The rational design of hybrid molecules with dual therapeutic actions offers a promising approach in anticancer drug development. In this study, four novel hybrid conjugates (3a, 3b, 5a, and5b) were synthesized by coupling sulfa drugs (sulfadiazine and sulfamethoxazole) with azo dye moieties via bioactive linkers-paracetamol and 2-hydroxy-1-naphthaldehyde. The compounds were fully characterized by FT-IR,H-1 NMR,C-13 NMR, mass spectrometry, elemental analysis, and HPLC, confirming high purity (>98%). The hybrids exhibited potent antioxidant activity and stronger inhibition of anti-inflammatory enzymes (COX1, COX2, 5-LOX) compared to their analogues. Notably,3band5bshowed significant cytotoxicity against Caco2 (IC50 = 11.2 and 15.1 mu M) and MCF-7 (IC50 = 19.2 and 33.4 mu M) cancer cell lines. Mechanistic studies revealed that these compounds significantly downregulated the mRNA expression of inflammation-and tumor progression-related genes (IL6, TNF-alpha, TGF-beta, and COX2) in Caco2 cells, as confirmed by qRT-PCR, highlighting their dual effects on tumor cell proliferation and the inflammatory tumor microenvironment. Molecular docking predicted strong binding affinities toward COX1 and COX2, particularly for3band5b, consistent with experimental results.In silicoADME analysis indicated favorable drug-like properties, suggesting that these compounds may serve as promising preliminary candidates for further pharmacological and toxicological evaluation as dual-target therapeutic agents against colorectal cancer.
Background Nocturnal enuresis adversely affects school-aged children and family quality of life. Aim To evaluate the effect of the empowerment program on mothers' knowledge, self-reported practices, and quality of life. Design Two-arm randomized controlled trial with assessments at baseline, four weeks, and three months post-intervention. Methods At the outpatient urinary incontinence clinic of the Center for Social and Preventive Medicine, Cairo University, Egypt, 200 purposively recruited mothers were randomly assigned 1:1 using a computer-generated sequence with allocation concealed in numbered, sealed envelopes. Outcomes were assessed using two researcher-developed, content-validated instruments and a modified Arabic Pediatric Enuresis Module on Quality of Life, Short Form. Linear mixed models compared groups over time. Results Groups were comparable at baseline. Group × time interactions favored the intervention for knowledge (F(2, 396) = 124.5), practices (F(2, 396) = 68.9), and quality of life (F(2, 396) = 92.3); all p < 0.001. At three months, improvements in intervention versus control groups were 8.23 versus 1.30 points for knowledge, 3.84 versus 0.72 for practices, and 19.9 versus 3.5 for quality of life. Between-group effect sizes were large (Cohen's d = 2.12, 1.17, and 1.78, respectively). Conclusion The program improved mothers' knowledge, self-reported practices, and quality of life, with effects maintained at three months. These mother-reported outcomes do not demonstrate improvement in children's enuresis. Recommendations The program may be considered an adjunct to standard care in outpatient settings. Multicenter trials with longer follow-up and objective child outcomes are needed before routine implementation.Trial registration: ClinicalTrials.gov NCT07753304 (retrospectively registered).
The increasing demand for compact and energy-efficient heat exchangers has accelerated the development of passive heat transfer enhancement techniques and intelligent predictive tools for improved thermal system design. In the present study, an experimental and machine learning-based investigation was conducted to evaluate the thermo-hydraulic performance of a counter-flow double-pipe heat exchanger equipped with helical wire coil (WC) inserts under turbulent flow conditions. The novelty of this work lies in the systematic assessment of fifteen insert configurations by combining three wire diameters (1.0, 1.5, and 2.0 mm) with five pitch ratios (P/Dc = 0.625, 1.25, 1.875, 2.5, and 3.125). Experiments were performed over a Reynolds number range of 5500-15000, and the experimental setup was validated against established Nusselt number and friction factor correlations. The thermo-hydraulic performance was evaluated using the heat transfer coefficient, Nusselt number, friction factor, pressure drop, and thermal performance factor. The results showed that the wire coil inserts generated strong swirl flow and secondary vortices, which enhanced fluid mixing and suppressed thermal boundary layer development, resulting in a maximum Nusselt number enhancement of 126.7% compared with the plain tube. The highest Nusselt number (180.24) was achieved using a 2 mm wire diameter with a P/Dc of 0.625. Although the friction factor increased by 156.5-410.8% due to greater flow resistance, the thermal performance factor remained above unity (1.01-1.35) for all configurations, confirming the overall thermohydraulic effectiveness of the inserts. Furthermore, Linear Regression, Ridge Regression, Random Forest, and Gradient Boosting models were developed to predict the heat transfer and flow characteristics. Among them, the Gradient Boosting model demonstrated the highest prediction accuracy, achieving R2 values of 0.9984 and 0.9971 for the Nusselt number and friction factor, respectively, highlighting the potential of machine learning for the rapid design and optimization of advanced heat exchanger systems.
Ischemic acute kidney injury (AKI) remains a major clinical challenge, characterized by high morbidity, mortality, and a substantial risk of progression to chronic kidney disease. Accumulating evidence indicates that ischemic AKI is not merely a transient hemodynamic disorder but a complex, biologically orchestrated process driven by microvascular dysfunction, innate immune activation, inflammatory signaling, and maladaptive tissue repair. Despite advances in supportive care, effective disease-modifying therapies are still lacking. Recent studies have highlighted that key signaling pathways, including Toll-like receptor/nuclear factor-κB (TLR/NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), purinergic P2X7 receptor–inflammasome signaling, heat-shock protein–mediated stress responses, and phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) cascades, govern the initiation, amplification, and resolution of ischemic renal injury. These pathways converge on downstream cellular effectors such as cell adhesion molecules (CAMs), which orchestrate leukocyte recruitment, endothelial-epithelial interactions, and spatial propagation of inflammation within the renal microvasculature. Natural compounds have emerged as promising therapeutic candidates for ischemic AKI due to their pleiotropic pharmacological properties and ability to modulate multiple pathogenic signaling networks simultaneously. A growing body of experimental evidence demonstrates that polyphenols, glycosides, saponins, and related phytochemicals attenuate ischemic renal injury by suppressing inflammatory signaling, reducing CAM expression, preserving microcirculatory integrity, and promoting adaptive repair. Furthermore, advances in nanocarrier-based delivery systems have substantially enhanced the translational potential of these compounds by improving bioavailability, renal targeting, and pathway-specific modulation. In this review, we provide a comprehensive, signaling-centered analysis of ischemic AKI pathogenesis and systematically map natural compounds to their molecular targets and downstream inflammatory effectors. By integrating mechanistic insights with emerging nanotherapeutic strategies, this work offers a structured framework for the rational development of multi-target, mechanism-based interventions for ischemic AKI. It highlights key challenges and future directions for clinical translation.
The traditional renin-angiotensin system (RAS) is involved in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). Combating the classical RAS cascade has a relevant therapeutic impact on osteoporosis. This study aimed to investigate the potential osteo-protective influence of diminazene, an angiotensin converting enzyme-2 (ACE-2) activator against GIO in rats. Forty adult male rats were equally classified into: control, GIO, diminazene, and GIO + diminazene groups. Rats were scanned via dual-energy X-ray absorptiometry for evaluation of bone mineral density (BMD) and bone mineral content (BMC). Serum levels of Ca2+, inorganic phosphorus (P), osteocalcin, bone-specific alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase-5b (TRACP-5b) were measured. Bone receptor activator NF-kB ligand (RANKL), Osteoprotegerin (OPG), angiotensin II (Ang II), ACE-2, Ang (1–7), malondialdehyde (MDA), superoxide dismutase (SOD) activity, tumor necrosis factor-alpha (TNF-α) were determined. Additionally, femoral TNFSF11 and TNFRSF11B gene expression were evaluated through RT-PCR, as well as histopathological examination of rats’ femur and immunohistochemistry for assessment of femoral interleukin-6 (IL-6). Rats with GIO displayed diminished BMD and BMC with elevated serum BALP and TRACP-5b. Bone RANKL/OPG ratio and Ang II levels were also increased, while serum Ca2+, osteocalcin, bone ACE-2 and angiotensin (1–7) were apparently reduced. They displayed oxidant/antioxidant imbalance, increased bone TNF-α and IL-6, disturbed TNFSF11 and TNFRSF11B gene expression and histopathological osteoporotic changes. Diminazene improved BMD, BMC and bone metabolic markers. It reversed most of histopathological abnormalities. Alongside, it markedly increased bone ACE-2, Ang (1–7) and SOD activity, while decreasing bone RANKL/OPG ratio, Ang II, MDA, TNF-α and IL-6 with modification of TNFSF11 and TNFRSF11B genes. Diminazene, alleviated GIO via mediating anti-oxidant, anti-inflammatory actions together with modulation of RANKL/OPG pathway.
