Search Results (460)

The microbial valorization of agro-industrial residues is a promising strategy for sustainable bioprocesses and the development of a circular bioeconomy. In this study, mixed fruit peel waste was anaerobically fermented in a stirred-tank bioreactor using Wickerhamomyces sp. UFFS-CE-3.1.2 to produce organic acids and a multifunctional enzymatic bioproduct. During fermentation, sugars decreased from 6.51 to 0.22 g L⁻¹, leading to the formation of citric acid (7.65 g L⁻¹), ethanol (3.77 g L⁻¹), glycerol (0.53 g L⁻¹), and acetic acid (0.37 g L⁻¹). The accumulation of organic acids likely imposed metabolic stress on the yeast, triggering physiological responses that mitigate oxidative stress. Consequently, the resulting enzymatic extract exhibited high lipase activity (185.63 U mL⁻¹), late catalase induction (520.97 U mL⁻¹), and stable superoxide dismutase activity (50 U mL⁻¹). This enzymatic profile indicates the formation of a stress-adapted microbial system with potential applicability in processes involving lipid hydrolysis and oxidative mechanisms. The process was conducted without supplementation of synthetic medium and operated stably in a stirred-tank bioreactor. Overall, these results suggest a feasible microbial strategy for converting fruit waste into value-added bioproducts, contributing to the development of sustainable biotechnological processes. Full article

This study systematically compared the induction and resuscitation characteristics of the viable but non-culturable (VBNC) state in Klebsiella pneumoniae FY170-1 following sublethal exposure to sodium hypochlorite (NaClO) or glutaraldehyde (GA). Treatment with 30 mg/L NaClO or 60 mg/L GA for 60 min reduced culturability to below the detection limit (<1 CFU/mL). However, CTC staining showed that 50.80% and 63.44% of cells, respectively, retained respiratory activity, while SYTO 9/PI staining indicated that membrane integrity was largely preserved, consistent with induction of the VBNC state. Scanning electron microscopy revealed distinct morphological alterations in the two groups. NaClO-induced VBNC cells showed surface depressions and wrinkling, consistent with oxidative damage, whereas GA-induced cells exhibited filamentous and net-like surface structures, consistent with aldehyde-mediated cross-linking. Among the tested additives, sodium succinate showed the strongest resuscitation-promoting effect under the experimental conditions, with OD600 increasing after approximately 2 h of incubation. Post-resuscitation analysis further revealed marked differences between the two VBNC states. In resuscitated NaClO-induced VBNC cells, ATP partially recovered, but reactive oxygen species remained elevated and catalase activity showed little recovery. In contrast, resuscitated GA-induced VBNC cells exhibited lower ATP recovery but more rapid normalization of ROS and better recovery of oxidative stress-related parameters. Total protein analysis and SDS-PAGE further supported distinct patterns of protein-level alteration between the two treatments. Overall, these findings suggest that NaClO and GA induce phenotypically distinct VBNC states in K. pneumoniae, with different recovery behaviors and stress response profiles. Sodium succinate was identified as the most effective recovery-promoting additive under the tested conditions. These results highlight the risk of underestimating bacterial survival when culturability is used as the sole indicator of disinfection efficacy and support the need for more comprehensive viability assessment. Full article

Successive cropping frequently causes a decline in Chinese Fir (Cunninghamia lanceolata) biomass, a problem intricately tied to soil nutrient shifts and microbial processes. This research investigates the mechanisms governing biomass carbon partitioning and soil nutrient shifts in these plantations. This study investigated five Chinese Fir clones (‘ck’, ‘b44’, ‘K13’, ‘F13’, and ‘kt13’) across two cultivation regimes: continuous cropping (second-generation plantation, G2) and first-generation plantation (G1). The focus was on their biomass and soil nutrient status. The results showed that: (1) The biomass of different Chinese Fir clones at 25 years of age decreased significantly with increasing generations of continuous cultivation. Tree height showed no significant differences among clones within the same generation; however, the G2 cultivation significantly inhibited diameter at breast height (DBH). (2) The changes in soil nutrients and microbial activity under different successive generations (G1, G2) was closely linked to the decline in Chinese Fir biomass carbon. Analysis revealed that the decreases in dissolved organic carbon (DOC), dissolved organic nitrogen (DON), and Catalase (CAT) activity were significantly positively correlated with the reduction in biomass carbon. Concurrently, the decrease in soil pH showed a significant negative correlation with microbial biomass carbon (MBC) and Sucrase (SUC) activity. (3) Regarding growth traits, although tree height showed no significant differences among clones within the same generation, DBH was generally and significantly inhibited under G2 cultivation. An exception was the ‘K13’ clone, which remained largely unaffected. In terms of carbon accumulation, G2 cultivation led to a universal decline in biomass carbon across clones; however, the magnitude of reduction in different components (leaf, branch, stem, root) and total biomass carbon varied clone-specifically. Notably, ‘K13’ exhibited the strongest tolerance, with a significantly smaller decrease in tree biomass carbon compared to the other four clones, which showed substantially lower tree carbon stocks across all components relative to G1 plantations. This indicates that successive cropping of Chinese Fir likely constrains the carbon sequestration capacity of plantations by altering soil nutrient properties, thereby suppressing tree DBH growth and biomass carbon accumulation, likely through reduced net primary productivity. Among the five clones, ‘K13’ was the least affected, demonstrating its high potential for adaptation to continuous cultivation. These findings provide implications for sustainable forest management by guiding clone selection to mitigate productivity decline under successive cropping. Full article

Saline-alkaline (SA) soils pose a serious threat to soybean production worldwide. Although severe saline-alkaline stress can reduce yield by up to 30%, the mechanisms underlying saline-alkaline-induced inhibition of root growth remain unclear. In this study, two soybean cultivars with contrasting tolerance, Chang Nong 26 (CN26) and Jiyu 441 (JY441), were exposed to saline-alkaline stress induced by NaHCO₃ and Na₂CO₃ at Na⁺ concentrations of 0, 21, and 45 mmol·L⁻¹. The effects on seed germination, early seedling growth, antioxidant responses, and root DNA damage were systematically examined. High-level saline-alkaline stress significantly inhibited germination and root elongation in both cultivars. Superoxide dismutase (SOD) and peroxidase (POD) activities increased markedly under stress, indicating activation of antioxidant defenses. Catalase (CAT) and ascorbate peroxidase (APX) to scavenge ROS and maintain cellular redox balance. Nevertheless, oxygen-free radicals (OFRs) accumulated to a significantly greater extent in the root tips of CN 26 than in JY441, suggesting lower tolerance in CN 26. Random amplified polymorphic DNA (RAPD) analysis revealed pronounced DNA damage in root tips under saline-alkaline stress, with more polymorphic bands detected in CN 26 than in JY441. Furthermore, qRT-PCR analysis demonstrated that the expression of DNA damage repair-related genes (RAD51, OGG1, RAD4, and ATM) was downregulated in CN 26 roots under stress, whereas E2FA and WEE1 expression was upregulated. In contrast, these DNA repair genes in JY441 were significantly induced during the early stage of stress exposure and subsequently declined. Collectively, this study demonstrates that saline-alkaline stress inhibits soybean growth through the induction of oxidative DNA damage and cell cycle arrest in roots. The reduced capacity for DNA repair in CN 26 likely contributes to its greater sensitivity to saline-alkaline stress. This study provides mechanistic insights into saline-alkaline stress-induced growth inhibition in soybean and offers a theoretical basis for breeding stress-tolerant cultivars. Full article

Isoflurane is a widely used volatile anesthetic with context-dependent effects on neuronal survival, particularly in neurodegenerative conditions. Increasing evidence suggests that brief, sublethal stress exposure can induce adaptive cellular responses through hormesis-based preconditioning mechanisms. In this study, we investigated whether isoflurane preconditioning enhances neuronal tolerance to amyloid-β (Aβ)-induced toxicity and explored the underlying redox-dependent molecular pathways. Using HT-22 murine hippocampal neuronal cells, we demonstrate that short-term exposure to low-dose isoflurane induces a delayed neuroprotective phenotype characterized by improved cell viability, reduced apoptotic signaling, and maintained mitochondrial membrane potential following Aβ challenge. Mechanistically, isoflurane preconditioning elicited a mild and transient increase in intracellular reactive oxygen species (ROS), which is critical for the activation of the PI3K/Akt signaling pathway. Pharmacological scavenging of reactive oxygen species abolished Akt phosphorylation and reduced the protective effects of preconditioning, supporting a hormetic signaling model rather than direct antioxidant action. Following Akt activation, isoflurane preconditioning promoted the inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β), decreased Keap1 protein levels, and facilitated nuclear translocation and transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Consequently, the expression of Nrf2-regulated antioxidant genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase 1 (NQO1), superoxide dismutase 1 and 2 (SOD1/2), and catalase, was significantly upregulated. Collectively, these findings indicate that isoflurane preconditioning confers neuroprotection through hormesis-like mild oxidative signaling and coordinated activation of endogenous antioxidant defenses rather than via direct antioxidant scavenging. Full article

Pomacea canaliculata, as a significant invasive alien species, poses severe threats to agricultural development. Currently, chemical applications demonstrate notable efficacy in controlling this pest. However, metaldehyde exhibits overly singular toxicity towards P. canaliculata; niclosamide sulfate is not a molluscicide; and fentin acetate is a fungicide. Currently, these findings fail to elucidate the physiological and biochemical effects of the compounds after they enter the P. canaliculata’s body. In this study, we evaluated the toxicity of metaldehyde (ME), niclosamide sulfate (NS), and fentin acetate (FA) against P. canaliculata and analyzed the morphological and physiological changes in response to chemical stress. The results indicated that three chemicals exhibited potent molluscicidal activity, especially in the NS treatment group. After 12 h exposure to LC₅₀ concentrations (48 h LC₅₀), the surface area of livers was reduced significantly by 12.1%, 13.9%, and 2.8% compared to the control group, while the kidneys expanded significantly by 6.4%, 3.2%, and 16.7%, respectively. The heart showed marked enlargement by 152.1% and 44.2% under niclosamide sulfate and metaldehyde treatments. The pulmonary sac significantly contracted by 23.6% under niclosamide sulfate stress but expanded by 6.1% under fentin acetate exposure. The stomach enlarged significantly after niclosamide sulfate treatment, whereas it shrank by 2.1% and 5.7% under metaldehyde and fentin acetate treatments, respectively. Metabolomic analysis of liver tissues revealed 553, 99, and 585 differential metabolites compared to the control group, respectively. KEGG pathway enrichment analysis showed that the metabolism pathway, lysine degradation, and bile secretion are likely related to the response to chemical stress in P. canaliculata. Further examination showed a significant decrease in total protein content and the activities of malondialdehyde (MDA), acetylcholinesterase (AChE), superoxide dismutase (SOD), and catalase (CAT) under chemical stress. These findings enhance our understanding of the targeted mechanisms of molluscicides against P. canaliculata. Metaldehyde may exert neurotoxic effects on the P. canaliculata, while niclosamide sulfate may interfere with its respiratory system. Additionally, both chemicals affect metabolic pathways in the snail’s liver, including lipid metabolism and metabolic pathways associated with energy metabolism. These findings provide valuable insights for designing a novel snail control agent and formulating scientific management strategy. Full article

Returning organic amendments to saline–alkali soils constitutes a key strategy for soil amelioration, as it enhances crop productivity by modulating the rhizosphere microenvironment. In this study, straw, biochar, and peat were selected as representative organic amendments, and a two-year field experiment—employing a rotational cropping system of Sesbania and Triticale—was conducted to investigate their differential regulatory effects on rhizosphere properties and root development. Results demonstrated that all three amendments induced coordinated shifts in the rhizosphere “extract–microbiota–enzymes–nutrients” nexus, concomitant with significant stimulation of root growth. The hypothesized pathways through which different organic amendments improve the rhizosphere environment vary mechanistically: straw application appears to enhance alkaline phosphatase activity and enrich phosphorus-solubilizing microorganisms; it is hypothesized that this promotes root growth by facilitating the mineralization of organic phosphorus. In contrast, peat amendment induces the most pronounced increases in esterase content and sucrase activity, and its growth-promoting effect is likely attributable to accelerated carbon and phosphorus cycling. Biochar, meanwhile, is associated with elevated catalase activity, improved potassium retention, and enhanced organic carbon sequestration; its beneficial function is postulated to stem from mitigation of oxidative stress. Collectively, this study provides initial evidence that distinct organic amendments modulate rhizosphere processes via divergent biochemical and microbial mechanisms—offering a theoretical foundation for their rational selection and application in saline–alkali soil remediation. Full article

Bacterial and fungal infections, together with oxidative stress-mediated damage, remain major challenges in human health and in the protection of materials, highlighting the need for new multifunctional molecules that combine antioxidant and antimicrobial properties. In this context, a new chloropyridine-based derivative, N4,N4-bis((6-chloropyridin-3-yl)methyl)-N1,N1-diethylpentane-1,4-diamine (AMZ), was synthesized via a simple, catalyst-free N-alkylation of N1,N1-diethylpentane-1,4-diamine with 2-chloro-4-(chloromethyl)pyridine in acetonitrile at 55 °C, affording a 62% yield. The structure of AMZ was confirmed by melting point determination, ¹H and ¹³C NMR spectroscopy, and EI–MS analysis. Its antioxidant activity was evaluated using DPPH and FRAP assays with BHT as a reference standard, while antibacterial and antifungal activities were assessed via disk diffusion and microdilution methods to determine inhibition zones and MIC/MBC values. In silico investigations included drug-likeness and ADMET predictions, as well as molecular docking on catalase (PDB: 2CAG) and fungal CYP51 (PDB: 1EA1). AMZ exhibited dose-dependent radical scavenging in the DPPH assay, reaching 76.88 ± 3.20% inhibition at 1000 µg/mL, with an EC₅₀ of 26.03 ± 0.21 µg/mL, close to that of BHT (23.65 ± 0.22 µg/mL). In the FRAP assay, AMZ showed a higher reducing power than BHT at a low concentration (OD₅₀ µg/mL 0.177 ± 0.023 vs. 0.134 ± 0.017), although its FRAP EC₅₀ was higher (700.48 ± 22.54 vs. 400.16 ± 8.67 µg/mL). AMZ displayed broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi, with particularly strong effects on Bacillus subtilis (44.5 ± 0.5 mm; MIC/MBC 0.008 mg/mL) and Aspergillus niger (30 mm; MIC/MBC 0.030 mg/mL), in some cases comparable or superior to streptomycin and fluconazole. In silico analysis indicated that AMZ fulfilled major drug-likeness rules, showed high predicted intestinal absorption (91.14%), and was classified as non-AMES toxic, while docking predicted favorable binding to catalase and CYP51, in agreement with the experimental antioxidant and antifungal activities. These findings highlight the potential of AMZ as a multi-target pyridine-based lead compound that warrants further structural optimization and in vivo evaluation for applications in oxidative-stress-related and infectious conditions. Full article

Salt stress severely constrains wheat growth and yield by inducing osmotic imbalance, ion toxicity, and excessive accumulation of reactive oxygen species (ROS). Although salt-tolerant cultivars can adapt through rapid signaling transduction and maintenance of cellular homeostasis, the underlying dynamic regulatory networks remain insufficiently characterized. In this study, we reanalyzed publicly available time-series RNA-seq data (0, 1, 3, 6, 12, and 24 h) from the salt-tolerant wheat cultivar Xiaoyan22 under salt stress and constructed a time-series-based co-expression network using weighted gene co-expression network analysis (WGCNA). Multiple gene modules were identified, among which the black module showed significant positive correlations with both salt treatment (treatment_bin) and stress duration (time_h). This module displayed a progressively increasing eigengene expression pattern throughout the stress period. Gene significance (GS) was positively correlated with module membership (MM), facilitating the identification of highly connected hub genes within this module. Functional enrichment analysis indicated that genes in the black module were primarily associated with DNA replication and genome stability maintenance, RNA metabolic regulation, phenylpropanoid metabolism, and cuticle/suberin/wax biosynthesis. Physiological analysis further revealed enhanced activities of superoxide (SOD), peroxide (POD), and catalase (CAT), enhanced accumulation of proline and soluble sugars, and a time-dependent increase in MDA under salt stress. qRT-PCR confirmed significant induction of candidate genes, including a ZAR1-like receptor kinase, Remorin, and NETWORKED 1D. Collectively, these findings integrate co-expression network inference with physiological and molecular validation, providing candidate regulators and pathways for understanding salt tolerance and supporting future molecular breeding efforts. Full article

Sweet potato (Ipomoea batatas L.) is cultivated globally and generates a large quantity of plant-derived residues, including leaves, stems, and non-commercial cull roots, which remain insufficiently utilized despite their potential functional value. Although the antioxidant properties of sweet potato leaves have been reported, comparative investigations of different plant parts evaluated under the same experimental conditions, particularly in relation to skin-associated biological functions, are still limited. In this study, aqueous extracts prepared from sweet potato leaves, stems, and cull roots were obtained using a food-grade extraction process suitable for practical application. The phenolic composition and biological properties of the extracts were comparatively analyzed. Antioxidant capacity was examined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, ferric reducing antioxidant power (FRAP), as well as assays associated with superoxide dismutase (SOD)-like and catalase-related activities. Skin-related biological responses were further evaluated by measuring elastase and collagenase inhibition, type I procollagen synthesis, and matrix metalloproteinase-1 (MMP-1) secretion in CCD-986Sk human dermal fibroblasts. Among the tested samples, the leaf-derived aqueous extract exhibited a higher total phenolic content, greater accumulation of chlorogenic acid, and stronger antioxidant responses compared with stem and cull root extracts. In addition, the leaf extract showed more pronounced effects on collagen metabolism, including enhanced procollagen synthesis and reduced MMP-1 secretion, while maintaining acceptable cell viability within the tested concentration range. Overall, these results demonstrate clear tissue-dependent functional differences among sweet potato residues and indicate that leaf-derived extracts represent a promising functional material for skin-related and cosmetic applications. Full article

The deterioration of water quality is associated with an increased disease risk, although the exact mechanism remains unclear. This study investigated the infection dynamics of cyprinid herpesvirus 2 (CyHV-2) in crucian carp (Carassius auratus gibelio) subjected to varying nitrite stress levels. A control group and three CyHV-2-infected groups exposed to nitrite concentrations of 0, 5, and 10 mg/L were set up. Results indicated that nitrite exposure caused a dose-dependent reduction in survival rates and decreased viral loads in the spleens of surviving fish. Nitrite stress elevated malondialdehyde (MDA) levels and glutathione peroxidase (GPx) activity, while reducing superoxide dismutase (SOD) and catalase (CAT) activities in the liver. Hepatic cytokine analysis revealed early peaks in tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), alongside delayed response of interferon γ (IFN-γ) and interleukin 10 (IL-10), indicating impaired anti-inflammatory regulation. In the kidney, nitrite stress amplified immune gene expression, characterized by the upregulation of tlr5 (Toll-like receptor 5) and nf-κb (nuclear factor κB) and the inhibition of iκκβ (inhibitor of NF-κB kinase subunit β), leading to prolonged NF-κB signaling. This was associated with a marked upregulation of il-1β and il-8 (interleukin 8), alongside a delayed ifn-γ response. The combination of nitrite stress and CyHV-2 infection exacerbated oxidative damage and triggered a maladaptive immune response, thereby accelerating disease progression. Full article

This study reports the first successful isolation and characterization of exosome-like nanoparticles from walnut kernels (WELNs). The isolated WELNs exhibited a typical cup-shaped morphology with an average diameter of 139.7 ± 67.5 nm, a concentration of 7.4 × 10¹¹ particles/mL, and a zeta potential of −17.47 ± 4.06 mV. Proteomic and small RNA sequencing analyses confirmed the presence of diverse proteins and microRNAs within WELNs. In vitro assays demonstrated their potent antioxidant capacity, with radical scavenging rates of 67.54% against ABTS⁺ and 48.59% against DPPH⁺ at 102 μg/mL and IC₅₀ values of 89.7 μg/mL and >102 μg/mL for scavenging of ABTS⁺ and DPPH⁺ radicals, respectively. Cytotoxicity assays indicated no adverse effects on RAW264.7 macrophage viability at concentrations up to 60 μg/mL. In LPS-stimulated RAW264.7 macrophages, WELN treatment (20–60 μg/mL) dose-dependently mitigated oxidative stress by reducing intracellular ROS levels (down to 81.22% of the control at 60 μg/mL) and malondialdehyde (MDA) content while restoring the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Furthermore, WELNs significantly suppressed the production of nitric oxide (NO) and pro-inflammatory cytokines TNF-α, IL-6, and IL-1β (reduced to approximately 30.8%, 22.7%, and 23.6% of LPS-induced levels, respectively, at 60 μg/mL). Mechanistic investigation revealed that the anti-inflammatory effect was mediated through the inhibition of the MAPK signaling pathway, as evidenced by decreased phosphorylation of p38, ERK, and JNK. In conclusion, WELNs exhibit dual anti-inflammatory and antioxidant properties. This study provides the first evidence of bioactivity for walnut-derived exosome-like nanoparticles, advancing the mechanistic understanding of walnuts’ health benefits and highlighting their potential as a natural component for functional food applications. Full article

The discovery of bidirectional microRNA transfer between two organisms during plant–microbe interactions and the ability of some fungal pathogens to absorb double-stranded RNA (dsRNA) or short interfering RNA (siRNA) from the environment provided an impetus for exploiting this mechanism in plant defense against pathogens. In this study, we investigated the role of conserved wheat microRNAs (miRNAs), miRNA408 and miRNA159, in inducing plant defense responses and suppressing the virulence of the phytopathogenic ascomycete fungus Parastagonospora nodorum, mediated by necrotrophic effectors (NEs) encoded by SnTox genes regulated by fungal transcription factors (TFs). The foliar spraying with in vitro synthesized siRNA408 and siRNA159 duplexes before inoculation with SnTox3-producing P. nodorum isolate increased wheat plant resistance to the SnB isolate and suppressed the pathogen growth and development. Most likely, silencing of the miRNA408 target genes TaCAT-2A, TaCAT-2B, and TaCLP1, and the miRNA159 target gene TaMYB65, led to the induction of a defense response of wheat plants against P. nodorum. This defense response was characterized by a decrease in the catalase activity, accumulation of hydrogen peroxide, activation of the expression of salicylic acid signaling pathway genes (TaWRKY13, TaPR1), and suppression of the expression of ethylene signaling pathway genes (TaEIN3, TaPR3). We demonstrated for the first time the ability of siRNA159 and siRNA408 to penetrate the mycelium of the pathogen P. nodorum and be involved in the cross-kingdom regulation of fungal genes to suppress the expression of some genes of NE (SnToxA, SnTox3) and fungal TFs (SnStuA). We predicted potential targets for wheat miRNA408 and miRNA159 in the P. nodorum transcriptome, making spray-induced gene silencing (SIGS) promising for use against this pathogen. These results provide valuable insights for studying the cross-kingdom transfer of plant miRNAs. Full article

Background: This study investigated the renoprotective potential of Nano-Cilostazol against cisplatin (CIS)-induced renal injury in male rats and explored its molecular mechanisms. Our results showed that Nano-Cilostazol has a favorable physicochemical characteristic, including a mean particle size of approximately 101 nm, narrow polydispersity, and high stability. FTIR analysis indicated successful drug entrapment, preserving functional groups and enhancing hydrogen bonding. Docking analysis showed that cilostazol had stronger binding affinities than disulfiram against seven acute kidney injury-related targets. Interaction profiling confirmed stable binding through hydrogen bonding, hydrophobic, and π-interactions with BAX, ASC, GSDMD, KIM-1, JAK2, NLRP3, and miRNA-155. In vivo, CIS administration led to marked renal dysfunction, showing up as significant elevations in serum urea, creatinine, cystatin-C, CRP, and NGAL which indicated by severe histopathological damage. Co-treatment with Nano-Cilostazol significantly lessened renal functional impairment biochemically and histopatologically. Nano-Cilostazol markedly reduced lipid peroxidation and oxidized glutathione while also restoring antioxidant defenses like superoxide dismutase and catalase, with total and reduced glutathione. Additionally, Nano-Cilostazol attenuated renal inflammation, inhibiting NF-κB activation, lowering pro-inflammatory cytokines (TNF-α and IL-1β), and downregulating inflammatory and injury-related genes. CIS-triggered apoptotic signaling was also mitigated, shown by increased caspase-3 and BAX expression with downregulation of BCL-2. Nano-Cilostazol significantly inhibited apoptosis and pyroptosis (NLRP3, ASC, GSDMD)-related pathways, modulated JAK2/STAT3 signaling, and downregulated miRNA-155 expression. In conclusion, Nano-Cilostazol offers potent protection against cisplatin-induced nephrotoxicity. Full article

Background: Sirtuin 3 (SIRT3), a mitochondrial NAD⁺-dependent deacetylase, plays a central role in regulating mitochondrial metabolism, oxidative stress, and cell survival. Although SIRT3 has been implicated in angiogenesis, apoptosis, and inflammation, its global proteomic impact on the brain remains unclear. This study aimed to systematically characterize alterations in angiogenesis-, apoptosis-, chemokine-, and cytokine-related proteins in the brains of SIRT3 knockout (SIRT3 KO aka SIRT3⁻/⁻) mice compared with wild-type (WT) controls. Methods: Adult male C57BL/6 WT and SIRT3 KO mice were analyzed using proteome profiler antibody microarrays covering 53 angiogenesis factors, 21 apoptosis markers, 28 chemokines, and 111 cytokines. Protein expression changes were quantified by chemiluminescence imaging and densitometric analysis. Results: The results showed a distinct suppression of angiogenic proteins (amphiregulin, angiogenin, DPPIV, GM-CSF, IGFBP-2, IGFBP-3, IL-1β, PDGF-AA, PDGF-BB, proliferin, serpin F1, thrombospeondin-2, TIMP-4, and VEGF-B), activation of both pro-apoptotic (BAD, cytochrome c, Smac/DIABLO, HIF-1α, Fas, TNF R1, and TRAILR2) and anti-apoptotic, stress-related proteins (Bcl-x, catalase, HO/HMOX2, HSP27, HSP70, and MCL1) in the SIRT3 KO animals compared with the WT controls. Notably, SIRT3 deficiency was associated with increased expression of inflammatory mediators linked to glial activation and neurodegeneration (BLC/CCL13, LIX/CXCL5, MIG/CXCL9, chitinase 3-like 1, CCL22/MDC, IL-6, myeloperoxidase, osteopontin, RBP4, Reg3G, and TNF-α), alongside disturbed proteins involved in immune surveillance and vascular remodeling (6Ckine/CCL21, chemerin, DF, EGF, fractalkine/CX3CL1, HGF, IGFBP-6, IL-16, and I-TAC). Conclusions: Collectively, these findings demonstrate that SIRT3 is a key regulator of mitochondrial-dependent vascular, apoptotic, and neuroimmune pathways in the brain, and that its loss creates a molecular environment consistent with heightened vulnerability to neurodegenerative processes. Full article