-
Scientific Reports Jun 2024In recent decades, the food system has been faced with the significant problem of increasing food waste. Therefore, the feed industry, supported by scientific research,...
In recent decades, the food system has been faced with the significant problem of increasing food waste. Therefore, the feed industry, supported by scientific research, is attempting to valorise the use of discarded biomass as co-products for the livestock sector, in line with EU objectives. In parallel, the search for functional products that can ensure animal health and performances is a common fundamental goal for both animal husbandry and feeding. In this context, camelina cake (CAMC), cardoon cake (CC) and cardoon meal (CM), due valuable nutritional profile, represent prospective alternatives. Therefore, the aim of this work was to investigate the antioxidant activity of CAMC, CC and CM following in vitro digestion using 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), Ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Total phenolic content (TPC) and angiotensin converting enzyme (ACE) inhibitory activity, actively involved in modulating antioxidant properties, were also studied. Further, a peptidomic analysis was adopted to substantiate the presence of bioactive peptides after in vitro digestion. The results obtained confirmed an interesting nutritional profile of CAMC, CC and CM and relevant antioxidant and ACE inhibitory activities. In particular, considering antioxidant profile, CM and CC revealed a significantly higher (10969.80 ± 18.93 mg TE/100 g and 10451.40 ± 149.17 mg TE/100 g, respectively; p < 0.05) ABTS value than CAMC (9511.18 ± 315.29 mg TE/100 g); a trend also confirmed with the FRAP assay (306.74 ± 5.68 mg FeSO/100 g; 272.84 ± 11.02 mg FeSO/100 g; 103.84 ± 3.27 mg FeSO/100 g, for CC, CM and CAMC, respectively). Similar results were obtained for TPC, demonstrating the involvement of phenols in modulating antioxidant activity. Finally, CAMC was found to have a higher ACE inhibitory activity (40.34 ± 10.11%) than the other matrices. Furthermore, potentially bioactive peptides associated with ACE inhibitory, anti-hypertensive, anti-cancer, antimicrobial, antiviral, antithrombotic, DPP-IV inhibitory and PEP-inhibitory activities were identified in CAMC. This profile was broader than that of CC and CM. The presence of such peptides corroborates the antioxidant and ACE profile of the sample. Although the data obtained report the important antioxidant profile of CAMC, CC, and CM and support their possible use, future investigations, particularly in vivo trials will be critical to evaluate and further investigate their effects on the health and performance of farm animals.
Topics: Antioxidants; Cynara; Brassicaceae; Angiotensin-Converting Enzyme Inhibitors; Phenols; Peptides; Animals; Plant Extracts; Animal Feed; Proteomics
PubMed: 38914602
DOI: 10.1038/s41598-024-64989-3 -
PloS One 2024The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This...
The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.
Topics: Animals; Asthma; Rosuvastatin Calcium; AMP-Activated Protein Kinases; Signal Transduction; Airway Remodeling; Mice; Disease Models, Animal; Ovalbumin; Female; Mice, Inbred BALB C; Bronchoalveolar Lavage Fluid; Chronic Disease; Inflammation; Lung; Immunoglobulin E
PubMed: 38913666
DOI: 10.1371/journal.pone.0305863 -
ACS Nanoscience Au Jun 2024Gold nanoparticles (AuNPs) are a promising platform for biomedical applications including therapeutics, imaging, and drug delivery. While much of the literature...
Gold nanoparticles (AuNPs) are a promising platform for biomedical applications including therapeutics, imaging, and drug delivery. While much of the literature surrounding the introduction of AuNPs into cellular systems focuses on uptake and cytotoxicity, less is understood about how AuNPs can indirectly affect cells via interactions with the extracellular environment. Previous work has shown that the monocytic cell line THP-1's ability to undergo chemotaxis in response to a gradient of monocyte chemoattractant protein 1 (MCP-1) was compromised by extracellular polysulfonated AuNPs, presumably by binding to MCP-1 with some preference over other proteins in the media. The hypothesis to be explored in this work is that the degree of sulfonation of the surface would therefore be correlated with the ability of AuNPs to interrupt chemotaxis. Highly sulfonated poly(styrenesulfonate)-coated AuNPs caused strong inhibition of THP-1 chemotaxis; by reducing the degree of sulfonation on the AuNP surface with copolymers [poly(styrenesulfonate--maleate) of different compositions], it was found that medium and low sulfonation levels caused weak to no inhibition, respectively. Small, rigid molecular sulfonate surfaces were relatively ineffective at chemotaxis inhibition. Unusually, free poly(styrenesulfonate) caused a dose-dependent reversal of THP-1 cell migration: at low concentrations, free poly(styrenesulfonate) significantly inhibited MCP-1-induced chemotaxis. However, at high concentrations, free poly(styrenesulfonate) acted as a chemorepellent, causing a reversal in the cell migration direction.
PubMed: 38912285
DOI: 10.1021/acsnanoscienceau.3c00055 -
ACS Omega Jun 2024Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate...
Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of improving drug efficacy. Although the efficient transport of siderophore-antibiotic conjugates into the cytosol still remains challenging, great success has been achieved in the delivery of β-lactam antibiotics into the periplasmic space via bacterial iron uptake pathways. Cefiderocol, the first siderophore-cephalosporin conjugate approved by the US Food and Drug Administration, is a good example. These conjugation strategies have also been applied to the precise delivery of β-lactamase inhibitors, such as penicillin-based sulfone , to restore β-lactam antibiotic efficacy in multidrug-resistant bacteria. Herein, we have explored the impact on the bacterial activity of by modifying its iron chelator moiety. A set of derivatives functionalized with diverse iron chelator groups and linkages to the scaffold (compounds -) were synthesized and assayed in vitro. The results on the ability of derivatives - to recover β-lactam antibiotic efficacy in difficult-to-treat pathogens that produce various β-lactamase enzymes, along with kinetic studies with the isolated enzymes, allowed us to identify compound , a novel β-lactamase inhibitor with an expanded spectrum of activity. Molecular dynamics simulation studies provided us with further information regarding the molecular basis of the relative inhibitory properties of the most relevant compound described herein.
PubMed: 38911797
DOI: 10.1021/acsomega.4c02984 -
ACS Omega Jun 2024Proton exchange membranes (PEMs) are subject to mechanical degradation, such as microcracks and pinhole formation, under real-world fuel cell operating conditions, which...
Proton exchange membranes (PEMs) are subject to mechanical degradation, such as microcracks and pinhole formation, under real-world fuel cell operating conditions, which leads to great issues in terms of device death and safety concerns. Therefore, PEMs with self-healing features are imperative but have rarely been used for proton exchange membrane fuel cells (PEMFCs). Here, a dimensionally stable and self-healing PEM is developed by tuning the hydrogen bond and dipole-dipole interactions between the mature perfluorinated sulfonic acid (PFSA) and a self-healing copolymer, which is specifically synthesized with hexafluorobutyl acrylate (HFBA) and acrylic acid (AA). This hexafluorobutyl acrylate-acrylic acid copolymer (HFBA--AA) is suggested as the key to improving the self-healing efficiency of the blended PFSA/HFBA--AA membrane. This PFSA/HFBA--AA membrane can recover 43.6% of the original tensile strength within only 20 min at 80 °C. This study may pave an avenue toward the development of reliable and durable PEM for fuel cells.
PubMed: 38911736
DOI: 10.1021/acsomega.4c02263 -
Journal of Zhejiang University.... Jun 2024: Following the short-term outbreak of coronavirus disease 2019 (COVID-19) in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19...
: Following the short-term outbreak of coronavirus disease 2019 (COVID-19) in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19 are lacking. : We conducted a single-center retrospective study to describe the clinical features, complications, and mortality rates of hospitalized KTRs infected with COVID-19 between Dec. 16, 2022 and Jan. 31, 2023. The patients were followed up until Mar. 31, 2023. : A total of 324 KTRs with COVID-19 were included. The median age was 49 years. The median time between the onset of symptoms and admission was 13 d. Molnupiravir, azvudine, and nirmatrelvir/ritonavir were administered to 67 (20.7%), 11 (3.4%), and 148 (45.7%) patients, respectively. Twenty-nine (9.0%) patients were treated with more than one antiviral agent. Forty-eight (14.8%) patients were treated with tocilizumab and 53 (16.4%) patients received baricitinib therapy. The acute kidney injury (AKI) occurred in 81 (25.0%) patients and 39 (12.0%) patients were admitted to intensive care units. Fungal infections were observed in 55 (17.0%) patients. Fifty (15.4%) patients lost their graft. The 28-d mortality rate of patients was 9.0% and 42 (13.0%) patients died by the end of follow-up. Multivariate Cox regression analysis identified that cerebrovascular disease, AKI incidence, interleukin (IL)-6 level of >6.8 pg/mL, daily dose of corticosteroids of >50 mg, and fungal infection were all associated with an increased risk of death for hospitalized patients. : Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality. The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival, while higher doses of corticosteroids may increase the death risk.
Topics: Humans; Kidney Transplantation; Middle Aged; Male; Female; COVID-19; Retrospective Studies; China; Antiviral Agents; Adult; SARS-CoV-2; Hospitalization; Transplant Recipients; Aged; COVID-19 Drug Treatment; Antibodies, Monoclonal, Humanized; Azetidines; Purines; Pyrazoles; Sulfonamides
PubMed: 38910497
DOI: 10.1631/jzus.B2300538 -
Chemical & Pharmaceutical Bulletin 2024We report the first total synthesis of silybin A (1). Key synthetic steps include the construction of the 1,4-benzodioxane neolignan skeleton, a modified Julia-Kocienski...
We report the first total synthesis of silybin A (1). Key synthetic steps include the construction of the 1,4-benzodioxane neolignan skeleton, a modified Julia-Kocienski olefination reaction between m-nitrophenyltetrazole sulfone (m-NPT sulfone) 10 and aldehyde 21, the formation of the flavanol lignan skeleton 28 via a quinomethide intermediate under acidic conditions, and stepwise oxidation of the benzylic position of flavanol 29.
Topics: Silybin; Stereoisomerism; Molecular Structure; Silymarin; Oxidation-Reduction
PubMed: 38910121
DOI: 10.1248/cpb.c24-00276 -
Environment International Jun 2024
Corrigendum to "Developmental toxicity of perfluorohexane sulfonate at human relevant dose during pregnancy via disruption in placental lipid homeostasis" [Environ. Int. 177 (2023) 108014].
PubMed: 38910050
DOI: 10.1016/j.envint.2024.108840 -
Journal of Experimental & Clinical... Jun 2024Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand...
BACKGROUND
Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment.
METHODS
First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model.
RESULTS
AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2.
CONCLUSION
Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients.
Topics: Humans; Leukemia, Myeloid, Acute; Animals; Mice; TNF-Related Apoptosis-Inducing Ligand; Bridged Bicyclo Compounds, Heterocyclic; Apoptosis; Sulfonamides; Drug Synergism; Cell Line, Tumor; Nucleophosmin; Xenograft Model Antitumor Assays; Cytoplasm; Female; Nuclear Proteins
PubMed: 38909249
DOI: 10.1186/s13046-024-03100-0 -
Cell Death & Disease Jun 2024The transmembrane death receptor Fas transduces apoptotic signals upon binding its ligand, FasL. Although Fas is highly expressed in cancer cells, insufficient cell...
The transmembrane death receptor Fas transduces apoptotic signals upon binding its ligand, FasL. Although Fas is highly expressed in cancer cells, insufficient cell surface Fas expression desensitizes cancer cells to Fas-induced apoptosis. Here, we show that the increase in Fas microaggregate formation on the plasma membrane in response to the inhibition of endocytosis sensitizes cancer cells to Fas-induced apoptosis. We used a clinically accessible Rho-kinase inhibitor, fasudil, that reduces endocytosis dynamics by increasing plasma membrane tension. In combination with exogenous soluble FasL (sFasL), fasudil promoted cancer cell apoptosis, but this collaborative effect was substantially weaker in nonmalignant cells. The combination of sFasL and fasudil prevented glioblastoma cell growth in embryonic stem cell-derived brain organoids and induced tumor regression in a xenograft mouse model. Our results demonstrate that sFasL has strong potential for apoptosis-directed cancer therapy when Fas microaggregate formation is augmented by mechano-inhibition of endocytosis.
Topics: Humans; Endocytosis; Apoptosis; Animals; Fas Ligand Protein; fas Receptor; Mice; Cell Line, Tumor; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Xenograft Model Antitumor Assays; Glioblastoma
PubMed: 38909035
DOI: 10.1038/s41419-024-06822-3