Search Results (2,687)

Background: Liver regeneration is essential for restoring hepatic mass after injury or resection, with metabolic reprogramming as a critical driver. Radix Rehmanniae Praeparata (RRP), a traditional Chinese medicine for chronic liver diseases, regulates glucose and lipid metabolism. This study evaluated the effects of RRP on liver regeneration and explored the underlying mechanisms. Methods: A 70% partial hepatectomy (PHx) mouse model was employed, and integrated transcriptomic and metabolomic analyses were conducted to characterize the global features of RRP-induced metabolic reprogramming and its association with hepatocyte proliferation. To further validate these findings, the AML12 hepatocyte cell line and primary mouse hepatocytes were used to identify key targets of RRP. Results: RRP significantly enhanced liver regeneration, as evidenced by the upregulation of hepatocyte proliferation markers. Transcriptomic, metabolomic, and biochemical analyses showed that RRP promoted lipid catabolism and H3K27ac remodeling-dependent hepatocyte proliferation by increasing acetyl-CoA flux. RRP also enhanced carbohydrate consumption and pentose phosphate pathway, as well as protecting mitochondrial integrity, which contribute to both energy production and nucleotide synthesis during cell cycle progression. Notably, RRP-induced AMPK activation was involved in these metabolic reprogramming events, since pharmacological inhibition of AMPK with Compound C attenuated the promotive effects of RRP on liver regeneration. Conclusions: RRP promotes liver regeneration by enhancing metabolic reprogramming mediated by AMPK activation, highlighting its therapeutic potential for metabolic adaptation and postoperative recovery in compromised liver. Full article

(1) Background: this study aimed to determine whether a serum parathyroid hormone (PTH) threshold of 40 pg/mL represents a clinically relevant risk factor for vitamin D (VitD) deficiency and reduced bone mineral density (BMD). It also investigated potential genetic interactions influencing PTH regulation and skeletal health in patients with periodontitis. (2) Methods: a cross-sectional analysis was conducted on 1038 periodontitis patients (35–75 years). Serum PTH, VitD, calcium (Ca), phosphate (P), and urinary parameters were assessed. Dual-energy X-ray absorptiometry (DXA) was used to evaluate BMD in 261 subjects. Vitamin D Receptor (VDR) and estrogen receptor alpha (ERα) polymorphisms were genotyped, and composite genetic risk scores were calculated. Statistical analyses included correlation tests, subgroup comparisons, and regression models. (3) Results: sixty-two percent of individuals had PTH > 40 pg/mL, which was associated with significantly lower 25(OH)D and Ca levels and reduced T-scores (p < 0.05). PTH levels negatively correlated with BMD (Pearson’s r = –0.159, p = 0.0105). Patients with higher ERα polymorphism scores showed increased PTH values (p < 0.05), while VDR variants demonstrated a positive but no significant trend. (4) Conclusions: a PTH threshold of 40 pg/mL identifies individuals at higher risk of VitD deficiency and skeletal fragility, even without overt hypercalcemia. Genetic factors, particularly ERα variants, may contribute to elevated PTH levels, suggesting value in integrating biochemical, densitometric, and genetic screening for early bone health risk stratification. Full article

The objective of this work was to analyze the effect of reducing Fe chelate fertilization (50% and 25% reduction) on soil nutrient content and on different physiological and biochemical parameters in mandarin leaves. The reduction in Fe fertilization efficiently decreased soil Fe content, even in the short-term, without affecting leaf Fe or chlorophyll contents. Reduced iron fertilization increased the accumulation of certain heavy metals in mandarin roots, indicating potential implications for phytoremediation. It is well-established that disturbances of foliar Fe homeostasis can impair the photosynthetic process. Nevertheless, reduction in Fe supply did not negatively affect photosynthetic performance (based on chlorophyll fluorescence parameters), nor did it influence the stress levels of the trees, as indicated by lipid peroxidation. In addition, reduced iron fertilization did not alter peroxidase activity, which is considered a biochemical marker of Fe nutrition in plants. Finally, mandarin production was evaluated over two consecutive years, with no significant variations among the different iron treatments, whereas only minor differences were observed in fruit quality. Overall, these results indicate that reducing Fe fertilization is a feasible strategy, as it does not adversely affect the physiological processes or yield of mandarin trees. Furthermore, this agricultural practice can enhance nutrient use efficiency, thereby contributing to the reduction in soil and aquifer contamination while providing economic benefits to farmers. Full article

Background/Objective: Fetal growth restriction (FGR) is a condition in which the fetus fails to grow as expected for gestational age, and its growth is restricted. This study aimed to investigate the role of SCUBE-1, a new ischemia marker, in the diagnosis of late-onset FGR and its contribution to its pathophysiology. Methods: The data of 33 cases with late-onset fetal growth restriction were compared with the data of 33 cases without any pregnancy complications. Only cases beyond 32nd weeks of gestation were included. Fetal sonography and maternal/fetal vascular Doppler parameters were recorded. Maternal serum SCUBE-1 and ischemia-modified albumin (IMA) levels were measured. Results: The mean maternal was 29.82 ± 5.66 years old in the study group and 30.15 ± 4.85 years old in the control group. The gestational ages in both groups were comparable. Maternal serum IMA levels were found to be similar in the late-onset FGR and control groups. However, serum SCUBE-1 levels were found to be statistically significantly higher in the study group than in the control group. In cases where the SCUBE-1 level was above 1.64, the sensitivity for predicting late-onset FGR was 93.9% and the specificity was 60.6% (AUC 0.891, p < 0.001, 95% CI 0.811–0.970). Conclusions: This study reported a significant increase in SCUBE-1, which may be important in determining oxidative stress in late-onset FGR cases. SCUBE-1 was an effective and highly sensitive marker that could provide results in a maternal blood sample within an average of one hour and may be useful in the biochemical diagnosis of late-onset FGR. It may also be a useful serum marker for timing and planning delivery. Full article

Osteoarthritis (OA), a degenerative joint disease primarily affecting the hips and knees, is characterized by multifactorial dysregulation of chondrocyte homeostasis and currently lacks curative treatment options. Intra-articular hyaluronic acid (HA) injections have clinically provided symptomatic relief for three decades; however, HA’s rapid in vivo degradation by free radicals and hyaluronidases limits its efficacy. We hypothesized that adding niacinamide (vitamin B3) to linear HA hydrogels would provide ancillary anti-inflammatory and anti-catabolic properties, thereby improving HA-based viscosupplementation therapy. This preliminary preclinical mechanistic study investigated the functional effects of incorporating niacinamide into linear HA-based hydrogels using in vitro cellular models. Initially, Raw 264.7 macrophages and C28/I2 or SW1353 human chondrocytes were pre-treated with varying concentrations of HA/B3, with or without lipopolysaccharide (LPS) or interleukin-1β (IL-1β), respectively. Subsequently, pro-inflammatory and pro-catabolic markers were quantified biochemically. Results demonstrated that HA/B3 hydrogels exhibited enhanced functional stability compared to HA alone and possessed significant anti-inflammatory and anti-catabolic properties, without inducing cytotoxicity in either cell line. In Raw 264.7 macrophages, HA/B3 inhibited LPS-induced tumor necrosis factor-α (TNF-α) release and suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression. In vitro, HA/B3 hydrogels reduced IL-1β-induced IL-6 production in primary chondrocytes by 16% and suppressed PGE₂ concentration in both macrophages and chondrocytes by 60%, effects superior to HA alone. Finally, a rat primary articular chondrocyte model suggested slight anti-hypertrophic effects of HA/B3 in vitro. Collectively, these findings suggest that HA/B3 hydrogels possess anti-arthritic potential, highlighting a novel strategy for next-generation viscosupplement systems. Full article

Background/Objectives: Galectins contribute to the pathogenesis of osteoarthritis (OA) by amplifying inflammatory and catabolic signaling, yet targeted therapeutic approaches remain limited. Three Dimensional (3D) models offer a promising platform to study human OA pathophysiology and evaluate novel interventions. Methods: We established 3D pellet cultures derived from human OA chondrocytes to investigate galectin-induced extracellular matrix (ECM) remodeling and the chondroprotective potential of phytochemicals. OA pellets were stimulated with individual galectins (Gal-1, -3, -4, -8) or a Gal-1/-3/-8 mixture, followed by co-treatment with Brazilin, Diacerein, Quercetin, Resveratrol, or Avocado-Soybean Unsaponifiables (ASU). Morphological, histological, biochemical, and gene expression analyses were performed to assess tissue integrity and molecular responses. Results: Galectin treatment induced pronounced pellet shrinkage, matrix depletion, and upregulation of matrix-degrading enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4), while suppressing matrix synthesis markers (COL2A1, COL1A1), highlighting their cooperative catabolic effects. Co-treatment with phytochemicals conferred differential protection: Brazilin and Diacerein most consistently preserved pellet size, reduced matrix-degrading gene expression, and attenuated pro-MMP-13 secretion. Resveratrol restored histological matrix density but failed to suppress pro-MMP-13 secretion. Notably, no phytochemical fully restored COL2A1 expression under galectin-induced stress. Conclusions: Our study identifies Brazilin, Diacerein, and Resveratrol as promising modulators of galectin-driven cartilage degeneration and demonstrates the translational potential of patient-derived chondrogenic pellets as a human-relevant platform for preclinical drug evaluation in OA. The 3D culture effectively recapitulates key aspects of OA pathophysiology and offers a robust system to advance therapeutic discovery targeting ECM remodeling. Full article

Background/Objectives: This research aims to offer significant insights into the prospective application of bioactive hydrogels composed of alginate, gelatin, and grape skin extract from Serbia (GSE) for treating diabetic wounds, supporting the circular economy and environmental protection. Methods: An acute dermal irritation study was conducted according to OECD guidelines, revealing no visible signs of erythema or edema, confirming the hydrogel’s dermal safety. Afterwards, male Wistar rats were divided into four groups: untreated control (NC), silver sulfadiazine-treated (PC), hydrogel without extract (HG), and hydrogel with GSE (HG + GSE). Wound healing was assessed through a comprehensive approach that included macroscopic wound contraction; biochemical assessment of hydroxyproline content and oxidative stress markers (TBARS, SOD, CAT, GSH); quantification of inflammatory cytokines (TNF-α, IL-6); and histological examination of skin samples using hematoxylin–eosin (H&E) and Masson’s trichrome staining. Results: Daily HG+GSE application over 15 days accelerated wound closure, reaching 99.3% by day 15, surpassing PC (91.2%) and HG (87.7 ± 2.1%). Hydroxyproline levels followed a treatment-dependent pattern, with HG+GSE achieving the highest values throughout, reaching 6.78 ± 0.1 µg/mg dry tissue by day 15—more than double NC. The HG+GSE reduced lipid peroxidation while enhancing enzymatic and non-enzymatic antioxidant defenses and markedly lowered pro-inflammatory cytokine levels, indicating systemic anti-inflammatory activity. Histological analysis revealed faster re-epithelialization, increased collagen deposition, and more organized tissue architecture in the HG+GSE group. These outcomes are attributed to the sustained release of bioactive polyphenols such as naringin, caffeic acid, and epicatechin. Conclusions: Overall, this GSE-based hydrogel presents a multifunctional, biocompatible, sustainable, and effective strategy for diabetic wound care. Full article

Conventional plastics are widely utilised across industrial sectors and in consumer products. However, the growing use of plastics has led to plastic pollution, including the formation of nanoplastics (NPs), which are harmful to aquatic organisms. Bioplastics are emerging alternatives. They are renewable and/or biodegradable and are supposed to be more environmentally friendly. However, the toxicity and environmental fate of bioplastics are not yet fully understood. This study evaluated the toxicity and fate of commercially available plain or fluorescent polylactic acid (PLA) NPs (250 nm) on aquatic organisms. Confocal microscopy demonstrated the uptake of fluorescent PLA NPs by the test organisms, marine rotifers (Brachionus plicatilis), brine shrimps (Artemia salina) and zebrafish (Danio rerio) embryos. However, the results of the bioassays indicate that plain PLA NPs did not induce acute toxicity in either of the two zooplankton species and did not cause substantial mortality, malformations, or hatching delays in zebrafish embryos at the tested concentrations (up to 100 mg/L). However, brine shrimp showed a significant decrease in ingestion capability. The biochemical biomarkers, catalase activity induction, as an indicator of oxidative stress, and acetylcholinesterase inhibition, as a marker of neurotoxicity, showed no significant alterations compared to the control of both zooplankton species and that of zebrafish embryos. Overall, the findings suggest a pattern of no acute and low sublethal toxicity for the tested plain PLA NPs in the studied organisms. Nonetheless, further research is imperative to comprehensively assess the environmental fate of bioplastics found in various consumer products, as these may contain harmful chemical additives, as well as the effects of prolonged exposure and their impact on physiological parameters, ensuring informed decisions before their widespread commercialisation and presence in the environment. Full article

Background and Objectives: Despite modern therapy algorithms, ST-elevation myocardial infarction (STEMI) substantially contributes to cardiovascular morbidity and mortality worldwide. Early Risk assessment is crucial to guide therapy allocation, especially in countries with limited healthcare resources. Electrocardiographic parameters such as QRS fragmentation (fQRS) evolved as an important prognostic marker. The underlying mechanisms and specific risk factors for the occurrence of fQRS in patients with STEMI undergoing PCI have not been analyzed yet. Materials and Methods: Between 09/2020 and 06/2021, out of 179 consecutive patients with STEMI undergoing primary percutaneous coronary intervention (pPCI), 122 patients were included in this study. The occurrence of fQRS was analyzed and correlated to clinical as well as biochemical parameters. Results: In this population, the fQRS pattern was present in 33.6% (n = 41) of patients. Besides gender, no statistically significant differences in baseline characteristics or comorbidities were observed between the two groups. In univariable logistic regression analysis, both glomerular filtration rate (GFR) (p = 0.050) and C-reactive protein (CRP) (p = 0.014) were significantly associated with the presence of fQRS. However, in the multivariable logistic regression model, only CRP levels on admission remained independently associated with fQRS (OR = 3.44, 95% CI: 1.95; 6.05), (p = 0.029). Conclusions: In this analysis, a correlation between fQRS and CRP levels in patients with STEMI undergoing pPCI could be demonstrated. Consequently, fQRS might serve as a marker for extensive inflammation in the context of myocardial ischemia. Full article

Background: Chitosan and Lavandula angustifolia (lavender) exhibit antibacterial, antioxidant, and anti-inflammatory effects, making them potential candidates for managing infected wounds. This study investigated the therapeutic efficacy of a chitosan nanoparticle-loaded hydrogel, lavender extract, and their combination in treating Staphylococcus aureus-infected wounds in rats. Methods: Forty-eight male Sprague-Dawley rats (250–350 g, 8–10 weeks) were divided into six groups: healthy control, infected untreated, Fucidin, lavender extract, chitosan hydrogel, and chitosan–lavender combination. Wound healing was evaluated on days 3, 7, and 14 using clinical assessment, histopathology, and biochemical markers. Non-parametric statistical tests were applied, with significance set at p < 0.05. Results: The chitosan–lavender group showed the most pronounced healing response, with significantly reduced WBC counts, lower levels of TNF-α, IL-6, and MDA, and enhanced SOD activity (p < 0.05). Histological analysis confirmed superior re-epithelialization, granulation tissue development, collagen deposition, and wound contraction in chitosan-based treatments, particularly their combination, compared to lavender or Fucidin alone (p < 0.001). Inflammatory infiltrates, angiogenesis, necrosis, and hemorrhage were also notably reduced across treated groups. Conclusion: Combining chitosan hydrogel with lavender extract exerts synergistic antibacterial and wound healing effects, offering a promising alternative therapy for infected wounds. Full article

Objectives: This study aimed to analyze metabolites changes in elite freestyle wrestlers during three specific training phases—pre-training, peak training, and recovery adjustment—through serum metabolomics analyses and biochemical indicator testing, providing preliminary insights for selecting effective functional assessment metrics. Methods: Five male wrestlers (20.40 ± 2.07 years) and five female wrestlers (19.60 ± 0.55 years) were enrolled. Morning fasting venous blood samples were collected before training, at peak training intensity, and after training adjustment and recovery. Serum metabolomic analyses using ¹H nuclear magnetic resonance (¹H NMR) spectroscopy and assessment of biochemical indicators were performed. Results: The metabolomic analysis identified six significantly altered serum biomarkers in male wrestlers and three in females across different training phases. These differential metabolites are primarily implicated in the regulation of energy and amino acid metabolism pathways. Additionally, significant alterations in conventional biochemical indices were observed. Conclusions: Metabolomic markers provide a more accurate and comprehensive reflection of metabolic characteristics in freestyle wrestlers, offering a promising complementary approach to traditional biochemical assessments for monitoring physiological states. Full article

Long-duration space missions expose astronauts to galactic cosmic radiation (GCR), a complex spectrum of high-charge, high-energy (HZE) ions that pose significant risks of chronic tissue injury. To model these effects, we examined intestinal outcomes in wild-type mice 5 months after low-dose (50 cGy) 33-ion mixed-field GCR simulation (GCRsim). GCRsim induced sustained DNA double-strand breaks (DSBs) and oxidative stress, as shown by elevated γH2AX foci and 4-HNE staining. Intestinal epithelial cells (IECs) exhibited pronounced senescence, marked by increased SA-β-gal activity, p16 upregulation, LaminB1 loss, and induction of senescence-associated secretory phenotype (SASP) cytokines (Cxcl10, IL-6, IL-1β, Icam1). GCRsim also elevated circulating LINE-1 DNA and reduced expression of DNA-degrading nucleases (DNase2, TREX1), indicating impaired extracellular DNA clearance. Targeted molecular study revealed persistent activation of the cGAS–STING pathway, with elevated cGAS, STING, pTBK1, pIKKα/β, and nuclear pIRF3, pIRF7, and p65, consistent with chronic innate immune signaling. Functionally, GCRsim altered nutrient absorption gene expression—upregulating glucose transporters (Slc2a2, Slc2a5, Slc5a1) and gut hormones (Cck, Gip), while downregulating cholesterol/fat transporters (Npc1, Npc1l1). Biochemical markers supported intestinal injury, with decreased serum citrulline and increased intestinal fatty acid-binding protein (I-FABP), indicating barrier compromise. Collectively, these findings demonstrate that GCRsim drives sustained intestinal dysfunction, highlighting the need for countermeasures to protect GI health during deep-space missions. Full article

Introduction: Polycystic ovary syndrome (PCOS) is associated with obesity, numerous metabolic complications, and an increased risk of cardiovascular disease. Adipokines, secreted by adipose tissue, may contribute to the development of these cardiometabolic disturbances. The aim of this study was to investigate the adipokine levels and their relationship with metabolic status in adolescent girls with PCOS. Patients and Methods: This cross-sectional study included 66 adolescent girls with PCOS (mean age: 16.5 ± 1.08 years; study group, SG) and 30 regularly menstruating girls (mean age: 16.2 ± 1.37 years; control group, CG) recruited between 2012 and 2017. All participants underwent physical examination, body composition assessment, liver ultrasonography, and biochemical and hormonal evaluations. Fasting venous blood samples were collected to determine the adipokine profile, and the leptin-to-adiponectin ratio (L/A) was calculated. Results: Compared with the control group, the PCOS group demonstrated significantly lower adiponectin (p = 0.019) and vaspin (p = 0.037) concentrations, and higher RBP-4 levels (p = 0.048). Positive correlations were observed between adiponectin, apelin, and omentin, while negative correlations were found between leptin and L/A and HDL cholesterol levels in the SG. Omentin showed a negative association, and leptin and L/A a positive association, with triglyceride concentration. In the SG, resistin and visfatin levels were negatively correlated with total cholesterol, and resistin also showed a negative correlation with LDL cholesterol. In patients with PCOS, adverse associations were observed between carbohydrate metabolism parameters and insulin resistance indices, while insulin sensitivity indices correlated positively with adiponectin and omentin concentrations. Visfatin levels in the SG correlated negatively with QUICKI. Conclusions: The adipokine profile of adolescent girls with PCOS differs from that of regularly menstruating peers, particularly in adiponectin, RBP-4, and vaspin concentrations. However, the absence of significant correlations between RBP-4 and vaspin and lipid or carbohydrate metabolism parameters suggests that these adipokines are not reliable markers of metabolic disturbances in adolescent girls with PCOS. Full article

Background: Malnutrition is a significant national health problem in countries with low and intermediate incomes and was announced in the United Nations’ 2030 Agenda for Sustainable Development Goals. Chemotherapy may have adverse effects on nutritional health issues and quality of life experience, particularly in patients with gastrointestinal (GIT) cancer. Our research’s objective was to determine the beneficial effects of oral nutrition supplements on nutritional status assessed by maintenance of whole-body composition and patient-generated subjective global assessment (PG-SGA) in all GIT cancer patients treated with chemotherapy medications. Methods: Among the patients, the nutrition support (NS) group (n = 75) received 500 kcal daily of a balanced oral nutrition supplement formula for 12 weeks, while the control (C) group (n = 75) did not. Anthropometric measures, whole-body composition, nutritional status biomarkers, and the PG-SGA questionnaire were assessed. Additionally, this study analyzed whole-body composition, skeletal mass, fat mass, laboratory data, the complete lipid profile, albumin, total protein, adverse effects, and therapy delays. Results: After 12 weeks, the NS group showed a significant increase in body weight, with a mean difference of 1.27 ± 3.39, while the C group showed a mean difference of only 0.15 ± 0.42. Moreover, fat mass increased in the NS group, showing a mean difference of 0.55 ± 3.69, while the C group showed a fat mass loss with a mean difference of −0.21 ± 2.93. The fat mass index (FMI) indicated statistical significance between the two groups. There was a statistically significant difference in the lean mass index between the two groups, favoring a steady increase in the NS group. The NS group showed improvements in the PG-SGA and nutritional biochemical markers, such as albumin. The initial findings from our study include data from a total of 150 patients, including 75 patients in the NS group and 75 patients in the C group. These results are consistent with earlier research. Conclusions: Early oral nutrition supplements for GIT cancer may enhance nutritional outcomes and reduce the delay of disease-related therapy. Additionally, they may help maintain body composition. Full article

Background: Febrile seizures (FS) are the most common seizures in childhood, yet their clinical, biochemical, and genetic risk factors are still being clarified. This study aimed to provide a comprehensive evaluation of FS from clinical, laboratory, and genetic perspectives. Methods: In this prospective cohort study, 124 children aged 6 months to 5 years presenting with FS and 93 febrile controls without seizures were evaluated. Clinical features, laboratory parameters (including trace elements and hormonal markers), and genetic analysis using a 37-gene epilepsy panel were assessed. Multivariate logistic regression analysis was performed to identify independent predictors of FS, complex FS, and recurrent seizures. Results: Children with FS had significantly lower serum sodium, vitamin D, and zinc levels compared to controls. Multivariate analysis identified low sodium and low vitamin D levels as independent risk factors for FS. In the subgroup analysis, lower sodium and vitamin D levels and elevated ferritin levels were independently associated with complex FS. Lower serum zinc levels were significantly associated with seizure recurrence. Genetic analyses revealed pathogenic or likely pathogenic variants in 15.7% of patients with FS, predominantly involving SCN1A and PCDH19 genes. Patients with pathogenic variants also exhibited significantly lower levels of zinc, and selenium compared to genetically negative patients. Conclusions: This study highlights that metabolic disturbances, particularly involving sodium, vitamin D, and zinc, play a crucial role in FS occurrence, complexity, and recurrence. Ferritin may serve as a more sensitive indicator of inflammatory processes influencing seizure severity compared to CRP. Furthermore, genetic predispositions, especially SCN1A and PCDH19 variants, may underlie susceptibility in a subset of children. Routine evaluation of biochemical markers and consideration of genetic testing in selected cases may enhance individualized management strategies for FS. Full article