Search Results (102)

Sepsis-associated acute kidney injury (AKI) is a severe inflammatory complication with limited therapeutic options. This study investigated the protective effects of Taiwan Chingguan Yihau (NRICM101), a herbal formulation, against lipopolysaccharide (LPS)-induced AKI. Male C57BL/6 mice were injected with LPS to induce AKI in vivo, followed by therapeutic administration of NRICM101. NRK-52E renal epithelial cells were stimulated with LPS to induce inflammatory responses and oxidative stress in vitro. Key bioactive compounds were identified via HPLC and analyzed using molecular docking. NRICM101 significantly alleviated renal dysfunction, as indicated by blood urea nitrogen (BUN) and serum creatinine (Scr) levels, and reduced histopathological damage in mice. It effectively suppressed the production of pro-inflammatory cytokines, attenuated intracellular and mitochondrial ROS, and preserved mitochondrial membrane potential. Mechanistically, NRICM101 markedly downregulated the expression of phosphorylated p65 (p-p65), NOD-like receptor protein 3 (NLRP3), and cleaved caspase-1, indicating modulation of nuclear factor kappa-B (NF-κB)/NLRP3 inflammasome signaling associated with renal pyroptosis. Molecular docking predicted potential interactions of NRICM101-derived bioactive constituents with the toll-like receptor 4 (TLR4)/MD-2 complex. Collectively, our findings suggest that NRICM101 ameliorates LPS-induced acute renal injury through anti-inflammatory and antioxidant effects associated with modulation of NF-κB/NLRP3-related signaling. Full article

Background/Objectives: The aim of this study was to examine the discrepancy between nutrition-related knowledge (NRK) and nutrition-related practice (NRP) among 1440 Polish school-aged students (10–18 years), according to BMI status, and to identify factors associated with this discrepancy. Methods: This cross-sectional study was conducted via the CAWI method using an author-developed, non-validated questionnaire. Questions assessing NRK and NRP were thematically aligned and referred to the recommendations of the Polish Healthy Eating and Lifestyle Pyramid for Children and Adolescents (aged 4–18 years). Results: Students with excess weight scored significantly lower in nutritional knowledge (NRK: 46%) and practices (NRP: 30%) than those with underweight or normal weight (NRK: 52–53%, NRP: 33–34%). Higher NRK was associated with older age, female sex, larger urban residence (for students with overweight and obesity), and higher maternal/legal guardian education level (for students with normal/underweight body weight). Better NRP was associated with higher NRK and higher physical activity, while rural or small-town living was positively associated with healthier dietary practices and maintenance of normal BMI. Conclusions: The present study confirms that nutritional knowledge is a necessary but insufficient condition for shaping appropriate dietary behaviors among adolescents with different BMI statuses; lifestyle factors, practical food-related skills—including self-assessment of knowledge and adherence to dietary recommendations—and the broader environmental context plays a crucial role. These findings highlight the need for targeted nutrition education programs that expand not only knowledge but also practical skills among students. Full article

Cisplatin (CP) chemotherapy is limited by nephrotoxicity, primarily involving tubular epithelial cell apoptosis. αB-crystallin (CryAB) is a small heat shock protein that plays a cytoprotective role in stressed kidneys but can also promote tumor progression. Its precise role and molecular mechanisms in CP-induced kidney injury remain largely unclear. This study highlighted the function of CryAB and its regulatory pathways in CP nephrotoxicity by employing in vitro models of rat renal tubular epithelial cells (NRK-52E) with CryAB gene knockdown/overexpression, and in vivo models of CryAB knockout/wild-type mice, followed by CP treatment. Apoptosis and key signaling pathways (NF-κB, MAPK, AKT) were evaluated in this study. The results indicated that CP treatment (20 µM) significantly upregulated CryAB expression in renal cells (p < 0.01) and triggered both apoptosis and MAPK activation. CryAB deficiency sensitized cells and mice to CP, exacerbating renal dysfunction, tubular injury, and apoptosis, as evidenced by increased Bax, cyt c release, and caspase-3 cleavage. Conversely, CryAB overexpression attenuated these effects. Furthermore, our findings suggest that the lack of CryAB favors the cytoplasmic retention of NF-κB, and that CryAB status can influence MAPK signaling, pointing to a potential regulatory loop. Additionally, CP-induced AKT phosphorylation was diminished in CryAB-deficient models. Therefore, CryAB may exert a cytoprotective role in CP nephrotoxicity, potentially mitigating tubular apoptosis by modulating the mitochondrial apoptotic pathway, supporting NF-κB-mediated survival signaling, and cross-talking with MAPK and AKT pathways. Our findings suggest that CryAB serves as an important regulator of renal cell fate and a potential therapeutic target for mitigating CP-induced kidney injury. Full article

Nicotinamide mononucleotide (NMN) plays vital physiological roles as a vitamin B derivative, with nicotinamide riboside kinase (NRK) serving as a key enzyme for its efficient and environmentally friendly synthesis. In this study, semi-rational design was employed to modify the Hi-NRK enzyme at the molecular level, leading to the identification of a critical mutant, Hi-NRK^G8S. This variant exhibited a twofold increase in enzymatic activity and significantly enhanced thermal stability, extending its half-life at 40 °C from 4 to 8 h. By optimizing reaction conditions, NMN yield reached 94.17% at a nicotinamide riboside (NR) substrate concentration of 50 g/L. Further addition of adenylate kinase (ADK) to facilitate ATP recycling increased the yield to 97.24% at 75 g/L NR. This study establishes a foundation for industrial-scale, efficient, and green NMN production. Full article

Cardio-renal metabolic (CRM) syndrome, characterized by insulin resistance and dyslipidemia, disrupts renal insulin signaling, enhances oxidative stress, and activates inflammasome pathways, ultimately promoting renal fibrosis and kidney dysfunction. Aberrant renal gluconeogenesis has emerged as a critical contributor to tubular injury under cardiometabolic stress; however, its mechanistic linkage to inflammatory and fibrotic remodeling remains incompletely defined. In this study, ApoE^−/− mice subjected to streptozotocin administration and a high-fat diet developed pronounced cardiometabolic dysfunction, accompanied by elevated blood urea nitrogen, creatinine, uric acid, and glycated hemoglobin levels, as well as severe renal histopathological alterations. N-Acetylcysteine (NAC) supplementation significantly improved metabolic abnormalities and attenuated tubular dilation, glomerular hypertrophy, and mesangial expansion. Mechanistically, NAC suppressed renal gluconeogenesis by downregulating glucose-6-phosphatase and phosphoenolpyruvate carboxykinase expression and mitigated epithelial–mesenchymal transition by restoring E-cadherin and reducing vimentin expression, thereby limiting fibrotic remodeling. Consistent with in vivo findings, NAC reduced reactive oxygen species production, restored PI3K/Akt-dependent insulin signaling, and inhibited inflammasome activation in NRK-52E renal tubular cells exposed to high glucose and oleic acid, resulting in attenuation of inflammatory signaling and gluconeogenic activity. Collectively, these results demonstrate that NAC mitigates cardiometabolic stress-induced renal injury by modulating inflammasome activation and gluconeogenic reprogramming, highlighting its potential as a mechanistic modulator of renal fibrosis under CRM conditions. Full article

Artemisia indica Willd. is widely used in traditional medicine and dietary practices. Phytochemical analysis of Artemisia indica Willd. aqueous extract (AAE) by HPLC–ESI–MS/MS identified isochlorogenic acid C (ICAC) as a major constituent. Angiotensin II (Ang II) disrupts renal tubular epithelial cell homeostasis and contributes to renal injury. In this study, we evaluated the protective effects of AAE and ICAC in Ang II-stimulated NRK52E cells. Both AAE and ICAC significantly reduced reactive oxygen species (ROS) production, mitochondrial dysfunction, and proinflammatory cytokine release. Mechanistic analyses showed that AAE inhibited Ang II type 1 receptor (AT1R)-mediated NF-κB activation and suppressed NLRP3 inflammasome signaling, thereby alleviating inflammatory responses and pyroptosis. In addition, AAE and ICAC restored sodium homeostasis by reactivating neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4-2), promoting epithelial sodium channel (ENaC) ubiquitination and reducing its apical membrane accumulation. Molecular docking suggested that ICAC interacts with the extracellular domain of α-ENaC, supporting its regulatory role. Overall, AAE and ICAC protect renal tubular epithelial cells against Ang II-induced injury by reducing oxidative stress, inflammation, and dysregulated sodium transport, highlighting their potential as plant-derived therapeutic agents for hypertension-associated renal dysfunction. Full article

Background/Objectives: Phillygenin (PHI), a natural lignan derived from Forsythia suspensa, has garnered attention for its potential to alleviate chronic diseases, including chronic colitis, pulmonary fibrosis, and diabetes. Chronic kidney disease (CKD) poses a global health challenge, characterized by high morbidity and mortality rates and associated with a spectrum of secondary complications. In this study, we aim to investigate the therapeutic effectiveness of PHI on CKD and also identify molecular signals by using a unilateral ureteral obstruction (UUO) mouse model and in vitro experiments. Methods: C57BL/6 mice were administered PHI at 50 mg/kg/day to assess its therapeutic effectiveness. In vitro, lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were used to induce pyroptosis, also known as pyroptosis, in renal proximal tubular cells (NRK52E). Results: After PHI treatment for 14 consecutive days, the collagen deposition and extracellular matrix (ECM) accumulation, the expression of oxidative stress response proteins (catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), pro-inflammatory markers (TNF-α and Cyclooxygenase-2(COX-2), and infiltration of neutrophils and macrophages were significantly ameliorated in the UUO mice. Interestingly, the pyroptosis-related proteins (NLRP3/Caspase-1/GSDMD/IL-1β) and cell apoptotic death were also conspicuously relieved after treatment with PHI. Furthermore, PHI administration significantly attenuated the ATP/LPS-induced NF-κB/NLRP3/Caspase-1/GSDMD pyroptosis signal pathway in NRK52E cells. Conclusions: These results demonstrate, for the first time, that PHI treatment ameliorates inflammation and the related pyroptosis via inhibitory regulation of the NF-κB/NLRP3/Caspase-1/GSDMD axis, leading to attenuated renal fibrosis and progressive CKD in UUO mice and in vitro. Our findings suggest that PHI could be a nutraceutical candidate for attenuating CKD progression. Full article

Five previously undescribed steroids, chrysogenones A–E (1–5), were isolated from the deep-sea-derived Penicillium sp. MCCC 3A00121. Their chemical structures were unambiguously established through comprehensive spectroscopic analyses, density functional theory (DFT)-based electronic circular dichroism (ECD) calculations, and X-ray crystallography. Chrysogenones represent a class of oxidatively modified ergosterone-type derivatives, with 1, 2, and 5 featuring an uncommon malonyl substitution at C-12 of the ergosterone skeleton. Biologically, 1–5 exhibited varying degrees of inhibitory activity against renal fibrosis, as evidenced by the downregulation of the key fibrotic markers α-smooth muscle actin (α-SMA) and collagen I (COL1A1). Among them, chrysogenone B (2) emerged as the most promising candidate, demonstrating superior potency and pronounced inhibition of activated NRK-49F cell proliferation. Integrated network pharmacology analysis and molecular docking studies further suggested that the anti-renal fibrotic effects of compound 2 may be mediated through its interaction with putative molecular targets, including AKT1, HSP90AA1, and MDM2. Full article

Chronic kidney disease (CKD) has emerged as a pressing global public health concern, making the identification of renal fibrosis inhibitors a key research focus. In this study, seven undescribed abietane-type diterpenoids, pinusyunins A–G (1, 2, 4, and 7–10) and three known analogues (3, 5, and 6), were isolated from Pinus yunnanensis resin, which were identified by spectroscopic analyses and quantum computational chemistry methods. Biological evaluation showed that all the isolates exhibited inhibitory activity against the expression of collagen I, fibronectin, and α-SMA in transforming growth factor-β1 (TGF-β1)-induced NRK-52E and NRK-49F cells. Specifically, compounds 1–10 reduced the expression of α-SMA at 40 μM in both cell lines, while compounds 6–8 and 10 decreased the expression of these three markers at 40 μM in both cell lines with the potency of compound 10 superior to the others in α-SMA inhibition in NRK-52E cells. Variations in activity are associated with differences in substituents at the C-13 position. Further studies demonstrated that these abietane-type diterpenoids block the TGF-β/Smad signaling pathway by inhibiting the phosphorylation of Smad2/3. In particular, compounds 1, 3, 6, and 7 suppressed only p-Smad3 other than p-Smad2, indicating their specificity. The research on these abietane-type diterpenoids provides novel candidate molecules and a scientific underpinning for developing anti-renal fibrosis drugs. Full article

The rhizome of Polygonatum sibiricum (PR) is a widely used medicinal and edible herb valued worldwide. Traditional processing by repeated steaming and sun-drying empirically enhances its therapeutic properties, primarily through alterations in its bioactive polysaccharides. This study aimed to elucidate the structure–activity relationship by systematically investigating the structural features and renoprotective activities of polysaccharides from PR and processed PR (PPR). Polysaccharides from PR and PPR (designated PRP and PPRP, respectively) were isolated and identified as five fractions (PRP-1, PRP-2, PPRP-1, PPRP-2, and PPRP-3). PPRP exhibited a broader molecular weight distribution (1.9–21.5 kDa) compared to PRP (2.6 kDa), indicating degradation and repolymerization. 1D/2D NMR analysis revealed that PRP-1 contained a backbone of →1)-β-D-Fruf-(2→, while processing introduced an additional →5)-α-L-Araf-(1→ linkage into PPRP-1. The acidic fractions, PPRP-2 and PPRP-3, showed a partial overlap of motifs, including →4)-α-D-GalAp-(1→ (in both methylated and non-methylated forms), →4)-β-D-Galp-(1→, →5)-α-L-Araf-(1→, and →2,4)-α-L-Rhap-(1→. Notably, PPRP-2 demonstrated superior renoprotective activity in high glucose-induced NRK-52E cells. These structural transformations provide a molecular basis for the enhanced bioactivity and functional-food potential of polysaccharides. Full article

The epiphytic community of Laminaria hyperborea, dominated by red algae, is typically discarded during industrial processing despite its potential as a source of high-value natural products. This study aims to valorize this underutilized biomass by characterizing its secondary metabolites and evaluating the biological activities of its major bromophenols. A combined chromatographic workflow enabled the isolation and structural elucidation of five bromophenols (1–5), including one previously undescribed compound (5). Among these, compound 4 exhibited the strongest cytotoxicity against the acute myeloid leukemia (AML) cell line MOLM-13 (EC₅₀ = 6.23 μM) and induced pronounced apoptotic features. When tested on two normal cell lines (NRK and H9c2) and in zebrafish larvae, it showed moderate toxicity at higher concentrations, indicating a reasonable selectivity window. In contrast, compound 5 was more toxic to normal cells than to MOLM-13 in vitro, while showing no acute toxicity in zebrafish; however, interpretations are preliminary due to compound purity. Bromophenols 1–4 were also tested for antioxidant activity, with 4 being the most potent (ABTS EC₅₀ = 22.1 μM), although this did not translate into protection against doxorubicin-induced cardiotoxicity. Additionally, non-targeted UHPLC-QTOF MS/MS analysis tentatively identified nine additional bromophenols and provided an estimation of their origin species within the epiphytic assemblage. Full article

This study investigates the phytochemical profile, antioxidant capacity, and antimicrobial potential of Crocus sativus L. (saffron) tepal extracts obtained via different solvent systems. Here, a biochemical screening was performed using spectrophotometry and HPLC-DAD, while molecular docking simulations were carried out to evaluate the possible interactions between saffron tepal metabolites and bacterial target proteins. In parallel, antioxidant activity was assessed using radical scavenging assays, whereas antimicrobial potential (i.e., MIC, MBC, and MFC) was tested against selected bacterial strains. Results indicated that aqueous successive and crude extracts yielded the highest concentrations of polyphenols, flavonoids, and condensed tannins. In detail, HPLC-DAD analysis specifically identified significant levels of gallic acid, epicatechin, and various anthocyanins. These extracts demonstrated robust antioxidant and antimicrobial activities. This latter evidence was corroborated by the docking analyses, which revealed that chlorogenic acid and petunidin-3-glucoside exhibited high binding affinities for 2NRK and 2NZF, whereas epicatechin and pelargonidin effectively targeted 8ACR. These findings underscore the therapeutic potential of C. sativus tepals as natural bioactive agents, suggesting a promising role in overcoming antibiotic resistance and supporting their development for pharmaceutical applications. Full article

Background/Objectives: To explore the protective effects of 7-Ketolithocholic acid (7-KLCA) against renal fibrosis and its mechanism, focusing on its interaction with farnesoid X receptor (FXR). Methods: In vitro, TGF-β-induced fibrosis in HK-2/NRK-49F cells and LPS-induced inflammation in HK-2 cells were detected by CCK-8, Western blot, and qPCR. In vivo, unilateral ureteral obstruction (UUO) and adenine (Ade)-induced mouse models were treated with a low/high-dose 7-KLCA or losartan. Renal injury was evaluated via H&E/Masson staining, serum creatinine (SCR), and blood urea nitrogen (BUN) levels. The 7-KLCA-FXR interaction was verified by molecular docking, CETSA, and DARTS. FXR downstream genes and related proteins were measured by WB and qPCR. Results: 7-KLCA inhibited the expression of fibrotic proteins (fibronectin, collagen-I) and reduced the LPS-induced release of inflammatory factors (IL-1β, IL-6). In mice, it alleviated renal swelling, collagen deposition, and tubular damage, while lowering serum SCR and BUN levels. Mechanistically, 7-KLCA stably bound to the FXR ligand-binding domain, enhanced its thermal stability and degradation resistance. It upregulated FXR and its downstream genes SHP and FGF15, thereby inhibiting the activation of TGF-β/Smad and Wnt/β-catenin pathways. Conclusions: This is the first study to clarify the molecular mechanism through which 7-KLCA targets FXR and dually suppresses the key pro-fibrotic pathways TGF-β/Smad and Wnt/β-catenin, thereby exerting anti-renal fibrosis effects. Full article

Background/Objectives: The purpose of this study was to examine nutrition-related knowledge (NRK) and the implementation of national dietary guidelines (NDGs) as nutrition-related practices (NRPs) among women, identifying profiles and their determinants. Methods: A cross-sectional study including 1294 Polish women (mean age 35.8 ± 14.6 years) was conducted in the period June 2021–December 2022 using the Computer Assisted Web Interview (CAWI) method. K-means cluster analysis was applied to standardized variables (NRK and NRP scores, age, and BMI), with the optimal number of clusters determined using the elbow method, to identify major participant profiles representing knowledge and practices with respect to the NDGs. Results: Three distinct clusters were identified. The “High” cluster showed median NRK and NRP scores of 15 (IQR = 14–17) and 11 points (IQR = 10–13), significantly higher than those of the “Low” (11 (IQR = 9–13) and 8 points (IQR = 7–10); p < 0.001) and “Moderate” cluster (13 (IQR = 11–14) and 7 points (IQR = 6–9); p < 0.001), respectively. There were significant differences between clusters in socio-demographics, lifestyle, and health-related distribution. Cluster “High” (38% of sample) had the best NRK and NRP scores and more advantageous socio-economic and lifestyle profiles (higher education, employment, better financial situation, normal BMI, less smoking and higher levels of physical activity), p < 0.001; “Moderate” (39%) was characterized by average to relatively good NRK but weaker implementation of NRPs, particularly among younger women, representing more advantageous socio-demographic, lifestyle, and health-related characteristics (p < 0.001); and “Low” (23% of sample) comprising middle-aged and older women with lower education, more frequent rural residence, poorer financial status, less favourable lifestyle factors, the lowest NRK and NRP scores, higher prevalence of overweight or obesity, and the lowest level of physical activity (p < 0.001)—thus indicating a marked knowledge–practice gap, with this group constituting a potential high-risk population. Conclusions: Greater awareness of national dietary guidelines among women is observed alongside higher nutrition-related knowledge and healthier dietary practices. A persistent gap between knowledge and practical implementation among women highlights the need for interventions that support behaviour change alongside nutritional education. Targeted public health strategies are required for women with lower levels of nutrition-related knowledge and less favourable lifestyle profiles. Full article

Through the mineralocorticoid receptor, aldosterone controls extracellular volume and arterial blood pressure by stimulating Na⁺ absorption and K⁺ secretion in epithelial cells of the kidney, colon, and several glands. Hyperaldosteronism promotes fibrosis and inflammation in epithelial and non-epithelial tissues, thereby favoring loss of kidney and heart function. Mineralocorticoid receptor blockade therefore gains relevance especially in renal and cardiac disease. Kidney-derived Klotho is a powerful anti-aging protein with anti-fibrosis and anti-inflammatory effects providing cardio- and nephroprotection. We wondered whether Klotho expression and production is influenced by mineralocorticoid receptor agonists and antagonists. Using four renal cell lines, Madin-Darby canine kidney (MDCK), normal rat kidney, subtype 52E (NRK-52E), human kidney 2 (HK2) cells, and primary renal proximal tubule epithelial cells (RPTECs), and the four most frequently prescribed mineralocorticoid receptor blockers, spironolactone, eplerenone, finerenone, and esaxerenone, we assessed Klotho gene expression by qRT-PCR and Klotho protein by Western blotting. Aldosterone and eplerenone did not significantly affect Klotho expression in either cell line. Spironolactone enhanced Klotho expression in MDCK and NRK-52E cells and downregulated Klotho in HK2 cells and RPTECs. Novel non-steroidal mineralocorticoid receptor antagonist finerenone downregulated Klotho expression in MDCK, NRK-52E, and low-dose finerenone in HK2 cells. To conclude, common mineralocorticoid receptor antagonists are characterized by highly diverse effects on Klotho in four renal cell lines. Further studies are needed to define the role of mineralocorticoid receptor blockade for Klotho production. Full article