Search Results (1,030)

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

Background: The differential effects of post-exercise rehydration beverages on inflammatory processes and organ protection remain incompletely characterized. This study investigated how beverages with distinct compositions influence urinary biomarkers following endurance exercise. Methods: In a randomized crossover design, eight trained male runners performed 6000 m pace running followed by consumption of 500 mL of either: water (Drink 1), hypotonic sports drink (Drink 2, 200 mOsm/L), oral rehydration solution (Drink 3, 270 mOsm/L), or modified hypotonic formulation (Drink 4, 200 mOsm/L). After 60 min, participants completed a 1000 m time trial. Urine samples were collected at baseline, post-6000 m, and post-1000 m for analysis of biochemical parameters and inflammatory cytokines. Results: No significant differences in 1000 m performance were observed between trials. Drink 3 significantly reduced creatinine and uric acid excretion compared to other beverages (p < 0.05), suggesting decreased waste product elimination. Creatinine-corrected intestinal fatty acid-binding protein values were lower with Drinks 2 and 3, indicating potential intestinal protection. Notably, Drink 4 showed modest but significant enhancement of IL-4 excretion (p < 0.05, ηp² = 0.347), demonstrating beverage-specific modulation of anti-inflammatory cytokines with moderate effect sizes. Conclusions: Different beverage formulations exert distinct effects on waste product elimination, intestinal organ damage markers, and inflammatory cytokine profiles. These findings suggest that beverage selection should be tailored to specific recovery priorities and training contexts. Full article

RNA-binding proteins (RBPs) are critical regulators of post-transcriptional processes, playing essential roles in nutrient metabolism and metabolic homeostasis. This literature review explores how RBPs influence the metabolism of glucose, lipid, and amino acid metabolism by controlling processes like mRNA stability and translation regulation. The dysregulation of RBPs, including HuR, PTB, and YTHDF1, is linked to metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease. Advances in techniques like TREX technology and transcriptome analysis have deepened our understanding of RBP functions. Additionally, RBPs show promise as potential biomarkers and targets for new therapies. Future research directions in RBPs could focus on tissue-specific regulation and nutrient–RBP interactions. This could pave the way for more personalized treatments and improved metabolic health. Full article

There is a present need to develop alternative biotherapeutic drugs to mitigate the exacerbated inflammatory immune responses characteristic of sepsis. The potent endotoxin lipopolysaccharide (LPS), a major component of Gram-negative bacterial outer membrane, activates the immune system via Toll-like receptor 4 (TLR4), triggering macrophages and a persistent cascade of inflammatory mediators. Our previous studies have demonstrated that Fh15, a recombinant member of the Fasciola hepatica fatty acid binding protein family, can significantly increase the survival rate by suppressing many inflammatory mediators induced by LPS in a septic shock mouse model. Although Fh15 has been proposed as a TLR4 antagonist, the specific mechanisms underlying its immunomodulatory effect remained unclear. In the present study, we employed a quantitative proteomics approach using tandem mass tag (TMT) followed by LC-MS/MS analysis to identify and quantify differentially expressed proteins that participate in signaling pathways downstream TLR4 of macrophages, which can be dysregulated by Fh15. Data are available via ProteomeXchange with identifier PXD065520. Based on significant fold change (FC) cut-off of 1.5 and p-value ≤ 0.05 criteria, we focused our attention to 114 proteins that were upregulated by LPS and downregulated by Fh15. From these proteins, TNFα, IL-1α, Lck, NOS2, SOD2 and CD36 were selected for validation by Western blot on murine bone marrow-derived macrophages due to their relevant roles in the NF-κB, iNOS, oxidative stress, and phagosome signaling pathways, which are closely associated with sepsis pathogenesis. These results suggest that Fh15 exerts a broad spectrum of action by simultaneously targeting multiple downstream pathways activated by TLR4, thereby modulating various aspects of the inflammatory responses during sepsis. Full article

This review explores the dual role of reactive oxygen species (ROS) and free radicals in the pathogenesis of endometriosis, aiming to deepen our understanding of these processes through a systematic literature review. To assess the induction and involvement of ROS in endometriosis, we conducted a comprehensive literature review using Cochrane Libraries, EMBASE, Google Scholar, PubMed, and SCOPUS databases. Of 30 qualifying papers ultimately reviewed, 28 reported a significant contribution of ROS to the pathogenesis of endometriosis, while two found no association. The presence of ROS in endometriosis is associated with infertility, irregular menstrual cycles, painful menstruation, and chronic pelvic discomfort. Among individual ROS types studied, hydrogen peroxide was most frequently investigated, followed by lipid peroxides and superoxide radicals. Notable polymorphisms associated with ROS in endometriosis include those for AT-rich interactive domain 1A (ARID1A) and quinone oxidoreductase 1 (NQO1) isoforms. Key enzymes for ROS scavenging and detoxification include superoxide dismutase, glutathione, and glutathione peroxidase. Effective inhibitors of ROS related to endometriosis are vitamins C and E, astaxanthin, fatty acid-binding protein 4, cerium oxide nanoparticles (nanoceria), osteopontin, sphingosine 1-phosphate, N-acetyl-L-cysteine, catalase, and a high-antioxidant diet. Elevated levels of ROS and free radicals are involved in the pathogenesis of endometriosis, suggesting that targeting these molecules could offer potential therapeutic strategies. Full article

The focus on selecting broilers for rapid growth rates and enhanced breast muscle yield has resulted in a decline in meat quality. The differences in carcass characteristics and meat quality between Hubbard white broilers (HWs, a commercial breed) and Xueshan chickens (XSs, an indigenous breed) at market age were analyzed to determine the potential mechanisms responsible for these differences. The results show that HWs exhibited significantly better carcass performance than XSs, including the larger weight of the carcass, the breast muscle, and the thigh muscle (p < 0.01). In addition, based on HE staining analysis, HWs’ breast muscles had a considerably larger average myofiber area and diameter than those of XSs (p < 0.01). Furthermore, the physical characteristics of the meat revealed that XSs had higher redness and yellowness and also higher lightness. HW meat had a higher pH and thermal loss, but a lower shear force and drip loss than XS meat (p < 0.01). The content of saturated fatty acids (SFAs) and polyunsaturated fatty acids (PUFAs) was, remarkably, lower in the breast muscles of HWs than of XSs (p < 0.01). In contrast, HWs had a larger concentration of monounsaturated fatty acids (MUFAs) than XSs (p < 0.01). Finally, the breast muscles of XSs had lower levels of mRNA expression for genes linked to lipid metabolism, such as fatty acid binding protein 4 (Fabp4) and peroxisome proliferator-activated receptor alpha (Pparα), and had higher levels of the phosphofructokinase muscle type (Pfkm) compared to HWs (p < 0.01). These results indicate that a lower carcass yield was observed in XSs compared with HWs, but that XSs showed better performance in terms of meat quality than HW. Full article

As tumor research has deepened, the deregulation of cellular metabolism has emerged as yet another recognized hallmark of cancer. Tumor cells adapt different biochemical pathways to support their rapid growth, proliferation, and invasion, resulting in distinct anabolic and catabolic activities compared with healthy tissues. Certain metabolic shifts, such as altered glucose and glutamine utilization and increased de novo fatty acid synthesis, are critical early on, while others may become essential only during metastasis. These metabolic adaptations are closely shaped by, and in turn remodel, the tumor microenvironment, creating favorable conditions for their spread. Anticancer metabolic strategies should integrate pharmacological approaches aimed at inhibiting specific biochemical pathways with well-defined dietary interventions as adjunctive therapies, considering also the role of gut microbiota in modulating diet and treatment responses. Given the established link between the consumption of foods rich in saturated fatty acids and sugars and an increased cancer risk, the effects of diet cannot be ignored. However, current evidence from controlled and multicenter clinical trials remains insufficient to provide definitive clinical recommendations. Further research using modern omics methods, such as metabolomics, proteomics, and lipidomics, is necessary to understand the changes in the metabolic profiles of various cancers at different stages of their development and to determine the potential for modifying these profiles through pharmacological agents and dietary modifications. Therefore, clinical trials should combine standard treatments with novel approaches targeting metabolic reprogramming, such as inhibition of specific enzymes and transporters or binding proteins, alongside the implementation of dietary restrictions that limit nutrient availability for tumor growth. However, to optimize therapeutic efficacy, a precision medicine approach should be adopted that balances the destruction of cancer cells with the protection of healthy ones. This approach, among others, should be based on cell type-specific metabolic profiling, which is crucial for personalizing oncology treatment. Full article

Background: The gut–brain axis (GBA) has been demonstrated to be involved in normal neurodevelopment, with its dysfunction potentially contributing to the onset of mental disorders. In this systematic review and meta-analysis, we aimed to examine the relationship between levels of specific biomarkers of intestinal permeability or inflammation and scores of depressive symptoms or suicidality. Methods: All studies investigating the link between depressive symptoms and/or suicidality and biomarkers associated with intestinal permeability or inflammation were included. Studies providing data for comparisons between two groups—depressive or suicidal patients vs. healthy controls, or suicidal vs. non-suicidal patients—were included in the meta-analysis. Studies examining the correlation between depressive symptoms and biomarker levels were also included into the review. Data were independently extracted and reviewed by multiple observers. A random-effects model was employed for the analysis, and Hedge’s g was pooled for the effect size. Heterogeneity was assessed using the I² index. Results: Twenty-two studies provided data for inclusion in the meta-analysis, while nineteen studies investigated the correlation between depressive symptoms and biomarker levels. For depressive symptoms, when compared to the controls, patients showed significantly increased levels of intestinal fatty acid-binding protein (I-FABP) (ES = 0.36; 95% CI = 0.11 to 0.61; p = 0.004; I² = 71.61%), zonulin (ES = 0.69; 95% CI = 0.02 to 1.36; p = 0.044; I² = 92.12%), antibodies against bacterial endotoxins (ES = 0.75; 95% CI = 0.54 to 0.98; p < 0.001; I² = 0.00%), and sCD14 (ES = 0.11; 95% CI = 0.01 to 0.21; p = 0.038; I² = 10.28%). No significant differences were found between the patients and controls in levels of LPS-binding protein (LBP) and alpha-1 antitrypsin (A-1-AT). For suicidality, four studies were identified for quantitative analysis, three of which focused on I-FABP. No significant differences in I-FABP levels were observed between suicidal patients and the controls (ES = 0.24; 95% CI = −0.30 to 0.79; p = 0.378; I² = 86.44%). Studies investigating the correlation between depressive symptoms and levels of intestinal permeability and inflammation biomarkers did not provide conclusive results. Conclusions: A significant difference was observed between patients with depressive symptoms and controls for biomarkers of intestinal permeability (zonulin, which regulates tight junctions), inflammatory response to bacterial endotoxins (antibodies to endotoxins and sCD14—a soluble form of the CD14 protein that modulates inflammation triggered by lipopolysaccharides), and acute intestinal epithelial damage (I-FABP, released upon enterocyte injury). Studies investigating suicidality and related biomarkers were limited in number and scope, preventing definitive conclusions. Overall, these findings suggest that biomarkers of gut permeability represent a promising area for further investigation in both psychiatric and forensic pathology. They may have practical applications, such as supporting diagnostic and therapeutic decision-making in clinical settings and providing pathologists with additional information to help determine the manner of death in forensic investigations. Full article

Fatty acids (FAs) play a crucial role in human physiology, including energy production and serving as signaling molecules. However, a dysregulation in their balance can lead to multiple disorders, such as obesity and metabolic syndrome. These pathological conditions alter the balance between the heart’s energetic substrates, promoting an increased reliance on FAs and decreased cardiac efficiency. A therapeutic application of a non-psychotropic phytocannabinoid, cannabigerol (CBG), seems to be a promising target since it interacts with different receptors and ion channels, including cannabinoid receptors—CB₁ and CB₂, α2 adrenoceptor, or 5-hydroxytryptamine receptor. Therefore, in the current study, we evaluated a concentration-dependent effect of CBG (2.5 µM, 5 µM, and 10 µM) on H9c2 cardiomyocytes in lipid overload conditions. Gas–liquid chromatography and Western blotting techniques were used to determine the cellular lipid content and the level of selected proteins involved in FA metabolism, glucose transport, and the insulin signaling pathway. The glucose uptake assay was performed using a colorimetric method. Eighteen-hour CBG treatment in the highest concentration (10 µM) significantly diminished the accumulation of diacylglycerols (DAGs) and the saturation status of this lipid fraction. Moreover, the same concentration of CBG markedly decreased the level of FA transporters, namely fatty acid translocase (CD36) and plasma membrane fatty acid-binding protein (FABPpm), in the presence of palmitate (PA) in the culture medium. The results of our experiment suggest that CBG can significantly modulate lipid storage and composition in cardiomyocytes, thereby protecting against lipid-induced cellular dysfunction. Full article

Poly-L-lactic acid (PLLA) filler, which increases volume and collagen synthesis, is used for skin rejuvenation. Subcutaneous adipose tissue (SAT) contains precursors that differentiate into mature adipocytes that secrete adiponectin, which modulates SAT function and increases adipogenesis. During aging, adiponectin and precursor cell functions decrease, reducing adipogenesis and facial volume. Adiponectin also increases collagen synthesis by stimulating fibroblasts. After hydrogen peroxide treatment to induce senescent adipocytes (3T3-L1) and aged skin, follow-up PLLA treatment increased adipogenesis by stimulating the nuclear factor erythroid-2-related factor 2 (NRF2)/peroxisome proliferator-activated receptor gamma (PPARγ)/CCAAT/enhancer binding protein alpha (C/EBPα) pathway. This resulted in increased adiponectin secretion, which promoted collagen synthesis and mitigated the loss of SAT volume. In the senescent adipocyte, PLLA increased NRF2/PPARγ/C/EBPα, adipogenesis factors (fatty acid binding protein 4, lipoprotein lipase, and cluster of differentiation 36), lipogenesis factors (ATP citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase), adiponectin, and lipid droplet size. Treatment of senescent fibroblasts with conditioned medium from PLLA-treated adipocytes increased collagen1 and 3 and decreased matrix metalloproteinase1 and 3 expressions. Similarly, PLLA increased NRF2/PPARγ/C/EBPα, adipogenesis, and lipogenesis factors in aged mouse SAT. Also, PLLA increased adiponectin and adipocyte numbers without hypertrophy and increased collagen accumulation and dermal thickness. In summary, PLLA increased adipogenesis and adiponectin, which increased the volume of SAT and collagen synthesis, thereby rejuvenating aged skin. Full article

Background/Objectives: Calprotectin and intestinal fatty acid-binding protein (IFABP) may reflect the intestinal maturation process of very preterm infants (VPI) but have also been associated with gut inflammation. To establish normative values for fecal calprotectin (FC) and urinary intestinal fatty acid-binding protein (uIFABP) in VPI and to study their correlations with demographic and clinical factors. Methods: A cohort of VPI (born before or at 32.0 weeks of gestation) was recruited in two neonatal intensive care units. Urine and fecal samples were collected at 1, 4 and 8 weeks of life to measure urinary IFABP (normalized to creatinine as uIFABP/Cr) and FC, respectively. UIFABP was determined by ELISA and FC by fluoroenzyme immunoassay. Results: 194 newborns had at least one valid biomarker measurement. The study cohort mean gestational age was 28.9 ± 2.3 weeks and mean birth weight 1178 ± 365 g. Although uIFABP/Cr concentrations differed between the two centres, they were negatively correlated with gestational age, with a statistically significant correlation observed in both centres at week 4 (Hospital Clínic: Spearman’s rho −0.500; p = 0.000 and Hospital Sant Joan de Déu: Spearman’s rho −0.474; p = 0.000). Conversely, FC showed a positive significant correlation at the same time point (Spearman’s rho 0.302; p = 0.006). At week one, FC increased with antibiotic exposure (28 mcg/g of stool per antibiotic day, 95%CI 3–57; p = 0.028). FC at week 4 was inversely correlated with mother’s own milk (MOM) exposure during the first month (Spearman’s rho −0.253; p = 0.023). Conclusions: uIFABP/Cr and FC are associated with gestational age at 4 weeks and FC is also influenced by antibiotic treatment and MOM exposure. Full article

Background/Objectives: Hepatic steatosis, characterized by abnormal fat accumulation in the liver, is a major health concern with limited effective treatments. Goat milk whey proteins have demonstrated various therapeutic benefits. This study aimed to evaluate the hepatoprotective effects of goat whey protein hydrolysate (GWPH) on high-fructose corn syrup (HFCS)-induced hepatic steatosis in a murine model. Methods: The GWPH was prepared through enzymatic hydrolysis using Alcalase^® and divided into fractions: GWPH03 (<3 kDa), GWPH0310 (3–10 kDa), GWPH1030 (10–30 kDa), and GWPH30 (>30 kDa). These fractions were administered to respective GWPH treatment groups at 200 mg/kg b.w/day via intragastric gavage for 8 weeks, with HFCS provided to all groups except the Naïve group. After dietary intervention, an oral glucose tolerance test (OGTT) was performed, and the mice were then sacrificed for further analysis. Results: Our results demonstrate that GWPH mitigates HFCS-induced hepatic steatosis, reduces body weight gain, improves glucose homeostasis, alleviates liver injury, and regulates hepatic lipid metabolism. Notably, GWPH treatment significantly suppressed hepatic fatty acid synthase (FASN) expressions, indicating reduced de novo lipogenesis (DNL). Molecular docking of the identified peptides from GWPH—particularly PFNVYNVV, which showed strong binding affinity for KHK—suggests that it has potential as a competitive inhibitor of fructose metabolism. Conclusions: Collectively, our findings suggest that GWPH and its derived peptides could be promising candidates for managing hepatic steatosis and related metabolic abnormalities. Full article

Background: Optimal tacrolimus dosing in the early post-transplant period is still challenging. We prospectively studied the possible associations between selected parameters of recipient body composition, markers of intestinal permeability and tacrolimus dosing and blood level in kidney transplant recipients (KTRs) treated with three different tacrolimus formulations. Methods: When discharged from hospital immediately after kidney transplantation, markers of intestinal permeability, body composition parameters and tacrolimus blood level were assessed in 165 KTRs treated with Prograf, Advagraf or Envarsus. Results: In the stepwise multivariate analysis performed in patients treated with Prograf, only age independently influenced the tacrolimus exposure expressed as area under the curve (AUC). In patients treated with Advagraf, eGFR (r_partial = 0.291; p < 0.05), antithymocyte globulin (vs. basiliximab) induction (r_partial = 0.445; p < 0.001), lipopolysaccharide (LPS) level (r_partial = 0.393; p < 0.01) and drug dose (r_partial = 0.433; p < 0.01) were independently associated with tacrolimus AUC. In patients treated with Envarsus, only age (r_partial = −0.365; p < 0.05) and fatty-acid-binding protein (FABP-2) level (r_partial = −0.364; p < 0.05) were independently associated with the tacrolimus AUC. Conclusions: We confirmed the significant association between markers of intestinal permeability and tacrolimus exposure in KTRs who underwent early post-transplant conversion from Prograf to Advagraf or Envarsus. This may suggest that the planned tacrolimus conversion from the twice-daily to the once-daily formulation should be performed later (at least 3 months after transplantation) to avoid unnecessary tacrolimus blood level instability. Full article

Adolescent binge drinking has lasting behavioral consequences by disrupting the endocannabinoid system (ECS) and depleting brain omega-3. The natural accumulation of omega-3 fatty acids in cell membranes is crucial for maintaining the membrane structure, supporting interactions with the ECS, and restoring synaptic plasticity and cognition impaired by prenatal ethanol (EtOH) exposure. However, it remains unclear whether omega-3 supplementation can mitigate the long-term effects on the ECS, endocannabinoid-dependent synaptic plasticity, and cognition following adolescent binge drinking. Here, we demonstrated that omega-3 supplementation during EtOH withdrawal increases CB1 receptors in hippocampal presynaptic terminals of male mice, along with the recovery of receptor-stimulated [³⁵S]GTPγS binding to Gαi/o proteins. These changes are associated with long-term potentiation (LTP) at excitatory medial perforant path (MPP) synapses in the dentate gyrus (DG), which depends on anandamide (AEA), transient receptor potential vanilloid 1 (TRPV1), and N-methyl-D-aspartate (NMDA) receptors. Finally, omega-3 intake following binge drinking reduced the time and number of errors required to locate the escape box in the Barnes maze test. Collectively, these findings suggest that omega-3 supplementation restores Barnes maze performance to levels comparable to those of control mice after adolescent binge drinking. This recovery is likely mediated by modulation of the hippocampal ECS, enhancing endocannabinoid-dependent excitatory synaptic plasticity. Full article

Microbial contamination is the leading cause of foodborne diseases and spoilage in food and personal care products. Previous studies by our group have demonstrated that vine tea extract (VTE) and dihydromyricetin (DMY) inhibit the growth of Escherichia coli. In this study, we further explored the inhibitory mechanisms of VTE and DMY against E. coli through a label-free proteomics approach. The proteomic analysis detected 130 and 81 differentially expressed proteins (DEPs) in E.coli following VTE and DMY treatment, respectively. The analysis indicated that VTE and DMY inhibit bacterial growth through multiple-target mechanisms. Specifically, they inhibit E. coli growth by disrupting the cationic antimicrobial peptide resistance pathway, amino acid biosynthesis and metabolism, and nucleotide metabolism. Additionally, VTE disrupts various secondary metabolic pathways, while DMY interferes with E. coli ribosome assembly and function, and disrupts cell membrane lipid homeostasis by interfering with fatty acid metabolism. RT-qPCR validation confirmed transcriptional alterations in genes encoding key target proteins. Molecular docking results indicated that DMY may affect bacterial protein synthesis, cationic antimicrobial peptide resistance, and transcriptional regulation by binding to target proteins such as RplB, RplV, LpxA, and YafC. In conclusion, this study systematically deciphered the multi-target inhibitory mechanisms of VTE and DMY against E. coli, providing a theoretical basis for developing plant-derived antimicrobial agents. Full article