Drug-drug interactions (DDIs) represent a major challenge in pharmaceutical research for ensuring safe and effective medication use in clinical practice. Pharmacological DDI assays generate data that underpin clinical guidelines, drug interaction checkers, and decision support systems. Although these approaches remain indispensable, contemporary clinical practice is far more complex, shaped by polypharmacy, multimorbidity, diverse phenotypes, and social determinants of health. Artificial intelligence (AI) offers opportunities to integrate molecular, pharmacokinetic, and pharmacodynamic knowledge with real-world observations, enabling more proactive and patient-centered approaches to DDI risk assessment. This perspective proposes a conceptual framework for transitioning from static, rule-based DDI tools toward human-augmented AI systems in which clinician feedback is embedded as an integral component of model learning and interpretation, rather than serving solely as post hoc validation. Through structured incorporation of clinical expertise, experimental pharmacology is continuously contextualized against real-world decision-making. The manuscript outlines an AI ecosystem that is ethically grounded, mechanistically informed, and enriched through pharmacovigilance data and systematic clinician input. By operationalizing human-in-the-loop learning as a core design principle, this framework establishes human-augmented AI as a foundational paradigm for future DDI research, drug development, and personalized medication safety.

Background/Objectives: Vaccination represents a significant achievement of public health and should be regarded not only as a protective measure against infectious diseases but also an active preventive intervention and a component of health promotion. Methods: This cross-sectional study assessed vaccination coverage among adults aged ≥60 years who attended a Primary Health Care Center during a predefined period of at least two months (November-December 2025) in a rural area of Crete, Greece, and examined determinants of immunization, including demographic, clinical, psychosocial, and health service utilization factors. The sample comprised 366 participants who consented to complete a structured questionnaire, primarily via interview, followed by verification of vaccination status through medical records. Results: High vaccination coverage was observed for influenza (82.5%), moderate coverage for pneumococcal (68.3%) and herpes zoster (56.0%) vaccines, and very low coverage for tetanus-diphtheria-pertussis booster doses (≈13%) and RSV vaccination (5.2%). For SARS-CoV-2, 96.2% received the three doses which were mandatory during the pandemic years. The overall Vaccination Coverage Score (VCS) averaged 43.1/100, while only 10.1% of participants achieved high coverage. Regression analysis showed that higher educational level, multimorbidity, and extensive use of health services were independently associated with better vaccination coverage (p < 0.05). Conclusions: The findings reveal fragmented vaccination patterns and underscore the need for systematic assessment of adult vaccination status within routine Primary Health Care. Targeted counseling, promotion of health literacy, and preventive vaccination strategies are expected to reduce vaccine-preventable morbidity and support healthy aging.

Artificial intelligence (AI) has emerged as a powerful tool in medical sciences that is revolutionizing various fields of drug research. AI algorithms can analyze large-scale biological data and identify molecular targets and pathways advancing pharmacological knowledge. An especially promising area is the assessment of drug interactions. The AI analysis of large datasets, such as drugs’ chemical structure, pharmacological properties, molecular pathways, and known interaction patterns, can provide mechanistic insights and identify potential associations by integrating all this complex information and returning potential risks associated with these interactions. In this context, an area where AI may prove valuable is in the assessment of the underlying mechanisms of drug interactions with natural products (i.e., herbs) that are used as dietary supplements. These products pose a challenging problem since they are complex mixtures of constituents with diverse and limited information regarding their pharmacological properties, especially their pharmacokinetic data. As the use of herbal products and supplements continues to grow, it becomes increasingly important to understand the potential interactions between them and conventional drugs and the associated adverse drug reactions. This review will discuss AI approaches and how they can be exploited in providing valuable mechanistic insights regarding the prediction of interactions between drugs and herbs, and their potential exploitation in experimental validation or clinical utilization.

The present study investigated the impact of boric acid (BA) and borax (BX) on markers of inflammation and modifications in miR-21/PTEN/AKT pathway genes in the liver and kidney tissues of Sprague Dawley male rats with sepsis induced by cecal ligation and puncture (CLP). A total of 60 male Sprague Dawley rats were randomly divided into 6 groups, each containing 10 animals as follows: Control, CLP (where the model was created), 20 mg/kg BX (CLP + BX1), 40 mg/kg BX (CLP + BX2), 20 mg/kg BA (CLP + BA1) and 40 mg/kg BA (CLP + BA2). Liver and kidney tissues were analyzed for histopathological changes, immunopositivity for tumor necrosis factor-alpha, interleukin (IL)-6 and IL-10, and gene expression of microRNA-21 (miR-21), phosphatase and tensin homolog (PTEN) and AKT. Gene expression analysis in the liver tissues revealed a significant decrease in miR-21, and a marked but not significant decrease in PTEN levels in the CLP group, while AKT expression was significantly increased in the CLP group, and was significantly decreased in CLP + BA1 group compared with in the CLP group. In the kidney tissues, miR-21 levels were significantly decreased in the CLP group, but the CLP + BA2 group showed a significant increase compared with in the CLP group. These results suggest the potential therapeutic benefits of low-dose BA and BX in ameliorating sepsis-induced tissue damage, emphasizing the need for further exploration of their mechanisms of action.

The significant progress in HIV research has led to the development of innovative medicines and protocols. Most people living with HIV (PLWH) achieve longer lifespans when adhering strictly to the therapeutic protocols. A notable characteristic of PLWH is a higher incidence of cardiovascular diseases. This may result from the disease itself or increased life expectancy. Regardless of the underlying cause, it often requires the concurrent use of antiretroviral therapy (ART) and cardiovascular disease (CVD) medications. In such cases, a key issue regarding optimal evidence-based practices is the management of potential and clinically significant drug–drug interactions (DDIs). Over time, our understanding of DDIs has advanced significantly. These advancements have led to the development of tools and approaches for identifying and managing DDIs, especially in special population groups such as PLWH. Clinically, recognizing and managing these interactions is key to preventing adverse effects and optimizing outcomes in PLWH, thereby enhancing patient safety and quality of care. This review discusses the latest data on DDIs between ART and CVD medications, emphasizing their clinical significance. Furthermore, it explores how established tools, such as the Liverpool Drug Interaction Checker and Lexidrug®, can support healthcare professionals. Combined with insights from the literature and summaries of product characteristics, these tools can guide the identification and management of DDIs between ART and CVD medications to ensure optimal therapeutic outcomes.

Herbal medicinal products are increasingly used alongside conventional medicines, raising the risk of potential interactions such as pharmacodynamic drug–herb interactions (PD-DHIs) that can cause serious adverse drug reactions (ADRs). This review aims to present available pharmacological, clinical and pharmacoepidemiological literature regarding potential DHIs associated with serotonin syndrome or cardiac arrhythmias. Furthermore, it assesses the current evidence using the Oxford Centre for Evidence-Based Medicine (CEBM) 2009 framework. Serotonin syndrome most often results from combining serotonergic herbs (e.g., St. John’s wort) with antidepressants like serotonin reuptake inhibitors (SSRIs), as supported by repeated case reports and mechanistic plausibility (CEBM Level 3, Grade C). Other herbs such as black cohosh, ginseng, Syrian rue, turmeric, rhodiola, ashwagandha, and L-tryptophan/5-HTP have been linked to serotonin syndrome when used with SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs), but evidence is limited (Levels 4–5, Grade D). For cardiac arrhythmias, PD-DHIs arise when herbs interact with drugs that alter cardiac electrophysiology—such as QT-prolonging agents, psychotropics, antiarrhythmics or digoxin—thereby amplifying arrhythmogenic risk. Ephedra with sympathomimetics is strongly associated with arrhythmias (Level 2–3, Grade B). Licorice may potentiate digoxin and QT-prolonging drugs via hypokalemia (Level 4, Grade C). Other related PD-DHIs include aconite with antiarrhythmics, bitter orange or caffeine with QT-prolonging psychotropics, yohimbine with cardiovascular agents, and aloe or senna with digoxin. Overall, the evidence for PD-DHIs varies from moderate to weak but large-scale pharmacoepidemiological data is scarce. Future approaches, including artificial intelligence with explainable machine learning and network pharmacology, may integrate mechanistic, clinical, and real-world data to improve early detection or prediction of PD-DHIs. However, several specific challenges must be addressed. Therefore, it is crucial for healthcare providers in both clinical and community settings to increase their awareness of these interactions and ADRs to ensure the safe use of herbal remedies alongside conventional therapies.

In modern athlete assessment, the integration of conventional biochemical and ergophysiologic monitoring with innovative methods like telomere analysis, genotyping/phenotypic profiling, and metabolomics has the potential to offer a comprehensive understanding of athletes' performance and potential longevity. Telomeres provide insights into cellular functioning, aging, and adaptation and elucidate the effects of training on cellular health. Genotype/phenotype analysis explores genetic variations associated with athletic performance, injury predisposition, and recovery needs, enabling personalization of training plans and interventions. Metabolomics especially focusing on low-molecular weight metabolites, reveal metabolic pathways and responses to exercise. Biochemical tests assess key biomarkers related to energy metabolism, inflammation, and recovery. Essential elements depict the micronutrient status of the individual, which is critical for optimal performance. Echocardiography provides detailed monitoring of cardiac structure and function, while burnout testing evaluates psychological stress, fatigue, and readiness for optimal performance. By integrating this scientific testing battery, a multidimensional understanding of athlete health status can be achieved, leading to personalized interventions in training, nutrition, supplementation, injury prevention, and mental wellness support. This scientifically rigorous approach hereby presented holds significant potential for improving athletic performance and longevity through evidence-based, individualized interventions, contributing to advances in the field of sports performance optimization.

INTRODUCTION:Telomeres, repetitive DNA sequences at chromosome ends, shorten with cell division, countered by telomerase. Short telomeres are linked to cardiovascular disease (CVD), alongside its risk factors like aging, hypertension, diabetes, obesity, inactivity, and smoking. Many studies have claimed the implication of telomere length (TL) in cardiac diseases. This study examined TL's impact on heart conditions using quantitative fluorescence in situ hybridization (Q-FISH) technology. METHODS:Thirteen CVD patients (nine men and four women) aged 30-70 years and aged-matched healthy participants from the BIOTEL population TL database, were included in the study. Each chromosome's TL from peripheral blood cells was measured using metaphase Q-FISH. An independent sample t test was used to compare participants' mean or median TL with various medical factors and habits. RESULTS:The mean TL of whole and short telomeres in cardiac disease patients was lower compared to aged-matched healthy controls; however, there was no statistical significance due to the limited patient sample. The mean TL of short telomeres in cardiac disease patients showed a remarkable decline with advanced age. Accordingly, the mean TL of whole and short telomeres in patients with cardiac diseases showed a similar reduced trend. CONCLUSION:In our study, shorter TL was observed in cardiac disease patients compared to those of healthy controls by using metaphase Q-FISH. However, more cases need to be studied to elucidate the use of TL as a potential biomarker for the diagnosis of patients with CVD.

In toxicology, the term resistance is referred to the inherent capability of an organism to counter the effects of a compound that is present in the organism in a toxic dose, often a lethal dose. This innate ability can be either through the deployment of physiological barriers or through the development of biochemical pathways to counter the effects of a toxin. Biological mechanisms that grant resistance to an organism can either be related with "pharmacodynamic" or "toxicodynamic" and/or "pharmacokinetic" or "toxicokinetic" processes. Factors such as chemical characteristics of the toxin, exposure mechanisms, and the surrounding medium as well as the organism itself (age, sex, species, or strain) may play an important role in acquired resistance. Often, the mechanism of resistance to a toxicant is unspecified or cannot be associated with the concentration or the accumulation of a toxicant at the site of toxicity. An increase in resistance within a previously exposed population is usually related to natural selection processes.

Respiratory disorders significantly impact adolescents' health, often resulting in hospital admissions. Meteorological elements such as wind patterns have emerged as potential contributors to respiratory symptoms. However, it remains uncertain whether fluctuations in wind characteristics over extended periods have a tangible impact on respiratory health, particularly in regions characterized by distinct annual wind patterns. Crete is situated in the central-eastern Mediterranean Sea and frequently faces southerly winds carrying Sahara Desert sand from Africa and northerly winds from the Aegean Sea. This retrospective study analyzes long-term wind direction data and their relationship to respiratory symptoms observed in children up to 14 years old admitted at the University Hospital of Heraklion between 2002 and 2010. Symptoms such as headache, dyspnea, dry cough, dizziness, tachypnea, throat ache, and earache were predominantly reported during the presence of southern winds. Fever, productive cough, and chest pain were more frequently reported during northern winds. Cough was the most common symptom regardless of the wind pattern. Southern winds were significantly associated with higher probabilities of productive or non-productive cough, headache, dyspnea, tachypnea, dizziness, earache, and throat ache. Northern winds were related to a higher incidence of productive cough. Rhinitis, asthma, allergies, pharyngitis, and sinusitis were related to southern winds, while bronchiolitis and pneumonia were associated with northern winds. These findings underscore the critical role of local climatic factors, emphasizing their potential impact on exacerbating respiratory conditions in children. Moreover, they point out the need for further research to elucidate the underlying mechanisms and develop targeted interventions for at-risk populations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) represented a global public health crisis and the most significant pandemic in modern times. Transmission characteristics, and the lack of effective antiviral treatment protocol and protective vaccines, pushed healthcare systems, particularly intensive care units (ICUs), to their limits and led to extreme quarantine measures to control the pandemic. It was evident from an early stage that patient stratification approaches needed to be developed to better predict disease progression. In the present study, the predictive value of clinical and blood biomarkers for the outcomes of patients with COVID-19 hospitalized in the ICU were investigated, taking age and sex into consideration. The present study analyzed blood samples from 3,050 patients with COVID-19 hospitalized in the ICU. The analysis revealed that the levels of procalcitonin, N-terminal pro-B-type natriuretic peptide, D-dimer, ferritin, liver enzymes, C-reactive protein and lactate dehydrogenase were increased and were associated with disease progression, resulting in a prolonged hospitalization period and severe COVID-19 related complications. Additionally, significant age and sex disparities among these biomarkers were documented and discussed in specific cases. On the whole, the results of the present study suggest a potential association of the demographic characteristics and blood biomarkers with prolonged hospitalization in the ICU and the mortality of patients with COVID-19.

(1) Background: Doxorubicin (DOX) is extensively used for cancer treatments; however, its clinical application is limited because of its cardiotoxic adverse effects. A combination of DOX and agents with cardioprotective properties is an effective strategy to ameliorate DOX-related cardiotoxicity. Polyphenolic compounds are ideal for the investigation of novel cardioprotective agents. Chlorogenic acid (CGA), an essential dietary polyphenol found in plants, has been previously reported to exert antioxidant, cardioprotective, and antiapoptotic properties. The current research evaluated CGA's in vivo cardioprotective properties in DOX-induced cardiotoxicity and the probable mechanisms underlying this protection. (2) Methods: CGA's cardioprotective properties were investigated in rats that were treated with CGA (100 mg/kg, p.o.) for fourteen days. The experimental model of cardiotoxicity was induced with a single intraperitoneal (15 mg/kg i.p.) injection of DOX on the 10th day. (3) Results: Treatment with CGA significantly improved the DOX-caused altered cardiac damage markers (LDH, CK-MB, and cTn-T), and a marked improvement in cardiac histopathological features accompanied this. DOX downregulated the expression of Nrf2/HO-1 signaling pathways, and the CGA reversed this effect. Consistently, caspase-3, an apoptotic-related marker, and dityrosine expression were suppressed, while Nrf2 and HO-1 expressions were elevated in the cardiac tissues of DOX-treated rats after treatment with the CGA. Furthermore, the recovery was confirmed by the downregulation of 8-OHdG and dityrosine (DT) expressions in immunohistochemical findings. (4) Conclusions: CGA demonstrated a considerable cardioprotective effect against DOX-induced cardiotoxicity. One of the possible mechanisms for these protective properties was the upregulation of the Nrf2/HO-1-dependent pathway and the downregulation of DT, which may ameliorate oxidative stress and cardiomyocyte apoptosis. These findings suggest that CGA may be cardioprotective, particularly in patients receiving DOX-based chemotherapy.

Background: Patients with respiratory disorders often have additional diseases and are usually treated with more than one medication to manage their respiratory conditions as well as additional comorbidities. Thus, they are frequently exposed to polypharmacy (≥5 drugs), which raises the risk for drug–drug interactions (DDIs) and adverse drug reactions (ADRs). In this work, we present the results regarding the prevalence of DDIs in hospitalized patients with respiratory disorders in Greece. Methods: A 6-month descriptive single-center retrospective observational study enrolled 102 patients with acute or chronic respiratory disorders. Clinical characteristics and medication regimens were recorded upon admission, hospitalization, and discharge. The prevalence of DDIs and their clinical significance was recorded and analyzed. Results: Unspecified acute lower respiratory tract infection (25%), exacerbations of chronic obstructive pulmonary disease (12%) and pneumonia (8%) were the most frequent reasons for admission. Cardiovascular disorders (46%), co-existing respiratory disorders (32%), and diabetes (25%) were the most prevalent comorbidities. Polypharmacy was noted in 61% of patients upon admission, 98% during hospitalization, and 63% upon discharge. Associated DDIs were estimated to be 55% upon admission, 96% throughout hospitalization, and 63% on discharge. Pharmacodynamic (PD) DDIs were the most prevalent cases (81%) and referred mostly to potential risk for QT-prolongation (31.4% of PD-DDIs) or modulation of coagulation process as expressed through the international normalized ratio (INR) (29.0% of DDIs). Pharmacokinetic (PK) DDIs (19% of DDIs) were due to inhibition of Cytochrome P450 mediated metabolism that could lead to elevated systemic drug concentrations. Clinically significant DDIs characterized as “serious-use alternative” related to 7% of cases while 59% of DDIs referred to combinations that could be characterized as “use with caution—monitor”. Clinically significant DDIs mostly referred to medication regimens upon admission and discharge and were associated with outpatient prescriptions. Conclusions: Hospitalized patients with respiratory disorders often experience multimorbidity and polypharmacy that raise the risk of DDIs. Clinicians should be conscious especially if any occurring arrhythmias, INR modulations, and prolonged or increased drug action is associated with DDIs.