Gerasimos Tsourouflis

Hyperforin, a polyprenylated acylphloroglucinol and major bioactive constituent of Hypericum perforatum L. (H. perforatum, St. John’s Wort), has attracted considerable interest because of its pleiotropic pharmacological properties. Although historically investigated primarily for its contribution to the antidepressant activity of H. perforatum, experimental studies have identified broader neuroprotective, anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, metabolic, anticancer, and tissue-regenerative actions. However, the evidence remains heterogeneous, and an important distinction exists between findings obtained with purified hyperforin and those derived from multicomponent H. perforatum preparations. Unlike previous reviews that have primarily summarized the pharmacological activities of hyperforin, the present review adopts a translational evidence framework that distinguishes purified hyperforin from multicomponent H. perforatum preparations and evaluates the maturity of evidence from molecular mechanisms and preclinical models through pharmacokinetics, human studies, safety, and clinical development. A comprehensive narrative review was conducted according to the Scale for the Assessment of Narrative Review Articles (SANRA) recommendations. PubMed/MEDLINE, Scopus, Web of Science, Embase, and Google Scholar were searched from database inception through 25 July 2026. Mechanistic, in vitro, animal, translational, pharmacokinetic, and clinical studies, together with relevant systematic reviews and meta-analyses, were critically synthesized according to intervention type, disease-specific evidence, pharmacokinetic and formulation characteristics, safety, and translational relevance. Hyperforin acts as a pleiotropic signaling modulator affecting interconnected pathways involved in neurotransmission and neuroplasticity, inflammatory and redox regulation, mitochondrial and cellular homeostasis, immune function, and metabolism. Extensive cellular and animal evidence supports biological activity across neuropsychiatric, neurodegenerative, inflammatory, immune-mediated, cardiometabolic, oncological, gastrointestinal, infectious, dermatological, and other chronic disease settings. Nevertheless, evidence maturity differs markedly among indications. The strongest human evidence concerns standardized hyperforin-containing H. perforatum preparations for mild-to-moderate depression, whereas most other applications remain preliminary or predominantly preclinical. Adequately powered randomized controlled trials of purified hyperforin are lacking, preventing attribution of the clinical effects of H. perforatum preparations specifically to hyperforin. Translation is further constrained by poor aqueous solubility, chemical instability, variable bioavailability and formulation composition, limited compound-specific pharmacokinetic data, and clinically important herb–drug interactions, particularly through PXR-mediated induction of CYP3A4 and P-glycoprotein. Hyperforin is a pharmacologically promising multifunctional natural compound, but its experimental activity currently exceeds the strength of compound-specific clinical evidence. Future research should prioritize chemically defined and preferably purified formulations, rigorous pharmacokinetic and dose-finding studies, biomarker-supported target-engagement assessment, and adequately powered randomized controlled trials, together with long-term safety, interaction, standardization, and regulatory evaluation. Demonstrating predictable human exposure, biologically relevant target engagement, clinically meaningful efficacy, and an acceptable long-term safety profile will be essential for determining whether hyperforin can progress from experimental promise to evidence-based therapeutic application.

Background: Laparoscopic cholecystectomy is considered the gold standard surgical technique for the treatment of gallbladder diseases worldwide. Nonetheless, despite its safety and popularity, it comes with certain complications. Duodenal injury is an extremely rare, but potentially fatal complication. The rarity of duodenal injuries, combined with under-reporting of incidents, has resulted in a scarcity of references in the international literature. Case Presentation: We present the case of a 72-year-old male patient, initially subjected to laparoscopic cholecystectomy that was intraoperatively converted to open cholecystectomy. During the laparoscopic approach, the patient experienced a major duodenal injury, which was treated intraoperatively using primary suturing. Upon postoperative failure of the indicated surgical treatment, extended individualized salvage surgery was performed, with an ultimately favorable outcome. Methods: When assessing the overall implications of this case, we conducted a review of the published literature in English, published up to November 2025 on patients with duodenal injury after exclusively laparoscopic cholecystectomy. Results: We then categorized the 105 cases described based on the therapeutic approach: surgical, conservative, and endoscopic, with a view to attempt to classify the available therapeutic options based on the time of diagnosis, the patient’s performance status, and the size and location of the injury. Conclusions: While laparoscopic cholecystectomy is a common surgical procedure, duodenal injuries remain rare. The treatment approach highly depends on the time of injury recognition, site and extent of the injury and patient’s status. Treatment should be personalized based on the aforementioned parameters.

Background/Objectives: The Mediterranean diet (MD) constitutes one of the most broadly studied dietary patterns, which has been linked to the prevention of non-communicable diseases and mental health disorders. University students, a population exposed to significant psychosocial stressors and lifestyle changes, may particularly benefit from healthy eating patterns such as the MD. This study was designed to examine the potential associations of MD adherence with symptoms of depression and anxiety among Greek university students. Methods: A cross-sectional study was initially conducted among 7160 active university students from ten diverse geographic regions in Greece. After the enrollment procedure and the application of relevant exclusion criteria, 5191 university students (52.0% female; mean age: 21.3 ± 2.4 years) constituted the study population. MD adherence was assessed using the KIDMED index, while depressive and anxiety symptoms were evaluated using the Beck Depression Inventory-II (BDI-II) and State–Trait Anxiety Inventory (STAI-6), respectively. Sociodemographic and anthropometric data were collected for all the enrolled university students. All the questionnaires were completed by face-to-face interviews with expert personnel. Results: Students with low adherence to the MD were significantly more likely to report symptoms of depression (OR = 2.12; p ˂ 0.001) and anxiety (OR = 2.27; p ˂ 0.001) and to be overweight or obese (OR = 2.45; p ˂ 0.001) after adjustment for multiple confounding factors. Low MD adherence was also associated with male gender (OR = 0.73; p ˂ 0.01), living alone (OR = 0.78; p ˂ 0.01), smoking (OR = 0.75; p ˂ 0.01), low physical activity (OR = 1.84; p = 0.001), and poorer academic performance (OR = 0.83; p ˂ 0.01). Conclusions: Low adherence to the MD is significantly associated with increased likelihood of depression, anxiety, and excess body weight among university students in Greece. These findings underscore the importance of promoting healthy dietary habits and related lifestyle behaviors in young adult populations as a potential strategy for mental health prevention and intervention. Due to the presence of several limitations in the present study, future longitudinal and interventional studies should be performed to confirm the present findings.

Background/Objectives: Emotional eating may be a consequence of acquired cue reactivity, a lack of control, or an inaccurate link between episodic overeating and negative affect, according to a new analysis of its standard measurement. This study was a controlled trial, which was designed to investigate the effect of personalized nutritional psychoeducation on emotional eating behavior. Methods: This study enrolled 95 participants (62 control group and 33 intervention group) who were randomized to treatment and assessed at 3-month follow-up. Over a period of 3 months, six thematic individual sessions were conducted with a frequency of every 15 days for the participants in the intervention group. The Three-Factor Eating Questionnaire (TFEQ) was used to assess feeding patterns and the manifestation of emotional food consumption in response to emotion. Results: At baseline, it appears that gender is positively related to TFEQ Emotional Score (β: 1.77 (random error: 0.57, p-value: 0.003). BMI (β: −0.11 (random error: 0.04, p-value: 0.003) and waist circumference are negatively related to the TFEQ Emotional Score. Conclusions: Although this study confirmed significant associations of emotional eating and gender, BMI, and waist circumference, the nutritional psychoeducation-based intervention did not exert the expected effects on emotional eating. More high-quality clinical trials need to further be designed to improve emotional eating behavior by applying relevant nutritional psychoeducation-based interventions.

Background: Mediterranean diet (MD) constitutes a commonly examined dietary model. It includes a plethora of bioactive ingredients with strong antioxidant, anti-inflammatory, antithrombotic and anticancer properties. Several substantial studies support strong evidence that MD can exert preventing actions against human morbidity and mortality, promoting human well-being and quality of life. The present study aims to evaluate whether childhood MD compliance may be associated with socio-demographic, anthropometric, and lifestyle factors in children at the age of 6–9 years. Methods: This is a cross-sectional survey on 3875 children aged 6–9 years old with their matched mothers. Qualified questionnaires were used to evaluate and collect by one-to-one interviews with trained professionals the above data. Results: Elevated MD adherence was observed only in 22.2% of the enrolled children, while 37.5% of children maintained intermediate MD adherence and 40.3% of children adopted lower MD levels. Children MD compliance was related at an independent manner with maternal education level, childhood anthropometric factors such as Body Mass Index (BMI), Waist circumference to Height ratio (WtHR), quality of life, and exclusively breastfeeding behaviors after adjusting for several possible confounders (p ˂ 0.05). Conclusions: Elevated MD adherence of children aged 6–9 years old showed a lower obesity of overweight/obesity, including abdominal obesity. A higher maternal educational status and adopting exclusively breastfeeding practices were associated with greater levels of children’s MD adherence, promoting their quality of life and well-being. Based on the present results, future prospective surveys need to be performed to evaluate if there is a causality relation concerning this topic.

Background: Peroxisome-proliferator-activated receptors (PPARs) constitute nuclear transcription factors controlling gene expression associated with cell growth and proliferation, diverse proteins, lipids, and glucose metabolism, being related to several other pathophysiological states such as metabolic disorders, atherogenesis, carcinogenesis, etc. The present survey aims to analyze the natural compounds that can act as agonists for the PPAR-α, PPAR-β/δ, and PPAR-γ system targeting, highlighting how the amazing biochemical diversity of natural compounds can yield new insights into this “hotspot” of the scientific field. Methods: A narrative review was performed by searching the recent international literature for the last two decades in the most authoritative scientific databases, like PubMed, Scopus, Web of Science, and Embase, using appropriate keywords. Results: Several natural compounds and/or their synthetic derivatives can act as ligands of PPARs, stimulating their transcriptional activity and enabling their use as preventive and/or therapeutic agents for several disease states, such as inflammation, oxidative stress, metabolic disturbances, atherogenesis, and carcinogenesis. Although synthetic compounds are increasingly used as drugs to manage health problems, serious side effects have been observed, while their natural analogues exhibit only few minor side effects. Conclusions: Further clinical studies on natural compounds such as ligands of PPARs and the evaluation of the related molecular mechanisms are needed to implement an effective strategy concerning the pharmaco-technology, food chemistry, and nutrition to introduce them as part of clinical and dietary practice.

Background and Objectives: Overweight and obesity are growing public health challenges, particularly concerning young adults. University life presents a unique set of stressors that may influence weight management alongside sleep quality. In this cross-sectional study, we aimed to investigate the association between overweight or obesity, stress, and sleep quality in a large sample of Greek university students. Materials and Methods: The study recruited 2116 active students from across various Greek universities. Participants completed questionnaires on sociodemographics, academic performance, and physical activity levels using the International Physical Activity Questionnaire (IPAQ). Stress and sleep quality were assessed using the Perceived Stress Scale (PSS) and the Pittsburgh Sleep Quality Index (PSQI), respectively. Body weight and height were directly measured to calculate Body Mass Index (BMI). Results: Our analysis of 2116 Greek university students revealed significant associations between various factors and overweight/obesity. Compared to their rural counterparts, young adults in urban areas had an 88% higher prevalence of overweight/obesity (p = 0.0056). Regular smokers were twice as likely to be overweight or obese (p = 0.0012). Notably, those with low physical activity levels displayed a more than two-fold increased risk (p = 0.0008) compared to those with moderate or high activity levels. Similarly, students with moderate or high perceived stress levels had a more than two-fold prevalence of overweight/obesity compared to those with low stress (p = 0.0005). Inadequate sleep quality was also associated with an 86% higher risk of overweight/obesity (p = 0.0007). Interestingly, good academic performance showed a 57% greater prevalence of overweight/obesity compared to very good/excellent performance (p = 0.0103). Conclusions: Our findings reveal that perceived stress and poor sleep quality are significant risk factors for overweight and obesity in this young adult population.

Background: The release of microvesicles (MVs) is an essential phenomenon for inter-cellular signaling in health and disease. The role of MVs in cancer is multidimensional and includes cancer cell survival, proliferation, and invasion. In this prospective study, we analyzed MV levels in colorectal cancer patients and assessed the importance of MV release in early-stage colorectal cancer and survival. Methods: This study included 98 patients and 15 controls. The characterization of MVs from human plasma was performed by flow cytometry using monoclonal antibodies. Results: The levels of total MVs and MUC-1-positive, tissue factor (TF)-positive, and endothelial cell-derived MVs (EMVs) were statistically significantly higher in the colon cancer patients than in the controls (p < 0.001). Furthermore, the subgroup of patients with very early-stage colorectal cancer also had statistically significant differences in the levels of the abovementioned MVs compared to the controls (p < 0.01). Highly differentiated tumors had lower levels of MUC-1-positive MVs (p < 0.02), EMVs (p < 0.002), and EMV/TF combinations (p < 0.001) versus those with tumors with low/intermediate differentiation. Conclusions: Our data demonstrate that the analysis of circulating MV levels in plasma could possibly become a tool for the early diagnosis of colon cancer at a very early stage of the disease.

Background: The Mediterranean diet (MD) is well-known as a diet which may exert a protective effect against neurodegenerative diseases, including multiple sclerosis (MS). To date, only a few clinical surveys have assessed the potential effects of the MD in patients with MS. The purpose of the present study is to evaluate the potential effects of MD compliance on disease disability, quality of life, physical activity, depressive symptomatology, and blood biochemical parameters related to nutritional status in MS patients, considering several socio-demographic, anthropometric, and lifestyle characteristics. Methods: This is a cross-sectional study conducted on 558 adults with MS aged 18–64 years. Relevant questionnaires were utilized to evaluate socio-demographic and anthropometric parameters, disease disability (Expanded Disability Status Scale, EDSS), multidimensional health-related quality (MS Quality of Life-54, MSQOL-54), physical activity levels (International Physical Activity Questionnaire, IPAQ), depression (Beck Depression Inventory II, BDI-II), and MD adherence (MedDietScore), while several blood biochemical parameters were retrieved from the patients’ medical records. Results: Enhanced MD compliance was independently associated with a decreased frequency of overweight/obesity, as well as abdominal obesity, in patients suffering from MS. Elevated MD compliance was also independently associated with a decreased incidence of advanced disease disability, a higher prevalence of elevated physical activity, an improved quality of life, and lower depressive symptoms, as well as higher levels of certain blood biochemical parameters, which are effective indicators of iron deficiency and malnutrition. Conclusions: The present study found that higher MD adherence may slow down disease disability, promoting a better quality of life and mental health in adults with MS. Future prospective surveys are required to obtain conclusive results.

Christian Orthodox fasting, a type of time-restricted diet, which presents some similarities to the Mediterranean Diet, also including certain similarities with periodic vegetarianism or other time-restricted diets (e.g., intermittent diet and Ramadan fasting), may cumulatively be related to the same or even better beneficial healthy effects as these well-recognized dietary patterns. The present study aimed to explore the potential beneficial impact of Christian Orthodox fasting in patients with metabolic disorders, such as diabetes mellitus type 2, excessive obesity, hypothyroidism and osteoporosis. This was a cross-sectional study, including 135 patients with metabolic disorders (67 fasters and 68 non-fasters). The enrolled fasters had adapted Christian Orthodox fasting recommendations for at least twelve consecutive years or even from childhood. Relevant questionnaires were used to record sociodemographic, anthropometric and lifestyle data of the study population through face-to-face interviews between the enrolled individuals and qualified personnel during a non-fasting period. Christian Orthodox fasting patients showed a significantly and independently lower prevalence of overweight/obesity and abdominal obesity, which is highly associated with cardiometabolic disease risks, as well as a significantly and independently lower incidence of hypertension, including separately lower systolic and diastolic pressure, than non-fasting patients. Fasters also had a significantly and independently increased prevalence of an advanced educational level and no smoking history, as well as a lower incidence of sedentary behavior, and a trend of a correlation with reduced c-reactive protein (CRP), an indicator of inflammation, compared to non-fasters. Fasters also exhibited higher serum albumin and high-density lipoprotein (HDL) levels, as well as lower glucose levels, than non-fasters. This is one of the few cross-sectional studies demonstrating that Christian Orthodox fasting may promote metabolic health by improving several aspects of metabolic disorders, being associated with specific sociodemographic, anthropometric and lifestyle factors. Further studies conducted on larger sample sizes from different countries and different ethnicities that include Christian Orthodox fasters are recommended to evaluate the impact of long-term religious fasting effects on human health, either as a preventative factor reducing the risk of chronic diseases and especially cardiometabolic disorders or as a nutritional intervention to ameliorate symptom severity.