Kerbala Journal of Pharmaceutical Sciences is a peer-reviewed academic journal published semi-annually by the College of Pharmacy at University of Karbala. First launched in 2010, the journal covers all aspects of pharmacy and pharmaceutical sciences including pharmacology, toxicology, pharmacognosy, clinical pharmacy, industrial pharmacy, pharmaceutical chemistry, biochemistry, and microbiology related to drugs and medicines. Kerbala Journal of Pharmaceutical Sciences provides a forum for disseminating innovative research, new discoveries, and practical applications in all fields of pharmacy.
Karbala Journal of Pharmaceutical Sciences
Association of CBC Laboratory Parameters with Respiratory Infection in Asthmatic Children
Background: This study investigates the sociodemographic factors influencing the severity of asthma among patients attending a hospital outpatient clinic. Asthma, a chronic respiratory condition, affects individuals globally and has varying degrees of severity based on numerous factors. Patients and methods: This cross-sectional study analyzed data from 100 patients, focusing on demographics, clinical characteristics, drug consumption, and bacterial culture Results: The results revealed that 64% of patients had uncontrolled asthma, with a higher prevalence among females and older adults. Most patients reported experiencing asthma symptoms for over 5 years, with frequent exacerbations observed in those with a history of respiratory infections. Additionally, bacterial cultures indicated a significant association between respiratory infections and the severity of asthma. Conclusion: Effective asthma management was found to be influenced by several factors, including patient education, treatment adherence, and socioeconomic conditions. This study highlights the importance of comprehensive care strategies tailored to individual patient needs to improve asthma control and reduce exacerbations.
الحقوق الفكرية (c) 2025 https://creativecommons.org/licenses/by-nc/4.0
Prevalence and Antimicrobial Resistance Profiles of Klebsiella Pneumoniae in Karbala, Iraq Hospitals
Background: Klebsiella pneumoniae a common pathogen emerging as Multidrug-resistant bacteria with high prevalence of infections in all clinical sites, having two pathotypes; classical K. pneumoniae (cKp) and hypervirulent K. pneumonia (HvKp), able to spread the resistance via Horizontal Gene Transfer mechanics. Objectives: We aim to determine the rate of infections caused by K. pneumoniae in Kerbala and check their phenotypic antimicrobial characteristics to assess the empirically used antibiotics. Materials and methods: Different clinical samples were collected from Al-Imam Al-Hassan Al-Mujtaba teaching hospital and Al-Hussien Medical City then screened for K. pneamoniae, 70 isolates were confirmed by VITEK-2 system, these samples were tested for aminoglycoside resistance, resistant isolates underwent a further investigation for 10 other antibiotics. Results: This study found (n=70, 13.01%) prevalence of K. pnuemoniae infections in urine, sputum, swab and blood samples, out of the 70 isolates only 20 (28.60%) of the isolates were HvKp, the samples manifested a high resistance rate against AMP (100%) and cephalosporins FOX (82.50%), CTX (73.0%), CRO (66.70%), FEB (66.70%), and fluroquinolones CIP (66.70%) and LEV (52.40%). The highest resisted aminoglycoside was KN (52.90%) while CN, TOB performed moderately showing only (37.10%) and (38.60%) resistance respectively, least resisted antibiotics were AK (31.40%), NET (28.60%) and carbapenems (30.20%) for MEM and (27.00%) for IMI, only 4 isolates were resistant to colistin (6.30%). Conclusion: With our results we concluded that K. pneumoniae has a high rate of infection in all clinical sources, K. pneumoniae isolates were highly resistant to cephalosporins and fluroquinolones due to improper and overuse of these antibiotics empirically, moderately resistant to aminoglycosides (KN, CN, TOB) and should not be used empirically while (AK, NET) are a good second-line treatment for ESBL-producing K. pneumoniae.
Synthesis, in silico Biological and ADMET Predictions, and Molecular Docking of Isatin Schiff Base Derivatives as Promising Antituberculosis Agents
Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a global health challenge, particularly with the rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. In this study, five isatin Schiff base derivatives were designed, synthesized, and evaluated using in silico approaches to identify potential antitubercular agents. The ADMET profiles of isatin Schiff base derivatives were studied via pkCSM, admetSAR, and SwissADME servers. Biological activity predictions were conducted using the PASS online tool, with significant activity considered at Pa > 0.7. Molecular docking studies were performed using MOE software targeting the InhA enzyme (PDB ID: 4TZK), a key protein in the fatty acid synthesis pathway of Mycobacterium tuberculosis. The docking results revealed that all five ligands exhibited favorable binding affinities and strong interactions with the enzyme’s active site. Additionally, the ADMET profiles suggested good drug-likeness and acceptable pharmacokinetic behavior. These findings suggest that the synthesized isatin Schiff base derivatives (A1–A5) are promising candidates for further development as antitubercular agents. Conclusion: This study demonstrated that the five isatin Schiff base derivatives (A1–A5) show strong potential as antitubercular agents. Molecular docking revealed promising interactions with the InhA enzyme, especially for ligand A5. ADMET studies analyses further supported their drug-likeness and biological activity. These findings warrant further experimental validation and optimization.
Design, ADME, In silico studies of Quinazoline-based Derivatives as New EGFR Tyrosine Kinase Inhibitors for Anticancer Therapy
Background: EGFR represents a critical therapeutic target in multiple cancer types, yet resistance mutations (T790M, C797S) limit the efficacy of current EGFR inhibitors. Quinazoline scaffolds, exemplified by clinically approved drugs (gefitinib, erlotinib, and osimertinib), offer a validated structural framework for EGFR inhibition. Early computational ADME profiling enables rapid identification of drug-like candidates, accelerating the discovery of novel EGFR inhibitors with enhanced potency and resistance profiles. Methods: Ten quinazoline-based derivatives (cp1–cp10) with diverse aromatic substituents were evaluated using integrated computational approaches: SwissADME for ADME profiling and drug-likeness assessment, Schrodinger Suite for molecular docking against EGFR (PDB: 3W33), and Desmond-based 50 ns molecular dynamics simulation for stability evaluation of the lead candidate cp6. Results: All derivatives exhibited excellent drug-likeness (Lipinski compliance), with molecular weights of 308.29–366.37 g/mol, optimal lipophilicity (iLOGP 1.6–2.68), high gastrointestinal absorption, and no blood-brain barrier permeability. Compound cp5 demonstrated superior docking affinity (−11.08 kcal/mol), approaching the reference inhibitor 19b (−11.94 kcal/mol). Cp6, selected as the lead based on balanced ADME and synthetic feasibility, showed stable binding interaction (docking score: −9.06 kcal/mol). Molecular dynamics confirmed robust complex stability (protein RMSD: 1.6–2.1 Å; ligand RMSD: < 2.0 Å) with critical interactions maintained for 60–85% of the trajectory. Conclusion: Quinazoline-based derivatives cp6 and cp5 emerge as promising EGFR inhibitor leads, combining excellent pharmacokinetic properties with strong binding affinity and computational stability. These candidates warrant experimental validation through in vitro EGFR enzymatic assays, cellular proliferation studies, and selectivity profiling against resistance-associated EGFR mutants.
New Biomarkers in Diagnosis of Diabetes Mellitus: A Review
Millions of individuals worldwide suffer from diabetes mellitus, a chronic metabolic condition caused by either insulin resistance or insufficiency. Accordingly, it is divided into Types 1 and 2 diabetes mellitus, and Gestational Diabetes (diabetes related to pregnancy). Insulin injections are used to treat diabetes type 1, which is caused by lack of insulin as a result of the autoimmune destroy of β-cells in pancreas. Insulin resistance (lack of insulin function) and impaired insulin secretion combine to cause diabetes type 2, which is the most common type. Consequently, there are anomalies in the metabolism of proteins, fats, and carbohydrates. By altering the endocrine glands' ability to produce hormones, diabetes mellitus also contributes to the emergence of secondary metabolic disorders. Diabetes mellitus is a serious health issue because of increased Incidence and mortality rate, increased cost of treatment, and considerable impact on people's lives owing to lost productivity. Furthermore, research conducted globally indicates that a large number of people have undiagnosed diabetes and prediabetes. Newly identified Important indicators for glucose regulation and the reason of metabolic diseases like diabetes mellitus have been brought to light by recent research. Presenting recently discovered Prognostic and diagnostic biomarkers of diabetes mellitus with recent advancements is the goal of this review. It has been suggested that employing novel Diabetes biomarkers as indicators of risk and associated information could help clinical evaluations by enabling the early detection of diabetic complications.
In Vitro Evaluation of Antioxidant Activity of Galangal (Alpinia Galanga) And Ginger (Zingiber Officinale) Aqueous Extracts
Introduction: Antioxidants prevent free radical-induced tissue damage by preventing the formation of radicals, scavenging them, or by promoting their decomposition. Natural antioxidants found in food, particularly fruits, vegetables, and other plant‐based diets, play an important role in disease prevention. Aim: The aim of this study was to evaluate antioxidative activities of aqueous extracts of ginger (Zingiber officinale) and galangal (Alpinia galanga) utilizing the DPPH assay method compared to that of ascorbic acid (Vit. C). Methods: The research was conducted at the Faculty of Pharmacy, University of Kufa, from February to July 2021. The aqueous extracts of these plants were made using both hot and cold extraction methods. The antioxidative activities of both cold and hot aqueous extracts of these plants at concentrations of 500 and 1000 µg/mL were made utilizing the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay method. Results: Both A. galanga and Z. officinale extracts demonstrated measurable activity comparable to ascorbic acid (vitamin C). The cold aqueous extract of A. galanga exhibited the highest antioxidant activity at a concentration of 500 µg/mL, while the hot aqueous extract of Z. officinale at 500 µg/mL showed the least activity. These findings suggest that the two plant extracts have different amounts of antioxidants at the same concentration. This indicates that A. galanga might be more effective at delivering antioxidant advantages than Z. officinale, and both the concentration and extraction method substantially affect antioxidant capacity, which is comparable to that of ascorbic acid. Conclusion: The aqueous extracts of Alpinia galanga and Zingiber officinale demonstrated quantifiable antioxidant activity, with A. galanga exhibiting greater efficacy under cold extraction conditions. Furthermore, these extracts demonstrate effective antioxidant activity in the DPPH assay, which is comparable to that produced by ascorbic acid (vitamin C).
Evaluation of the Relationship Between Integrons and Class A and B Carbapenem Resistance Genes in Escherichia coli Isolated from Patients with Urinary Tract Infections
Recently Carbapenem resistant reports increased among E.coli isolates from patients with urinary tract infection. Otherwise integrons are genetic elements with ability of integration of resistance gene cassettes in their structure facilitating the dissemination of antibiotic resistance genes. The study highlighting the detection of carbapenem resistance genes in Escherichia coli and how they are affected by the bacterial integron from 200 patients with Urinary tract infection. This cross-sectional study was conducted in Al-Sadder Medical City in Al-Najaf from the first of September to end of December 2024. E .coli isolates were identified using conventional biochemical tests and VITEK-2®System, while biofilm formation tested by Congo red agar. Antimicrobial susceptibility and phenotypic detection of carbapenemase were done using VITEK-2 AST card with disk diffusion and mCIM methods respectively. The presence of carbapenemase gene (bla-KPC, bla-GES, bla-NDM, bla-VIM and bla-IMP), Int-1and Int-2 were examined by polymerase chain reaction. Approximately 49 (24.5%) isolates of Eschericichia coli were identified from which 38(78%) were biofilm producers. Antibiotic resistant recorded in low rate to imipenem (20.4%), meropenem (22% (and ertapenem (24%). All E.coli isolates were MDR 46(94%) except 3(6%) were XDR. The positive results of Modified Carbapenem inactivation method (mCIM) recorded in 13 isolates. The gene bla-KPC found in 6(46%) isolates, bla-NDM in 11(85%) isolates and bla-VIM in 3(23%) isolates. Neither bla-GES nor bla-IMP genes were found. All isolate have Int-1 while only 1 isolate have Int-2. The presence of integrons mainly class-1 encourage Carbapenem and multi-drug resistant, indicating their role in enhancing and spreading resistant genes.
Assessment of Some Biochemical Parameters, Neutrophil Gelatinase Lipocalin, And Kidney Injury Molecule-1 in Type 2 Diabetic Patients with Chronic Kidney Disease
Diabetic kidney disease (DKD), often referred to as diabetic nephropathy (DN), is a microvascular complication of diabetes that may progress to end-stage renal disease (ESRD), a condition associated with high rates of morbidity and mortality. The principal etiological factors contributing to the development of DKD include glomerulocapillary angiopathy and prolonged duration of diabetes, both of which are major contributors to morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the diagnostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) as early biochemical markers of DKD by determining their sensitivity and specificity in Iraqi patients with T2DM. This cross-sectional study included 170 participants divided into three groups: Group I consisted of 50 healthy control subjects with an estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m²; Group II included 60 patients with T2DM and chronic kidney disease (CKD); and Group III comprised 60 patients with T2DM without CKD. All participants underwent fasting blood sampling for the assessment of glycated hemoglobin (HbA1c), serum creatinine (SCr), blood urea nitrogen (BUN), fasting blood sugar (FBS), serum electrolytes, NGAL, and KIM-1. The results demonstrated that patients with DKD had significantly elevated levels of urea, creatinine, HbA1c, and FBS, along with highly significant alterations in serum electrolytes, particularly calcium and phosphorus. Serum levels of NGAL and KIM-1 were significantly higher in the DKD group, with a strong positive correlation observed between the two biomarkers. Serum NGAL and KIM-1 levels increased progressively from the control group (168.68 ± 3.63 ng/mL; 79.39 ± 3.06 pg/mL) to diabetic patients without CKD (352.52 ± 6.56 ng/mL; 104.47 ± 1.88 pg/mL), and were highest in diabetic patients with CKD (935.50 ± 36.51 ng/mL; 309.15 ± 12.97 pg/mL). Receiver operating characteristic (ROC) curve analysis revealed a cutoff value of >421.76 ng/mL for NGAL and >134.91 pg/mL for KIM-1. Conclusion: Serum NGAL and KIM-1 levels, in combination with eGFR and other renal function parameters indicative of declining kidney function, may be considered reliable early biomarkers for the detection of diabetic kidney disease.
Oral Delivery of Monoclonal Antibodies: Challenges, Emerging Strategies, And Future Perspectives: A Review
Monoclonal antibodies (mAbs) have changed modern medicine by making it possible to treat complicated diseases with specific and selected drugs. But giving these treatments by mouth is still quite hard. In the gastrointestinal tract, they have to deal with acidic pH, digestive enzymes, mucus barriers, and a limited ability to cross the intestinal wall, making them much less stable and less able to be absorbed. This review shows new solutions for these problems, such as liposomes and other nanoparticles as protective nanocarriers, mucoadhesive systems, enteric coatings, enzyme inhibitors, and permeability enhancers. It also shows new ideas like receptor-mediated transport, targeted diseases, and advanced oral delivery systems. New developments in antibody engineering and artificial intelligence are making it possible to make oral formulations that are more stable and selective. Problems that also limit the use of mAbs such as safety, cost, and consistency, but the quick development in this area shows that oral mAbs could one day be an easier option for patients to use compared to injections.
Ultrasound Assisted Extraction, Phytochemical Investigation and Antioxidant Potency of Local Vitis Vinifera Leaves
Background: Since many of the therapeutic claims of medicinal plants are supported by reliable scientific data, their long-standing use traditionally to treat common ailments such as fever and colds has received considerable attention. Extraction is the first step in medicinal plant research, given its importance in determining the yield and phytochemical composition of the extract through specific chemical tests, which in turn influences the results of subsequent biological tests. Ultrasound Assisted Extraction (UAE) is one of the most common modern extraction methods, due to its use of fewer solvents and shorter processing time. It is important to remember that ultrasound frequencies above 20 kHz may produce free radicals, which may cause the decomposition of sensitive phytochemicals. Method: Vitis Vinifera leaves were weighed after being shade-dried. (UAE) was used to extract the active chemical components. Dried Vitis Vinifera leaves, weighing 15 g each, were extracted using petroleum ether (40-60°C) (500) ml and methanol: water in a 50:50 ratio subsequently. The ultrasonic treatment time was 13 minutes at room temperature using an UP400St. Chemical screening tests were performed on two different polar aqueous methanol extracts and a non-polar organic petroleum ether extract after drying. The non-polar petroleum ether extract was analysed using Gas Chromatography-Mass Spectrometry (GC-MS) method. Results: Flavonoids, saponins, tannins, terpenes, and alkaloids were found at high concentrations in Vitis Vinifera L. extracts, according to chemical screening tests. Substances detected by the GC-MS approach included steroids, fatty acids, aldehydes, and hydroxylated compounds. The present study confirmed that the aqueous methanolic extracts at doses of 100, 200, 400,600 and 800, 1000 μg/ml were examined against oxidative compound DPPH. According to the results, the methanol/water extract showed its efficacy to scavenge free radicals in vitro and the IC50 was measured. Ascorbic acid is used reference substances. Conclusion: Given the elevated levels of phenols and total flavonoids in the extract, its antioxidant efficacy was assessed, beginning with its capacity to scavenge free radicals in vitro. Ultrasound-assisted extraction (UAE) is a prevalent contemporary extraction technique employed effectively, owing to its reduced solvent usage and abbreviated processing duration.
Formulation and Evaluation of Apigenin-Loaded Topical Organogel for the Wound Healing
Wound healing is a complicated process that requires the use of many medications including anti-inflammatory and antioxidants. A naturally occurring flavonoid, apigenin can be found in a variety of fruits, vegetables, and medicinal plants that has versatile benefits and medical uses including wound healing, antioxidant, antiaging and others. Organogel is one of the promising topical drug delivery strategies which have many potentials in drug delivery effect. Organogel will be used for the topical delivey of apigenin. Different organogels were prepared by using lecithin, isopropyl myristate, pluronic F127, PEG 400 and water. The formulations were evaluated for their gelation temperature, pH, drug content, viscosity and drug release. The results demonstrated that without PEG 400 only 55% of the drug was released after 6 hours while 91% was released when PEG 400 was used. Formulation F5 was the optimum formula with appropriate viscosity (3372 mPs), pH (6.33), drug content (91%) and 27◦C gelation temperature. Drug release was around 91% within 6 hours. The formulated APN topical organogel will have the potential to improve wound healing by delivering the medication to the wound site in a sustained and localized approach.
Clinical and Hematological Evaluation of Hydroxyurea Therapy in Iraqi Patients with Sickle Cell Anemia
Background: Sickle cell anemia (SCA) is a chronic inherited hemoglobinopathy associated with severe morbidity and reduced quality of life. Hydroxyurea (HU) is the most effective disease-modifying pharmacological therapy for SCA; however, continuous evaluation of its clinical and hematological impact in different populations is essential. Objective: To assess the clinical efficacy and hematological effects of hydroxyurea therapy in Iraqi patients with sickle cell anemia. Materials and Methods: A cross-sectional observational study was conducted on 50 Iraqi patients diagnosed with SCA and treated with hydroxyurea for at least six months. Clinical outcomes included frequency of vaso-occlusive crises and pain intensity. Hematological parameters assessed were hemoglobin concentration and fetal hemoglobin (HbF) percentage. Data were analyzed using descriptive and comparative statistical methods. Results: Hydroxyurea therapy resulted in a significant increase in HbF levels and total hemoglobin concentration. Additionally, patients experienced a notable reduction in pain intensity and frequency of vaso-occlusive crises. The drug was generally well tolerated, and no severe adverse drug reactions were observed. Conclusion: Hydroxyurea demonstrates significant clinical and hematological benefits in Iraqi patients with sickle cell anemia. The findings support its role as a safe and effective pharmacological therapy and highlight its importance in routine clinical practice.
Evaluation of GDF11 And Lipid Profile in Diabetic Dyslipidemia
Background Diabetic dyslipidemia is a major risk factor for atherosclerosis and cardiovascular complications. Growth differentiation factor 11 (GDF11), a member of the transforming growth factor beta (TGF-β) superfamily, has a role in metabolic regulation, vascular health, and aging, but its role in diabetic dyslipidemia remains unclear. Patients and Methods: A comparative analysis was conducted between diabetic patients with dyslipidemia and those without. Serum GDF11 concentrations and lipid parameters were measured, along with additional markers of oxidative stress and inflammation. Statistical analysis was performed to assess group differences and correlations. Result: GDF11 shows a strong positive correlation with total cholesterol and triglycerides in diabetic patients, suggesting a role in lipid abnormalities, while no significant association is seen with HDL or LDL. A modest positive correlation is also observed between GDF11 and AST, indicating a possible link to liver involvement. Hematological findings reveal distinct patterns between diabetic patients with and without dyslipidemia. Those without dyslipidemia exhibit higher WBCs, granulocytes, lymphocytes, and platelets, reflecting greater inflammatory and immune activity. In contrast, patients with dyslipidemia have elevated erythrocytic indices (hemoglobin, RBC count, hematocrit, and MCHC), indicating altered red cell production. Additionally, RDW and platelet indices are higher in the non-dyslipidemia group, suggesting increased variability in cell size. Overall, dyslipidemia in diabetes is associated with enhanced erythropoietic changes, while non-dyslipidemic patients display stronger inflammatory and platelet responses Conclusion: Higher GDF11 levels are strongly associated with higher LDL, total cholesterol, and triglycerides. GDF11 also rises with HDL, but less strongly compared to LDL/TC. This suggests that GDF11 may play a role in lipid metabolism regulation, possibly being more tightly linked to lipid markers (LDL, TG, TC) than protective HDL.
The Association of Biofilm Formation and Antibiotic Resistance in Staphylococcus Aureus Isolated from Otitis Media in Najaf Governorate
Background: antibiotic resistance and biofilm formation in Staphylococcus aureus Otitis media is an inflammation of the middle ear and the tympanic membrane that often ensues upper respiratory tract infection it is causes a spectrum of diseases If inadequately treated, it results in numerous severe problems. The aim of the study was to Assess biofilm formation using the microtiter plate method and establish presence. ica operon genes that encoded of biofilm production in some strains of Staphylococcus aureus and the correlation between biofilm formation and antibiotics resistance. Patients and methods: Out of 130 otitis media isolates, we get 40 isolates of staphylococcus aureus and identified by using conventional technique then, confirming by Vitek 2compact system technique. then performed an antibiotic susceptibility test by using the automated identification usingVITEK2® compact system [BioMérieux, France], Following that, we used the microtiter plate method [MTP] to demonstrate the isolates' capacity to formation of biofilm. Following that, we carried out an identified to ica operons [A,B,C and D that encoding biofilm formation by using polymer chain reaction [PCR]. Results: after analysis of results all isolates resistance to beta lactam at varying resistance to another antibiotics and as a following: fusidic acid [80%], tobramycin [62.5%], tetracycline [45%], erythromycin [42.5%],gentamycin [42.5%], clindamycin [37.5%] and Rifampicin [35%] respectively .while all of isolates able to formation of biofilm and difference rates as a following [27.5% ]as a strong isolates and [72 .5% ] as a moderate isolates respectively, The molecular analysis of the ica operon found that ica A was detected in 6[15%] isolates, ica B in 3 [7.5%] isolates, and ica D in 19 isolates [47.5%]. Furthermore, 6 isolates [15%] harbored and 2 [5%] isolates ica A and ica Band D, respectively. All isolate of S.aureus which taken from otitis media patients by physicians of Ear, Nose and Tonsillitis. Conclusion: All isolates appearance high resistance to antibiotic that consider at serious health problem to individuals and populations, The findings indicated a correlation between treatment resistance and the existence of biofilm, It lowers the rate of healing or response to treatment and makes treatment more challenging and The low level of ica operon [A,B,C and D] in current study and non-correlation of biofilm formation but, entrance to detect typing of biofilm.
Design, Synthesis and Cytotoxic Evaluation of New Quinolinedione Derivatives as Potential Candidates for the Treatment of Cancer
Background: Carbonic anhydrase IX (CAIX) affected by hypoxia and thus lead to upregulated in many types of tumors and thus helps in maintain tumor pH balance under these conditions. Pharmacologic inhibition of CAIX has been shown in mouse models to slow tumor growth, curb metastasis, and limit tumor stem cell expansion. Therefore, inhibiting the overexpression of CA, particularly CA IX, consider a promising anticancer therapy. Objective: The primary objective of this study was to design and synthesis of a set of new quinolinedione derivatives (5a-c), study antiproliferative activity by MTT assay against HCT116 cell lines and MCF-7 cell lines and molecular docking studies to prioritize candidates’ compounds with the highest predicted binding. Methods: The synthesis of new quinolinedione derivatives (5a-c) through derivatives bearing methylsulfonyl aniline scaffolds, characterized via TLC, melting point, and spectral data acquisition (HNMR, and CNMR), and cytotoxic evaluated for the synthesised derivatives using antiproliferative activity by MTT assay against HCT116 cell lines and MCF-7 cell lines. Results: Among the tested compounds, 7-methoxy-3,4-dihydroquinolin-2(1H)-one (compound 5c) exhibited markedly stronger antiproliferative activity in HCT116 cells (IC₅₀ = 0.98 μM) and MCF-7 cell lines (IC₅₀ = 1.39 μM) versus acetazolamide (IC₅₀ = 1.69 μM, IC₅₀ = 2.45 μM). While, both compounds 5a and 5b showed a close cytotoxic activity results to acetazolamide. These results position quinolinedione derivatives (5a-c) as a promising starting point for further development as an anticancer agent. Docking study indicated that 5c achieved good S-scores (-6.211) in compare with acetazolamide (-5.574), suggesting stronger affinity for the CA IX active site. The substituted methoxy group and quinolinedione scaffold appear to enhance flexibility and receptor interactions. Conclusion: Overall, the quinolinedione derivatives (5a-c) were effectively synthesized and exhibit meaningful CA IX inhibition and cytotoxic activity, supporting their further evaluation as potential anticancer leads.
Niosomes As A Drug Delivery System: A Review
The invention of advanced drug delivery systems has received a lot of attention in the last few decades. The sophisticated drug delivery systems are designed to meet two requirements: they deliver drugs at a rate determined by the body's needs over the course of therapy, and they deliver the drug directly to inflamed or damaged tissues and/ or organs. Niosome-based drug delivery is one of these systems that encapsulate the medication in a vesicle. The vesicle formed by a bilayer of non-ionic surface-active agents. Niosomes offer promising drug delivery mechanisms. Being of non-ionic materials makes them less risky; hence, increases the therapeutic index of drugs by restricting their action to target cells. The goal of niosomes construction is to control the drug release in a sustained manner, a further change in the distribution profile of drug and targeting to the specific body site. The use of niosomes to encapsulate drugs may improve the protection of peptide-based medications. Insulin-loaded niosomes; for example, have a high tolerance to proteolytic enzymes. They are also effective in the topical delivery due to their ability to prolong the residence time of the drug and its active components in the stratum corneum and epidermis while minimizing systemic absorption.
Asthma Characteristics of School Aged Children in Different Asthma Phenotypes
Background: Asthma is a disease of the airways with different phenotypes in terms of origin, clinical presentation and response to treatment. Knowledge of these phenotypes is important in pediatrics, as it guides and optimizes management. The aim of this study was to study the asthma characteristics in asthma phenotypes of school-aged children. Patients and methods: This were a cross-sectional study, conducted in the Center of Pediatric Pulmonology/ Karbala teaching hospital for children on 80 asthmatic children (aged between 5 and 17 years) and they were classified into four phenotypes: allergic, eosinophilic, mixed allergic and eosinophilic (MAAE), and non-allergic non-eosinophilic (NANE). Demographic variables, clinical characteristics, and treatment details were also collected. Results: MAAE (34%) and allergic (32%) were the most frequent phenotypes. In all phenotypes, there was a male dominance and there was not difference of BMI and residence between them. Only 26% of asthma was well controlled, 38% uncontrolled and 36% partially controlled. The prevalence of severe asthma was significantly higher among those in the MAAE group (p-value< 0.001). There is a significant relationship between family history and allergic phenotype (p-value= 0.02). Conclusion: The findings emphasizes that there is a diversity of asthma phenotypes in school-aged children, and the allergic and the mixed allergic and eosinophilic phenotypes predominate. Most children had moderate asthma, but control was often poor with the allergic and mixed allergic and eosinophilic groups. Furthermore, allergic phenotype had a strong family history association in comparison to another phenotype.
Effect of Modified Nanoparticles on the Levels of Some Important Proteins in Blood
Manganese dioxide nanoparticles (MnO₂-NPs) and graphene oxide–based nanocomposites have attracted increasing attention for protein recovery applications. In this study, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were investigated as model glycoproteins for adsorption onto chitosan-coated MnO₂ nanoparticles (MnO₂-NPs) and chitosan/graphene oxide–MnO₂ nanocomposites (CS/GO-MnO₂-NPs). The CS/GO-MnO₂ nanocomposite was synthesized using a co-precipitation method and characterized by SEM, EDS, FT-IR, XRD, and particle size analysis. Adsorption experiments were conducted using fixed nanoparticle doses and varying hormone concentrations, and thermodynamic parameters were evaluated at different temperatures. The CS/GO-MnO₂-NPs exhibited high adsorption capacity for both hormones, following the Freundlich isotherm, indicating surface heterogeneity. Thermodynamic analysis confirmed that the adsorption process was spontaneous and exothermic. These findings suggest that MnO₂-based nanocomposites are promising platforms for hormone extraction and analytical applications involving human serum.
The Impact of the SLC5A2 Gene Polymorphism on the Treatment Efficacy of Empagliflozin in Iraqi Patients with Type 2 Diabetes
Background: Diabetes is a prevalent, life-threatening chronic disease and one of the leading causes of death worldwide. sodium glucose co-transporter 2, is the major co-transporter involved in renal glucose uptake, and its inhibition has been shown to be a relatively new strategy for managing diabetes. The gene encoding sodium glucose co-transporter 2 is located on chromosome 16 and is also known as soluble carrier family 5 member 2. Empagliflozin is a relatively new agent that improves glycemic control by increasing glucose excretion and inhibiting sodium–glucose cotransporter 2. The aim of study: was to investigate the potential effects of common single nucleotide polymorphisms in the sodium–glucose cotransporter 2 encoding gene soluble carrier family 5 member 2 on diabetes-related metabolic characteristics in patients who are at risk of type 2 diabetes. Secondly, we investigated whether these single nucleotide polymorphisms have pharmacogenetic significance by potentially influencing the response of type 2 patients to empagliflozin treatment. Methodology: The study participants included 50 healthy subjects and 110 diabetics who were selected during outpatient clinic visits with age range 30 to 65 years. Each subject underwent glycemic analysis, renal parameters, and genetic analysis of the soluble carrier family 5-member 2 reference SNP 121918621 polymorphism with blood samples that collected from different cities of Iraq. Each patient received 10 mg oral tablet of empagliflozin daily as monotherapy. Results: The findings of the study revealed significant variability with P-value less 0.05 in each of the glycemic and renal parameters among the study groups, with diabetic patients having significantly higher glycemic and renal parameters than healthy samples. soluble carrier family 5 member 2 reference SNP 121918621genotype distribution showed that (Fasting Serum Insulin, Fasting blood glucose, Glycated hemoglobin) levels did not differ significantly. The results also showed significant differences in (Serum creatinine, blood Urea) levels. Conclusion: The soluble carrier family 5-member 2 polymorphism is one of the genetic variables that contribute to heterogeneity in empagliflozin responsiveness in people with type 2 diabetes.
Influence of Valeriana Officinalis Extract and Zusanli Acupoint Stimulation on Serum ALT and Creatinine Levels in Rats
Background Traditionally used for its calming and antioxidant qualities, Valeriana officinalis has been shown to have beneficial benefits on liver and kidney functioning. Zusanli is a popular acupuncture point that is frequently linked to immunological and metabolic control. The purpose of this study was to assess how rats. serum levels of creatinine and alanine aminotransferase were affected by Zusanli acupoint stimulation and Valeriana officinalis extract, both separately and in combination. The study focuses on their possible contribution to renal and hepatic function supported. Methods Four groups of male Wistar rats were randomly selected, control Zusanli stimulation, Valeriana officinalis extract, and combined treatment, Zusanli was activated by electroacupuncture while the extract was taken orally once a day, Standard enzymatic assays were used to evaluate serum ALT and creatinine levels both prior to and followed the therapy period. Results Rats given Valeriana officinalis extract had significantly lower serum ALT levels than the control group,with the combination treatment group showing the biggest drop,The Zusanli stimulation and combined groups had much lower serum creatinine levels,These results show improved biochemical indicators for the liver and kidneys. Conclusion This study showed that rats liver and kidney function may be protected by Zusanli acupoint stimulated and Valeriana officinalis extract.The greatest improvement was seen with the combined treatment, indicating a possible synergistic effect.To clarify the underlying mechanisms and therapeutic relevance.
An Investigation of the Correlation Between the ABCB1 Rs4728709 Gene Polymorphism with Rivaroxaban Response and Bleeding Events in Patients with Atrial Fibrillation from Tthe Southern Region of Iraq
Background: Atrial fibrillation (AF) is a frequently occurring heart rhythm disorder that causes substantial morbidity and mortality due to thromboembolic events. Rivaroxaban, a direct oral anticoagulant (DOAC), is often prescribed to prevent strokes in patients with non-valvular AF. However, the impact of genetic variables on the pharmacokinetics and clinical effects of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) in Iraq still insufficiently explored. Aim of Study: This study explores the link between the single-nucleotide polymorphism (SNP) in the ABCB1 gene (rs4728709 G>A), rivaroxaban response, and the occurrence of bleeding events in patients with atrial fibrillation (AF). Patients and Methods: This cross-sectional study examines patients with atrial fibrillation (AF) treated with rivaroxaban anticoagulation from September 2024 to March 2025 in Iraq. We gathered clinical data covering demographics, comorbidities, and treatment adherence. Biochemical tests assessed coagulation parameters (INR, PT) and complete blood count (CBC) for (HB, PLT). Genotyping for the ABCB1 SNP was conducted using allele-specific polymerase chain reaction (AS-PCR). Results: This study included 100 participants, comprising 45 males and 55 females, predominantly over 46, and exhibited a high obesity rate of 52%. The genotype distribution for rs4728709 was 72% GG, 13% GA, and 15% AA. The rs4728709 polymorphism was not significantly associated with rivaroxaban response and occurrences of bleeding events. Conclusion: The rs4728709 polymorphism in the ABCB1 gene showed no significant association with rivaroxaban response or bleeding events among Iraqi patients with non-valvular atrial fibrillation, indicating limited pharmacogenomic relevance of this SNP in anticoagulation response within the studied population.
Computational Insights into Quinazoline-Isatin Conjugates as VEGFR Inhibitors: Anticancer Candidates
Background: As one of the most significant contributors to global mortality, cancer continues to stimulate intensive investigations into the anticancer and free radical-scavenging properties of new conjugates as potential therapeutic agents for advanced cancer treatment strategies. Method: This study reports the rational design and systematic assessment of four quinazoline-isatin hybrids (HK1-HK4) as potential VEGFR tyrosine kinase inhibitors through molecular docking and dynamic simulations, with binding affinities evaluated based on docking scores and RMSD values. Results: SwissADME analysis confirmed excellent drug-likeness with complete Lipinski's Rule of Five compliance (MW: 347-401 Da, iLOGP: -0.44 to 1.02). All conjugates showed high GI absorption, no BBB penetration, and 0.55 bioavailability scores. Molecular docking revealed superior VEGFR binding affinities (-7.8 to -9.681 kcal/mol), with HK1 demonstrating optimal binding (-9.681 kcal/mol) through interactions with Lys868, Cys919, and Asp1046. Conclusion: The quinazoline-isatin hybrids demonstrate excellent drug-likeness with complete Lipinski compliance and superior VEGFR binding. These promising computational results warrant experimental validation through in vitro enzymatic assays and cytotoxicity studies to advance clinical anticancer drug recognition.
Impact of CYP3A4 rs2242480 Gene Polymorphism on Rivaroxaban Plasma Level Concentration and Bleeding Risks among Iraqi Patients with Atrial Fibrillation
Background: A prevalent cardiac arrhythmia that dramatically raises the risk of stroke and systemic embolism is atrial fibrillation (AF). Moreover, because of their known pharmacokinetic and pharmacodynamic profile, convenience of administration, and fixed-dose administration, anticoagulants, such as rivaroxaban, are important and widely used to treat atrial fibrillation and prevent stroke. However, various factors, including genetic variations in the drug's metabolism, may have a role in the variation responsible for the response's interindividual heterogeneity. Cytochrome P450 3A4 is the major enzyme responsible for the metabolism of rivaroxaban. So, the polymorphisms on this enzyme (such as rs2242480) may change the metabolism, and then a change in plasma concentration may increase or decrease bleeding events. Study objectives: This study aims to determine the frequency of the CYP3A4 single-nucleotide polymorphism (SNP) rs2242480 in this cross-sectional study to examine the effect of the polymorphism on the plasma concentration of rivaroxaban and risk of bleeding in patients with atrial fibrillation (AF) from Iraq Patients and Methods: This study examined the effect of the CYP3A4 rs2242480 polymorphism on the rivaroxaban plasma concentration levels in 100 Iraqi atrial fibrillation patients receiving a fixed dose of 20 mg/day. Genotyping was done with allele-specific PCR, and the plasma levels were determined with HPLC. Results: The genotype distributions for rs2242480 were 10% TT, 29% CT, and 61% CC (wild-type). The mean rivaroxaban concentration was greater in patients with the T allele (CT and TT) (341.60 (336.80) ng/mL for CT and 399.00 (349.78) ng/mL for TT) than in patients with the CC genotype (152.60 (344.40) ng/mL). Still, this difference was not statistically significant (p = 0.248). Clinical and biochemical indicators did not significantly correlate with genotype, so bleeding events were reported in 10% of patients; there was also no significant association between bleeding events and CYP3A4 rs2242480 genotype. The bleeding episodes were generally mild and did not result in significant complications. Conclusion: In Iraqi individuals with atrial fibrillation, the CYP3A4 rs2242480 polymorphism has no recognized effect on rivaroxaban plasma levels or bleeding episodes. These findings imply that rivaroxaban treatment in this cross-sectional study may not require routine genotyping for this variant. Further extensive research and genetic analyses are needed to validate these results and investigate additional genetic factors impacting rivaroxaban metabolism.
Microbial Biomarkers in Clinical Chemistry, Diagnostic and Prognostic Application: A Review
Background These biomarkers assisted medical professionals in predicting clinical outcomes, guiding antibiotic stewardship, and differentiating between infectious and non-infectious inflammatory illnesses. However, the limitations of traditional biomarkers such as poor specificity, inter-patient variability, and overlap with non-infectious diseases led to the development of more sophisticated diagnostic instruments. Real-time PCR, multiplex pathogen detection panels, and next-generation sequencing NGS. are examples of significant advancements in molecular diagnostics that have expanded the biomarker spectrum beyond host derived analytes to include direct microbial fingerprints. Even in complex or culture-negative disorders, accurate organism identification was made possible by metagenomic sequencing, microbial cell free DNA, and pathogen-specific proteins. Precision medicine initiatives were encouraged, diagnostic accuracy was enhanced, and early detection was made possible when these molecular approaches were integrated with traditional clinical chemistry processes. Emerging multi-omics tools, such as proteomics, metabolomics, transcriptomics, and microbiome profiling, have enabled the discovery of novel biomarkers that captured dynamic host-pathogen interactions at previously un heard of resolution. In order to maximize patient survival and reduce unnecessary drug exposure, timely and correct diagnosis was essential. Infectious illnesses continued to be a major worldwide health burden. Because it provided an overview of current research on host response, biomarkers and pathogen, directed molecular technologies and demonstrated how their combination improved clinical decision making, antibiotic stewardship, and individualized patient care, The goal of this study. The goal of this study is to provide a thorough evaluation of both traditional biochemical biomarkers and advanced molecular diagnostic methods, highlighting their combined diagnostic and prognostic significance in infectious diseases. This review also aims to highlight current problems, clinical applications, and possible future directions to improve the accuracy of pathogen detection and patient treatment.
ESBL, AmpC β-Lactamases, and NDM Genes' Co-Existence and its Association with Multidrug Resistance among E. coli Isolated from UTI
The occurrence of multidrug-resistant Escherichia coli in urinary tract infections is considered the emergent health concern among world countries, particularly in the regions with limited clear antimicrobial resistance surveillance. The aime is assessed the β-lactamase-production profile of the E. coli and evaluate the complicated resistance pattern as gene co-occurrence outcomes among UTI patients. This study includes 212 urine samples collected from males and females, where 168 samples exhibited microbial growth, where the E. coli demonstrated a predominance (68%) among the isolated pathogens. However, the antimicrobial susceptibility reveals an elevated resistance rate toward most tested antibiotics, including amoxicillin/clavulanic acid (80%) and third-generation cephalosporins (≥61%). While nitrofurantoin (13%), carbapenem (≤12%), and aminoglycoside resistance (≤8%) remained the most susceptible ones. Additionally, the phenotypic confirmation demonstrated 67% of isolates were ESBL producers and AmpC producers. The genotypic investigation exposed a high frequency of ESBL genes: CTX-M-1 (86%), TEM-1 (85%), and OXA-1 (75%), with frequent co-occurrence between them. SHV-1 was the least distinguished gene (30%). The pAmpC is predominantly revealed (97%) among the isolates, in contrast to the CMY gene and the NDM gene, which were noticed in 19% and 9% of the isolates, respectively. However, a strong correlation has been found between the existence of ESBL genes and the resistance pattern of tested beta-lactam antibiotics (p< 0.001). In conclusion, the high occurrence of ESBL, AmpC, and NDM genes contributes to increasing the intensity and complexity of resistance patterns, therefore accelerating the occurrence of MDR among E. coli isolates.
Measles Resurgence Amidst Declining Vaccination Rates: A Global Public Health Threat: A Review
Measles is still one of the leading causes of mortality for children globally and is the most contagious disease known to science. It is a highly contagious, and potentially fatal virus, which has resurfaced as a major global public health issue, even in highly industrialized nations. This comeback is mainly due to a worrying decrease in vaccination rates, which has been made worse by the COVID-19 pandemic's disruptions. Approximately three out of every 1,000 cases of measles result in death. Measles has no known cure, but vaccinations have been a preventive measure since the 1960s. Even though measles still causes a great deal of morbidity, and death worldwide, there has been a lot of progress. Measles killed an estimated 777,000 people worldwide annually just twenty years ago in 2000. It killed 128,000 people worldwide in 2021. According to the analysis, measles outbreaks were widespread in 37 nations in 2022 as opposed to 22 the previous year. There were outbreaks in 37 countries, with 28 in Africa, 6 in the eastern Mediterranean, 2 in Southeast Asia, and 1 in Europe. Despite the recent year's decline in measles infection, this year it has resurged, both around the world and in Iraq. According to the Control Disease Center (CDC), Iraq ranked number five of countries with the most measles outbreaks between August 2023 and January 2024. Nearly, in Iraq, the current number of cases is three times more than in all of 2008, since the beginning of the year around 1,000 cases continue to be recovered every week, while over than 22.000 children have been infected. At the end of March ninety-three children had perished. The rise is attributed to the low immunity of the reduced coverage population that has resulted from reduced coverage of routine vaccination during 2005-2008 due to insecurity. The spread of this disease among school students is being noticed across the Iraq governorates and health authorities. This article highlights the critical need for a reinvigorated worldwide commitment to measles vaccination programs, looks at the alarming rise in measles cases, and investigates the factors causing a reduction in vaccinations.
Caesarean Section Rates and Associated Factors in Karbala: A Retrospective Study
Background: The most common obstetric surgical procedure performed worldwide is a Caesarean Section (CS). When performed properly, CS can enhance maternal and/or newborn outcomes. Although it saves the mother and child in some cases, it carries risks and complications, and the percentage of women who choose it without a medical reason is increasing, so awareness must be increased. Objective: Determine the frequency of CS and analyze the indications, so as to introduce measures to control the CS rate, as decreasing this rate will reduce maternal morbidity and mortality and increasing awareness among women about CS. Participants and method: The ongoing study was conducted from various hospitals in Karbala during December 2024. In this study, information and data were taken from all women who underwent a CS and Vaginal delivery by a questionnaire designed for this purpose. Results: The percentage of CS is 60% and the percentage of elective ones were 43.3% The most common indication for CS was inability to give birth naturally, followed by a previous CS, health problems for the mother (hypertension or diabetes), and pregnancy with twins, the rate of complications also increased after CS, (bladder and intestine injury, postpartum hemorrhage, and admission to the intensive care unit etc.) While in natural childbirth, complications are few and less severe. Conclusions: The increasing rate of the CS rate in Karbala populations highlight the need to apply more improvement and attention to primary health care in order to increase awareness and cooperation of health institutions and medical staff to spread risks and complications.
Potential Health Risks Due to Heavy Metals in Indian Rice Available in Karbala Markets, Iraq
Background: Hypothyroidism, characterized by insufficient thyroid hormone production by This study aims to assess the concentrations of six heavy metals, lead (Pb), cadmium (Cd), chromium (Cr), Nickel (Ni), Arsenic (As), and Selenium (Se), in samples of Indian basmati rice available in Karbala markets, Iraq. The concentrations of (As, Cr, Se, Ni, Pb, and Cd) were measured using atomic absorption spectroscopy (AAS), to evaluate the potential human health risks associated with the consumption of this rice, several health risk assessment parameters were calculated, including the Estimated Daily Intake (EDI), Target Hazard Quotient (THQ), Hazard Index (HI), and Cancer risk (CR). The average concentrations of As, Cr, Se, Ni, Pb, and Cd in the analyzed rice samples were 94.77, 326.06, 132.58, 179.39, 164.42, and 156.90 µg/kg, respectively. The average value of the Hazard Index (HI) was 4.242, which exceeded safe levels. The corresponding average carcinogenic risk (CR) values for As, Cr, Ni, Pb, and Cd were 8.21×10-04, 8.71×-04, 9.40×10-04, 8.05×10-06, and 5.70×10-03, respectively. However, the concentrations of As and Cd in several samples exceeded the maximum permissible limits set by European Union regulations. The calculated health risk indicators (EDI, THQ, HI, and CR) remained within internationally recognized safe exposure levels. In conclusion, although specific heavy metal concentrations in Indian basmati rice sold in Karbala exceed regulatory limits, the overall risk to human health from regular consumption appears minimal under current dietary exposure scenarios. Continuous monitoring and stricter import quality control are recommended to ensure long-term food safety for the local population.