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Multi-objective mathematical programming subject to box constraints on system parameters is an important problem in the fields of computer-aided design and decision-making theory, when there is an apparent conflict between multiple preference criteria. In this work, mathematical programming methodology has been proposed using a modern algorithm to solve multi-objective mathematical problems. The proposed algorithm to perform the ranking and classification procedures for the set of alternative solutions with boundary constraints is based on the concepts of parametric multi-aspect modeling of flexible complex systems. Interactive software has been implemented in the .Net environment to aid the decision-maker to identify the preference criteria and constraints on the system parameters, and then to choose the best solution from the morphological set depending on the developed algorithm. In addition, an illustrative numerical example solved by the proposed algorithm is presented at the end of this work.

This paper provides a recent overview of the exact, approximate, and hybrid optimization methods that handle Multi-Objective Mixed-Integer Non-Linear Programming (MO-MINLP) problems. Both the domains of exact and approximate research have experienced significant growth, driven by their shared goal of addressing a wide range of real-world problems. This work presents a comprehensive literature review that highlights the significant theoretical contributions in the field of hybrid approaches between these research areas. We also point out possible research gaps in the literature. Hence, the main research questions to be answered in this paper involve the following: (1) how to exactly or approximately solve a MO-MINLP problem? (2) What are the drawbacks of exact methods as well as approximate methods? (3) What are the research lines that are currently underway to enhance the performances of these methods? and (4) Where are the research gaps in this field? This work aims to provide enough descriptive information for newcomers in this area about the research that has been carried out and that is currently underway concerning exact, approximate, and hybrid methods used to solve MO-MINLP problems.

The present study was planned to evaluate the infection concerning Anaplasma platys in dogs for the first time in Nineveh Province, Iraq, using microscopic examination and conventional polymerase chain reaction (PCR) techniques. Eighty-one blood samples were randomly collected from dogs (31 household dogs and 50 stray dogs). Those samples were drained from dogs introduced to the Veterinary Teaching Hospital at the University of Mosul and private veterinary clinics in Nineveh province. The microscopic examination was used to check the blood films prepared for preliminary detection of morulae of A. platys within platelets; furthermore, the molecular technique was used to validate the presence of A. platys by targeting the gltA gene. In that, PCR yielded an amplification of 690 bp band size products, which was the expected size of the targeted gene. After that, these PCR amplicons were sent for sequencing to verify the presence of the pathogen, and then the sequence results were subsequently aligned with other strains available on the NCBI database. Finally, a phylogenetic tree for the related strains was constructed by Mega-11 software. The outcomes indicated that the overall infection rate of A. platys infection in dogs was 6/81 (7.4%) and 11/81 (13.6%) using microscopic examination and molecular techniques, respectively. Additionally, there was no significant difference within the dogs' categories in this study. In conclusion, it has been shown that A. platys in dogs were circulating in Nineveh province; therefore, plans for control measures are advised.

This study targeted to determine the prevalence of Mycoplasma bovis in cattle in Nineveh Governorate, Iraq, based on three genes, including 16S rRNA, uvrC, and gapA using polymerase chain reaction (PCR) techniques, and to investigate the phylogenetic analysis of M. bovis diagnose in the study. Various samples, including 352 blood samples, 352 nasal swabs, 40 ocular swabs, 65 synovial fluid, and 30 milk samples, were randomly obtained from 352 cattle. Based on the amplified 16S rRNA gene, the prevalence of Mycoplasma spp was 38.63% in cattle using the c-PCR technique. At the same time, there was no significant in the prevalence of M. bovis in cattle based on amplified uvrC and gapA genes, which were 30.68% and 28.69%, respectively, using the m-PCR technique. No significant difference was found between the types of samples for detecting M. bovis. The phylogenetic analysis for ten local sequences of the uvrC (5 sequence) and gapA (5 sequence) that were deposited in the NCBI GenBank under the accession numbers OR784598.1-OR784602.1 and OR792211.1-OR792215.1, with highly related 99.13-100% identity and 99.81% identity, respectively, to the other sequences that registered in the GenBank from different countries, including Canada, Egypt, Iran, Poland, and Switzerland. This study concludes that M. bovis is widespread in Nineveh Governorate, Iraq. This first study highlights the phylogenetic analysis of M. bovis in Nineveh Governorate, Iraq.

Background Helicobacter pylori and intestinal parasites are well-known for their high prevalence in children, especially in developing countries. However, their concomitant infections are poorly documented. In this study, we aimed to evaluate the association between intestinal parasites and H. pylori among hospitalized children and adolescents with upper gastrointestinal complaints in Northern Lebanon. Methods A cross-sectional study was conducted involving 297 hospitalized pediatric patients, aged between 1 and 15 years, who presented with gastrointestinal symptoms. The socio-demographic, lifestyle, and gastrointestinal characteristics of all participants were analyzed. Fresh stool samples were collected and screened for the presence of intestinal parasites and H. pylori infections. Results 6.4% of the patients were positive for intestinal parasitic infections, 5.4% were positive for H. pylori infection, and 11.8% were co-infected. The results of the Chi-square test showed that H. pylori infection is significantly associated with parasitic infection but not with a particular species. The most frequent coinfection was H. pylori-Entamoeba histolytica (77.1%). Moreover, H. pylori infection was associated with overcrowding and infrequent washing of vegetables before eating. The prevalence of co-infections increased in patients of mothers with a primary educational level or less. In regards to clinical characteristics, our findings showed a statistically significant relationship between i) gastric reflux and H. pylori, and ii) severe diarrhea and parasitic infection. Conclusion Our data highlighted the association between H. pylori and intestinal parasitic infections. Thus, H. pylori detection could be taken into consideration while screening for parasitic infections in children and adolescents.

IntroductionThe Eastern Mediterranean Regional Office (EMRO) region accounts for almost 8% of all global Mycobacterium tuberculosis (TB) cases, with TB incidence rates ranging from 1 per 100,000 per year in the United Arab Emirates (UAE) to 204 per 100,000 in Djibouti. The national surveillance data from the Middle East and North Africa (MENA) region on the epidemiology and antimicrobial resistance trends of TB, including MDR-TB remains scarce.MethodsA retrospective 12-year analysis of N = 8,086 non-duplicate diagnostic Mycobacterium tuberculosis complex (MTB complex) isolates from the UAE was conducted. Data were generated through routine patient care during the 2010–2021 years, collected by trained personnel and reported by participating surveillance sites to the UAE National Antimicrobial Resistance (AMR) Surveillance program. Data analysis was conducted with WHONET, a windows-based microbiology laboratory database management software developed by the World Health Organization Collaborating Center for Surveillance of Antimicrobial Resistance, Boston, United States (https://whonet.org/).ResultsA total of 8,086 MTB-complex isolates were analyzed. MTB-complex was primarily isolated from respiratory samples (sputum 80.1%, broncho-alveolar lavage 4.6%, pleural fluid 4.1%). Inpatients accounted for 63.2%, including 1.3% from ICU. Nationality was known for 84.3% of patients, including 3.8% Emiratis. Of UAE non-nationals, 80.5% were from 110 countries, most of which were Asian countries. India accounted for 20.8%, Pakistan 13.6%, Philippines 12.7%, and Bangladesh 7.8%. Rifampicin-resistant MTB-complex isolates (RR-TB) were found in 2.8% of the isolates, resistance to isoniazid, streptomycin, pyrazinamide, and ethambutol, was 8.9, 6.9, 3.4 and 0.4%, respectively. A slightly increasing trend of resistance among MTB-complex was observed for rifampicin from 2.5% (2010) to 2.8% (2021).ConclusionInfections due to MTB-complex are relatively uncommon in the United Arab Emirates compared to other countries in the MENA region. Most TB patients in the UAE are of Asian origin, mainly from countries with a high prevalence of TB. Resistance to first line anti-tuberculous drugs is generally low, however increasing trends for MDR-TB mainly rifampicin linked resistance is a major concern. MDR-TB was not associated with a higher mortality, admission to ICU, or increased length of hospitalization as compared to non-MDR-TB.

يهدف البحث الحالي إلى تعرف مدى توافر مهارات التواصل الرياضي ضمن محتوى كتاب الرياضيات المُقرر للصف الثالث الأساسي في الجمهورية العربية السورية، ولتحقيق أهداف البحث تم اتباع المنهج الوصفي، وإعداد قائمة بمهارات التواصل الرياضي (الرئيسة والفرعية)، ثم تصميم استمارة تحليل محتوى، وذلك بغرض تحليل كتاب الرياضيات وتعرف مهارات التواصل الرياضي المتضمنة في الكتاب المقرر ونسب توافر كل مهارة، وكانت قد بينت نتائج التحليل توافر مهارات التواصل الرياضي كافةً وبنسب متفاوتة، إذ جاءت مهارة التعبير الكتابي الرياضي في المرتبة الأولى بنسبة (45,19%)، تلتها مهارة القراءة الرياضية بنسبة (26,51%)، ثم مهارة التمثيل الرياضي بنسبة (16,37%)، بينما جاءت مهارة التعبير الشفوي الرياضي بنسبة (8,36%)، ومهارة الاستماع الرياضي بنسبة (3,55%)، وبناءً على النتائج السابقة تم تقديم عدد من التوصيات أبرزها إعادة النظر بمحتوى كتاب الرياضيات للصف الثالث الأساسي، من حيث تضمينه لكافة مهارات التواصل الرياضي وتوزيعها بشكل متساوٍ، مع التركيز على المهارات التي حققت نسب متدنية ضمن نتائج التحليل.

Introduction: The United Arab Emirates (UAE) serves as an effective epidemiological site for assessing Helicobacter pylori (H. pylori) infection due to its diverse population. However, comprehensive studies on the prevalence of H. pylori in the UAE are notably scarce. In depth prevalence studies are needed as a preventive measure against gastric cancer and other emerging extra gastric diseases associated with H. pylori infection. Aim: This study aimed to assess H. pylori infection and its virulent oncoprotein, the Cytotoxin-Associated Gene (Cag A) and its association with ferritin and vitamin B12 deficiencies. Methods: The study was conducted on 1094 healthy asymptomatic volunteers residents in the Sharjah Emirate, UAE. Enzyme-linked immunosorbent assay (ELISA) was performed to assess H. pylori infection using H. pylori antibodies (IgG), and detection of CagA protein using Cag A antibody (IgG) in the human serum. Ferritin and vitamin B12 serum levels were assessed and correlated to H. pylori infection. Results: This study focuses mainly on the assessment of H. pylori and its virulent factor CagA, in relation to vitamin B12 and ferritin deficiencies. Remarkably, 49.6 % of the participants were detected positive for H. pylori, with over half of these cases involving CagA positive strains. Notably, among Emirati participants, 76.11 % of those with H. pylori infection were CagA positive. Statistical analysis revealed a significant correlation between H. pylori, CagA level, and ferritin/vitamin B12 deficiencies. Conclusion: These findings emphasize the importance of timely detection and eradication of H. pylori not only as a preventive strategy against gastric cancer but also as an effective strategy to rescue the adverse effects from ferritin and vitamin B12 deficiencies, thereby improving the overall health outcomes of individuals affected by H. pylori infection.

Breast cancer is the predominant form of cancer among women and ranks as the second most prevalent cancer globally, affecting both developed and less developed countries. Presently, accessible cancer treatment methods either employ recently created, secure, and efficient chemotherapeutic medications or directly target innovative pathways that cause apoptosis. One of the indirect strategies for treating this fatal illness has mostly depended on its essential role in cell cycle arrest and apoptosis induction, as well as the antagonistic interaction between the Bcl-2 and Mcl-1 proteins, in order to avert major health repercussions. We reported that newly synthesized fused chromenopyrimidines (3a and 4a) showed potential cell cycle arrest and dual Bcl-2 and Mcl-1 inhibitory characteristics. Bcl-2 and Mcl-1 were the targets of a molecular docking procedure. The previous docking results are in line with the biological data and suggest that 3a may have promising anti-cancer activity.

Cancer immunotherapy has emerged as a transformative approach in oncology, utilizing the body’s immune system to specifically target and destroy malignant cells. This review explores the scope and impact of various immunotherapeutic strategies, including monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy, checkpoint inhibitors, cytokine therapy, and therapeutic vaccines. Monoclonal antibodies, such as Rituximab and Trastuzumab, have revolutionized treatment paradigms for lymphoma and breast cancer by offering targeted interventions that reduce off-target effects. CAR-T cell therapy presents a potentially curative option for refractory hematologic malignancies, although challenges remain in effectively treating solid tumors. Checkpoint inhibitors have redefined the management of cancers like melanoma and lung cancer; however, managing immune-related adverse events and ensuring durable responses are critical areas of focus. Cytokine therapy continues to play a vital role in modulating the immune response, with advancements in cytokine engineering improving specificity and reducing systemic toxicity. Therapeutic vaccines, particularly mRNA-based vaccines, represent a frontier in personalized cancer treatment, aiming to generate robust, long-lasting immune responses against tumor-specific antigens. Despite these advancements, the field faces significant challenges, including immune resistance, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Future research should address these obstacles through emerging technologies, such as next-generation antibodies, Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based gene editing, and AI-driven drug discovery. By integrating these novel approaches, cancer immunotherapy holds the promise of offering more durable, less toxic, and highly personalized treatment options, ultimately improving patient outcomes and survival rates.

Background Helicobacter pylori and intestinal parasites are well-known for their high prevalence in children, especially in developing countries. However, their concomitant infections are poorly documented. In this study, we aimed to evaluate the association between intestinal parasites and H. pylori among hospitalized children and adolescents with upper gastrointestinal complaints in Northern Lebanon. Methods A cross-sectional study was conducted involving 297 hospitalized pediatric patients, aged between 1 and 15 years, who presented with gastrointestinal symptoms. The socio-demographic, lifestyle, and gastrointestinal characteristics of all participants were analyzed. Fresh stool samples were collected and screened for the presence of intestinal parasites and H. pylori infections. Results 6.4% of the patients were positive for intestinal parasitic infections, 5.4% were positive for H. pylori infection, and 11.8% were co-infected. The results of the Chi-square test showed that H. pylori infection is significantly associated with parasitic infection but not with a particular species. The most frequent coinfection was H. pylori-Entamoeba histolytica (77.1%). Moreover, H. pylori infection was associated with overcrowding and infrequent washing of vegetables before eating. The prevalence of co-infections increased in patients of mothers with a primary educational level or less. In regards to clinical characteristics, our findings showed a statistically significant relationship between i) gastric reflux and H. pylori, and ii) severe diarrhea and parasitic infection. Conclusion Our data highlighted the association between H. pylori and intestinal parasitic infections. Thus, H. pylori detection could be taken into consideration while screening for parasitic infections in children and adolescents.

In the context of global efforts to mitigate climate change by pursuing sustainable energy sources, wind energy has emerged as a critical contributor. However, the wind energy industry faces substantial challenges in maintaining and preserving the integrity of wind turbine blades. Timely and accurate detection and classification of blade faults, encompassing issues such as cracks, erosion, and ice buildup, are imperative to uphold wind turbines' ongoing efficiency and safety. This study introduces an inventive approach that amalgamates hyperspectral imaging and 3D Convolutional Neural Networks (CNNs) to augment the precision and efficiency of wind turbine blade fault detection and classification. Hyperspectral imaging is harnessed to capture comprehensive spectral information from blade surfaces, facilitating exact fault identification. The process is streamlined through Incremental Principal Component Analysis (IPCA), reducing data dimensions while maintaining integrity. The 3D CNN model demonstrates remarkable performance, achieving high accuracy in detecting all fault categories in full-band hyperspectral images. The model retains high accuracy even with dimensionality reduction to 20 spectral bands. The reduced processing time of the 20-band image enhances the practicality of real-world applications, thereby reducing downtime and maintenance expenditures. This research represents a significant advancement in wind turbine blade inspection, contributing to the sustainability and dependability of wind energy systems and furthering the cause of a cleaner and more sustainable energy future as part of the broader fight against climate change.

Disulfiram (DS) has been shown to have potent anti-cancer activity; however, it is also characterised by its low water solubility and rapid metabolism in vivo. Biodegradable polylactic-co-glycolic acid (PLGA) polymers have been frequently employed in the manufacturing of PLGA nano-carrier drug delivery systems. Thus, to develop DS-loaded PLGA nanoparticles (NPs) capable of overcoming DS’s limitations, two methodologies were used to formulate the NPs: direct nanoprecipitation (DNP) and single emulsion/solvent evaporation (SE), followed by particle size reduction. The DNP method was demonstrated to produce NPs of superior characteristics in terms of size (151.3 nm), PDI (0.083), charge (−37.9 mV), and loading efficiency (65.3%). Consequently, NPs consisting of PLGA and encapsulated DS coated with mPEG2k-PLGA at adjustable ratios were prepared using the DNP method. Formulations were then characterised, and their stability in horse serum was assessed. Results revealed the PEGylated DS-loaded PLGA nano-carriers to be more efficient; hence, in-vitro studies testing these formulations were subsequently performed using two distinct breast cancer cell lines, showing great potential to significantly enhance cancer therapy.

The majority of new particle formation (NPF) events observed in Hada Al Sham, western Saudi Arabia, during 2013–2015 showed an unusual progression where the diameter of a newly formed particle mode clearly started to decrease after the growth phase. Many previous studies refer to this phenomenon as aerosol shrinkage. We will opt to use the term decreasing mode diameter (DMD) event, as shrinkage bears the connotation of reduction in the sizes of individual particles, which does not have to be the case. While several previous studies speculate that ambient DMD events are caused by evaporation of semivolatile species, no concrete evidence has been provided, partly due to the rarity of the DMD events. The frequent occurrence and large number of DMD events in our observations allow us to perform statistically significant comparisons between the DMD and the typical NPF events that undergo continuous growth. In our analysis, we find no clear connection between DMD events and factors that might trigger particle evaporation at the measurement site. Instead, examination of air mass source areas and the horizontal distribution of anthropogenic emissions in the study region leads us to believe that the observed DMD events could be caused by advection of smaller, less-grown particles to the measurement site after the more-grown ones. Using a Lagrangian single-particle growth model, we confirm that the observed particle size development, including the DMD events, can be reproduced by non-volatile condensation and thus without evaporation. In fact, when considering increasing contributions from a semivolatile compound, we find deteriorating agreement between the measurements and the model. Based on these results, it seems unlikely that evaporation of semivolatile compounds would play a significant role in the DMD events at our measurement site. In the proposed non-volatile explanation, the DMD events are a result of the observed particles having spent an increasing fraction of their lifetime in a lower-growth environment, mainly enabled by the lower precursor vapor concentrations further away from the measurement site combined with decreasing photochemical production of condensable vapors in the afternoon. Correct identification of the cause of the DMD events is important as the fate and the climate relevance of the newly formed particles heavily depend on it – if the particles evaporated, their net contribution to larger and climatically active particle sizes would be greatly reduced. Our findings highlight the importance of considering transport-related effects in NPF event analysis, which is an often overlooked factor in such studies.

IntroductionAcinetobacter spp., in particular A. baumannii, are opportunistic pathogens linked to nosocomial pneumonia (particularly ventilator-associated pneumonia), central-line catheter-associated blood stream infections, meningitis, urinary tract infections, surgical-site infections, and other types of wound infections. A. baumannii is able to acquire or upregulate various resistance determinants, making it frequently multidrug-resistant, and contributing to increased mortality and morbidity. Data on the epidemiology, levels, and trends of antimicrobial resistance of Acinetobacter spp. in clinical settings is scarce in the Gulf Cooperation Council (GCC) and Middle East and North Africa (MENA) regions.MethodsA retrospective 12-year analysis of 17,564 non-duplicate diagnostic Acinetobacter spp. isolates from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010–2021, collected by trained personnel and reported by participating surveillance sites to the UAE National AMR Surveillance program. Data analysis was conducted with WHONET.1ResultsSpecies belonging to the A. calcoaceticus-baumannii complex were mostly reported (86.7%). They were most commonly isolated from urine (32.9%), sputum (29.0%), and soft tissue (25.1%). Resistance trends to antibiotics from different classes during the surveillance period showed a decreasing trend. Specifically, there was a significant decrease in resistance to imipenem, meropenem, and amikacin. Resistance was lowest among Acinetobacter species to both colistin and tigecycline. The percentages of multidrug-resistant (MDR) and possibly extensively drug-resistant (XDR) isolates was reduced by almost half between the beginning of the study in 2010 and its culmination in 2021. Carbapenem-resistant Acinetobacter spp. (CRAB) was associated with a higher mortality (RR: 5.7), a higher admission to ICU (RR 3.3), and an increased length of stay (LOS; 13 excess inpatient days per CRAB case), as compared to Carbapenem-susceptible Acinetobacter spp.ConclusionCarbapenem-resistant Acinetobacter spp. are associated with poorer clinical outcomes, and higher associated costs, as compared to carbapenem-susceptible Acinetobacter spp. A decreasing trend of MDR Acinetobacter spp., as well as resistance to all antibiotic classes under surveillance was observed during 2010 to 2021. Further studies are needed to explore the reasons and underlying factors leading to this remarkable decrease of resistance over time.

IntroductionNational surveillance of antimicrobial resistance (AMR) is an important public health function. Published national AMR surveillance data from the Middle East/North Africa (MENA) region is scarce. This paper describes the early implementation phase of establishing AMR surveillance in the United Arab Emirates (UAE).Materials and methodsBuilding on the existing AMR surveillance system in the Emirate of Abu Dhabi, and adopting the WHO-GLASS methodology, the UAE Ministry of Health and Prevention (MOHAP) established the national AMR Surveillance program in 2015, in collaboration with regional health authorities and healthcare providers. Main objectives of this program are to (a) set AMR surveillance standards, (b) collect and analyze AMR surveillance data for common bacterial and fungal infections, (c) report on AMR levels and trends in the UAE, (d) strengthen local and national capacity for AMR surveillance, and (e) support AMR prevention and control strategies in the UAE. AMR surveillance data is collected through a network of 317 surveillance sites (including 84 hospitals and 233 centers/clinics), and 45 microbiology labs across all seven Emirates of the UAE.ResultsSurveillance of antimicrobial resistance has been successfully established since 2010 in the UAE. A national AMR surveillance protocol has been developed, adopting the WHO GLASS protocol. Extensive capacity-building and training activities have strengthened the local and national capacity for AMR surveillance. Between 2010 and 2021, a network of 317 surveillance sites and 45 laboratories have reported a total of 1,277,080 isolates from 662,065 non-duplicate patients to the national level. AMR data is reported annually by MOHAP through a National AMR surveillance report. National AMR data is utilized for informing the development of standard treatment guidelines at national level.ConclusionNational surveillance of antimicrobial resistance has been successfully established in the United Arab Emirates, allowing to monitor levels and trends of antimicrobial resistance for common bacterial and fungal pathogens, and detecting emerging resistance. The availability of such national AMR surveillance data allows for the first time to inform the development of national standard treatment guidelines for empiric treatment of common bacterial and fungal infections in the UAE.

Current medical approaches to control the Covid-19 pandemic are either to directly target the SARS-CoV-2 via innovate a defined drug and a safe vaccine or indirectly target the medical complications of the virus. One of the indirect strategies for fighting this virus has been mainly dependent on using anti‐inflammatory drugs to control cytokines storm responsible for severe health complications. We revealed the discovery of novel fused pyrrolopyrimidine derivatives as promising antioxidant and anti-inflammatory agents. The newly synthesised compounds were evaluated for their in vitro anti-inflammatory activity using RAW264.7 cells after stimulation with lipopolysaccharides (LPS). The results revealed that 3a, 4b, and 8e were the most potent analogues. Molecular docking and simulations of these compounds against COX-2, TLR-2 and TLR-4 respectively was performed. The former results were in line with the biological data and proved that 3a, 4b and 8e have potential antioxidant and anti-inflammatory effects.

Rho-kinase (ROCK) inhibitors represent a new category of anti-glaucoma medications. Among them, Fasudil hydrochloride, a selective ROCK inhibitor, has demonstrated promising outcomes in glaucoma treatment. It works by inhibiting the ROCK pathway, which plays a crucial role in regulating the trabecular meshwork and canal of Schlemm’s aqueous humor outflow. This study aims to investigate the ocular absorption pathway of Fasudil hydrochloride and, subsequently, develop a nanoparticle-based delivery system for enhanced corneal absorption. Employing the ionic gelation method and statistical experimental design, the factors influencing chitosan nanoparticle (Cs NP) characteristics and performance were explored. Fasudil in vitro release and ex vivo permeation studies were performed, and Cs NP ocular tolerability and cytotoxicity on human lens epithelial cells were evaluated. Permeation studies on excised bovine eyes revealed significantly higher Fasudil permeation through the sclera compared to the cornea (370.0 μg/cm2 vs. 96.8 μg/cm2, respectively). The nanoparticle size (144.0 ± 15.6 nm to 835.9 ± 23.4 nm) and entrapment efficiency range achieved (17.2% to 41.4%) were predominantly influenced by chitosan quantity. Cs NPs showed a substantial improvement in the permeation of Fasudil via the cornea, along with slower release compared to the Fasudil aqueous solution. The results from the Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) and Bovine Corneal Opacity and Permeability (BCOP) tests indicated good conjunctival and corneal biocompatibility of the formulated chitosan nanoparticles, respectively. Lens epithelial cells displayed excellent tolerance to low concentrations of these nanoparticles (>94% cell viability). To the best of our knowledge, this is the first report on the ocular absorption pathway of topically applied Fasudil hydrochloride where the cornea has been identified as a potential barrier that could be overcome using Cs NPs.

Zinc diethyldithiocarbamate (Zn (DDC)2), a disulfiram metabolite (anti-alcoholism drug), has shown a strong anti-cancer activity in vitro. However, its application was limited by its low aqueous solubility and rapid metabolism. In this study, the solubility enhancement of Zn (DDC)2 is investigated by forming inclusion complexes with cyclodextrins. The inclusion complexes were prepared using two different types of beta-cyclodextrins, SBE-CD and HP-CD. Phase solubility diagrams for the resulting solutions were assessed; subsequently, the solutions were freeze-dried for further characterisation studies using DSC, TGA, XRD, and FTIR. The cytotoxic activity of the produced inclusion complexes was evaluated on human lung carcinoma cells using the MTT assay. The solubility of Zn (DDC)2 increased significantly upon adding beta-cyclodextrins, reaching approximately 4 mg/mL for 20% w/w CD solutions. The phase solubility diagram of Zn (DDC)2 was of the Ap-type according to the Higuchi and Connors model. Characterisation studies confirmed the inclusion of the amorphous drug in the CD-Zn (DDC)2 complexes. The cytotoxicity of Zn (DDC)2 was enhanced 10-fold by the inclusion complexes compared to the free drug. Overall, the resulting CD-Zn (DDC)2 inclusion complexes have a potential for treatment against lung cancer.

Dua Hammash,1,2 Mona Mahfood,3 Ghalia Khoder,4 Munazza Ahmed,1,2 Abdelaziz Tlili,3 Rifat Hamoudi,2,5,6 Rania Harati1,2 1Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates; 2Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; 3Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates; 4Department of Pharmaceutics and Pharmaceutical Technologies, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates; 5Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 6Division of Surgery and Interventional Science, University College London, London, UKCorrespondence: Rania Harati, Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates, Tel +971 6 505 7438, Fax +971 6 558 5812, Email rharati@sharjah.ac.aeBackground: Most breast cancer-related deaths result from metastasis. Understanding the molecular basis of metastasis is needed for the development of effective targeted and preventive strategies. Matrix metalloproteinase-1 (MMP1) plays an important role in brain metastasis (BM) of triple-negative breast cancer (TNBC) by promoting extravasation of cancer cells across the brain endothelium (BE). MMP1 expression is controlled by endogenous microRNAs. Preliminary bioinformatics analysis has revealed that miR-623, known to target the 3ʹUTR of MMP1, is significantly downregulated in brain metastatic tumors compared to primary BC tumors. However, the involvement of miR-623 in MMP1 upregulation in breast cancer brain metastatic cells (BCBMC) remains unexplored. Here, we investigated the role of miR-623 in MMP1 regulation and its impact on the extravasation of TNBC cells through the BE in vitro.Materials and Methods: A loss-and-gain of function method was employed to address the effect of miR-623 modulation on MMP1 expression. MMP1 regulation by miR-623 was investigated by real-time PCR, western blot, luciferase and transwell migration assays using an in vitro human BE model.Results: Our results confirmed that brain metastatic TNBC cells express lower levels of miR-623 compared with cells having low propensity to spread toward the brain. miR-623 binds to the 3′-untranslated region of MMP1 transcript and downregulates its expression. Restoring miR-623 expression significantly decreased MMP1 expression, preserved the endothelial barrier integrity, and attenuated transmigration of BCBMC through the BE.Conclusion: Our study elucidates, for the first time, the crucial role of miR-623 as MMP1 direct regulator in BCBMC and sheds light on miR-623 as a novel therapeutic target that can be exploited to predict and prevent brain metastasis in TNBC. Importantly, the presents study helps in unraveling a brain metastasis-specific microRNA signature in TNBC that can be used as a guide to personalized metastasis prediction and preventive approach with better therapeutic outcome.Keywords: brain metastasis, triple-negative breast cancer, brain endothelium, brain endothelial junctions, matrix metalloproteinase-1, microRNA-623, personalized preventive therapy, targeted prevention, metastasis prediction, precision medicine, primary and secondary care