To evaluate the cardioprotective effects of luteolin, a naturally occurring flavonoid, in mitigating critical pathological processes linked to cardiovascular diseases (CVDs), including oxidative stress, inflammation, mitochondrial dysfunction, and endothelial damage. Luteolin, found in celery, parsley, green peppers, and chamomile tea, exhibits significant cardioprotective properties through various mechanisms. It activates the Nrf2/HO-1 antioxidant pathway, suppresses NF-κB-mediated inflammation, regulates apoptosis, and preserves the functionality of endothelial nitric oxide synthase (eNOS). In preclinical studies involving isoproterenol- and doxorubicin-induced cardiotoxicity, luteolin was shown to reduce oxidative stress, decrease apoptosis, and improve cardiac structure and function. Compared to other flavonoids like quercetin and resveratrol, luteolin demonstrates more potent endothelial-protective effects and a balanced modulation of antioxidant and apoptotic pathways. The diverse actions and natural origin of luteolin make it a promising candidate for CVD prevention and as an adjunctive therapy. Future research should focus on rigorously designed clinical trials to validate its efficacy in heart failure, ischemic injury, and drug-induced cardiotoxicity, thus enhancing its application in clinical practice.
Pregnancy profoundly alters drug disposition through dynamic physiologic adaptations affecting absorption, distribution, metabolism, and excretion. Although pharmacogenomics has transformed precision therapeutics across multiple medical specialties, its application during pregnancy remains limited because conventional pharmacogenomic models assume stable genotype-phenotype relationships that do not account for the temporal biologic changes of gestation. This mini-review proposes a conceptual framework for obstetric-pharmacogenomics in which maternal, placental, and fetal-genomes interact within a continuously evolving physiologic environment to shape drug exposure, therapeutic efficacy, and toxicity. Pregnancy-induced alterations in cytochrome P450 enzyme activity, drug transporters, placental metabolism, and immune regulation may amplify, attenuate, or fundamentally modify genetically determined drug responses, rendering static pharmacogenomic classifications insufficient. We discuss the clinical implications of this dynamic paradigm across several therapeutic areas, including antiretroviral therapy, maternal mental health, hypertensive disorders of pregnancy, and analgesia, and highlight the need for trimester-specific approaches to individualized drug therapy. We further examine current barriers to implementation, including the exclusion of pregnant women from pharmacogenomic research, limited longitudinal data, and ethical considerations surrounding fetal genetics. Integrating pharmacogenomics with physiologically based pharmacokinetic modeling and multi-omics technologies offers an opportunity to redefine precision-medicine in obstetrics and advance safer, more effective, and individualized pharmacotherapy for pregnant-women and their offspring.
OBJECTIVES:Incisional hernia is a complication after abdominal surgery and is particularly challenging in patients with ascites because of increased intra-abdominal pressure, impaired wound healing, and infection risk. Evidence on surgical repair remains limited, particularly for incisional rather than umbilical hernias. METHODS:This retrospective multicenter study included 31 cirrhotic patients with ascites (22 males, 9 females; 45-72 years) who underwent incisional hernia repair between 2000 and 2025 at three tertiary General and Emergency Surgery Units. Liver disease severity was assessed using the Child-Pugh classification. Following preoperative ascites optimization, repair was performed with primary suture or mesh reinforcement. Primary outcomes were perioperative morbidity and mortality; secondary outcome was hernia recurrence. RESULTS:Perioperative mortality occurred in 5 patients (16.1 %), all with advanced liver disease. Major complications occurred in 8 patients (25.8 %), while minor complications developed in 10 (32.3 %), mainly surgical site infection, seroma or hematoma, and postoperative ileus. After a median follow-up of 26 months, hernia recurrence occurred in 11 patients (35.5 %) and was higher after primary suture than mesh repair. CONCLUSIONS:Elective repair is feasible in selected patients after ascites optimization. Mesh reinforcement provides greater durability when infection risk is acceptable. Patient selection and perioperative management remain essential.
OBJECTIVES:Conventional semen analysis often fails to detect hidden functional defects contributing to male infertility. Factors such as sperm DNA-integrity, oxidative stress, MMP, and acrosome integrity are critical for fertilization and early embryonic development. This study aimed to evaluate sperm function defects in normozoospermic infertile men and highlight limitations of routine semen parameters in infertility assessment. METHODS:Semen samples underwent standard semen analysis. Sperm DNA damage was assessed using Acridine Orange staining, acrosome integrity by FITC-PSA staining, and ROS levels along with MMP were measured using flow cytometry. Appropriate statistical analyses were performed to compare infertile men and fertile controls and determine correlations among functional parameters. RESULTS:Among clinically screened infertile patients, 23 % were normozoospermic according to WHO 2010 criteria. Sperm function parameters were evaluated in normozoospermic infertile men (n=45) and fertile controls (n=17). Infertile men exhibited significantly higher ROS levels and DNA damage (p<0.001), alongside reduced acrosome integrity and MMP (p<0.001) compared to controls. ROS showed a positive correlation with DNA damage and acrosome-reacted sperm, and a negative correlation with MMP. CONCLUSIONS:Functional sperm defects may underlie infertility in a substantial proportion of normozoospermic men. Incorporating sperm function tests as second-line investigations may improve diagnosis and management of unexplained male infertility.
OBJECTIVES:To determine the frequency and pattern of potentially inappropriate prescriptions, including potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs), among elderly inpatients aged 65 years and above in a tertiary care hospital. METHODS:This hospital-based observational Cross-sectional study was conducted from January 2019 to January 2020 in the Medicine Department. Four hundred patients aged ≥65 years with at least one chronic illness and complete medication records were included. The STOPP/START version 2 criteria were applied to identify PIMs and PPOs. Demographic details, clinical diagnoses, and hospitalization data were collected and analyzed. RESULTS:Among 400 patients (233 men, 167 women; mean age 69 ± 4.94 years), cardiovascular diseases were the most common cause of admission (30 %), followed by respiratory (21 %) and nervous system disorders (12.5 %). A total of 4,337 medications were prescribed, averaging 10.87 per patient. PIMs were identified in 48 patients (12 %), most frequently cardiovascular drugs (36 %), fall-risk-increasing drugs (16 %), and antiplatelet/anticoagulant agents (13 %). PPOs were observed in 38 patients (9.5 %), commonly involving cardiovascular and preventive therapies. CONCLUSIONS:Inappropriate prescribing remains prevalent among elderly inpatients. Routine use of structured tools such as STOPP/START may enhance safer, evidence-based prescribing and improve outcomes.
OBJECTIVES:Diabetic retinopathy (DR) causes retinal detachment, capillary degeneration, and diabetic macular edema. Chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs). This activates the receptor for advanced glycation end-products (RAGE) signaling pathway, resulting in inflammation, oxidative stress, and cellular issues in the retina. The AGE-RAGE axis and signaling pathways are attractive therapeutic targets. METHODS:This study investigated the protective effects of trans-anethole (TA) and the RAGE inhibitor FPS-ZM1 in an in vitro model of high glucose-induced retinal injury. Both compounds were initially evaluated by molecular docking against GSK-3β. As FPS-ZM1 demonstrated higher predicted binding affinity than TA, further computational analyses, including molecular dynamics simulations and MM/GBSA binding free energy calculations, were performed only for FPS-ZM1. RESULTS:Both only TA and its combination with FPS-ZM1 greatly improved the healing response when glucose levels were high. This suggests that TA may have considerable therapeutic potential for wound healing. In addition, molecular docking and molecular dynamics simulations revealed that FPS-ZM1 may interact with GSK-3β ligand binding site. CONCLUSIONS:Further investigations utilizing in vivo models are necessary to validate the inhibitory impact of FPS-ZM1 on GSK-3β and to elucidate the molecular mechanisms responsible for the protective benefits of trans-anethole.
OBJECTIVES:Proper cardiac function depends on adequate supply and metabolism of energy substrates. Aluminum chloride exposure has been linked to adverse cardiac events. This study investigated the ameliorative effect of ferulic acid and ascorbic acid in dysregulated cardiac energy metabolism in aluminum chloride-exposed mice. METHODS:Thirty mice were randomized into five groups (n=6): control (0.1 % distilled water), aluminum chloride (AlCl3, 100 mg/kg, p.o), aluminum chloride and ferulic acid (AlCl3, 100 mg/kg; FA20, 10 mg/kg, p.o), aluminum chloride and ferulic acid (AlCl3, 100 mg/kg; FA10, 10 mg/kg, p.o), aluminum chloride and ascorbic acid (AlCl3, 100 mg/kg; Vit. C, 100 mg/kg), daily for 7 days. Cardiac metabolic enzymes activities were analyzed spectrophotometrically; substrate transporters and regulators of energy metabolism were analyzed using immunohistochemistry. RESULTS:AlCl3 increased hexokinase activity and reduced pyruvate-dehydrogenase activity compared with the control. AlCl3 significantly reduced the expression of glucose transporter-4 (GLUT 4), carnitine palmitoyl-transferase 1β (CPT1β), peroxisome proliferator-activated receptor-alpha (PPARα) and AMP-activated protein kinase (AMPK) compared with the control. However, FA reversed the effect of AlCl3 by significantly increasing hexokinase and pyruvate dehydrogenase activities, increasing the expression of GLUT4, CPT1β, PPARα and AMPK. CONCLUSIONS:FA mitigate against cardiac metabolic disruption caused by acute exposure to AlCl3 through PPARα and AMPK modulation.
Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy and is increasingly recognized as a marker of long-term metabolic vulnerability. Beyond its established association with cardiometabolic diseases, emerging epidemiological evidence suggests a potential link between GDM and increased cancer risk, particularly hormone-sensitive malignancies such as endometrial and breast cancer. This narrative review integrates epidemiological and mechanistic evidence exploring the relationship between GDM and long-term oncological susceptibility. Hyperglycemia, hyperinsulinemia, and chronic low-grade inflammation associated with GDM may contribute to proliferative signaling and metabolic dysregulation. Among the proposed mechanisms, insulin/IGF-1 signaling represents one of the most biologically plausible links, whereas pathways involving PI3K/Akt/mTOR activation, metabolic reprogramming, and tumor microenvironment alterations remain largely inferred from broader oncological literature. In addition, persistent metabolic stress during pregnancy may induce long-term epigenetic and immunometabolic changes potentially associated with carcinogenic susceptibility. Although current evidence does not establish a direct causal relationship between GDM and cancer, the integration of epidemiological and mechanistic findings supports the hypothesis that GDM may function as an early marker of systemic metabolic vulnerability associated with increased long-term oncological risk. Further longitudinal and mechanistic studies are needed to clarify this relationship and its clinical implications.
The increase in the incidence of type 2 diabetes mellitus (T2DM) worldwide cannot be attributed solely to genetic and lifestyle factors, underscoring the growing role of environmental metabolic disruptors. Microplastics are increasingly being identified as potential environmental diabetogens, owing to the high risk of human exposure and the potential of microplastics to act as EDC carriers. This review aims to integrate the biochemical and molecular evidence for the association between microplastic exposure and the development of impaired glucose metabolism via endocrine, inflammatory, and metabolic signaling pathways. These microplastics and additives, such as bisphenols, phthalates, and POPs, interact with nuclear hormone receptors, including the estrogen receptor, peroxisome proliferator-activated receptor, and aryl hydrocarbon receptor, resulting in aberrant transcriptional control of genes involved in the regulation of metabolism. Microplastics exposure may cause oxidative stress-mediated activation of stress kinases, inhibition of insulin receptor substrate-1, suppression of PI3K-Akt signaling, GLUT4 translocation, and mitochondrial dysfunction, which together result in systemic insulin resistance. In addition, β-cell damage, systemic inflammation, and changes in the gut microbiome interfere with the regulation of glucose metabolism in the liver, muscle, and adipose tissues.
OBJECTIVES:White adipose tissue (WAT) browning enhances energy expenditure and represents a promising target for metabolic disease. Growth differentiation factor 11 (GDF-11), a circulating member of the TGF-β superfamily, has been implicated in metabolic regulation, but its role in adipose tissue plasticity remains unclear. This study investigated whether GDF-11 regulates WAT browning and the underlying mechanisms. METHODS:Mice were exposed to cold to induce browning, and GDF-11 expression and SMAD2/3 activation were assessed in brown adipose tissue (BAT), visceral and subcutaneous WAT, and skeletal muscle. We combined in vivo results to in vitro approaches, 3T3-L1 cells were differentiated into white or brown adipocytes and treated with recombinant GDF-11 to evaluate gene expression and cellular phenotype. RESULTS:Cold exposure increased GDF-11 expression and activated SMAD2/3 signaling, particularly in BAT and subcutaneous WAT. This was associated with upregulation of thermogenic and metabolic genes, including Ucp1, Ucp3, Dio2, and PGC-1α. In vitro, GDF-11 enhanced thermogenic and adipogenic gene expression and induced morphological features consistent with browning. GDF-11 also increased SmyD1 expression, supporting a role in metabolic activation. CONCLUSIONS:GDF-11 promotes adipose tissue thermogenic remodeling through SMAD2/3 signaling and may represent a potential therapeutic target for metabolic diseases.
OBJECTIVES:Early identification of complicated acute appendicitis remains a clinical challenge. Serum bilirubin has been proposed as a potential biomarker reflecting disease severity rather than primary diagnosis. To evaluate the diagnostic accuracy of serum bilirubin in predicting complicated acute appendicitis using histopathology as the reference standard. METHODS:A cross-sectional diagnostic accuracy study was conducted among 150 adult patients undergoing appendectomy for suspected acute appendicitis at a tertiary care center. Preoperative serum bilirubin levels were recorded. Histopathological examination served as the gold standard. Diagnostic performance indices, including sensitivity, specificity, predictive values, accuracy, and receiver operating characteristic (ROC) analysis, were calculated. RESULTS:Acute appendicitis was confirmed by histopathology in 82.7 % of cases, of which 11.3 % were complicated. Elevated serum bilirubin (≥1.2 mg/dL) was observed in 71.4 % of complicated appendicitis cases compared to 26.4 % of non-complicated cases (p=0.001). For predicting complicated appendicitis, serum bilirubin demonstrated a sensitivity of 71.4 %, specificity of 73.6 %, and a high negative predictive value of 95.3 %. ROC analysis yielded an AUC of 0.712, indicating fair diagnostic accuracy, with an optimal cut-off of 1.15 mg/dL. CONCLUSIONS:Serum bilirubin is a valuable adjunctive biomarker for predicting complicated appendicitis and effectively ruling out severe disease when levels are normal. Its integration into preoperative assessment may aid risk stratification and clinical decision-making.
Experience of visceral pain occurs when there is discomfort originating from internal organs of the body, often resulting from injury, infection, inflammation, ischemia, tumors, or neuropathy. In clinical practice, visceral pain is recognized as one of the most prevalent and incapacitating types of pain. It encompasses a diverse range of conditions impacting organs within thoracic, pelvic, and abdominal regions. Specifically, visceral pain of abdominal origin often presents as diffuse and poorly defined sensations of varying intensities. This characteristic arises from relatively sparse sensory innervation of visceral organs and divergent nature of visceral inputs. In addition, visceral noxious stimuli differ significantly from somatic pain triggers. Perception of visceral noxious stimuli from abdominal organs starts with transduction of signals at peripheral processes of sensory neurons, and transmission of these impulses to cortical centers, processing pain. Pathways concerned with nociceptive signaling from abdomen include intricate meshwork of neurons interconnecting different functional loci within nervous system. This review brings together current concepts on how abdominal pain is processed at several interconnected levels. Understanding of physiological pathways involved in abdominal pain processing supplemented with history, physical examinations, necessary biochemical, histopathological and radiological investigations constitute the cornerstone for abdominal pain management in clinical settings.
Hepatic encephalopathy (HE) encompasses a wide spectrum of neuropsychiatric disturbances that arise as a consequence of acute or chronic liver dysfunction. It represents a critical event in the natural history of cirrhosis and serves as an independent predictor of morbidity and mortality in affected patients worldwide. The clinical manifestations of HE range from subtle cognitive impairments, such as poor concentration, memory deficits, anxiety, depression, and insomnia, to severe psychomotor abnormalities, disorientation, and coma. Hyperammonemia is widely regarded as the central hallmark of HE pathogenesis and remains a cornerstone in both diagnosis and therapeutic monitoring. However, elevated ammonia levels do not always correlate with clinical severity, and some patients may present with significant neurological impairment despite near-normal ammonia concentrations. This discrepancy highlights the multifactorial mechanisms underlying HE, including neuroinflammation, oxidative stress, alterations in neurotransmission, and gut-liver-brain axis dysregulation. In this review, we provide a comprehensive overview of the pathogenesis, clinical spectrum, diagnostic approaches, and current as well as emerging therapeutic strategies for hepatic encephalopathy, with a focus on recent advances that may improve patient outcomes.
OBJECTIVES:To determine whether ginsenoside Rg1 attenuates right ventricular remodeling in hypoxic pulmonary hypertension and whether this effect is associated with suppression of HIF-1α-related glycolytic signaling. METHODS:Male C57BL/6 mice were exposed to normobaric hypoxia (10 % O2) for 4 weeks and assigned to control, model, sildenafil, Rg1, or HIF-1α knockdown groups (n=10 per group). Pulmonary function, hemodynamic parameters, right ventricular hypertrophy, histopathology, oxidative stress, apoptosis, immunofluorescence, and protein expression in right ventricular tissue were evaluated. RESULTS:Hypoxia reduced forced expiratory volume in 0.3 s/forced vital capacity and increased mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricular hypertrophy index. It also induced myocardial disorganization, collagen deposition, oxidative stress, apoptosis, and increased expression of HIF-1α, glucose transporter 1, hexokinase 2, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3, lactate dehydrogenase A, transforming growth factor beta 1, Smad2, and collagen I. Rg1 significantly attenuated these abnormalities, with a pattern broadly comparable to HIF-1α knockdown. CONCLUSIONS:Rg1 attenuated hypoxia-induced right ventricular remodeling and fibrosis and was associated with reduced oxidative injury, apoptosis, and HIF-1α-related glycolytic and profibrotic signaling.
OBJECTIVES:Lead (Pb) exposure is a major environmental risk factor for male reproductive dysfunction, primarily mediated through oxidative stress and endocrine disruption. This study evaluated the effects of lead acetate on testicular antioxidant status and serum testosterone levels and investigated the ameliorative role of ascorbic acid (AA) in adult male Wistar rats. METHODS:Thirty-five male Wistar rats were randomly assigned to seven groups (n=5): control, low- and high-dose lead (100 and 200 mg/kg), lead plus AA cotreatment, and withdrawal groups. Testicular antioxidant enzymes (SOD, CAT, GPx), reduced glutathione (GSH), and malondialdehyde (MDA) were assessed spectrophotometrically. Serum testosterone was measured using enzyme immunoassay. Data were analyzed using one-way ANOVA (p<0.05). RESULTS:Lead exposure significantly increased MDA levels and reduced antioxidant enzyme activities and testosterone concentrations in a dose-dependent manner (p<0.05). Ascorbic acid coadministration significantly restored antioxidant status, elevated GSH levels, reduced lipid peroxidation, and improved testosterone levels compared with lead-only and withdrawal groups. CONCLUSIONS:Lead acetate induces oxidative and endocrine disturbances in testicular tissue. Ascorbic acid effectively mitigates lead-induced reproductive toxicity by preserving antioxidant defenses and maintaining testosterone homeostasis.
OBJECTIVES:Male reproductive health is vital for societal stability, and lifestyle-related factors significantly influence fertility. Tobacco smoking is a major modifiable risk factor implicated in male infertility. This study aimed to assess differences in semen fluid dynamics and quality parameters between smokers and nonsmokers. METHODS:This observational, cross-sectional study was conducted at PSGIMS&R, Coimbatore. Seventy-four males aged 20-50 years were enrolled. A detailed clinical history was obtained, and semen analysis was performed according to WHO 2010 guidelines. Statistical analysis was carried out using SPSS version 23.0, with p<0.05 considered statistically significant. RESULTS:Baseline characteristics did not differ significantly between smokers and nonsmokers. Smokers showed a significantly higher rate of increased semen turbidity (29 vs. 1 %, p=0.002) and delayed liquefaction time (43 vs. 1 %, p=0.002). Mean sperm motility (49.90 vs. 59.45 %, p=0.01) and vitality (42.71 vs. 50.70 %, p=0.04) were significantly reduced among smokers. Regression analysis indicated that coffee consumption, reported by all smokers, did not act as a confounding variable. CONCLUSIONS:Tobacco smoking has a deleterious effect on semen fluid dynamics, resulting in delayed liquefaction and increased turbidity, along with reduced sperm motility and vitality, thereby negatively impacting male fertility.
OBJECTIVES:Post-infarction ventricular septal defect is a rare but severe mechanical complication of acute myocardial infarction that can lead to cardiogenic shock and carries a high mortality rate. Early recognition and multidisciplinary management are essential for improving survival. CASE PRESENTATION:A 58-year-old previously healthy woman presented to the Emergency Department with syncope and cardiogenic shock due to an anterior myocardial infarction. Echocardiography revealed an apical ventricular septal defect with severe biventricular dysfunction and right ventricular failure, confirmed by computed tomography. Urgent coronary angiography demonstrated total occlusion of the left anterior descending artery, treated with stent implantation. Despite maximal medical therapy, she required emergency surgical repair with patch closure and concomitant coronary bypass grafting. CONCLUSIONS:This case highlights the challenges of post-infarction VSD presenting with predominant right sided heart failure, requiring rapid and multidisciplinary management, including prompt surgical intervention, and advanced mechanical circulatory support.
OBJECTIVES:Osteoarthritis (OA) is a degenerative joint disease affecting millions worldwide, causing disability, reduced quality of life, and significant economic burden. Current clinical practices often fail to provide optimal symptom relief and functional improvement, necessitating evidence-based evaluation of integrated management strategies. This systematic literature review to identify effective integrated interventions for alleviating OA symptoms, enhancing functional outcomes, and improving patient adherence and satisfaction. METHODS:A systematic literature review was conducted following PRISMA guidelines. Peer-reviewed articles published between 2000 and 2024 were retrieved from major scientific databases, including PubMed, Science Direct, Springer Link, Elsevier, Taylor & Francis, and Google Scholar. Studies evaluating integrated or multidisciplinary approaches for OA management were included. RESULTS:Integrated management strategies demonstrated superior outcomes compared with isolated interventions. Pain reduction was reported in 28 out of 32 studies, with significant improvements in joint function, mobility, and quality of life. Nonpharmacological components enhanced pharmacological treatments. Patient adherence increased by 30-45 % with integrated care. Key barriers implementation included fragmented health care systems, lack of provider training, and inconsistent insurance coverage. CONCLUSIONS:Integrated approaches to OA management provide clinically meaningful improvements in pain, function, and patient-centered outcomes. These SLR actionable insights are for optimizing OA management through holistic, patient-centered strategies. Future research should prioritize cost-effectiveness analyses and long-term outcomes of integrated models.
OBJECTIVES:Chronic kidney disease (CKD) is a global health issue with significant morbidity and mortality, particularly due to cardiovascular events. Early identification and management of risk factors are crucial to prevent CKD progression and complications. CKD is heterogeneous with diverse etiologies and presentations, generalizing across populations challenging. This study aims to develop accurate predictive models for cardiovascular events in CKD patients. METHODS:Biosensors capture key parameters, including SpO2 (Oxygen saturation), PR (Pulse rate), Pi (Perfusion index), RRp (Respiration rate), and PVi (Pleth variability index), enabling comprehensive evaluation of physiological dynamics in CKD patients. Stacked Auto-Encoders (SAEs) are applied for diagnostics. Genetic risk score (GRS) and nongenetic risk score (NGRS) models are developed using natural logarithms of odds ratios (OR) of risk factors. RESULTS:The models integrate properties of each factor with weighted contributions to create predictive models for CKD. A novel machine learning technique incorporates automatic machine learning (AutoML). CONCLUSIONS:The models integrate properties of each factor with weighted contributions to create predictive models for CKD. A novel machine learning technique incorporates automatic machine learning (AutoML).
Concerns regarding contrast-induced acute kidney injury (CI-AKI) remain significant due to the increasing use of iodinated contrast agents (ICM) in diagnostic and medical procedures. Although the frequency of CI-AKI has decreased over the decades, it continues to be a major cause of hospital-acquired acute kidney damage, thereby elevating the risk of mortality, morbidity, and prolonged hospital stays. The complex pathophysiology of CI-AKI involves vasoconstriction, oxidative stress, renal medullary hypoxia, inflammatory responses, and direct tubular toxicity. Recent discoveries have identified ferroptosis and neutrophil extracellular traps (NETs) as additional mechanisms contributing to endothelial and tubular damage. Furthermore, microRNAs such as miR-30c, miR-21, and miR-141-3p have emerged as preliminary biomarkers and therapeutic targets due to their regulatory effects on cellular apoptosis and inflammatory pathways. Procedural controversies persist regarding the risk differences between intravenous and intra-arterial contrast administration; however, evidence suggests that patient comorbidities and procedural complexity, rather than the route of administration alone, determine the risk of CI-AKI. Risk stratification tools, such as the Mehran and ACEF scores, provide frameworks for identifying high-risk patients and guiding preventive strategies. This review integrates an understanding of the molecular pathogenesis of CI-AKI, clarifies procedural debates, and highlights emerging biomarkers and risk models.
