Inflammation is a worldwide concern that impeded in various diseases, even cancer. In an attempt to generate potent and safer anti-inflammatory drug candidates, we rationally designed and synthesized a new library of dihydropyrimidine 5-carbonitrile derivatives 5 and 6a-e and investigated their inhibitory activity against the COX-2 enzyme. All final products were fully authenticated using 1H NMR, 13C NMR, HRMs, and IR spectral data. Compounds 6c, 6d, and 6e demonstrated significant anti-inflammatory inhibitory potential with IC50 values ranging between 0.099 and 0.297 μM compared to the standard drug diclofenac (0.079 μM). Notably, the para-methyl substituent 6c was the most active and selective analogue of the series (IC50 = 0.099 μM; SI = 10.43), showing superior selectivity compared with diclofenac sodium (SI = 7.65). Docking simulations provided insights into the binding scenarios of the compounds at COX-2. These findings indicate compound 6c represents an advantageous structural feature to advance the development of targeted COX-2 inhibitors.
The results showed that the (NGAL) in female patients increased to (230.52 ± 42.25 pg/mL) compared to healthy patients, which was (188.01 ± 33.20 pg/mL), with a statistically significant difference at a probability level of P ≤ 0.05. A ROC curve analysis was also conducted, revealing moderate discriminatory performance (AUC = 0.744), suggesting that serum NGAL may serve as a complementary biomarker rather than a standalone diagnostic test. Three dihydropyrimidine derivatives were synthesized and characterized spectroscopically and subsequently added to patients’ serum under cell-free experimental conditions. Addition volumes of 50 and 5 μL were evaluated. The highest numerical reduction in measured NGAL was observed in the V1 group at the 50 μL addition volume; however, this finding should not be interpreted as evidence of true biological alteration or inhibition of NGAL biosynthesis, but rather as an alteration in the measured signal, because the experiment was performed in separated serum without viable cells. The results indicate increased serum NGAL in women with UTI and a decrease in its measured analytical signal after some compound additions, particularly at the 50 μL addition volume. Because the experiment was conducted under cell-free conditions, these changes should be interpreted as alterations in the measured ELISA signal or detectable immunoreactivity rather than proof of reduced NGAL production or Alteration in measured signal efficacy.
Cyclophosphamide (CP) is an alkylating agent used to treat cancer, but it induces developmental alterations during organogenesis. Antioxidants like vanadium can reduce CP adverse effects, which is a trace element with preventive effects against chemotherapy-induced external malformations. This investigation aims to demonstrate the vanadium ameliorating effect on CP-induced adverse effects on embryonic mouse ovary development. Forty pregnant mice were used; the control group was administered distilled water. The CP group was injected with CP. The V group received vanadium, and the V/CP group was injected with vanadium along with CP. Vanadium dose was 4mg/kg received intraperitoneally on 8th,10th and 12th ED, while CP dose was 10 mg/kg received intraperitoneally on the 11th ED. To harvest the embryos, the animals were euthanized on the 19th day of pregnancy. The histological sections from the embryos were prepared for analysis. The results revealed that CP induced developmental alterations in ovaries of CP group compared to embryos in V and control groups, while vanadium improved these abnormalities in V/CP group significantly (p≤0.05). The count of germ cell cysts in the CP group decreased compared to the V group (p≤0.05). Also revealed that the diameter of the ovary, percentage of normal oocytes in the CP group decreased, and the percentage of atretic oocytes in the V/CP group increased in comparison to control group (p≤0.05), the diameter of the ovary, the percentage of normal oocytes increased, and atretic oocytes percentage decreased compared to the CP (p≤0.05). Accordingly, vanadium improved the adverse effects of CP in embryos.
Background: Withania somnifera (Ashwagandha) has exceptional medicinal capabilities. However, the therapeutic usefulness of its main bioactive indicators, withanolides, is frequently limited by poor water solubility, low skin permeability, and quick degradation. Nanogel delivery technologies provide a viable approach to overcoming these biologic limits. Objective: The purpose of this research was to design a nanogel loaded with ashwagandha root extract using a chitosan matrix and a Carbopol base for improved topical or transdermal administration. Methods: The ionic gelation approach was used to create ashwagandha-loaded chitosan nanoparticles. Results: UV-Vis spectroscopy revealed the effective entrapment of the bioactive withanolides. Fourier Transform Infrared (FTIR) spectroscopy confirmed the intermolecular crosslinking between nanoparticles. Scanning Electron Microscopy (SEM) indicated that the produced nanoparticles were spherical, evenly distributed, and embedded in the porous, three-dimensional network of the Carbopol hydrogel foundation. Energy Dispersive X-ray Spectroscopy (EDS) elemental mapping revealed distinct peaks for carbon, oxygen, nitrogen, and phosphorus, indicating effective cross-linking and purity. The resulting mixture had a homogeneous, spreadable consistency. Conclusion: The developed nanogel effectively overcomes the solubility concerns with raw Withania somnifera extract. The created formulation is a durable, bioadhesive, and highly localized carrier matrix, indicating tremendous potential for enhanced biological applications.
To assess urinary heat shock proteins HSP90, HSP70, and HSP60 and conductivity in patients with uric acid kidney stones and to study physicochemical factors influencing in vitro uric acid crystallization. Methods: The present study included 22 healthy controls and 64 patients with uric acid kidney stones confirmed by Fourier-transform infrared spectroscopy. Urinary HSPs were determined by ELISA. Receiver operating characteristic analysis was performed for diagnostic performance, and urinary biochemical parameters including pH, specific gravity, conductivity were measured. The in vitro uric acid crystallization was studied by optical density at 620 nm under different pHs, four media: artificial urine, stone-former urine, non-stone-former urine, and deionized water as a control, incubation times, and seeded and non-seeded conditions. Results: Urinary HSP90, HSP70, HSP60, and conductivity were significantly higher in patients than in controls. HSP90 showed the highest diagnostic performance (AUC = 0.865), followed by HSP70 and HSP60. Multivariate logistic regression showed urinary conductivity to be a significant independent predictor of stone-forming status. In vitro crystallization was greatest at pH 4.01, while seeded conditions produced significantly higher optical density values than non-seeded conditions. Conclusions: Increased urinary heat shock proteins and conductivity are associated with uric acid stone disease. Uric acid crystallization is strongly promoted by low pH and crystal seeding, suggesting a role for the interaction between renal stress responses and physicochemical urinary conditions in stone formation.
Oxadiazoles are an important class of heterocyclic compounds with diverse biological activities. In this study, four novel 1,3,4-oxadiazole derivatives (L1–L4) were synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR, EI-MS, and CHN elemental analysis. Their structural, electronic, and pharmacokinetic properties were investigated using DFT at the B3LYP/6-311++G(d,p) level, molecular docking against potential estrogen receptor α (ERα, PDB: 3ERT), and SwissADME-based drug-likeness and ADMET prediction. Compound L3 exhibited the most favorable predicted binding affinity (−7.1172 kcal/mol), whereas L4 showed the strongest hydrogen-bonding interaction with GLU353. Based on the molecular docking results, only compounds L3 and L4 were selected for in vitro cytotoxic evaluation against MCF-7 breast cancer cells, whereas L1 and L2 were not included in the biological evaluation. Although all derivatives satisfied Lipinski's Rule of Five and showed favorable predicted ADMET properties, the in vitro studies demonstrated weak cytotoxic activity over the tested concentration range (12.5–1000 µM), and IC₅₀ values could not be determined for either compound. These findings indicate that favorable computational predictions did not translate into significant cytotoxic activity under the present experimental conditions, highlighting the limitations of molecular docking alone in predicting biological activity.
Background: Infected burn wounds remain a major therapeutic challenge because of bacterial colonization, biofilm formation, persistent inflammation, and antimicrobial resistance. Conventional antibiotics often exhibit poor wound retention and limited biofilm penetration. Calcium phosphate (CaP) nanoparticles offer a biocompatible platform for localized, sustained antibiotic delivery. Objective: To develop and evaluate ciprofloxacin lactate-loaded calcium phosphate nanoparticles (CIP-Lac/CaP NPs) as a nanoantibiotic system for infected burn wound treatment. Methods: CIP-Lac/CaP NPs were prepared by co-precipitation and optimized by formulation screening. Nanoparticles were characterized by particle size analysis, TEM, FT-IR, PXRD, and DSC. Encapsulation efficiency, drug release, antibacterial and antibiofilm activities, cytocompatibility, and in vivo wound healing efficacy were evaluated. Results: Optimized CIP-Lac/CaP NPs showed a particle size of 145.3 ± 7.8 nm, PDI of 0.21 ± 0.04, zeta potential of −32.7 ± 2.5 mV, and encapsulation efficiency of 78.4 ± 3.1%. Solid-state analyses confirmed successful drug incorporation with reduced crystallinity and no chemical incompatibility. Nanoparticles provided sustained drug release and significantly enhanced antibiofilm activity, achieving 89.4 ± 2.5% and 82.1 ± 3.1% inhibition against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. MBEC values decreased to 8 and 16 µg/mL, compared with 64 and 128 µg/mL for free ciprofloxacin. Cell viability remained >82% after 48 h. Conclusion: In vivo, CIP-Lac/CaP NPs improved bacterial clearance, re-epithelialization, collagen deposition, and inflammatory regulation. These findings demonstrate that CIP-Lac/CaP NPs provide controlled antibiotic delivery, potent antibacterial and antibiofilm activity, excellent biocompatibility, and enhanced burn wound healing, supporting their potential as an effective multifunctional therapy for infected burn wounds.
This study evaluated the polyphenolic content and anti-inflammatory and hypoglycemic activities of the mother plant and callus cultures of Teucrium polium L. subsp. geyrii Maire from Algeria. The mother plant and calli aged 2–12 months were analysed for total polyphenolic content and profiled by high-performance liquid chromatography. Anti-inflammatory activity was assessed using the carrageenan-induced paw oedema model, and hypoglycemic effects of the mother plant and 12‑month‑old callus infusions were evaluated by normoglycaemia and oral glucose tolerance tests. The highest polyphenolic content was observed in 8‑month‑old calli (2.54 ± 0.02 mg of gallic acid equivalent per g of dry matter). Callus infusions showed stronger inhibition of carrageenan induced paw oedema and more effectively attenuated the peak of glucose induced hyperglycaemia. These findings suggest that the richer profiles of flavones–flavonols and phenolic acids in callus contribute to their enhanced anti-inflammatory and hypoglycemic potential, thereby supporting the traditional use of T. polium in local medicine.
Background and Aims: Diabetic foot ulceration (DFU) is a serious complication of diabetes, often leading to infection, amputation, and increased morbidity and mortality. Early identification of causative pathogens and their resistance patterns is essential for effective management. This study aimed to determine the bacterial profile and antibiotic susceptibility patterns among DFU patients. Materials and Methods: A cross-sectional study was conducted on 249 DFU patients from November 2025 to February 2026. Samples were collected aseptically and processed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: A total of 258 bacterial isolates were recovered. Most patients were males aged 50–59 years. Gram-negative bacilli predominated (73.1%), while Gram-positive bacteria accounted for 26.9%. The most common isolates were Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Monomicrobial infections were observed in 91.2% of cases. S. aureus was predominant in Wagner grade 2, whereas P. aeruginosa was more common in grade 4 ulcers. High resistance rates were noted for Cefotaxime, Oxacillin, Methicillin, and Vancomycin. Multidrug resistance was detected in 67.4% of isolates, and extensive drug resistance in 11.6%. Conclusion: The predominance of Gram-negative organisms and high antimicrobial resistance emphasizes the need for regular surveillance and targeted antibiotic therapy to improve clinical outcomes in DFU patients.
Background: The liver and heart, due to high metabolic demands, are vulnerable to oxidative damage. Glycerol administration induces acute cardiac and hepatic injury, reflected by elevated biomarkers: creatine kinase (CK), lactate dehydrogenase (LDH), troponin I, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Carvedilol (CAR), a non-selective β-blocker with antioxidant properties, and sodium copper chlorophyllin (SCC), a stable chlorophyll derivative with free radical scavenging activity, may offer protection. Methods: Fifty female Wistar rats were randomly divided into five groups (n=10): control (saline), glycerol-induced injury (8 mL/kg/day IM for 5 days), CAR (2.5 mg/kg/day oral for 14 days), SCC (50 mg/kg/day oral for 14 days), and combination (CAR+SCC). Liver function tests (ALT, AST, ALP), cardiac biomarkers (CK, LDH, troponin I), and histology of liver and heart were assessed. Results: Glycerol treatment significantly increased all injury markers vs. controls (p<0.05). CAR and SCC both reduced these elevations, with SCC showing more effective responses. Combination therapy (G5) lowered CK from 1753±875 to 389±61 U/L, LDH from 1301±140 to 317±105 U/L, troponin I from 87±8 to 23±2.6 pg/mL, ALT from 101±44 to 41±16 U/L, AST from 487±90 to 172±50 U/L, and ALP from 499±35 to 385±62 U/L. Histopathology showed severe cardiac congestion and hepatocyte destruction in G2, whereas G5 exhibited nearly normal cardiac muscle fibers and hepatocytes with minimal damage. Conclusion: Carvedilol and sodium copper chlorophyllin protect against glycerol-induced oxidative cardiotoxicity and hepatotoxicity in rats via ROS reduction, membrane stabilization, and anti-inflammatory mechanisms. Dual therapy synergistically restores biochemical markers and normal histology.
Background: Acinetobacter spp. are important causes of healthcare-associated infections (HAIs) in intensive care units (ICUs) and are frequently associated with antimicrobial resistance. This study aimed to determine the prevalence and antimicrobial susceptibility of Acinetobacter spp. isolated from ICU patients with HAIs. Methods: A cross-sectional study was conducted in the ICUs of Assiut University Hospital, Egypt, from August 2024 to August 2025. Clinical specimens were collected from ICU patients who developed confirmed HAIs. Presumptive Acinetobacter isolates were identified using phenotypic and biochemical methods and confirmed by polymerase chain reaction (PCR) amplification of the partial beta subunit of RNA polymerase (rpoB) gene. Antimicrobial susceptibility testing was performed using the disc diffusion method according to Clinical and Laboratory Standards Institute (CLSI) 2024 guidelines. Results: Thirty-six of 334 ICU patients with HAIs (10.8%) were infected with Acinetobacter spp. Lower respiratory tract specimens accounted for the largest proportion of isolates (45.9%), followed by blood specimens (37.8%). High resistance rates were observed against ceftazidime (97.3%), ceftriaxone (91.9%), cefotaxime (91.9%), and levofloxacin (86.5%), whereas doxycycline showed the lowest resistance rate (24.3%). Multidrug-resistant (MDR) and carbapenem-non-susceptible (Carb-NS) phenotypes were detected in 86.5% and 70.3% of isolates, respectively. Conclusion: Acinetobacter spp. accounted for a considerable proportion of HAIs among ICU patients and exhibited high resistance to several commonly used agents, with most isolates demonstrating MDR and Carb-NS phenotypes. These findings highlight the substantial burden of resistant Acinetobacter and the limited remaining treatment options in ICU settings.
Abstract Background: While pregabalin treats neuropathy and epilepsy, high-dose abuse raises severe safety concerns. Its subacute high-dose on electrolyte balance, hepatic, and renal functions remain poorly understood. Objectives: This study evaluated the subacute pregabalin administration in the liver and kidneys of adult albino rats using a multiparametric assay. Methods: Twenty-four male albino rats were divided into four groups (n=6) and orally administered pregabalin (50, 150, or 300 mg/kg) for eight days. Assessed parameters included renal function (BUN, creatinine), liver enzymes (ALT, AST, ALP, GGT), protein synthesis, electrolytes, pancreatic enzymes, oxidative stress, and cardiac biomarkers. Hepato-renal tissues underwent histopathological examination. Results : Pregabalin dramatically a decrease of total protein, albumin, and magnesium (p<0.05) while enhancing BUN, BUN/creatinine ratio, phosphorus, and Ca×P product (all p<0.05). Although AST enhanced at 50 and 300 mg/kg (p=0.0066), ALT exhibited a U-shaped signal with a major increase only at 50 mg/kg (p=0.0001). TBA (oxidative stress) enhanced in a dose-dependent pattern (p=0.0099). The hepatorenal histopathological results revealed dose-dependent congestion, inflammation, and structural injury. The values of creatinine, ALP, GGT, lipase, amylase, CK, LDH, and electrolytes failed to change. In conclusion: subacute pregabalin at elevated therapeutic concentrations leads to oxidative stress, diminished protein synthesis, prerenal azotemia, hepatocellular dysfunction (with a U-shaped ALT response), and mineral imbalances. Dose-dependent organ injury is proven by histological evidence. Such results indicate concerns regarding the safety of pregabalin abuse, especially in hepato-renal impaired patients.
