Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

Background and Objectives: Preoperative biliary stenting (PBS) is commonly used to manage obstructive jaundice in patients undergoing pylorus-preserving pancreaticoduodenectomy (PPPD). However, the impact of PBS on intestinal barrier function and perioperative complications remains controversial. This study aims to evaluate the effect of PBS on intestinal dysfunction and surgical outcomes, focusing on the influence of the stent duration. Materials and Methods: In this prospective cohort study, 235 patients undergoing PPPD for resectable pancreatic neoplasms at Timișoara Municipal Emergency Clinical Hospital (2016–2024) were analyzed. Patients were divided into two groups: those with PBS (n = 98) and without PBS (n = 137). Intestinal barrier function was assessed pre- and postoperatively using biomarkers such as zonulin, fecal calprotectin, and serum lipopolysaccharides (LPS). Perioperative outcomes, including pancreatic fistula, delayed gastric emptying (DGE), infections, and hospital stay, were compared. Additionally, outcomes were stratified based on stent duration (2–3 weeks vs. 3–4 weeks). Results: PBS was associated with significantly higher levels of zonulin, fecal calprotectin, and serum LPS postoperatively, indicating compromised intestinal barrier function. The stented group had a higher incidence of pancreatic fistulas (Grade B/C: 27.5% vs. 13.1%, p < 0.01), DGE (25.5% vs. 13.1%, p = 0.008), postoperative infections (34.7% vs. 17.5%, p = 0.002), and prolonged hospital stay (16.9 ± 4.2 days vs. 14.5 ± 3.7 days, p = 0.019). Prolonged stenting (3–4 weeks) was associated with worse outcomes compared to shorter stenting durations (2–3 weeks), including increased rates of infections, sepsis, and ICU stay (p < 0.05 for all comparisons). Conclusions: Preoperative biliary stenting is associated with increased intestinal barrier dysfunction, systemic inflammation, and higher rates of perioperative complications following PPPD. Prolonged stenting durations (>3 weeks) further exacerbate these risks. Limiting the PBS duration to 2–3 weeks, alongside optimized perioperative management, may help reduce postoperative morbidity and improve surgical outcomes.

Background: Pancreatic ductal adenocarcinoma is an aggressive neoplasm with a complex carcinogenesis process that must be understood through the interactions between tumor cells and tumor microenvironment cells. Methods: This study was retrospective with a chronological extension period of 16 years and included 56 cases of pancreatic ductal adenocarcinoma. This study identified, quantified, and correlated the cells of the tumor immune microenvironment in pancreatic ductal adenocarcinoma with major prognostic factors as well as overall survival, using an extensive panel of immunohistochemical markers. Results: Three tumor immunotypes were identified: subtype A (hot immunotype), subtype B (intermediate immunotype), and subtype C (cold immunotype). Patients with immunotype C exhibit considerably higher rates of both pancreatic fistulas and acute pancreatitis. Immunotypes B and C significantly increased the risk of this complication by factors of 3.68 (p = 0.002) and 3.94 (p = 0.001), respectively. The estimated probabilities of fistula formation for each immunotype are as follows: 2.5% for immunotype A, 25% for immunotype B, and 28% for immunotype C. There was a statistically significant difference in median survival times according to tumor immunotype (p < 0.001). Specifically, patients with immunotype C tumors had a median survival time of only 120.5 days, compared to 553.5 days for those with immunotype A and 331.5 for immunotype B tumors. Conclusions: The identification of the immunotype of pancreatic ductal adenocarcinoma can be a predictive factor for the occurrence of complications such as pancreatic fistula as well as for overall survival.

(1) Background: The modified Whipple procedure, or pylorus-preserving pancreaticoduodenectomy, is a complex surgical intervention used to treat pancreatic head tumors. While preserving digestive function, it is associated with significant perioperative risks. This study explores the clinical, immunological, and microbiome-related factors influencing postoperative complications, focusing on the interplay between patient comorbidities, systemic inflammation, and gut dysbiosis. (2) Methods: A retrospective analysis was conducted on 123 patients undergoing the modified Whipple procedure for pancreatic head tumors. Patients were categorized into two groups based on the occurrence of significant postoperative complications (Group A: with complications; Group B: without complications). Data on demographics, comorbidities, inflammatory markers (CRP, IL-6, procalcitonin), and gut microbiome composition were collected. Microbial diversity was evaluated using the Shannon Index, and logistic regression was performed to identify independent predictors of complications. (3) Results: Patients in Group A had a significantly higher prevalence of diabetes mellitus (43.1% vs. 20.8%; p = 0.02) and cardiovascular disease (35.3% vs. 13.9%; p = 0.01). Elevated inflammatory markers (CRP ≥ 40 mg/L, IL-6 ≥ 30 pg/mL, procalcitonin ≥ 0.5 ng/mL) were strongly associated with higher complication rates. Microbiome analysis indicated dysbiosis in Group A, with reduced Lactobacillus and Bifidobacterium levels, increased Enterobacteriaceae abundance, and a lower Shannon Index (<2). Patients exhibiting both dysbiosis and elevated inflammation had the highest complication rate (60%). Multivariate analysis identified diabetes, elevated IL-6, and dysbiosis as independent predictors of adverse outcomes. (4) Conclusions: Postoperative complications after the modified Whipple procedure are influenced by systemic inflammation and gut dysbiosis. A systematic preoperative assessment of microbiome health and inflammatory markers enables accurate risk stratification and personalized interventions, potentially reducing the incidence of complications and improving overall surgical outcomes.

Chronic wounds represent a growing global healthcare burden driven by persistent inflammation, polymicrobial biofilm formation, impaired tissue regeneration, and increased antimicrobial resistance. This review examines the mechanistic interplay between chronic wound pathophysiology, biofilm persistence, and antimicrobial peptide (AMP)-based therapeutics, with particular emphasis on translational barriers and advanced biomaterial-enabled delivery strategies. Current evidence demonstrates that AMPs exert multifactorial activities extending beyond direct antimicrobial effects, including membrane disruption, quorum-sensing inhibition, extracellular polymeric substance (EPS) destabilization, immune modulation, angiogenic stimulation, and promotion of re-epithelialization. However, their clinical translation remains limited due to proteolytic degradation, poor stability, cytotoxicity, rapid clearance, and inadequate retention within the hostile chronic wound microenvironment. To address these limitations, emerging biomaterial platforms—including hydrogels, electrospun nanofibers, nanoparticles, self-assembling peptide systems, and stimuli-responsive smart dressings—have been developed to improve AMP stability, controlled release, biofilm penetration, and regenerative efficacy. This review further highlights current preclinical and clinical challenges, including the lack of standardized polymicrobial biofilm models and translationally relevant wound systems, while discussing future perspectives such as artificial intelligence-assisted peptide design and precision wound therapeutics. We argue that peptide discovery is no longer the principal bottleneck: the rate-limiting steps are now peptide stabilization, biofilm-targeted delivery, and dosing, and no current platform yet couples validated eradication of mature polymicrobial biofilms with validated tissue regeneration in a clinically representative model. Collectively, AMP-enabled smart biomaterials may support the transition from passive wound management toward responsive, biofilm-targeted regenerative therapy.

Background: Antenatal depression has been associated with systemic inflammation, autonomic imbalance, and vascular dysfunction, yet its relationship with clinically relevant cardiovascular complications during pregnancy remains insufficiently defined. Objective: To evaluate whether antenatal depression diagnosed before cardiologic assessment is associated with gestational hypertension, preeclampsia, and clinically significant Holter-confirmed arrhythmias in a tertiary-care population of pregnant women referred for cardiology assessment. Methods: We conducted a retrospective secondary matched cohort analysis nested within a prospectively approved doctoral research protocol (approval no. 76/02.10.2023; approved study interval: 2 October 2023–10 February 2025), including deliveries from October 2023 to February 2025. During this 16-month interval, 12,436 deliveries were recorded. The index point was the first cardiology specialist evaluation performed between 22 + 0 and 36 + 6 weeks’ gestation. Pregnancies with a depressive disorder diagnosed by structured psychiatric interview (SCID-5) before cardiology evaluation were classified as exposed. Depression severity was categorized as mild (n = 44), moderate (n = 62), or severe (n = 24), and psychotropic medication class at index was recorded. Each depressed case was matched 1:3 with non-depressed controls by gestational age at index, calendar year, maternal age, BMI category, smoking status, and parity; adjusted models included BMI and psychotropic medication class. Results: The final referral-enriched cohort included 130 depressed pregnancies and 390 matched controls (n = 520), all of whom underwent cardiology evaluation. Between 22 + 0 and 36 + 6 weeks’ gestation, gestational hypertension occurred in 18.5% vs. 10.0% (p = 0.010), preeclampsia in 8.5% vs. 4.9% (p = 0.12), and clinically significant Holter-confirmed arrhythmias in 15.4% vs. 6.9% (p = 0.003) in depressed versus control groups, respectively. After adjustment, depression remained independently associated with gestational hypertension (aOR 1.85, 95% CI 1.12–3.05; p = 0.016) and arrhythmia (aOR 2.05, 95% CI 1.18–3.57; p = 0.011). A numerical, exploratory severity-response gradient was observed across mild, moderate, and severe depression strata, most clearly for Holter-confirmed arrhythmias; however, the severe-depression stratum was small (n = 24). Conclusions: Antenatal depression was associated with a modest but significant increase in gestational hypertension and clinically significant Holter-confirmed arrhythmias during late pregnancy among women referred for cardiology assessment. The higher preeclampsia rate in depressed pregnancies was not statistically significant. These findings support antenatal depression as a cardiovascular risk marker in gestation rather than proof of causality.