, as it possessed a high amount of phenolic molecules (0.042 ± 0.001 mg GAE/mL of scrub) and good stability and could be safely applied to the skin with no irritation phenomena. Overall results underlined that exhausted grape seed residues can be transformed into promising systems for both physical and chemical exfoliation, thus confirming the importance of the effective exploitation of agro-industrial by-products for the development of high value cosmeceutics towards a more sustainable and zero-waste approach.

Encapsulation of morin in lipid core/PLGA shell nanoparticles significantly enhances its anti-inflammatory activity and oral bioavailability.

Morin (3,5,7,2',4'-pentahydroxyflavone; MR) is a bioactive plant polyphenol whose therapeutic efficacy is hindered by its poor biopharmaceutical properties. The purpose of this study was to develop a nanoparticle (NP) formulation to enhance the bioactivity and oral bioavailability of MR. The nanoprecipitation technique was employed to encapsulate MR in lipid-cored poly(lactide-co-glycolide) (PLGA) NPs. The optimal NPs were about 200 nm in size with an almost neutral surface charge and a loading efficiency of 82%. The NPs exhibited sustained release of MR within 24 h. In vitro antioxidant assays showed that MR encapsulation did not affect its antioxidant activity. On the other hand, anti-inflammatory assays in lipopolysaccharide-stimulated macrophages revealed a superior anti-inflammatory activity of MR NPs compared to free MR. Furthermore, oral administration of MR NPs to mice at a single dose of 20 mg/kg MR achieved a 5.6-fold enhancement in bioavailability and a prolongation of plasma half-life from 0.13 to 0.98 h. The results of this study present a promising NP formulation for MR which can enhance its oral bioavailability and bioactivity for the treatment of different diseases such as inflammation.

The Length of Hospital Stay of Patients with Venous Thromboembolism: A Cross-Sectional Study from Jordan.

Background and Objectives: Venous thromboembolism is one of the leading causes of mortality and disability worldwide. Treatment with anticoagulation therapy is essential and requires a delicate approach to select the most appropriate option to improve patient outcomes, including the length of hospital stay (LOS). The aim of this study was to determine the LOS among patients with acute onset of VTE in several public hospitals in Jordan. Materials and Methods: In this study, we recruited hospitalized patients with a confirmed diagnosis of VTE. We reviewed the electronic medical records and charts of VTE admitted patients in addition to a detailed survey to collect the patients' self-reported data. Hospital LOS was categorized into three levels: 1-3 days, 4-6 days, and ≥7 days. An ordered logistic regression model was used to study the significant predictors of LOS. Results: A total of 317 VTE patients were recruited, with 52.4% of them were male and 35.3% aged between 50 and 69 years. Most patients had a deep vein thrombosis (DVT) diagnosis (84.2%), and most of the VTE cases were admitted for the first-time (64.6%). The majority of the patients were smokers (57.2%), overweight/obese (66.3%), and hypertensive (59%). Most of the VTE patients received Warfarin overlapped with low molecular weight heparins as their treatment regimen (>70%). Almost half of the admitted VTE patients (45%) were hospitalized for at least 7 days. Longer LOS was significantly associated with hypertension. Conclusions: We recommend using therapies that have been proven to reduce hospital LOS, such as non-vitamin K antagonist oral anticoagulants or direct oral anticoagulants, to treat VTE patients in Jordan. Additionally, preventing and controlling comorbidities such as hypertension is essential.

Effect of Cigarette Smoke Exposure and Aspirin Treatment on Neurotransmitters' Tissue Content in Rats' Hippocampus and Amygdala.

Cigarette smoke withdrawal can cause anxiety-like behavior and modulate neurotransmitter-related proteins in the brain. We examined the effects of cigarette smoke with and without aspirin treatment on the concentrations of neurotransmitters, including dopamine, serotonin, glutamate, glutamine, and GABA in the amygdala and hippocampus. Sprague-Dawley rats were randomly assigned to four different groups: (1) control group exposed only to standard room air, (2) cigarette smoke exposed group treated with saline vehicle, (3) cigarette smoke exposed group treated with aspirin (30 mg/kg), and (4) control group treated only with aspirin (30 mg/kg). Cigarette smoke exposure was performed for 2 h/day, 5 days/week, for 31 days. Behavioral testing was carried out weekly, 24 h after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either distilled water (1 mL) or aspirin 45 min before cigarette exposure for 11 days. Dopamine, serotonin, glutamate, glutamine, and GABA were extracted from both the amygdala and hippocampus and were separated and quantified using a developed and validated HPLC-MS/MS method. Cigarette smoke withdrawal induced anxiety behaviors, and aspirin treatment reduced this effect. Cigarette smoke exposure increased tissue content of dopamine, serotonin, glutamate, glutamine, and GABA, and aspirin treatment reversed this effect. Cigarette smoke caused an increase in tissue content of several neurotransmitters as well as anxiety-like behavior, and these effects were normalized by aspirin treatment.

The Role of Vitamin E in Protecting against Oxidative Stress, Inflammation, and the Neurotoxic Effects of Acute Paracetamol in Pregnant Female Rats.

Paracetamol (acetaminophen, APAP) is the most common non-prescription analgesic drug used during pregnancy. The aim of this study was to investigate the effect of vitamin E on acute APAP toxicity in pregnant rats. Toxicity in the liver, kidney, and brain (hippocampus, cerebellum, and olfactory bulb) was examined. Twenty pregnant female Wistar rats at gestational day 18 were used. Pregnant rats were divided into four groups: Control, APAP, E + APAP, and APAP + E. The Control group was treated with 0.5 mL p.o. corn oil. The APAP group received 3000 mg/kg p.o. APAP. The E + APAP group received 300 mg/kg p.o. vitamin E one hour before 3000 mg/kg APAP. The APAP + E group received 3000 mg/kg paracetamol one hour before 300 mg/kg p.o. vitamin E. Twenty-four hours after the last treatment administration, rats were euthanized and blood, brain, liver, and kidney samples were collected. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine levels, uric acid (UA), and superoxide dismutase (SOD) levels, as well as the relative mRNA expression of Cyp1a4, Cyp2d6, and Nat2, were determined. Acute APAP treatment upregulated ALT, AST, BUN, and creatinine levels. APAP treatment downregulated UA and SOD levels. APAP treatment upregulated the relative mRNA expression of Cyp1a4 and Cyp2d6, but downregulated Nat2 expression. Vitamin E treatment, either before or after APAP administration, attenuated the toxic effects of APAP. In conclusion, the results showed that an acute toxic APAP dose in late pregnancy can cause oxidative stress and dysregulation in Cyp isoform expression, and that vitamin E treatment attenuates these effects.

Nanoassemblies from the aqueous extract of roasted coffee beans modulate the behavioral and molecular effects of smoking withdrawal-induced anxiety in female rats.

Antioxidant-rich plant extracts have demonstrated tremendous value as inflammatory modulators and as nanomaterial precursors. Chronic cigarette smoking alters neurotransmitter systems, particularly the glutamatergic system, and produces neuroinflammation. This study aimed to investigate the behavioral and molecular correlates of cigarette smoking withdrawal-induced anxiety-like behavior in rats, and whether these effects could be mitigated by the administration of antioxidant nanoassemblies prepared by spontaneous oxidation of dark-roasted Arabica coffee bean aqueous extracts. Four experimental groups of female Sprague-Dawley rats were randomly assigned to: (i) a control group that was only exposed to room air, (ii) a COF group that was administered 20 mg/kg of the coffee nanoassemblies by oral gavage, (iii) a SMOK group that was exposed to cigarette smoke and was given an oral gavage of distilled water, (iv) and a SMOK + COF group that was exposed to cigarette smoke and administered 20 mg/kg of the coffee nanoassemblies. Animals were exposed to cigarette smoke for 2 h per day, five days per week, with a 2-day withdrawal period each week. At the end of the 4th week, rats began receiving either distilled water or the coffee nanoassemblies before being exposed to cigarette smoke for 21 additional days. Weekly behavioral tests revealed that cigarette smoking withdrawal exacerbated anxiety, while the administration of the coffee nanoassemblies reduced this effect. The effect of cigarette smoking on astroglial glutamate transporters and nuclear factor kappa B (NF-κB) expression in brain subregions was also measured. Smoking reduced the relative mRNA and protein levels of the glutamate transporter 1 (GLT-1) and the cystine/glutamate antiporter (xCT), and increased the levels of NF-κB, but these effects were attenuated by the coffee nanoassemblies. Thus, administration of the antioxidant nanoassemblies decreased the negative effects of cigarette smoke, which included neuroinflammation, changes in glutamate transporters' expression, and a rise in anxiety-like behavior.

In Vitro Evaluation of ALDH1A3-Affinic Compounds on Breast and Prostate Cancer Cell Lines as Single Treatments and in Combination with Doxorubicin.

Aldehyde dehydrogenase (ALDH) enzymes are involved in the growth and development of several tissues, including cancer cells. It has been reported that targeting the ALDH family, including the ALDH1A subfamily, enhances cancer treatment outcomes. Therefore, we aimed to investigate the cytotoxicity of ALDH1A3-affinic compounds that have been recently discovered by our group, on breast (MCF7 and MDA-MB-231) and prostate (PC-3) cancer cell lines. These compounds were investigated on the selected cell lines as single treatments and in combination with doxorubicin (DOX). Results showed that the combination treatment experiments of the selective ALDH1A3 inhibitors (compounds 15 and 16) at variable concentrations with DOX resulted in significant increases in the cytotoxic effect on the MCF7 cell line for compound 15, and to a lesser extent for compound 16 on the PC-3 cell line, compared to DOX alone. The activity of compounds 15 and 16 as single treatments on all cell lines was found to be non-cytotoxic. Therefore, our findings showed that the investigated compounds have a promising potential to target cancer cells, possibly via an ALDH-related pathway, and sensitize them to DOX treatment.

Effect of amoxicillin/clavulanic acid in attenuating pregabalin-induced condition place preference.

Substance abuse is a worldwide problem with serious repercussions for patients and the communities where they live. Pregabalin (Lyrica), is a medication commonly used to treat neuropathic pain. Like other analgesic medications there has been concern about pregabalin abuse and misuse. Although it was initially suggested that pregabalin, like other gabapentinoids, has limited abuse liability, questions still remain concerning this inquiry. Changes in glutamate system homeostasis are a hallmark of adaptations underlying drug dependence, including down-regulation of the glutamate transporter 1 (GLT-1; SLC1A2) and the cystine/glutamate antiporter (xCT; SLC7A11). In this study, it was found that pregabalin (90 mg/kg) produces a conditioned place preference (CPP), indicative of reinforcing effects that suggest a potential for abuse liability. Moreover, like other drugs of abuse, pregabalin also produced alterations in glutamate homeostasis, reducing the mRNA expression of Slc1a2 and Slc7a11 in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). Amoxicillin clavulanic acid, a ß-lactam antibiotic, blocked the reinforcing effects of pregabalin and normalized glutamate homeostasis. These results suggest that pregabalin has abuse potential that should be examined more critically, and that, moreover, the mechanisms underlying these effects are similar to those of other drugs of abuse, such as heroin and cocaine. Additionally, these results support previous findings showing normalization of glutamate homeostasis by ß-lactam drugs that provides a novel potential therapeutic approach for the treatment of drug abuse and dependence.

Rapid and sensitive HPLC-MS/MS method for the quantification of dopamine, GABA, serotonin, glutamine and glutamate in rat brain regions after exposure to tobacco cigarettes.

Tobacco smoking is a preventable main cause of fatal diseases. Accurate measurements of the effects it has on neurotransmitters are essential in developing new strategies for smoking cessation. Moreover, measurements of neurotransmitter levels can aid in developing drugs that counteract the effects of smoking. The aim of this study is to develop and validate a fast, simultaneous and sensitive method for measuring the levels of neurotransmitters in rat brain after the exposure of tobacco cigarettes. The selected neurotransmitters include dopamine, GABA, serotonin, glutamine and glutamate. The method is based on high-performance liquid chromatography-tandem mass spectrometry. Chromatographic separation was achieved within 3 min using a Zorbax SB C18 column (3.0 × 100 mm, 1.8 µm particle size). The mobile phase consisted of HPLC-grade water and acetonitrile each containing 0.3% heptafluorobutyric acid and 0.5% formic acid at gradient conditions. The linear range was 0.015-0.07, 825-7,218, 140-520, 63.42-160.75 and 38.25 × 103 to 110.35 × 103  ng/ml for dopamine, GABA, serotonin, glutamine and glutamate, respectively. Inter- and intra-run accuracy were in the range 97.82-103.37% with a precision (CV%) of ≤0.90%. The results revealed that 4 weeks of cigarette exposure significantly increased neurotransmitter levels after exposure to tobacco cigarettes in various brain regions, including the hippocampus and the amygdala. This increase in neurotransmitters levels may in turn activate the nicotine dependence pathway.

Microemulsions as Lipid Nanosystems Loaded into Thermoresponsive In Situ Microgels for Local Ocular Delivery of Prednisolone.

This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a drug concentration of 0.25-0.75%. PRD microgels were prepared by incorporating PRD-MEs into 10 and 12% Pluronic® F127 (F127) or combinations of 12% F127 and 1-10% Kolliphor®P188 (F68). PRD microgels were characterized for physicochemical, rheological, and mucoadhesive properties, eye irritation, and stability. Results showed that PRD-MEs were clear, miscible, thermodynamically stable, and spherical with droplet size (16.4 ± 2.2 nm), polydispersity index (0.24 ± 0.01), and zeta potential (-21.03 ± 1.24 mV). The PRD microgels were clear with pH (5.37-5.81), surface tension (30.96-38.90 mN/m), size, and zeta potential of mixed polymeric micelles (20.1-23.9 nm and -1.34 to -10.25 mV, respectively), phase transition temperature (25.3-36 °C), and gelation time (1.44-2.47 min). The FTIR spectra revealed chemical compatibility between PRD and microgel components. PRD microgels showed pseudoplastic flow, viscoelastic and mucoadhesive properties, absence of eye irritation, and drug content (99.3 to 106.3%) with a sustained drug release for 16-24 h. Microgels were physicochemically and rheologically stable for three to six months. Therefore, PRD microgels possess potential vehicles for local ocular delivery.

Rhoifolin loaded in PLGA nanoparticles alleviates oxidative stress and inflammation in vitro and in vivo.

Rhoifolin (ROF) is a bioactive plant flavonoid with potent antioxidant and anti-inflammatory activity. However, no delivery system has yet been developed for ROF to overcome its biopharmaceutical limitations. The purpose of this study was to design a ROF-loaded polymeric nanocarrier as a potential anti-inflammatory nanomedicine. ROF was isolated from Jordanian Teucrium polium L. and entrapped into poly(lactide-co-glycolide) nanoparticles (PLGA NPs), followed by tannic acid-mediated surface modification with poly(ethylene glycol) (PEG). The optimal ROF NPs were highly monodisperse with an average diameter of 204 nm, a zeta potential of -28 mV, an entrapment efficiency of 45%, and drug loading of 9% w/w. The NPs exhibited excellent colloidal stability during storage and in the presence of serum and achieved sustained drug release for up to 96 h at physiologic (7.4) and acidic pH (5.0). In vitro cell-free antioxidant assays confirmed the potent radical scavenging activity of free ROF and ROF NPs. Moreover, ROF NPs were superior to free ROF in relieving oxidative stress in stimulated RAW 264.7 murine macrophages, which was attributed to enhanced cellular uptake of the NPs as confirmed by confocal microscopy and fluorimetry. In vivo anti-inflammatory activity was evaluated in a formalin-induced rat paw edema model. The results showed that ROF NPs were superior to free ROF in mitigating the histopathological changes in the inflamed paw tissues. Moreover, the NPs were equally potent to free ROF and the nonsteroidal anti-inflammatory drug diclofenac in terms of inhibiting the increase in paw thickness, normalizing nitric oxide levels, and modulating the gene expression of pro-inflammatory cytokines in the inflamed paw tissues. Our findings present a promising nanocarrier platform that can enhance the solubility and control the release of ROF, which will facilitate its administration in the treatment of inflammatory diseases.

Misconceptions Related to COVID 19 Vaccines Among the Jordanian Population: Myth and Public Health.

OBJECTIVE: This study assesses misconceptions about coronavirus disease 2019 (COVID-19) vaccine and the factors associated with misconception among Jordanians. METHODS: A cross-sectional online survey was conducted. The survey was formulated on Google Forms, and was hosted on an online platform. These questions were created based on extensive review of online information about the vaccines. Frequencies and percentages (%) were used for categorical variables, while means and standard deviations (SDs) were used for continuous variables. Stepwise binary logistic regression was conducted to evaluate variables associated with participant's misconception questions. RESULTS: Of 1195 survey respondents who participated in the study, 41.3% had received the COVID-19 vaccine. The mean misconception score was (60.0 ± 19.1). The statement with the highest mean was "The vaccine hasn't been tested on enough people" (3.6 ± 1.0). The statement with the lowest mean was "The COVID-19 vaccine includes a microchip to control us" (2.2 ± 1.1) in the conspiracy theory portion. Females, 18- to 29-age group, higher educational level, living in a city, the participants who took lectures about the COVID-19 vaccine and vaccinated participants had higher odds of being in the low misconception level group. CONCLUSION: Targeted campaigns and vaccine safety information should be part of a broader health education campaign to alleviate vaccination safety concerns.

Role of suppressing GLT-1 and xCT in ceftriaxone-induced attenuation of relapse-like alcohol drinking in alcohol-preferring rats.

Alcohol dependence results in long-lasting neuroadaptive changes in meso-corticolimbic system, especially in the nucleus accumbens (NAc), which drives relapse-like ethanol drinking upon abstinence or withdrawal. Within NAc, altered glutamate homeostasis is one of the neuroadaptive changes caused by alcohol dependence. Accumbal glutamate homeostasis is tightly maintained through glutamate transporter 1 (GLT-1) and cystine-glutamate antiporter (xCT). But the role of GLT-1 and xCT in relapse-like ethanol drinking is poorly understood. Here, we used alcohol-preferring (P) rats in relapse-like ethanol drinking paradigm to (a) determine the effect of relapse-like ethanol drinking on gene and protein expression of GLT-1 and xCT in NAc, measured by quantitative polymerase chain reaction (qPCR) and Western blot, respectively; (b) examine if glutamate uptake is affected by relapse-like ethanol drinking in NAc, measured by radioactive glutamate uptake assay; (c) elucidate if upregulation of either/both GLT-1 or/and xCT through ceftriaxone is/are required to attenuate relapse-like ethanol drinking. The GLT-1 or xCT protein expression was suppressed during ceftriaxone treatments through microinjection of GLT-1/xCT anti-sense vivo-morpholinos. We found that relapse-like ethanol drinking did not affect the gene and protein expression of GLT-1 and xCT in NAc. The glutamate uptake was also unaltered. Ceftriaxone (200 mg/kg body weight, i.p.) treatments during the last 5 days of abstinence attenuated relapse-like ethanol drinking. The suppression of GLT-1 or xCT expression prevented the ceftriaxone-induced attenuation of relapse-like ethanol drinking. These findings confirm that upregulation of both GLT-1 and xCT within NAc is crucial for ceftriaxone-mediated attenuation of relapse-like ethanol drinking.

Identifying Drug-Therapy Problems among Syrian Refugees in Zaatari Refugee Camp.

Background: Due to a lack of proper pharmaceutical care, Syrian refugees in the Zaatari refugee camp are more likely to have drug-related issues, such as prescription errors and adverse drug occurrences. Aim: The current study aims to identify drug-therapy problems among Syrian refugees in the Zaatari refugee camp. Method: This is a retrospective cross-sectional study. Patients' files were collected from the Zaatari camp database. Patients who were 18 years or older and were previously diagnosed with a chronic disease were included. A classification of drug therapy problems (DTPs) was adapted. Results: The data of 1530 adult patients (896 females) were collected. The mean age of the sample was 53.7 years and the mean Body mass Index (BMI) was 27.20. The mean of all taken medications was 4.01 (±2.33) medications, with a maximum number of 13. A total of 3572 DTPs was identified, with a mean of 2.33 (±1.26) DTPs per patient. Based on the above-mentioned classification, 70.32% of the DTPs were related to indication, 26.65% were related to effectiveness, and 3.03% were related to safety. Conclusion: This study found that refugees in the Zaatari refugee camp have numerous DTPs among their medications. Greater focus should be placed on their medical care, in order to prevent any future complications due to DTPs.