Search Results (70)

Background: Gastrectomy for gastric cancer is associated with substantial metabolic, nutritional, and immunological disturbances that may significantly influence postoperative recovery. Increasing evidence suggests that perioperative immunonutritional status, particularly when assessed by the Controlling Nutritional Status (CONUT) score, represents an important predictor of surgical outcomes. However, prospective data evaluating sex-related differences in postoperative nutritional recovery after gastrectomy remain limited. The aim of this study was to evaluate sex-related differences in perioperative immunonutritional status and functional recovery after gastrectomy for gastric cancer using serial CONUT score assessment. Methods: This prospective observational cohort study included 150 consecutive patients undergoing curative-intent gastrectomy for gastric adenocarcinoma at a tertiary referral center between 2021 and 2024. Nutritional and immune status were longitudinally assessed using the CONUT score at predefined perioperative timepoints: preoperatively (T0), early postoperatively (T1), and at 3-month follow-up (T3). Functional recovery outcomes, postoperative complications, and mid-term functional parameters were compared between male and female patients. Multivariable logistic regression analysis was performed to identify independent predictors of delayed postoperative recovery. Results: The study population included 91 male patients (60.7%) and 59 female patients (39.3%). Significant postoperative deterioration in albumin levels, lymphocyte counts, total cholesterol, and CONUT scores were observed in the entire cohort (p-time < 0.001 for all comparisons), followed by partial recovery during follow-up. No significant sex-related differences were identified regarding longitudinal immunonutritional evolution, postoperative complications, gastrointestinal recovery, or functional outcomes (p > 0.05). Overall postoperative complications occurred in 31.3% of patients, while 90-day mortality was 2.7%. An elevated baseline CONUT score ≥ 5 (OR 2.74, 95% CI 1.48–5.09, p = 0.001), postoperative CONUT score T1 ≥ 5 (OR 3.36, 95% CI 1.82–6.19, p < 0.001), ASA class III (OR 2.08, 95% CI 1.19–3.63, p = 0.010), and anastomotic leakage (OR 4.91, 95% CI 1.74–13.88, p = 0.003) independently predicted delayed functional recovery. Male sex was not independently associated with adverse postoperative recovery (OR 1.18, 95% CI 0.74–1.89, p = 0.44). Conclusions: Gastrectomy induces significant postoperative immunonutritional deterioration irrespective of sex. Although biological sex did not independently influence postoperative recovery trajectories, impaired perioperative immunonutritional status—particularly elevated postoperative CONUT score—was strongly associated with delayed functional recovery. Serial perioperative CONUT assessment may represent a valuable tool for individualized postoperative risk stratification and nutritional management in gastric cancer patients undergoing gastrectomy. Full article

Background: Magnetic particle imaging (MPI) is an emerging, tracer-based modality that directly detects superparamagnetic iron oxide nanoparticles (SPIONs) with exceptional sensitivity, quantitative signal behavior, and full immunity to air–tissue susceptibility artifacts. These features make MPI particularly well-suited for pulmonary imaging, where traditional techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine-based ventilation/perfusion (V/Q) imaging are limited by radiation exposure, low contrast, and motion-related signal degradation. Objective: This review synthesizes the current state of MPI for lung imaging, with emphasis on its physical principles, tracer development, preclinical applications, and its potential role in assessing pulmonary perfusion, vascular integrity, inflammation, and therapeutic responses. Methods: A systematic evaluation of preclinical studies was performed across three major application domains: pulmonary perfusion mapping, cell tracking and therapeutic monitoring, and vascular injury and permeability assessment. Study designs, SPION formulations, MPI acquisition strategies, and validation methods, including histopathology, biodistribution, broncho-alveolar lavage fluid (BALF) analysis, and Evans Blue assays, were examined to characterize methodological consistency and imaging performance. Results: MPI consistently demonstrated high-contrast, quantitative visualization of pulmonary blood flow, endothelial barrier disruption, inflammatory signaling, and transplanted or inhaled cell populations. Tracer engineering played a critical role: macroaggregated albumin superparamagnetic iron oxide nanoparticles (MAA-SPIONs) enabled capillary-level perfusion mapping, LS-008 improved temporal resolution and vascular delineation, Synomag/Synomag-D allowed quantification of vascular leakage in acute and chronic lung injury, and vascular cell adhesion molecule-1 (VCAM-1)-targeted probes provided molecular-level assessment of inflammation. Hybrid MPI-CT and MPI-MRI approaches further enhanced anatomic localization and enabled accurate pulmonary blood volume (PBV) estimation. Across studies, MPI measurements showed strong agreement with established biological assays and remained free of the artifacts that limit CT and MRI in the lung. Conclusions: Preclinical evidence demonstrates that MPI is a robust, radiation-free, and quantitatively precise modality for functional and molecular lung imaging. Its ability to map perfusion, track therapeutic agents, and noninvasively quantify vascular permeability positions MPI as a promising future alternative or complement to CT, MRI, and nuclear medicine for pulmonary assessment. Continued tracer optimization, system scaling, and clinical validation are key steps toward translating MPI into routine clinical use. Full article

Background: Esophagectomy is associated with substantial postoperative morbidity, with infectious complications remaining a leading cause of mortality. Septic shock represents the most severe infectious complication; however, data on its perioperative predictors and long-term impact after esophagectomy are limited. Methods: We conducted a retrospective observational study including consecutive adult patients who underwent esophagectomy with curative intent for esophageal cancer between January 2015 and December 2024 at a tertiary referral center. Postoperative septic shock was defined according to Sepsis-3 criteria. Demographic, clinical, surgical, laboratory, and oncological variables were analyzed. Independent risk factors for septic shock were identified using multivariate logistic regression. Overall survival was assessed using Kaplan–Meier analysis. Results: Among 106 patients, 19 (17.9%) developed postoperative septic shock. These patients had a lower body mass index, reduced preoperative and postoperative albumin levels, and a higher incidence of advanced lymph node involvement. Septic shock was strongly associated with severe postoperative complications, including anastomotic leakage, hemorrhagic shock, acute respiratory distress syndrome, acute kidney failure, and increased rates of PICU readmission. In multivariate analysis, lower albumin levels at PICU admission (OR 0.54; 95% CI 0.29–0.99) and advanced nodal stage (OR 4.98; 95% CI 1.36–18.3) were independently associated with the development of septic shock. Patients who developed septic shock had significantly higher in-hospital mortality (31.6% vs. 1.1%, p < 0.001) and markedly reduced long-term survival, even among those discharged alive. Conclusions: Postoperative septic shock after esophagectomy is a devastating complication with a profound negative impact on both short- and long-term survival. Hypoalbuminemia and advanced lymph node involvement are independent predictors of septic shock. These findings support the integration of simple clinical and laboratory markers into personalized perioperative risk stratification models, enabling individualized management strategies to reduce severe postoperative complications. Full article

Background: Colistin (Col) resistance and heteroresistance in extensively drug-resistant (XDR) Acinetobacter baumannii severely limit therapeutic options. We investigated the activity and mechanism of human albumin nanoparticles (haNPs) as colistin potentiators against genetically characterized clinical isolates. Methods: Sixteen clinical isolates were analyzed. Col MICs were determined by broth microdilution, and heteroresistance by population analysis profiling. Potentiation of Col activity was assessed using both Col-loaded haNPs (Col/haNPs) and free Col co-administered with empty haNPs, alongside the proton motive force (PMF) uncoupler carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Assays included checkerboard synergy (FICI), membrane potential analysis (DiOC₂(3)), intracellular Col quantification (UPLC–MS/MS), zeta potential measurements, transmission electron microscopy (TEM), protein leakage, and ROS detection. Results: Heteroresistance was detected in 9/16 isolates. Col/haNPs reduced Col MICs by 4–64-fold in resistant strains and shifted MICs to ≤2 mg/L in most heteroresistant isolates. Empty haNPs displayed no intrinsic antibacterial activity yet selectively potentiated Col, with strong synergy (FICI down to 0.035). Membrane depolarization and increased intracellular Col accumulation under haNP-treated conditions paralleled the effects of CCCP, indicating that haNPs elicit a CCCP-like functional response. These findings are compatible with perturbation of membrane energetics and possible downstream effects on PMF-dependent transport processes. TEM and surface charge analyses supported direct nanoparticle–envelope interaction and progressive membrane disruption. Conclusions: haNPs enhance Col activity across genetically diverse A. baumannii isolates, with particularly strong effects in heteroresistant strains. The combined effects of PMF modulation, increased intracellular drug availability, and envelope interaction provide a mechanistic rationale for the use of albumin-based nanoparticles, either as Col carriers or in combination with free drug, to overcome Col resistance and heteroresistance. Full article

Background: Dengue fever is one of the most common mosquito-borne viral infections, with severe cases characterized by plasma leakage, hemorrhage, and multi-organ involvement. Identification of dengue serotypes and reliable biomarkers is essential for predicting disease progression and guiding timely interventions. Methods: This prospective cohort study was conducted at a super-speciality tertiary care hospital in southern India from July 2024 to July 2025. A total of 69 patients presenting with dengue warning signs were included in the study. Patients were categorized into the severe dengue group (n = 25) and non severe dengue group (n = 44). Clinical data, laboratory findings, dengue serotype, and serial serum samples collected on Days 1, 4, and 8 were analyzed to evaluate the predictive and monitoring efficacy of Interleukin-6 (IL-6) and Interleukin-8 (IL-8), and followed up till discharge. Results: Out of 69 dengue patients with warning signs, 32 dengue-positive patients were serotyped, which included DEN V-1 (31.3%), DEN V-2 (31.3%), DEN V-3 (15.6%), DEN V-4 (18.8%), and mixed DEN V-(2 + 3) (3.1%). Severe dengue patients exhibited a higher frequency of secondary dengue infection (IgG) than primary dengue infection (88% vs. 12%), with statistically significantly higher packed cell volume, hemoglobin levels, high AST levels, and prolonged activated partial thromboplastin time, as well as lower platelet counts and albumin levels. Platelet transfusion was given to 35 dengue patients, which had also resulted in significant length of stay in hospital in comparison to non-transfused patients. IL-6 and IL-8 levels were significantly elevated in severe dengue patients when compared to non-severe dengue patients on Day 1 and Day 4, followed by a decline on Day 8, corresponding with clinical recovery. However, the elevated IL-8 levels were observed to be significantly associated with longer hospital stays, indicating its potential role as an early predictor of disease progression. Conclusions: The observed co-circulation of multiple serotypes reflects the hyper-endemic pattern reported across India. Early measurement of these cytokines IL-6 and IL-8 helps distinguish severe from non-severe dengue among patients presenting with warning signs. IL-6 and IL-8 may have potential as biomarkers for disease severity. However their role in guiding platelet transfusion requires further investigation in non-severe cases and prioritizing timely management for those at higher risk of severe disease. Full article

Cyclophosphamide (CYP) is an effective chemotherapeutic, but its use is limited by hemorrhagic cystitis caused by its toxic metabolite acrolein. Acrolein, when concentrated in the urine, triggers oxidative stress, leading to urothelial inflammation and cell death. Given that albumin is the most abundant plasma protein that contains free thiol groups capable of neutralizing electrophiles and oxidants, we, therefore, hypothesized that albumin could mitigate CYP-induced bladder injury. Here, we tested this hypothesis. In CYP-induced mouse cystitis, albumin administration markedly reduced bladder enlargement, edema, and hemorrhage, effectively normalizing the bladder weight. Albumin also reduced bladder oxidative injury and preserved the expression of anti-ferroptotic proteins, including the cystine/glutamate antiporter xCT and glutathione peroxidase 4 (GPX4). In addition, albumin-treated mice showed less leakage of inflammatory protein into bladder tissue. In vitro, albumin protected urothelial cells from acrolein-induced cell death. It also significantly prevented H₂O₂-induced cytotoxicity. Mechanistically, albumin acted as an extracellular scavenger that preferentially reacted with acrolein and H₂O₂, thereby sparing cellular components from oxidative damage. Notably, oral albumin supplementation similarly attenuated CYP-induced cystitis. Furthermore, albumin administration improved survival in a high-dose CYP toxicity model. These findings establish albumin as a potent protector against CYP-induced toxicity by sequestering acrolein and scavenging reactive oxygen species. Albumin supplementation could be a practical strategy to mitigate chemotherapy-associated bladder and systemic injury. Full article

Background: In sepsis, albumin homeostasis is altered by capillary leak and recovery mechanisms (synthesis and interstitial–lymphatic return), which are difficult to capture clinically. A joint evaluation of ratio-based escape dynamics and mass-based balance may clarify their temporal interplay in sepsis. Methods: In a prospective longitudinal cohort of 389 sepsis patients admitted to an intermediate medical care unit, serial daily sampling (up to five reassessments; 1897 observations) was used to derive: a transcapillary escape rate (TER)-like index from the hourly percent change in the albumin/hemoglobin ratio and net albumin leakage (NAL) from changes in intravascular albumin mass normalized to plasma volume. Indices were analyzed as continuous measures and by sign-defined combined states. Generalized estimating equations (GEE), patient-level slope analyses, and state-transition analyses were performed. Baseline SOFA and 30-day mortality were explored as effect modifiers. Results: The TER-like index peaked early (median +0.34%/h at day 1) and declined to negative values by day 5 (median −0.07%/h), with the TER-like index > 0 decreasing from 65.3% to 45.8%. NAL was frequently negative and heterogeneous (NAL ≥ 0 in 37.5% of observations). TER-like index and NAL were inversely correlated (ρ = −0.54; p < 0.001). In GEE, the TER-like index was associated with NAL (β = −7.46 g/L per 1%/h; 95% CI −8.69 to −6.22; p < 0.001) with time-varying effects (interaction p < 0.01). The dissociation state (TER-like index ≤ 0 with NAL < 0) increased from 2.3% at day 1 to 22.6% at day 5 (p < 0.001). Conclusions: TER-like index escape dynamics attenuate early; however, net intravascular albumin balance often remains negative, supporting temporal uncoupling between “leak” and recovery. An integrated TER-like/NAL assessment offers a pragmatic framework for the clinical phenotyping of albumin homeostasis using routine laboratory data. Full article

Background: Anastomotic leakage (AL) remains one of the most feared complications after colorectal surgery. This study aimed to identify preoperative risk factors for AL using a five-year dataset from two Romanian surgical clinics. Materials and Methods: A retrospective cohort of 155 patients undergoing colorectal resection with primary anastomosis (105 from “Colentina” Hospital and 50 from “Dr. I. Cantacuzino” Hospital) was analyzed. Preoperative demographic, clinical, and laboratory data were extracted and assessed using univariate and multivariable logistic regression. Statistical analyses were performed using IBM SPSS. Results: The overall AL rate was 10.3%. Multivariable analysis identified high ASA class (OR 17.6; p = 0.001), emergency surgery (OR 32.2; p = 0.0007), and heavy alcohol use (OR 15.3; p = 0.004) as independent predictors of leakage. While low preoperative albumin and smoking were associated with leakage in a bivariate analysis, these did not remain significant after adjustment. Notably, all laboratory markers were based on preoperative values, distinguishing our approach from prior studies that commonly evaluated postoperative biomarkers. No statistically significant effect was found for neoadjuvant chemotherapy or radiotherapy after controlling for other covariates. Conclusions: High ASA score, alcohol abuse, and emergency surgery were the strongest independent predictors of AL in our cohort. The lack of predictive power of certain widely reported factors, such as low albumin, may reflect our dataset’s focus on preoperative optimization. These findings support the use of individualized risk assessment and reinforce the role of preoperative preparation in reducing leak incidence in colorectal surgery. Full article

Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. At present, multi-agent chemotherapy and surgery provide only limited effects and the prognosis for patients with recurrent or metastatic disease remains poor, with 5-year survival rates below 30%. These challenges highlight the need for innovative therapeutic approaches targeting osteosarcoma more effectively. Fenretinide, a synthetic derivative of all-trans retinoic acid, has shown significant antitumor activity in various cancers. In a recent high-throughput drug screening study, fenretinide emerged as the most active molecule against diffuse midline glioma over more than 3500 compounds. Fenretinide also demonstrated cytotoxic activity against osteosarcoma cell lines in vitro and in preclinical models and is endowed with a favorable safety and toxicity profile. However, its poor water solubility and limited bioavailability have hindered its clinical translation. To improve fenretinide bioavailability and enhance tumor exposure, different nanotechnology-based drug delivery systems have been proposed. Here we propose a tertiary complex made of fenretinide, bovine serum albumin, and hydroxypropyl-betacyclodextrin, indicated as BSAF. Methods: BSAF was evaluated for the main physico-chemical parameters such as hydrodynamic size, zeta potential, stability to drug leakage, and the biological effect on the osteosarcoma cell line MG63. Results: BSAF showed hydrodynamic size at the nanoscale, enhanced drug solubilization, high drug loading and size stability to dilution, characteristics that make this complex useful for targeted therapy. When tested on the MG63 osteosarcoma cell line, BSAF demonstrated significantly enhanced cytotoxicity, with half-maximal inhibitory concentration (IC₅₀) values ~50% lower than free fenretinide. The complex was more efficient than free fenretinide in inhibiting cell migration as demonstrated by wound healing assay. Live-cell imaging analyses revealed a cytostatic effect at sub-cytotoxic concentrations. Specifically, treatment with concentrations below the IC₅₀ resulted in significantly prolonged cell doubling time, decreased cell divisions, increased cellular sphericity and thickness, and decreased cell area. These morphological changes are more consistent with cell cycle arrest rather than apoptosis. These findings were corroborated by stable dry mass measurements, an indication of a cytostatic state rather than progressive cell death. In addition, cell motility parameters (e.g., instantaneous velocity, track speed, and displacement) at the single-cell and population level were markedly reduced at sub-IC₅₀ concentrations, further supporting a cytostatic phenotype. Conclusions: Collectively, the new BSAF complex showed promise as a potential therapeutic agent for treating osteosarcoma cancer, due to the favorable physico-chemical characteristics and the cytotoxic/cytostatic effects on MG63 cells. BSAF effects may be therapeutically valuable, particularly in preventing tumor recurrence by suppressing the proliferative and migratory potential of residual drug-resistant clones. Unlike conventional anticancer agents that mainly rely on cell death, fenretinide, when complexed, demonstrates a dual capacity to induce both cytotoxic and cytostatic responses, depending on concentrations, potentially overcoming multiple resistance mechanisms that are generally associated with tumor exposure to drug sub-cytotoxic concentrations. Full article

Cytokine storm is a critical driver of acute respiratory distress syndrome and multiple organ failure. Human β-defensin 2 (HBD-2) is the first inducible defensin discovered in human body. Defensin can resist pathogenic microorganisms invading the body through direct bactericidal effect and also modulates acquired immune response. Albumin exhibits immunomodulatory properties and can reduce the level of inflammatory cytokines to improve the systemic inflammatory response. We previously engineered a recombinant fusion protein, DF₂-HSA, comprising two HBD-2 molecules linked to human serum albumin. Here, we evaluated its effect on cytokine storm using a lipopolysaccharide (LPS)-induced cytokine storm murine model (BALB/c athymic mice, female). DF₂-HSA reduced the mortality in cytokine storm murine model and prolonged the retention time of HBD-2 in the body. A Luminex assay showed that DF₂-HSA reduced the production of multiple inflammatory cytokines in cytokine storm murine model. Evans blue staining showed that DF₂-HSA reduced vascular leakage. Transmission electron microscopy showed that DF₂-HSA reduced the lung injury of cytokine storm mice. The pathological results showed that DF₂-HSA alleviated the lung and small intestine damage of cytokine storm mice. In summary, DF₂-HSA effectively inhibits cytokine storms and ameliorates associated tissue damage. Full article

Objective: This study compares the brain protective effects of L-borneolum and its main components (a combined application of L-borneol and L-camphor) on the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). It also makes clear the intrinsic regulatory mechanisms that link the neuroprotective effects of these compounds on IS to the blood-brain barrier (BBB), based on network pharmacology predictions. Furthermore, the study investigates the relationship between these compounds and the Major Facilitator Superfamily Domain-containing Protein 2A (MFSD2A)/Caveolin-1 (Cav-1) signaling axis. Methods: The MCAO/R model in rats was established to evaluate the therapeutic effect of L-borneolum (200 mg/kg) and its main components combination of L-borneol and L-camphor (6:4 ratio, 200 mg/kg). Neurological scores, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Nissl staining were performed to evaluate the neurological damage in the rats. Cerebral blood flow Doppler was applied to monitor the cerebral blood flow changes. Immunofluorescence analysis of albumin leakage and transmission electron microscopy (TEM) were conducted to evaluate blood-brain barrier (BBB) integrity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the optimal drug concentration. Trans-epithelial electrical resistance (TEER) and horseradish peroxidase (HRP) assays were employed to confirm the successful establishment of an in vitro BBB co-culture model. Network pharmacology was utilized to predict the biological processes, molecular functions, and cellular components involved in the treatment of ischemic stroke (IS) by the main components of L-borneolum (L-borneol and L-camphor). Finally, immunofluorescence, real-time fluorescent quantitative PCR (RT-qPCR) and western blot analyses were performed to detect the expression of Major Facilitator Superfamily Domain Containing 2A (MFSD2A), caveolin-1 (CAV-1), sterol regulatory element-binding protein 1 (SREBP1) in brain tissue and hCMEC/D3 cells. Results: Network pharmacology prediction indicated that L-borneolum and its main components (L-borneol and L-camphor) in the treatment of IS are likely associated with vesicle transport and neuroprotection. Treatment of IS with L-borneolum and its main components significantly decreased neurological function scores and cerebral infarction area, while alleviating pathological morphological changes and increasing the number of Nissl bodies in the hippocampus. Additionally, it improved cerebral blood flow, reduced albumin leakage, and decreased vesicle counts in the brain. The trans-epithelial electrical resistance (TEER) of the co-culture model stabilized on the fifth day after co-culture, and the permeability to horseradish peroxidase (HRP) in the co-culture model was significantly lower than that of the blank chamber at this time. RT-qPCR and Western blot results demonstrated that, compared to the model group, the expression of SREBP1 and MFSD2A significantly increased, while the expression of Cav-1 decreased. Conclusions: L-borneolum and its main components combination (L-borneol/L-camphor, 6:4 ratio) may exert a protective effect in rats with IS by improving BBB transport function through modulation of the MFSD2A/Cav-1 signaling pathway. Full article

Background/Objectives: Vitamin B₁₂ deficiency is increasingly recognized as a contributor in both vascular and neurodegenerative aging-related disorders. Its deficiency disrupts one-carbon metabolism, leading to impaired homocysteine (Hcy) cycling. Elevated Hcy is a well-established risk factor for vascular dysfunction. Previously, we established that elevated Hcy contributes to aging retinal diseases and plays a central role in blood retinal barrier (BRB) dysfunction. Building on this foundation, the present study examines how B-vitamin deficiency disrupts one-carbon metabolism and whether restoring these vitamins can serve as a preventive or therapeutic strategy. Since B-vitamins (B₆, B₉, and B₁₂) are crucial cofactors in the metabolism of Hcy, we investigated how dietary changes in these vitamins affect serum Hcy levels and retinal vascular integrity in mice. Methods: C57BL/6- Wild-type (WT) and cbs^+/− mice (Cystathionine Beta-Synthase heterozygotes, common mouse model for elevated Hcy) were fed specially formulated diets, which contained different levels of B-vitamins (normal, deficient (B-Vit (−)) or enriched (B-Vit (+)). Initially, two groups of mice were placed on either a normal or a deficient diet. After 12–16 weeks, the success of the diet regimes was confirmed by observing serum B₁₂ deficiency in the B-Vit (−) group, along with elevated Hcy levels. Subsequently, a subgroup of the B-Vit (−) mice was switched to an enriched diet. The BRB integrity was evaluated in living mice using fluorescein angiography (FA), optical coherence tomography (OCT), and in the perfused mice retinas with Western blot analysis of leaked retinal albumin and tight junction proteins (occludin and ZO-1) levels. Results: The B-vitamin deficiency caused significant drop in serum vitamin B₁₂ and an increase in plasma Hcy, leading to vascular leakage, altered retinal thickness, choroidal neovascular changes, increased retinal albumin leak, and decreased tight junction protein expression, indicating BRB disruption, which was restored with B-vitamin supplementation. Conclusions: a long-term deficiency of vitamins B₆, B₉, and B₁₂ can lead to disruptions in the BRB. However, supplementation with these B-vitamins has the potential to reverse these effects and help maintain the integrity of BRB. This under-score the significance of one-carbon metabolism for retinal health and suggests that ensuring adequate levels of B-vitamins may aid in preventing aging retinal diseases with BRB disruption such as diabetic retinopathy and age-related macular degeneration. Full article

Background: China is currently developing standards for Food for Special Medical Purposes (FSMP) targeting for oncology patients. However, substantial challenges remain in defining optimal fortification levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). Accumulating evidence suggests that ω-3 PUFA intake improves postoperative prognosis by modulating oncological parameters in colorectal cancer (CRC) patients. This meta-analysis aimed to evaluate the therapeutic efficacy of ω-3 PUFA supplementation in enhancing postoperative safety and recovery stability following CRC surgery, to address critical gaps in nutritional interventions for optimizing clinical outcomes. These findings are expected to FSMP standard development, clinical nutrition protocols and product innovation. Methods: A systematic literature search was conducted, in accordance with PRISMA guidelines, across major databases until June 16, 2025. Data were analyzed using RevMan v5.4 (Cochrane Collaboration). Results: Thirty-four randomized controlled trials (RCTs) (n = 2889) were included. Compared to controls, the ω-3 PUFAs group showed significantly increased levels of nutritional markers: total protein (p < 0.00001), albumin (p = 0.001); immunological parameters: CD3⁺/CD4⁺/CD8⁺ T-cells, CD4⁺/CD8⁺ ratio (all p < 0.0001); Karnofsky Performance Status (KPS) scores (p = 0.04); and serum ω-3 PUFA concentrations (p = 0.0004). Significant reductions were observed in inflammatory markers, such as procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) (p = 0.004 to < 0.00001); and clinical outcomes, such as hospitalization duration (p < 0.00001), infectious complications (p < 0.00001), anastomotic leakage (p = 0.0005), surgical site infections (p = 0.03). No significant intergroup differences were detected for white blood cells, transcription factor activity, mortality, or crypt cell proliferation indices (p = 0.06–0.55). Conclusions: Overall, ω-3 PUFA supplementation significantly attenuates postoperative inflammation, enhances immune function, shortens hospitalization, and improves the quality of life in CRC patients, though without mortality benefit. Notably, post hoc dose–response analysis identified a supplementation range of 0.16–0.30 g/kg/day as a potentially optimal supplementation range for Chinese CRC populations, providing foundational evidence for clinical practice and FSMP standardization. Full article

Background/Objective: Early hemodynamic instability in sepsis arises from endothelial dysfunction and vasoplegia before capillary leakage and organ failure occur. Albumin administration guided by serum concentration or shock criteria has not improved outcomes. This review synthesized evidence supporting an early, physiology-guided framework for albumin and norepinephrine use in pre-δ vasoplegic sepsis. Methods: A narrative synthesis of experimental and clinical studies examined endothelial injury, sepsis phenotypes, hemodynamic monitoring, biochemical markers, and intravascular albumin mass. Evidence from phenotype cohorts was integrated to construct a physiology-based therapeutic framework. Results: The δ phenotype consistently emerged as a vasoplegic, hyperinflammatory endotype with hypoalbuminemia, elevated lactate, and the highest mortality. Studies showed 20–25% of patients with community-acquired sepsis exhibit early vasoplegia, with low systemic vascular resistance and high cardiac output. Mass-balance analyses showed intravascular albumin mass declines early in sepsis, correlate inversely with fluid balance, and predict mortality. These findings suggest early low-dose norepinephrine may stabilize perfusion pressure, while albumin use should follow intravascular albumin mass trajectories. A dynamic exclusion concept proposes withholding albumin during capillary leak and reintroducing it when intravascular albumin mass stabilizes. Conclusions: Albumin therapy in sepsis should shift from late concentration-based to early physiology-guided endothelial protection. Monitoring intravascular albumin mass, lactate, and fluid balance may guide targeted norepinephrine and albumin use before δ-type endothelial failure occurs. This framework needs phenotype-stratified validation. Full article

The blood–brain barrier (BBB) is essential for maintaining cerebral homeostasis, and its dysfunction is increasingly recognized as an active driver of epilepsy. This review explores the mechanisms by which BBB disruption contributes to seizures and the development of chronic epilepsy. Potentially epileptogenic insults, including traumatic brain injury, stroke, and status epilepticus, induce acute and often persistent BBB leakage. This breach permits the extravasation of serum albumin, which activates transforming growth factor-beta (TGF-β) signaling in astrocytes. This cascade leads to astrocytic dysfunction, impaired potassium buffering, neuroinflammation, and synaptic remodeling, collectively fostering neuronal hyperexcitability. Furthermore, BBB disruption facilitates the infiltration of peripheral immune cells, amplifying neuroinflammation and propagating a pathologic cycle of BBB damage and seizure activity. BBB damage is mediated by multiple processes, including the activation of the plasminogen activation (PA) system. Furthermore, these processes of BBB disruption and neuroinflammation provide a shared pathological basis for neuropsychiatric disorders like depression and anxiety, which are common comorbidities of epilepsy, through shared mechanisms of neuroinflammation and neurovascular unit (NVU) dysregulation. BBB dysfunction can also contribute to the resistance to antiepileptic drugs. Finally, we discuss the therapeutic potential of stabilizing the BBB as a viable strategy for developing disease-modifying therapies for epilepsy. Full article