Search Results (1,478)

2-acetylfuran is a product of the Maillard reaction and is widely found, especially in heat-processed foods such as grain products, baked goods, and dairy products. Although 2-acetylfuran contributes to flavor, high concentrations may be toxic. Its target organs and dose–response relationships remain poorly characterized. In this study, transgenic zebrafish with fluorescently labeled immune and neural systems were used to assess the effects of 2-acetylfuran on immune and neural development. Wild-type zebrafish were employed to assess the toxicity of 2-acetylfuran on locomotor ability, gastrointestinal development, and liver function. The maximum non-lethal concentration (MNLC) and the 10% lethal concentration (LC₁₀) for zebrafish embryos were 0.844 and 0.889 μL/mL, respectively. Regarding immunotoxicity, at concentrations of 0.281, 0.844, and 0.889 μL/mL, 2-acetylfuran significantly reduced the numbers of neutrophils, T cells, and macrophages. Regarding locomotor and neurotoxicity, motor speed and total locomotor distance were significantly reduced at 0.844 and 0.889 μL/mL. These findings were consistent with neurodevelopmental assessments, in which 0.844 μL/mL 2-acetylfuran resulted in a significant increase in apoptotic cells in the central nervous system and markedly shortened peripheral motor nerve lengths. Regarding gastrointestinal toxicity, 0.844 and 0.889 μL/mL 2-acetylfuran significantly reduced the gastrointestinal area, while neutrophil counts showed no significant changes, suggesting a relatively mild effect on the gastrointestinal tract. Regarding hepatic toxicity, all tested concentrations of 2-acetylfuran primarily increased the delayed yolk sac absorption area. Furthermore, at 0.844 μL/mL, histological examination revealed hepatic pathological changes characterized by hepatocyte nuclear swelling, vacuolar degeneration, and hepatocyte necrosis. In summary, this study reveals the multi-organ toxicity profile of 2-acetylfuran in the zebrafish model, with particularly high sensitivity in the immune system and liver. This research provides theoretical support for risk assessment and process control of 2-acetylfuran in foods. Full article

Hepatocellular injury syndrome represents a pathological process with a broad etiological spectrum, including viral infections, autoimmune diseases, or intoxications. Clinicians must identify the potential cause using both anamnestic data and available paraclinical examinations. We present the case of a 55-year-old female patient, admitted to the Internal Medicine 1 Department at the Clinical County Emergency Hospital Bihor, Oradea, Romania. The patient exhibited nonspecific complaints and insignificant pathological antecedents, but from a biochemical perspective, substantial changes in liver transaminase levels were evident. To establish differential diagnoses, a series of biochemical and immunological tests were performed, along with a thorough medical history. It was concluded that the patient regularly consumes herbal infusions, specifically Laurus nobilis leaves, commonly known as Bay Laurel. Although this might be easily overlooked at first glance, a closer examination could explain the current clinical picture. In April 2024, a 55-year-old female patient with no history of liver pathology was admitted. She complained of asthenia fatigue, anorexia, mixed dyspeptic symptoms, diffuse abdominal pain, and a weight loss of 12 kg. The pathology had insidiously started approximately 3 months prior. On examination, the patient had altered general status, anorexia, and was overweight. Biochemically, the patient had elevated liver transaminase values (AST = 196 U/L and ALT = 357 U/L) that continued to rise during hospitalization, despite hepatoprotective treatment. Various paraclinical examinations were performed to exclude other potential causes of hepatic aggression, having excluded ordinary causes. Consequently, a liver biopsy was performed, and the histopathological examination leaned toward a toxic hepatitis etiology. Application of the updated RUCAM scale yielded a score of eight points (“probable” HILI—Herb-Induced Liver Injury). Clinical and biochemical improvement was observed after complete cessation of bay leaf tea consumption. This case highlights the potential hepatotoxicity of commonly used culinary herbs when consumed in large quantities or as concentrated infusions and emphasizes the importance of detailed anamnesis regarding herbal product use. Full article

Microplastics are pervasive in aquatic environments; however, their impacts on aquatic organisms at environmentally relevant concentrations remain poorly understood, particularly under field conditions. To address this gap, we employed high-throughput sequencing to assess these impacts under both field and laboratory conditions using crucian carp (Carassius auratus) as a model organism. Following a 4-week exposure in situ, the abundance of intestinal microplastics slightly increased from an initial level of 55.00 ± 59.73 items/fish to 72.67 ± 27.50 items/fish (p > 0.05). Accordingly, a total of 3036 differentially expressed genes (DEGs) were identified in the hepatic transcriptome, with notable enrichment in pathways related to lipid metabolism and oxidative stress. Furthermore, a positive correlation between intestinal microplastic abundance and exposure concentration was observed in fish following a 2-week laboratory exposure to polyamide (PA), with intestinal burdens ranging from 7.50 ± 3.54 to 367.50 ± 17.68 items/fish. The number of DEGs in the hepatic transcriptome, ranging from 41 to 380 items, demonstrated a nonlinear relationship with microplastic levels. Furthermore, these DEGs were primarily enriched in pathways associated with lipid metabolism and oxidative stress, including the PPAR signaling pathway (ko03320) and fatty acid degradation (ko00071). This suggests that microplastics at environmental levels may have detrimental effects on organisms through perturbations in lipid metabolism and oxidative stress. As expected, these findings provide essential insights for evaluating the ecological risks linked to microplastic pollution at environmental levels. Full article

Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular carcinoma (HCC), but decline with fibrosis progression in end-stage liver disease (ESLD). CCL5 has also been linked to atherosclerosis. This study aimed to evaluate serum CCL5 levels in ESLD patients listed for liver transplantation (LT) and to assess their potential role as markers of cardiovascular (CV) risk and portal hypertension. Methods: We conducted an observational cohort study. Between 2019 and 2022, patients with ESLD evaluated for LT were enrolled. Data on liver pathology, CV risk, and laboratory parameters were collected. Serum CCL5 concentrations were measured using Sigma Aldrich^® CCL5 ELISA kits (MilliporeSigma, St. Louis, MO, USA). The database was analyzed with IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA). Results: Overall, 46 patients were included, 50% with viral hepatitis and 28.3% with alcohol-related liver disease. HCC was present in 37% of cases. The median CV risk scores (CAD_LT = 7, mCAD_LT = 7, CAR_OLT = 18) placed the population at moderate CV risk. Serum CCL5 levels did not vary significantly between viral vs. non-viral cirrhosis (5511.8 vs. 6272.5 pg/mL, p = 0.15) and were not influenced by the presence of HCC (6098.4 vs. 5771.3 pg/mL, p = 0.55). We did not detect a correlation with MELD score (p = 0.21) or CV risk scores (CAD_LT: p = 0.58; mCAD_LT: p = 0.70; CAR_OLT: p = 0.22). Patients with thrombocytopenia (<100,000/µL, 54.3%) or a history of esophageal variceal ligation had lower CCL5 levels (5170.9 vs. 6750.8 pg/mL, p = 0.002 and 4252.0 vs. 6237.5 pg/mL, p = 0.003, respectively). Similarly, patients with a history of previous variceal bleeding and spontaneous bacterial peritonitis (SBP) had lower levels of CCL5 (4373.8 vs. 6119.9 pg/mL, p = 0.02 and 3404.3 vs. 6606.7 pg/mL, p = 0.01, respectively). We found a negative correlation between CCL5 and QTc interval duration (τ = −0.216, p = 0.037), left ventricle size (LV: τ = −0.235, p = 0.027), and pulmonary artery pressure (RV/RA gradient: τ = −0.225, p = 0.03). CCL5 correlated positively with the inflammatory markers C-reactive protein (CRP) (τ = 0.246, p = 0.018) and fibrinogen (r = 0.216, p = 0.04). Conclusions: In liver transplant candidates, serum CCL5 is not associated with cardiovascular risk scores or coronary atherosclerotic burden, but is inversely associated with clinical markers of portal hypertension severity. These findings suggest that CCL5 may serve as a potential non-invasive surrogate marker of portal hypertension rather than a cardiovascular risk biomarker in ESLD. Full article

Due to improper nutrition, high-density lipoproteins (HDLs) can be subjected to structural changes, acquiring a dysfunctional phenotype. Therefore, research efforts are currently focused on improving HDL functionality despite its blood level. The aim of this study was to evaluate the effect of phycocyanin concentrate (as part of a food matrix) on the functional properties of HDL. Male Wistar rats were fed a high-fat diet containing 2% cholesterol for 113 days. Experimental animals were treated with 30 and 300 mg/kg b.w. of phycocyanin concentrate mixed with soy protein isolate. Serum and hepatic cholesterol and triglyceride levels, and the content of protein, triglycerides, choline-containing phospholipids, malondialdehyde, sphingosine-1-phosphate, and paraoxonase-1 in HDL fractions were assessed. The decrease in protein in HDL particles is characteristic for dysfunctional phenotype of these particles. Phycocyanin concentrate diet prevented the depletion of protein in HDL particles, regardless of the dosage. The functionality of HDL is associated with paraoxonase-1 activity, which inhibits lipid peroxidation in lipoproteins. Our results have shown a significant increase in the level of paraoxonase-1 in HDL particles in groups treated with phycocyanin. HDL particles become more enriched with triglycerides with the development of hyperlipidemia. Triglycerides in HDL particles and in serum decreased by two times in animals receiving 30 mg/kg b.w. of phycocyanin. The MDA content in HDL particles decreased in all animals receiving a high-fat diet with the addition of 2% cholesterol. The introduction of 300 mg/kg of phycocyanin returned this indicator to the values of the Control group. Thus, biomarkers of dysfunctional changes in HDL in rodent hyperlipidemia models may be a useful tool for assessing lipid metabolism disorders. Also, the results confirm the potential ability to use phycocyanin concentrate as part of lipid-lowering products. Full article

Background: Hepatitis B vaccination is the most effective strategy for preventing chronic hepatitis B virus (HBV) infection; however, interindividual variability in vaccine-induced antibody responses remains a significant challenge in the field. Innate immune components, particularly lectin complement pathway proteins such as mannose-binding lectin (MBL), mannose-associated serine protease 1 (MASP-1), and mannose-associated serine protease 2 (MASP-2), may contribute to this variability in outcomes. This study aimed to evaluate the association between serum MBL, MASP-1, and MASP-2 levels, birth weight, and humoral response to hepatitis B vaccination in infants. Methods: This single-center prospective observational study included 37 term infants who received hepatitis B vaccinations at birth, 1 month, and 6 months of age according to the national immunization schedule. Venous blood samples were collected at month 6, before, and month 7 after the 3rd vaccine dose. Serum MBL, MASP-1, MASP-2, and antiHB levels were measured using commercial ELISA and chemiluminescence assays. Data were analyzed using non-parametric statistical tests and Spearman’s correlation analysis. Results: AntiHB levels increased significantly following vaccination (median Pre-3rdVac: 125.8 mIU/mL; Post-3rdVac: 609.7 mIU/mL; p < 0.001). MASP-1 concentrations also showed a significant Post-3rdVac increase (median Pre-3rdVac: 809.52 ng/mL; Post-3rdVac: 1133.93 ng/mL; p = 0.019). Birth weight was positively correlated with both MASP-1 levels (r_s = 0.492, p = 0.004) and changes in MASP-1 concentrations (r_s = 0.524, p = 0.002) after the third dose. In addition, MASP-1 levels were positively associated with antiHB levels (r_s = 0.385, p = 0.030) and Post-3rdVac antiHB titers (r_s = 0.493, p = 0.004). In contrast, serum MBL and MASP-2 concentrations were not significantly associated with antiHB levels before or after vaccination. Conclusions: MASP-1, but not MBL or MASP-2, is associated with the magnitude of the antibody response to hepatitis B vaccination in infants. These findings suggest that specific components of the lectin pathway may influence vaccine-induced immunity, independent of MBL. Further large-scale studies incorporating genetic and functional analyses are warranted to clarify the mechanisms by which lectin pathway proteins shape hepatitis B vaccine response. Full article

Background/Objectives: Resveratrol is a multi-target polyphenolic stilbene widely studied for its antioxidant, anti-inflammatory, cardioprotective, hepatoprotective, neuroprotective, immunomodulatory and anticancer properties. This review summarizes current evidence on its molecular mechanisms, therapeutic potential, metabolic interactions and biological implications, with particular emphasis on bioavailability, signaling pathways and organ-specific actions. Methods: A comprehensive literature review was conducted focusing on recent in vitro, in vivo and clinical studies evaluating resveratrol’s biochemical activity, molecular targets and physiological effects. Special attention was given to oxidative stress regulation, inflammatory signaling, mitochondrial function, metabolic pathways, gut microbiota interactions, and its influence on chronic diseases. Results: Resveratrol modulates several key signaling pathways including NF-κB, SIRT1, AMPK, MAPK, Nrf2 and PI3K/AKT/mTOR. It reduces oxidative stress, inhibits inflammatory cytokines, regulates apoptosis, improves mitochondrial performance, and activates endogenous antioxidant systems. The compound demonstrates protective effects in cardiovascular diseases, hepatic steatosis, neurodegenerative disorders, metabolic dysfunction, and various cancers through anti-inflammatory, anti-proliferative and anti-fibrotic mechanisms. Additionally, resveratrol beneficially alters gut microbiota composition and microbial metabolites, contributing to improved metabolic homeostasis. Despite high intestinal absorption, systemic bioavailability remains low; however, novel nanoformulations significantly enhance its stability and plasma concentrations. Conclusions: Resveratrol exhibits broad therapeutic potential driven by its capacity to regulate oxidative, inflammatory, metabolic and apoptotic pathways at multiple levels. Its pleiotropic activity makes it a promising candidate for prevention and complementary treatment of chronic diseases. Advances in delivery systems and microbiota-derived metabolites may further enhance its clinical applicability. Full article

Background: Administering several separate childhood vaccines can reduce adherence to immunization schedules due to missed appointments and the burden of repeated injections. A hexavalent formulation targeting diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type B, and poliovirus offers a practical approach to improve compliance and streamline immunization. Methods: Toxicity testing was performed in Wistar rats and New Zealand White rabbits (60 rats and 30 rabbits). Animals were distributed into three groups: hexavalent vaccine + low-dose sIPV, hexavalent vaccine + high-dose sIPV, and control. Each animal received a 0.5 mL intramuscular injection at weeks 0, 4, 8, and 12. Clinical observations were conducted throughout the study. Serum samples were collected one day before each injection and at the endpoint, while liver tissue was collected at the endpoint. ALT and AST concentrations were analyzed using an automated analyzer, and hepatic morphology was evaluated microscopically. Results: No abnormal clinical signs related to vaccination were observed. ALT concentrations showed no significant differences (p > 0.05). AST differences (p < 0.05) were detected between the high-dose group and the control on day 27 in female rabbits and on day 83 in female rats; however, all values remained within normal physiological limits. Histopathological examination revealed no irreversible hepatic lesions, including hydropic degeneration, portal inflammation, focal necrosis, or connective tissue proliferation, and no significant differences were noted (p > 0.05). Conclusions: Repeated administration of the hexavalent vaccine candidate at low and high doses produced no toxicological effects in animal models, supporting its safety for further clinical development. Full article

The increasing accumulation of plastic debris in aquatic environments has raised concerns about the ecotoxicological effects of polystyrene nanoplastics (PSNPs). This study examined PSNPs toxicity during a critical developmental stage by exposing 15 days post-fertilization (dpf) larvae of blotched snakehead (Channa maculata), an economically important freshwater fish, to PSNPs concentrations of 0.05–20 mg/L for 15 days. Histopathological analysis showed concentration-dependent damage, including hepatocellular vacuolization (5–10 mg/L) and hepatic sinusoidal dilation (20 mg/L) in the liver, alongside intestinal injuries ranging from villus erosion to rupture (5–20 mg/L). Biochemically, PSNPs triggered a biphasic oxidative response, where superoxide dismutase (SOD) and catalase (CAT) activities peaked at 5 mg/L before declining, while malondialdehyde (MDA) levels exhibited an opposite trend. Transcriptomic analysis and Quantitative real-time PCR (qRT-PCR) indicated that PSNPs disrupted growth, energy metabolism, and immune regulation in C. maculata larvae, evidenced by the dysregulation of growth hormone/insulin-like growth factor (GH/IGF) axis genes and up-regulation of immune-related genes. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) identified the heterogeneous nuclear ribonucleoproteins (HNRNP) gene family as hub genes from the key turquoise module, suggesting that PSNPs interfere with RNA processing and post-transcriptional control. In summary, PSNPs caused multi-level toxicity in C. maculata larvae, providing new insights into their ecotoxicological hazards in freshwater ecosystems. Full article

Background/Objectives: Chemical and metabolic kinetics have historically been derived from mass balance differential equations expressed in terms of amounts, and this framework was later extended to pharmacokinetics by converting amount-based equations to concentration-based clearance relationships. That conversion is valid for fixed-volume in vitro experiments, but may be unreliable in vivo, where input, distribution, and elimination can occur in different volumes of distribution. The objective of this study is to present an alternate, mechanistically agnostic framework for deriving pharmacokinetic relationships by adapting Kirchhoff’s Laws to treat pharmacokinetic systems as networks of parallel and in-series rate-defining processes, and to identify where differential equation approaches fail in vivo. Methods: Clearance and rate constant equations were derived using the adapted Kirchhoff’s Laws by summing parallel rate-defining processes and summing inverses for in-series processes, explicitly incorporating organ blood flow, net transporter, and delivery site effects. The resulting expressions were compared with differential equation hepatic disposition elimination models (well-stirred, parallel tube, dispersion) and the Extended Clearance Concept (ECC). Mean residence time concepts were used to extend the framework to oral input, and the full approach was applied to a case study of a hypothetical drug (KL25A). Results: The adapted Kirchhoff-based approach reproduced standard pharmacokinetic analyses without mechanistic organ assumptions and yielded model-independent hepatic and renal clearance equations that include blood flow, net transport, and delivery kinetics. Inconsistencies with the traditional differential-based derivations were highlighted, including the interpretation of pharmacokinetics associated with slow absorption site clearance, as illustrated by KL25A. Conclusions: For linear drug metabolism and pharmacokinetics, clearance and rate constant relationships can be derived by summing parallel and in-series rate-defining processes, without differential equations. Differential equation methods may misestimate in vivo clearance and bioavailability when drug input is slow or when volumes of distribution differ across processes. The adapted Kirchhoff framework offers a simpler, model-independent basis for interpreting clinical data. Full article

This study was focused on the assessment of fungal occurrence, mycotoxin dynamics, aflatoxin carry-over, and associated biochemical responses in dairy cattle. Moisture emerged as the dominant factor for fungal communities, promoting the co-proliferation of fungal genera adapted to high water activity conditions (a_w > 0.90) and antagonism against xerotolerant and xerophilic species. Aspergillus spp. dominated dry substrates (a_w < 0.75), Fusarium spp. showed strong positive associations with high-moisture matrices (a_w > 0.90), and Penicillium spp. exhibited intermediate, substrate-dependent behavior. Mycotoxin levels fluctuated non-linearly, independently of fungal counts: ochratoxin A (OTA) concentrations in corn silage increased from approximately 12 μg/kg at the onset of the ensiling period to >240 μg/kg at silo opening, indicating dynamic mycotoxin accumulation during storage, while zearalenone (ZEA) oscillated from 40 to 170 µg/kg. Despite the variation in total aflatoxins (AFLA-T) across feed matrices, aflatoxin M1 (AFM1) in milk remained low (0.0020–0.0093 μg/kg), confirming limited carry-over. Serum biochemical parameters—alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (BIL-T), total protein (PROT-T)—remained within physiological limits, yet multivariate analyses revealed metabolic modulation linked to aflatoxin exposure. AFM1 explained >7% of the variance in serum biochemical profiles according to PERMANOVA (p = 0.002), showed significant MANOVA effect (Pillai = 0.198), and displayed a significant canonical association (p < 10⁻¹³). Linear discriminant analysis further separated Normal vs. Borderline hepatic profiles, indicating subclinical physiological adaptation to chronic low-dose exposure. Full article

Background: Methanol poisoning remains a major cause of fatal toxic exposures worldwide, yet the diagnostic value of postmortem methanol and formic acid levels in relation to organ-specific pathology is not fully understood. This study aimed to provide a comprehensive forensic and diagnostic evaluation of fatal methanol intoxications using multiple biochemical and pathological parameters. Methods: A total of 138 autopsy-confirmed methanol poisoning cases were retrospectively analyzed. Quantitative methanol and formic acid levels were measured in blood and vitreous humor. Autopsy reports, demographic characteristics, and histopathological findings in major organs were systematically reviewed. The presence of ethanol and other substances, including stimulants and narcotic drugs, was also recorded. Results: Blood methanol concentrations averaged 142.47 ± 139.20 mg/dL (range: 0–595), and formic acid levels averaged 258.62 ± 197.89 mg/dL (range: 0–618). Vitreous humor concentrations showed comparable distributions. Common pathological findings included cerebral edema, putaminal discoloration or necrosis, myocardial ischemia, hepatic steatosis, pulmonary edema, and acute pancreatitis. Ethanol or other substances were detected in several cases, with stimulants or narcotic drugs present in 10.4% (n = 13). Importantly, the combined interpretation of postmortem biochemical markers and organ pathology allowed clearer differentiation of methanol-related injury patterns compared with prior reports. Conclusions: Methanol intoxication produces variable but characteristic biochemical and pathological profiles. Integrating toxicological markers with organ-specific pathology enhances the diagnostic accuracy of postmortem evaluations and supports more reliable identification of methanol-related deaths. Full article

Background: Uncontrolled diabetes is characterised by a loss of blood glucose control and increased oxidation of fatty acids to produce ATP. Use of metabolic inhibitors to blunt fatty acid oxidation and restore glucose metabolism is a poorly studied intervention for diabetes. Methods: Steptozotocin-induced diabetes was developed in Wistar male rats. A subset was supplemented with mildronate (100 mg/kg—14 days). Exploiting liquid chromatography-mass spectrometry for workflows including ion exchange-, C18-reverse phase- and HILIC-based chromatography methods, metabolite levels were quantified in plasma liver and brain tissue. Using both untargeted and targeted metabolomic analysis changes to the global tissue metabolome and individual metabolic pathways were estimated. Results: We document that an inhibitor of carnitine synthesis, mildronate, decreased plasma (50% p < 0.01) carnitine abundance and decreased plasma glucose concentration by one-third compared to streptozotocin (STZ)-treated rats (p < 0.001). Targeted metabolomic analysis of the liver showed decreased alpha-ketoglutarate abundance (35% p < 0.05) by STZ diabetes that was further decreased following mildronate treatment (50% p < 0.05). For both beta-hydroxybutyrate and succinate levels, STZ diabetes increased hepatic abundance by 50% (p < 0.05 for both), which was restored to control levels by mildronate (p < 0.05 for both). In contrast, brain TCA intermediate abundances were unaffected by either STZ diabetes or mildronate (NS for all). STZ diabetes also decreased abundance of pentose phosphate pathway (PPP) metabolites in the liver (glucose-6-phosphate, 6-phosphogluconolactone, 6-phosphogluconate 50% for all; p < 0.05), which was not restored by mildronate treatment. However, brain PPP metabolite abundance was unchanged by STZ diabetes or mildronate (NS for all). However, mildronate treatment did not affect the increased abundance of brain sorbitol, sorbitol-6-phosphate and glucose-6-phosphate as a result of STZ diabetes. Conclusions: Together, these observations highlight the potential role that metabolic inhibitors, like mildronate, may play in restoring blood glucose for diabetic patients, without a direct effect of tissues that represent obligate consumers of glucose (e.g., brain) whilst manipulating fat oxidation in tissues such as the liver. Full article

Diabetic wounds exhibit impaired immune function, delayed neutrophils recruitment, and heightened infection risk which compromises early infection control and delays healing. We have demonstrated that topical CCL3 treatment restores neutrophil influx, reduces bacterial infection by ~99%, and accelerates wound healing in diabetic mice. As per Food and Drug Administration (FDA) Guidelines for Investigational New Drug (IND), we conducted a 14-day acute toxicity study in diabetic mice following a single topical administration of CCL3 at effective low dose (1 µg) and high dose (10 µg) per wound. Mice were monitored for clinical signs, body weight, and food intake throughout the study period. On day 14, serum biochemistry (ALT, AST, BUN, creatinine, metabolic markers) and histopathology of major organs (liver, kidney, heart, lungs, spleen) were assessed. CCL3-treated diabetic mice exhibited no adverse clinical effects. Hematological and biochemical parameters remained within normal limits, and histopathological analyses revealed no additional organ injury in CCL3-treated groups compared to diabetic control mice. Intriguingly, CCL3-treated mice showed improved ALT levels and reduced hepatic pathology, suggesting hepatoprotective effects and reduced serum IgG, indicating reduced systemic inflammation. Overall, our study demonstrates that diabetic mice tolerate topical CCL3 at doses up to 10 times the effective therapeutic concentration without evidence of systemic organ toxicity. These findings provide strong preclinical support for the translational development of CCL3 as a novel therapy for diabetic wound care. Full article

Background: Obesity is characterized by chronic low-grade inflammation and metabolic disturbances, including an altered tryptophan (Trp) catabolism through the kynurenine pathway (KP). Since the KP is closely linked to immune activity, energy metabolism, and hepatic function, modulating its flux through lifestyle interventions has gained interest as a potential therapeutic strategy. Objective: This exploratory study aimed to investigate the impact of a structured 12-week weight loss program (WLP) on serum KP metabolites in a sample of Mexican women with obesity. Methods: This study involved a pre–post-intervention design conducted in twenty-four women with clinically diagnosed obesity from the Mexican Navy who underwent a structured 12-week weight loss program combining a hypocaloric diet with moderate-intensity aerobic exercise; no control group was included. Anthropometric parameters, serum biochemistry, and circulating levels of Trp, kynurenine (KYN), kynurenic acid (KYNA), and 3-hydroxykynurenine (3-HK) were assessed before and after intervention. Psychological assessments of anxiety and depression were also conducted in a subset of participants. Results: The WLP significantly reduced body weight, BMI, fat mass, fasting insulin, and C-reactive protein levels. Serum concentrations of Trp, KYN, and KYNA decreased, while 3-HK showed a non-significant upward trend. Enzymatic indexes revealed a significant increase in the 3-HK/KYN ratio and a decrease in the KYNA/3-HK ratio, suggesting a shift toward kynurenine monooxygenase (KMO) branch. Notably, higher KYNA-related ratios were inversely associated with depressive symptoms. Conclusions: These findings position the KP as a responsive metabolic interface potentially linking improvements in body composition, liver function, and psychological status during structured weight loss efforts. Full article