Search Results (308)

Objectives: The current study focused on the kidney protection and antioxidant properties along with the potential anti-ferroptotic activity of Geranium macrorrhizum L. (G. macrorrhizum) oil to ameliorate the acute renal oxidative tissue damage and toxicity of the aminoglycoside antibiotic gentamicin (GM) in an experimental murine model. Methods: The research was carried out with mature Balb/c mice distributed into four groups (n = 6). Application of GM (200 mg kg⁻¹ intraperitoneal injection for 10 days) was performed to induce kidney injury. Only saline was administered to the controls. The remaining groups were administered G. macrorrhizum oil (50 mg kg⁻¹ per dose) either used alone or in combination with GM. To assess the renal antioxidant status, the activities of specific antioxidant enzymes, indicators of lipid and DNA peroxidation and renal functional damage were examined using standard commercial kits, ELISA and EPR spectroscopy. Results: G. macrorrhizum oil analysis revealed 20 organic components belonging to mono- and sesquiterpenoids and long-chain hydrocarbons. The antioxidant and anti-inflammatory effects of G. macrorrhizum oil were demonstrated by reduced malondialdehyde, ROS, 8-hydroxy-2′-deoxyguanosine and cytokine levels (especially interleukin-1β) compared with GM. Furthermore, increased activation of superoxide dismutase, catalase and glutathione (GSH) were observed in the kidney homogenates of the animals which received GM in combination with G. macrorrhizum oil compared with the GM group. Additional changes in the GSH/glutathione peroxidase-4 axis were detected, suggesting the possible anti-ferroptotic potential of the oil. Nephroprotection was also demonstrated by elevated PGC-1α expression (peroxisome proliferator-activated receptor γ coactivator 1-alpha) and reduced KIM-1 levels (kidney injury molecule-1) following application of the oil. Conclusions: The preserved kidney antioxidant and functional properties in the groups treated with oil suggest that Geranium macrorrhizum L. could be utilized clinically to mitigate the toxic effects of GM application. Full article

Endothelial dysfunction underlies several vascular complications, including diabetes and atherosclerosis. However, the underlying role of long non-coding RNAs (lncRNAs) remains poorly understood. This study elucidated the role of lncRNA Gm39822 in regulating endothelial dysfunction under healthy and diabetic conditions. Our data revealed that Gm39822 is enriched and upregulated in non-diabetic endothelial cells when exposed to high glucose or inflammatory cytokines (TNF-α and IL-1β). Gm39822 overexpression promoted the expression of vascular cell adhesion molecule-1 (VCAM-1) and the adhesion of leukocytes in non-diabetic ECs but not in diabetic ECs. Conversely, Gm39822 silencing reduced VCAM1 expression and leukocyte adhesion in non-diabetic ECs and not in diabetic ECs. Gm39822 deficiency reduced the expression of inflammatory mediators (including p-P65, P65, P50, p-P38, P38, P-ERK1/2, and ERK1/2) in non-diabetic ECs. Furthermore, Gm39822 knockdown inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, suggesting that Gm39822 regulates EC inflammatory responses. Mechanistically, we identified C1D, a nuclear-enriched corepressor, as an interacting partner of Gm39822 that could play an important role in mediating Gm39822 functions in non-diabetic ECs. Collectively, our results identify a novel lncRNA Gm39822 and provide insights into the molecular mechanisms underlying endothelial dysfunction. These findings highlight Gm39822 as a potential therapeutic target for mitigating vascular complications associated with non-diabetic endothelial dysfunction. Full article

Neuroinflammation driven by microglial activation and α-synuclein (αSyn) aggregation is one of the central features driving Parkinson’s disease (PD) pathogenesis. GM1 ganglioside’s oligosaccharide moiety (OligoGM1) has shown neuroprotective potential in PD neuronal models, but its direct effects on inflammation remain poorly defined. This study investigated the ability of OligoGM1 to modulate microglial activation and αSyn handling in a human in vitro model. Human embryonic microglial (HMC3) cells were exposed to αSyn pre-formed fibrils (PFFs) in the presence or absence of OligoGM1. Microglial activation markers, intracellular αSyn accumulation, and cytokine release were assessed by immunofluorescence and ELISA. OligoGM1 had no effect on microglial morphology or cytokine release under basal conditions. Upon αSyn challenge, cells exhibited increased amounts of ionized calcium-binding adaptor molecule 1 (Iba1), triggered receptor expressed on myeloid cells 2 (TREM2), elevated αSyn accumulation, and secreted pro-inflammatory cytokines. OligoGM1 pre-treatment significantly reduced the number and area of Iba1(+) cells, the intracellular αSyn burden in TREM2(+) microglia, and the release of interleukin 6 (IL-6). OligoGM1 selectively attenuated αSyn-induced microglial activation and enhanced αSyn clearance without compromising basal immune function. These findings confirm and support the potential of OligoGM1 as a multitarget therapeutic candidate for PD that is capable of modulating glial reactivity and neuroinflammatory responses. Full article

The influence of the copper (Cu) content on the corrosion resistance of 3.5%Ni low-carbon weathering steel was investigated using periodic dry–wet cycle accelerated corrosion tests. The mechanical properties of the steels were assessed via tensile and low-temperature impact tests, while corrosion resistance was evaluated based on weight loss measurements. Surface oxide layers were characterized using three-dimensional laser confocal microscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and electrochemical methods. Electron probe microanalysis (EPMA) was employed to examine the cross-sectional morphology of the oxide layer after 72 h of accelerated corrosion tests. The results indicate that the solution state of Cu increased the strength of 3.5%Ni steels but significantly damaged the low-temperature toughness. As the Cu content increased from 0.75% to 1.25%, the corrosion rate decreased from 4.65 to 3.74 g/m² h. However, when there was a further increase in the Cu content to 2.15%, there was little decrease in the corrosion rate. With the increase in the Cu content from 0.75% to 2.15%, the surface roughness of 3.5%Ni weathering steel after corrosion decreased from 5.543 to 5.019 μm, and the corrosion behavior was more uniform. Additionally, the α/γ protective factor of the oxide layer of the surface layer increased from 2.58 to 2.84 with an increase in the Cu content from 0.75% to 1.25%, resulting in the oxide layer of the surface layer being more protective. For 1.25%Cu steel, the corrosion current density of rusted samples is lower (ranging from 1.2609 × 10⁻⁴ A/cm² to 3.7376 × 10⁻⁴ A/cm²), and the corrosion potential is higher (ranging from −0.85544 V to −0.40243 V). Therefore, the rusted samples are more corrosion resistant. The Cu in the oxide layer of the surface layer forms CuO and CuFeO₂, which are helpful for increasing corrosion resistance, which inhibits the penetration of Cl⁻. Full article

Monitoring soil moisture (SM) using permanently installed gamma radiation (GR) detectors is a promising non-invasive method based on the inverse relationship between SM and soil-emitted GR. In a previous study, we successfully estimated SM from environmental gamma radiation (EGR) measured by a low-cost counter-tube detector. Since this detector type provides a bulk GR response across a wide energy range, EGR signals are influenced by several confounding factors, e.g., soil radon emanation, biomass. To what extent these confounding factors deteriorate the accuracy of SM estimates obtained from EGR is not fully understood. Therefore, the aim of this study was to compare the accuracy of SM estimates from EGR with those from reference ⁴⁰K GR (1460 keV) measurements which are much less influenced by these factors. For this, a Geiger–Mueller counter (G–M), which is commonly used for EGR monitoring, and a gamma spectrometer were installed side by side in an agricultural field equipped with in situ sensors to measure reference SM and a meteorological station. The EGR_G–M and spectrometry-based ⁴⁰K measurements were related to reference SM using a functional relationship derived from theory. We found that daily SM can be predicted with an RMSE of 3.39 vol. % from ⁴⁰K using the theoretical value of α = 1.11 obtained from the effective ratio of GR mass attenuation coefficients for the water and solid phase. A lower accuracy was achieved for the EGR_G–M measurements (RMSE = 6.90 vol. %). Wavelet coherence analysis revealed that the EGR_G–M measurements were influenced by radon-induced noise in winter. Additionally, biomass shielding had a stronger impact on EGR_G–M than on ⁴⁰K GR estimates of SM during summer. In summary, our study provides a better understanding on the lower prediction accuracy of EGR_G–M and suggests that correcting for biomass can improve SM estimation from the bulk EGR data of operational radioactivity monitoring networks. Full article

Young leaves of reed (Phragmites communis) have been reported to exhibit antioxidant effects; however, their anti-inflammatory properties have not yet been investigated. In this study, we evaluated the effects of young reed leaf extract (PCE) on LPS-induced inflammation in RAW 264.7 cells and elucidated the underlying molecular mechanisms. Our results demonstrate that PCE significantly inhibited the production of nitric oxide (NO) by approximately 45% at 100 μg/mL (p < 0.01) and pro-inflammatory cytokines such as IL-6, TNF-α, and GM-CSF by 40–60% (p < 0.01) in LPS-stimulated RAW 264.7 macrophages, without cytotoxicity up to 100 μg/mL. PCE also downregulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and upregulated heme oxygenase-1 (HO-1) expression by approximately 2-fold at 100 μg/mL (p < 0.05). Mechanistically, these effects were associated with the inhibition of IκBα phosphorylation/degradation, IKKα/β phosphorylation, and AP-1 activation via the suppression of JNK and ERK signaling pathways, as well as the inhibition of STAT1/3 phosphorylation. Collectively, our findings suggest that PCE exerts anti-inflammatory effects by modulating the IκB, AP-1, and STAT1/3 signaling pathways, thereby suppressing inflammatory mediator production and enhancing antioxidant defense mechanisms in LPS-treated macrophages. Full article

Cardiotoxicity related to anthracyclines and trastuzumab represents a significant clinical challenge in cancer therapy, often limiting treatment efficacy and patient survival. The underlying mechanisms of cardiotoxicity involve the activation of NLRP3 and the MyD88-dependent signaling pathway. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), such as inclisiran, are known for their lipid-lowering effects, but emerging data indicate that they may also exert pleiotropic benefits beyond cholesterol reduction. This study investigates whether inclisiran can mitigate the cardiotoxic effects of anthracyclines and trastuzumab through reduction of NLRP3 activation and MyD88 signaling, independently of its effects on dyslipidemia. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to subclinical concentrations of doxorubicin (1 µM) and trastuzumab in sequential therapy (200 nM), alone or in combination with inclisiran (100 nM) for 24 h. After the incubation period, we performed the following tests: determination of cardiomyocytes apoptosis, analysis of intracellular reactive oxygen species, lipid peroxidation products (including malondialdehyde and 4-hydroxynonenal), intracellular mitofusin-2 and Ca⁺⁺ levels. Troponin and BNP were quantified through selective ELISA methods. A confocal laser scanning microscope was used to study cardiomyocyte morphology and F-actin staining after treatments. Moreover, pro-inflammatory studies were also performed, including the intracellular expression of NLRP-3, MyD-88 and twelve cytokines/growth factors involved in cardiotoxicity (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IFN-γ, TNF-α, G-CSF, GM-CSF). Inclisiran co-incubated with doxorubicin and trastuzumab exerts significant cardioprotective effects, enhancing cell viability by 88.9% compared to only DOXO/TRA treated cells (p < 0.001 for all). Significant reduction of oxidative stress, and intracellular levels of NLRP-3, MyD88, IL-1α, IL-1β, IL-6, IL-12, IL17-α, TNF-α, G-CSF were seen in the inclisiran group vs. only DOXO/TRA (p < 0.001). For the first time, PCSK9i inclisiran has been shown to exert significant anti-inflammatory effects to reduce anthracycline-HER-2 blocking agent-mediated cardiotoxicity through NLRP-3 and Myd-88 related pathways. The overall conclusions of the study warrant further investigation of the use of PCSK9i in primary prevention of CTRCD in cancer patients, independently from dyslipidemia. Full article

Diagnosis of histoplasmosis is challenging. A rapid, sensitive, and specific method is essential. Serum is a non-invasive and easy sample to obtain in any hospital. The diagnostic accuracy of different techniques that use serum has been evaluated. Forty-one serum samples from patients with proven or probable histoplasmosis were analyzed. Different diagnostic techniques based on the detection of antibodies (ID Fungal Antibody System), antigens (Histoplasma GM EIA and Platelia^TM Aspergillus Ag), and DNA (“in-house” real-time PCR (RT-PCR) were tested and compared. Additionally, the quantification of cytokines and biomarkers related to histoplasmosis was performed. Global results from 27 samples in which all the tests were performed showed that the sensitivity of the Histoplasma GM EIA kit was 87.5% in patients with disseminated infection and HIV as an underlying disease; in immunocompetent (IC) patients, it was 54.5%. The detection of Histoplasma spp. with the ID Fungal Antibody System was positive in 90.9% of IC and in 62.5% of HIV patients. The Platelia-Asp kit had a low performance in both groups of patients (37.5% in HIV and 9% in non-HIV), and, finally, RT-PCR was better in immunosuppressed patients (44% in HIV vs. 27% in non-HIV). The combination of diagnostic techniques increased the detection of Histoplasma infection in inmunosupressed patients. Overall, patient groups infected with H. capsulatum (Hc) showed higher IL-8, IL-6, IL-1β, TNF-α, and IL-18 median values compared to non-Hc-infected controls. The effectiveness of diagnostic techniques on serum samples is highly influenced by the patient’s clinical presentation and underlying condition. Consequently, a thorough assessment of the patient’s clinical presentation and disease phenotype is crucial in selecting the most suitable diagnostic method. Full article

Background/Objectives: Ivy leaf extract has been shown to alleviate bronchial infection symptoms through various mechanisms, including anti-inflammatory effects. However, its impact on adaptive immunity, particularly dendritic cell (DC)/T-cell interactions, remains unexplored. This study investigated the immunomodulatory potential of ivy leaf extract (EA 575^®) using human monocyte-derived DCs (MoDCs). Methods: Immature MoDCs (imMoDCs) were differentiated with IL-4/GM-CSF and matured with LPS/IFN-γ (mMoDCs). MoDCs, treated with EA 575^® during differentiation, were co-cultured with purified T cells. Results: EA 575^® (non-cytotoxic up to 100 µg/mL) inhibited MoDC differentiation and maturation by reducing the expression of CD1a, CD83, CD40, CD86, HLA-DR, Dectin-1, CD206, CD209, HIF-1α, and proinflammatory cytokines (IL-12, IL-23, IL-27, IL-1β, IL-6, TNF-α). EA 575^®-treated mMoDCs suppressed allogeneic T-cell proliferation and reduced Th1 (IFN-γ), Th17 (IL-17A, IL-22), Th9 (IL-9), Th21 (IL-21), TNF-α, and IL-6 responses. Effects were dose-dependent, with higher concentrations (100 µg/mL) showing stronger inhibition. At lower concentrations (20 µg/mL), EA 575^® increased Th2 (IL-4, IL-5) and IL-10 responses, and the frequencies of CD4+ T cells with Treg properties, such as CD25hiFoxp3+, Tr1 (IL-10+Foxp3−), and IL-35+ Foxp3+ cells. Immunoregulatory mechanisms mediated by EA 575^®-treated mMoDCs correlated with the upregulation of tolerogenic markers (PD-L1, ILT3, ILT4, IDO1) on mMoDCs and the increased frequency of exhausted CD4+ T cells (PD-1+CD69+) and cytotoxic T cells (Granzyme B+PD-1+). Conclusions: EA 575^® induces tolerogenic DCs with significant anti-inflammatory and immunoregulatory properties, a previously undescribed phenomenon. Lower concentrations primarily enhance immunoregulatory responses, while higher concentrations exert more pronounced anti-inflammatory effects. Full article

The gut-liver-adipose axis plays a pivotal role in metabolic regulation, and its dysregulation contributes to obesity and metabolic syndrome. Probiotics and polycosanol have shown potential in modulating gut barrier integrity, lipid metabolism, and inflammation. This study aimed to evaluate their combined effects using an in vitro model of the gut-liver-adipose axis. Transwell^® system was used to recreate the interaction between intestinal (CaCo-2), hepatic (HepG2), and adipose (3T3-L1) cells. Cells were treated with Bifidobacterium bifidum GM-25, Bifidobacterium infantis GM-21, Lacticaseibacillus rhamnosus GM-28, and polycosanols. The effects were assessed by analyzing intestinal barrier integrity (TEER, tight junction proteins), hepatic and adipose lipid accumulation (Oil Red O staining), oxidative stress (ROS production, lipid peroxidation), inflammation (TNF-α) and lipid metabolism (CD36, PPARγ, AMPK and SREBP-1 levels). Probiotics and polycosanols improved intestinal integrity, increased butyrate production, and reduced ROS levels. Hepatic lipid accumulation was significantly decreased, with enhanced PPARγ and AMPK activation. In adipocytes, probiotic-polycosanols treatment suppressed SREBP-1 expression, enhanced lipid oxidation, and promoted UCP1 and PGC-1α expression, suggesting activation of thermogenic pathways. These findings underline a possible biological relevance of probiotics and polycosanols in modulating metabolic pathways, improving gut barrier integrity, and reducing inflammation, supporting their role as functional ingredients for metabolic health. Full article

Background: Renal injury is a critical health issue in pet dogs, often exacerbated by drug-induced nephrotoxicity such as gentamicin (GM). This study investigated the protective effects of ergosterol (Erg), a natural compound from edible mushrooms, against GM-induced damage in Madin–Darby canine kidney (MDCK) cells. Methods: MDCK cells were treated with GM (0.5–3 mmol/L) for 12 h to establish injury. Erg (1 to 32 μg/mL) was pretreated for 12 h before GM exposure (2 mmol/L). Cell viability, nitric oxide (NO), lactate dehydrogenase (LDH), oxidative stress markers (SOD, GSH, CAT, MDA), inflammatory cytokines (IL-1β, IL-6, TNF-α), renal function indicators (Scr, BUN), and autophagy/apoptosis-related proteins (ATG5, Beclin1, P62, BAX, BCL-2) were assessed via CCK-8, ELISA, fluorescence staining, and Western blot. Statistical significance (p < 0.05) was determined by ANOVA and LSD post hoc tests. Results: GM (2 mmol/L) significantly reduced cell viability (p < 0.01) and elevated NO and LDH levels (p < 0.01). Erg pretreatment (4–8 μg/mL) restored cell viability (p < 0.01), suppressed NO (p < 0.01) and LDH release (p < 0.01), and enhanced antioxidant enzyme activities (SOD, GSH, CAT; p < 0.01). Erg attenuated GM-induced reactive oxygen species (ROS) overproduction (p < 0.01) and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; p < 0.01). Renal markers Scr and BUN were reduced (p < 0.01). Mechanistically, Erg upregulated autophagy proteins ATG5 and Beclin1 (p < 0.01), reduced P62 accumulation (p < 0.01), and lowered the BAX/BCL-2 ratio (p < 0.01). Conclusions: Erg protects MDCK cells from GM-induced nephrotoxicity by restoring autophagy flux, suppressing mitochondrial apoptosis, and mitigating oxidative stress and inflammation. These findings highlight Erg’s potential as a natural therapeutic agent for canine renal injury. Further in vivo studies are needed to validate its clinical efficacy. Full article

We evaluated inflammatory markers among 389 surgically confirmed endometriosis cases and 505 controls from the Women’s Health Study: From Adolescence to Adulthood (A2A) cohort. Participants reported dysmenorrhea, acyclic pelvic pain, dyspareunia, and pain with bowel movements. Using multiplex assays, we measured their levels of plasma interleukin (IL)-1β, -6, -8, -10, and -16, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1 and -4, thymus and activation-regulated chemokine (TARC), and interferon gamma-induced protein (IP)-10. For each symptom, we computed biomarker-level geometric means (GMs) with 95% confidence intervals (95% CI) using multivariate linear regression among the endometriosis cases and controls, with interactions with case/control status tested using Wald statistics. Among the controls, those with dyspareunia had lower levels of IL-8 (GM_present = 4.64 [95% CI = 4.41–4.89] pg/mL vs. GM_absent = 4.99 [95% CI = 4.82–5.17] pg/mL; p = 0.02), and the IL-8 levels were lower for controls reporting pain with bowel movements (GM_present = 4.66 [95% CI = 4.43–4.89] vs. GM_absent = 4.96 [95% CI = 4.82–5.11] pg/mL, p = 0.03). No significant associations between pelvic pain symptoms and inflammatory markers were observed among the endometriosis cases; however, the relationship between inflammatory marker levels and pain experience varied by analgesic use at blood draw. Dyspareunia and pain with bowel movements were associated with inflammatory markers among the controls, while the associations between pelvic pain symptoms and inflammatory markers among the endometriosis cases differed by analgesic use. Full article

Reducing the use of chemical inputs (fertilizers, pesticides) in agriculture while maintaining crop productivity is the main challenge facing sub-Saharan African family farming systems. The use of effective microorganisms (EM) is among the various innovative approaches for minimizing chemical inputs and the environmental impact of agricultural production and protecting soil health while enhancing crop yields and improving food security. This study sought to characterize the microbial biodiversity of local beneficial microorganisms (BMs) products from locally fermented forest litter and investigate their ability to enhance tomato plant growth and development. Beneficial microorganisms (BMs) were obtained by anaerobic fermentation of forest litter collected in four agroecological regions of Senegal mixed with sugarcane molasses and various types of carbon sources (groundnut shells, millet stovers, and rice bran in different proportions). The microbial community composition was analyzed using next-generation rDNA sequencing, and their effects on tomato growth traits were tested in greenhouse experiments. Results show that regardless of the litter geographical collection site, the dominant bacterial taxa in the BMs belonged to the phyla Firmicutes (27.75–97.06%) and Proteobacteria (2.93–72.24%). Within these groups, the most prevalent classes were Bacilli (14.41–89.82%), α-proteobacteria (2.83–72.09%), and Clostridia (0.024–13.34%). Key genera included Lactobacillus (13–65.83%), Acetobacter (8.91–72.09%), Sporolactobacillus (1.40–43.35%), and Clostridium (0.08–13.34%). Fungal taxa were dominated by the classes Leotiomycetes and Sordariomycetes, with a prevalence of the acidophilic genus Acidea. Although microbial diversity is relatively uniform across samples, the relative abundance of microbial taxa is influenced by the litter’s origin. This is illustrated by the PCoA analysis, which clusters microbial communities based on their litter source. Greenhouse experiments revealed that five BMs (DK-M, DK-G, DK-GM, NB-R, and NB-M) significantly (p < 0.05) enhanced tomato growth traits, including plant height (+10.75% for DK-G and +9.44% for NB-R), root length (+56.84–62.20%), root volume (+84.32–97.35%), root surface area (+53.16–56.72%), and both fresh and dry shoot biomass when compared to untreated controls. This study revealed that forest-fermented litter products (BMs), produced using litter collected from various regions in Senegal, contain beneficial microorganisms known as plant growth-promoting microorganisms (PGPMs), which enhanced tomato growth. These findings highlight the potential of locally produced BMs as an agroecological alternative to inorganic inputs, particularly within Senegal’s family farming systems. Full article

Background: Tay–Sachs disease (TSD) is an autosomal recessive lysosomal storage disorder characterized by the accumulation of GM2 ganglioside due to mutations in the HEXA gene, which encodes the α-subunit of β-Hexosaminidase A. This accumulation leads to significant neuropathological effects and premature death in affected individuals. No effective treatments exist, but enzyme replacement therapies are under investigation. In our previous work, we demonstrated the internalization and efficacy of human recombinant lysosomal β-hexosaminidase A (rhHex-A), produced in the methylotrophic yeast Pichia pastoris, in reducing lipids and lysosomal mass levels in fibroblasts and neural stem cells derived from patient-induced pluripotent stem cells (iPSCs). In this study, we further evaluated the potential of rhHex-A to prevent GM2 accumulation using fibroblast and neuroglia cells from a TSD patient alongside a relevant mouse model. Methods: Fibroblasts and neuroglial cell lines derived from a murine model and TSD patients were treated with 100 nM rhHexA for 72 h. After treatment, cells were stained by anti-GM2 (targeting GM2 ganglioside; KM966) and anti-LAMP1 (lysosomal-associated membrane protein 1) colocalization staining and incubated with 50 nM LysoTracker Red DND-99 to label lysosomes. In addition, GM2AP and HEXB expression were analyzed to assess whether rhHex-A treatment affected the levels of enzymes involved in GM2 ganglioside degradation. Results: Immunofluorescence staining for LysoTracker and colocalization studies of GM2 and Lamp1 indicated reduced lysosomal mass and GM2 levels. Notably, rhHex-A treatment also affected the expression of the HEXB gene, which is involved in GM2 ganglioside metabolism, highlighting a potential regulatory interaction within the metabolic pathway. Conclusions: Here, we report that rhHex-A produced in yeast can efficiently degrade GM2 ganglioside and rescue lysosomal accumulation in TSD cells. Full article

Skin sensitivity is increasingly prevalent, necessitating new therapeutic agents. This study screened multifunctional peptides from Takifugu fasciatus skin for transient receptor potential vanilloid 1 (TRPV1)-inhibitory and anti-inflammatory activities and investigated their mechanisms in alleviating sensitive skin (SS). A low-molecular-weight hydrolysate was prepared through enzymatic hydrolysis of T. fasciatus skin, followed by ultrafiltration, with subsequent peptide identification performed using nano-HPLC-MS/MS and molecular docking-based virtual screening. Among 20 TRPV1-antagonistic peptides (TFTIPs), QFF (T10), LDIF (T14), and FFR (T18) exhibited potent anti-inflammatory effects in (lipopolysaccharide) LPS-induced RAW 264.7 macrophages. T14 showed the strongest TRPV1 inhibition; T14 (200 μM) inhibited Ca²⁺ in capsaicin-stimulated HaCaT cells by 73.1% and showed stable binding in molecular docking, warranting further analysis. Mechanistic studies revealed that T14 suppressed NF-κB signaling by downregulating p65 protein expression, thereby reducing pro-inflammatory cytokine secretion (G-CSF, GM-CSF, ICAM-1, IL-6, TNF-α) in RAW 264.7 cells. Additionally, T14 (400 μM) inhibited ET-1 in LPS-stimulated endothelial cells by 75.0%; ICAM-1 reached 49.0%. Network pharmacology predicted STAT3, MAPK3, SPHK1, and CTSB as key targets mediating T14’s effects. These study findings suggest that T14 may be a promising candidate for skincare applications targeting SS. Full article