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1.
Materials (Basel) ; 17(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38730953

RESUMO

In this article, ABA triblock copolymer (tri-BCP) thermoplastic elastomers with poly(ethylene oxide) (PEO) middle block and polyzwitterionic poly(4-vinylpyridine) propane-1-sulfonate (PVPS) outer blocks were synthesized. The PVPS-b-PEO-b-PVPS tri-BCPs were doped with lithium bis-(trifluoromethane-sulfonyl) imide (LiTFSI) and used as solid polyelectrolytes (SPEs). The thermal properties and microphase separation behavior of the tri-BCP/LiTFSI hybrids were studied. Small-angle X-ray scattering (SAXS) results revealed that all tri-BCPs formed asymmetric lamellar structures in the range of PVPS volume fractions from 12.9% to 26.1%. The microphase separation strength was enhanced with increasing the PVPS fraction (fPVPS) but was weakened as the doping ratio increased, which affected the thermal properties of the hybrids, such as melting temperature and glass transition temperature, to some extent. As compared with the PEO/LiTFSI hybrids, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids could achieve both higher modulus and higher ionic conductivity, which were attributed to the physical crosslinking and the assistance in dissociation of Li+ ions by the PVPS blocks, respectively. On the basis of excellent electrical and mechanical performances, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids can potentially be used as solid electrolytes in lithium-ion batteries.

2.
Bioconjug Chem ; 35(5): 693-702, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38700695

RESUMO

The development of oligomeric glucagon-like peptide-1 (GLP-1) and GLP-1-containing coagonists holds promise for enhancing the therapeutic potential of the GLP-1-based drugs for treating type 2 diabetes mellitus (T2DM). Here, we report a facile, efficient, and customizable strategy based on genetically encoded SpyCatcher-SpyTag chemistry and an inducible, cleavable self-aggregating tag (icSAT) scheme. icSAT-tagged SpyTag-fused GLP-1 and the dimeric or trimeric SpyCatcher scaffold were designed for dimeric or trimeric GLP-1, while icSAT-tagged SpyCatcher-fused GLP-1 and the icSAT-tagged SpyTag-fused GIP were designed for dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist. These SpyCatcher- and SpyTag-fused protein pairs were spontaneously ligated directly from the cell lysates. The subsequent icSAT scheme, coupled with a two-step standard column purification, resulted in target proteins with authentic N-termini, with yields ranging from 35 to 65 mg/L and purities exceeding 99%. In vitro assays revealed 3.0- to 4.1-fold increased activities for dimeric and trimeric GLP-1 compared to mono-GLP-1. The dual GLP-1/GIP receptor agonist exhibited balanced activity toward the GLP-1 receptor or the GIP receptor. All the proteins exhibited 1.8- to 3.0-fold prolonged half-lives in human serum compared to mono-GLP-1 or GIP. This study provides a generally applicable click biochemistry strategy for developing oligomeric or dual peptide/protein-based drug candidates.


Assuntos
Química Click , Peptídeo 1 Semelhante ao Glucagon , Peptídeo 1 Semelhante ao Glucagon/química , Humanos , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/química , Receptores dos Hormônios Gastrointestinais/metabolismo , Desenho de Fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/química , Polipeptídeo Inibidor Gástrico/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas
3.
J Agric Food Chem ; 72(19): 10842-10852, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38708761

RESUMO

Guvermectin, as a novel nucleoside-like biopesticide, could increase the rice yield excellently, but the potential environmental behaviors remain unclear, which pose potential health risks. Therefore, the uptake and biotransformation of guvermectin in three types of crops (rice, lettuce, and carrot) were first evaluated with a hydroponic system. Guvermectin could be rapidly absorbed and reached equilibrium in roots (12-36 h) and shoots (24-60 h) in three plants, and guvermectin was also vulnerable to dissipation in roots (t1/2 1.02-3.65 h) and shoots (t1/2 9.30-17.91 h). In addition, 8 phase I and 2 phase II metabolites, transformed from guvermectin degradation in vivo and in vitro exposure, were identified, and one was confirmed as psicofuranine, which had antibacterial and antitumor properties; other metabolites were nucleoside-like chemicals. Molecular simulation and quantitative polymerase chain reaction further demonstrated that guvermectin was metabolized by the catabolism pathway of an endogenous nucleotide. Guvermectin had similar metabolites in three plants, but the biotransformation ability had a strong species dependence. In addition, all the metabolites exhibit neglectable toxicities (bioconcentration factor <2000 L/kg b.w., LC50,rat > 5000 mg/kg b.w.) by prediction. The study provided valuable evidence for the application of guvermectin and a better understanding of the biological behavior of nucleoside-like pesticides.


Assuntos
Biotransformação , Daucus carota , Ivermectina , Lactuca , Oryza , Raízes de Plantas , Ivermectina/metabolismo , Ivermectina/análogos & derivados , Raízes de Plantas/metabolismo , Raízes de Plantas/química , Raízes de Plantas/crescimento & desenvolvimento , Lactuca/metabolismo , Lactuca/química , Lactuca/crescimento & desenvolvimento , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/química , Daucus carota/metabolismo , Daucus carota/química , Produtos Agrícolas/metabolismo , Produtos Agrícolas/química , Produtos Agrícolas/crescimento & desenvolvimento
4.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167210, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704001

RESUMO

Oxaliplatin has been included as a basal drug in various chemotherapy regimens for colorectal cancer (CRC), a global health concern. However, acquired resistance to oxaliplatin affects the prognosis. This study aimed to determine whether the consumption of a KD increases the sensitivity of CRC cells to oxaliplatin via the inhibition of a classical stem cell marker, Krupple-like factor 5 (KLF5). KLF5 functions as a transcription factor for the leukemia inhibitory factor (LIF) and directly binds to its promoter region. LIF upregulation induces dephosphorylation of metal regulatory transcription factor 1 (MTF1), which is recruited to the promoter area of Ferroportin (FPN1), the only cellular iron exporter. FPN1 upregulation reduces the labile iron pool (LIP) and ferroptosis in CRC cells. KLF5 knockdown inhibits the LIF/MTF1/FPN1 axis and induces iron overload, thereby conferring sensitivity to oxaliplatin to CRC cells. KD mimicked KLF5 silencing and sensitized CRC cells to oxaliplatin via a similar mechanism. Thus, potential correlations were observed among ketogenesis, stemness, and iron homeostasis. This finding can be used to formulate a new strategy for overcoming oxaliplatin resistance in patients with CRC.

5.
Toxicol Appl Pharmacol ; 487: 116969, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38744347

RESUMO

Cysteine and glycine-rich protein 2 (CSRP2) is expressed differently in numerous cancers and plays a key role in carcinogenesis. However, the role of CSRP2 in glioma is unknown. This study sought to determine the expression profile and clinical significance of CSRP2 in glioma and explore its biological functions and mechanisms via lentivirus-mediated CSRP2 silencing experiments. Increased CSRP2 was frequently observed in gliomas, which was associated with clinicopathological characteristics and an unfavourable prognosis. Decreasing CSRP2 led to the suppression of malignant proliferation, metastasis and stemness in glioma cells while causing hypersensitivity to chemotherapeutic drugs. Mechanistic investigations revealed that CSRP2 plays a role in mediating the Notch signalling cascade. Silencing CSRP2 decreased the levels of Notch1, cleaved Notch1, HES1 and HEY1, suppressing the Notch signalling cascade. Reactivation of Notch markedly diminished the tumour-inhibiting effects of CSRP2 silencing on the malignant phenotypes of glioma cells. Notably, CSRP2-silencing glioma cells exhibited reduced potential in the formation of xenografts in nude mice in vivo, which was associated with an impaired Notch signalling cascade. These results showed that CSRP2 is overexpressed in glioma and has a crucial role in sustaining the malignant phenotypes of glioma, suggesting that targeting CSRP2 could be a promising strategy for glioma treatment.

7.
Toxics ; 12(5)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38787086

RESUMO

Cadmium ion (Cd2+) stress is a major abiotic stressor affecting plant photosynthesis. However, the impact of sustained high-concentration Cd stress on the photosynthetic electron transport chain of aquatic plants is currently unclear. Here, prompt fluorescence (PF), delayed fluorescence (DF), and P700 signals were simultaneously measured to investigate the effect of Cd stress on photosynthesis in water dropwort [Oenanthe javanica (Blume) DC.]. We aimed to elucidate how Cd stress continuously affects the electron transport chain in this species. The PF analysis showed that with prolonged Cd stress, the FJ, FI and FP steadily decreased, accompanied by a positive shift in the K-band and L-band. Moreover, JIP-test parameters, including TRO/ABS, ABS/CSO, TRO/CSO and PIABS, were significantly reduced. The P700 signals showed that exposure to Cd stress hindered both the fast decrease and slow increase phases of the MR transient, ultimately resulting in a gradual reduction in both VPSI and VPSII-PSI. The DF analysis showed a gradual decrease in the I1 and I2 values as the duration of stress from Cd increased. The above results suggested that Cd stress affected the photosynthetic electron transport in water dropwort by influencing the amount of active PSII and PSI, primarily affecting PSII RCs in the early to mid-stages and PSI reductive activity in the later stage.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38769349

RESUMO

This study delves into the clinical implications of cyclin-dependent kinase inhibitor 2 (CDKN2) deletion in adult T-lineage acute lymphoblastic leukemia (T-ALL). Among 241 patients included in this study, 57 had CDKN2 deletion and 184 had CDKN2 wild-type (WT), and 165 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 76 did not undergo allo-HSCT. CDKN2 deletion correlated with higher white blood cell count, more high-risk diseases, and complex karyotype. The 5-year overall survival (OS) was 36.8% and 58.2% (P < 0.001), 5-year disease-free survival (DFS) was 47.1% and 59.3% (P = 0.018), and 5-year cumulative incidence of relapse (CIR) was 33.7% and 22.3% (P = 0.019) in patients with CDKN2 deletion and WT, respectively. Multivariate analysis identified CDKN2 deletion as an independent adverse prognostic factor for OS (HR 2.11, P = 0.003). In the CDKN2 deletion subgroup, landmark analysis showed that the 5-year OS was 56.7% and 19% (P = 0.002) for patients who underwent allo-HSCT and those who did not, respectively. And multivariate analysis confirmed the beneficial role of allo-HSCT in OS (HR 0.23, P < 0.001). In conclusion, CDKN2 deletion was associated with a poor prognosis in adult T-ALL, and allo-HSCT might be beneficial for this population.

9.
Anal Chim Acta ; 1306: 342581, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692785

RESUMO

Cancer detection is still a major challenge in public health. Identification of oncogene is the first step toward solving this problem. Studies have revealed that various cancers are associated with miRNA expression. Therefore, the sensitive detection of miRNA is substantially important to solve the cancer problem. In this study, let-7a, a representative substance of miRNA, was selected as the detection target. With the assistance of magnetic beads commonly used in biosensors and self-synthesized graphene oxide materials, specificity and sensitivity detection of the target gene let-7a were achieved via protease-free signal amplification. The limit of detection (LOD) was as low as 15.015pM. The fluorescence signal intensity showed a good linear relationship with the logarithm of let-7a concentration. The biosensor could also detect let-7a in complex human serum samples. Overall, this fluorescent biosensor is not only simple to operate, but also strongly specificity to detect let-7a. Therefore, it has substantial potential for application in the early diagnosis of clinical medicine and biological research.


Assuntos
Técnicas Biossensoriais , Grafite , Limite de Detecção , MicroRNAs , Técnicas Biossensoriais/métodos , Humanos , Grafite/química , MicroRNAs/análise , MicroRNAs/sangue , Espectrometria de Fluorescência , Corantes Fluorescentes/química , Neoplasias/diagnóstico , Neoplasias/sangue
10.
J Ethnopharmacol ; 330: 118217, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38641072

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The natural anodyne Ligustilide (Lig), derived from Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort., has been traditionally employed for its analgesic properties in the treatment of dysmenorrhea and migraine, and rheumatoid arthritis pain. Despite the existing reports on the correlation between TRP channels and the analgesic effects of Lig, a comprehensive understanding of their underlying mechanisms of action remains elusive. AIM OF THE STUDY: The objective of this study is to elucidate the mechanism of action of Lig on the analgesic target TRPA1 channel. METHODS: The therapeutic effect of Lig was evaluated in a rat acute soft tissue injury model. The analgesic target was identified through competitive inhibition of TRP channel agonists at the animal level, followed by Fluo-4/Ca2+ imaging on live cells overexpressing TRP proteins. The potential target was verified through in-gel imaging, colocalization using a Lig-derived molecular probe, and a drug affinity response target stability assay. The binding site of Lig was identified through protein spectrometry and further analyzed using molecular docking, site-specific mutation, and multidisciplinary approaches. RESULTS: The administration of Lig effectively ameliorated pain and attenuated oxidative stress and inflammatory responses in rats with soft tissue injuries. Moreover, the analgesic effects of Lig were specifically attributed to TRPA1. Mechanistic studies have revealed that Lig directly activates TRPA1 by interacting with the linker domain in the pre-S1 region of TRPA1. Through metabolic transformation, 6,7-epoxyligustilide (EM-Lig) forms a covalent bond with Cys703 of TRPA1 at high concentrations and prolonged exposure time. This irreversible binding prevents endogenous electrophilic products from entering the cysteine active center of ligand-binding pocket of TRPA1, thereby inhibiting Ca2+ influx through the channel opening and ultimately relieving pain. CONCLUSIONS: Lig selectively modulates the TRPA1 channel in a bimodal manner via non-electrophilic/electrophilic metabolic conversion. The epoxidized metabolic intermediate EM-Lig exerts analgesic effects by irreversibly inhibiting the activation of TRPA1 on sensory neurons. These findings not only highlight the analgesic mechanism of Lig but also offer a novel nucleophilic attack site for the development of TRPA1 antagonists in the pre-S1 region.


Assuntos
4-Butirolactona , Analgésicos , Ratos Sprague-Dawley , Canal de Cátion TRPA1 , Animais , Canal de Cátion TRPA1/metabolismo , Analgésicos/farmacologia , Analgésicos/química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , 4-Butirolactona/química , Ratos , Humanos , Dor/tratamento farmacológico , Cisteína/farmacologia , Cisteína/química , Masculino , Simulação de Acoplamento Molecular , Células HEK293 , Sítios de Ligação , Feminino
11.
Nature ; 629(8013): 951-956, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38632403

RESUMO

Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich domain to their 7-transmembrane domain1. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the extracellular ligand-binding domain to the G protein-coupling 7-transmembrane domain2. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging, we reveal distinct receptor conformations upon allosteric modulator and G protein binding.


Assuntos
Modelos Moleculares , Receptor de Glutamato Metabotrópico 5 , Humanos , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptor de Glutamato Metabotrópico 5/química , Regulação Alostérica , Ligantes , Imagem Individual de Molécula , Ligação Proteica , Domínios Proteicos , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de Glutamato Metabotrópico/química
12.
Arch Biochem Biophys ; 756: 110002, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636689

RESUMO

BACKGROUND: Phospholipid scramblase 1 (PLSCR1) is a calcium-dependent endofacial plasma-membrane protein that plays an essential role in multiple human cancers. However, little is known about its role in glioma. This study aimed to investigate PLSCR1 function in glioma, and elucidate its underlying molecular mechanisms. METHODS: PLSCR1 expression in human glioma cell lines (U87MG, U251, LN229, A172 and T98G) and human astrocytes was detected by western blot and qRT-PCR. PLSCR1 was silenced using si-PLSCR1-1 and si-PLSCR1-2 in LN229 and U251 cells. PLSCR1 was overexpressed using the pcDNA-PLSCR1 plasmid in T98G cells. Colony formation, 5-ethynyl-2'-deoxyuridine, flow cytometry and transwell assays were employed for measuring cell proliferation, apoptosis and mobility after PLSCR1 knockdown or overexpression. PLSCR1 function in glycolysis in glioma cells was determined through measuring the extracellular acidification rate, oxygen consumption rate, glucose consumption and lactate production. Besides, immunohistochemistry, western blot and qRT-PCR were utilized to assess mRNA and protein expression. Besides, the effect of PLSCR1 silencing on subcutaneous tumor was also monitored. RESULTS: PLSCR1 expression was upregulated in glioma. The downregulation of PLSCR1 repressed the proliferation, mobility, epithelial-to-mesenchymal transition (EMT) and glycolysis; however, it facilitated apoptosis in glioma cells. Whereas, PLSCR1 upregulation had the opposite effect. Moreover, PLSCR1 promoted the activation of the IL-6/JAK/STAT3 pathway in glioma cells. Besides, IL-6 treatment significantly reversed the function of PLSCR1 silencing on cell proliferation, mobility, EMT, apoptosis and glycolysis. In a nude mouse tumor model, silencing PLSCR1 suppressed tumor growth via inactivating IL-6/JAK/STAT3 signaling. CONCLUSION: Our results indicated that PLSCR1 could facilitate proliferation, mobility, EMT and glycolysis, but repress apoptosis through activating IL-6/JAK/STAT3 signaling in glioma. Therefore, PLSCR1 may function as a potential therapeutic target for glioma.


Assuntos
Proliferação de Células , Glioma , Interleucina-6 , Proteínas de Transferência de Fosfolipídeos , Fator de Transcrição STAT3 , Transdução de Sinais , Humanos , Glioma/metabolismo , Glioma/patologia , Glioma/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Proteínas de Transferência de Fosfolipídeos/metabolismo , Proteínas de Transferência de Fosfolipídeos/genética , Linhagem Celular Tumoral , Animais , Interleucina-6/metabolismo , Camundongos , Camundongos Nus , Janus Quinases/metabolismo , Apoptose , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Glicólise , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB C , Movimento Celular
13.
Sci Total Environ ; 929: 172648, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38649036

RESUMO

Growing attention is being directed towards exploring the potential harmful effects of microplastic (MP) particles on human health. Previous reports on human exposure to MPs have primarily focused on inhalation, ingestion, transdermal routes, and, potentially, transplacental transfer. The intravenous transfer of MP particles in routine healthcare settings has received limited exploration in existing literature. Standard hospital IV system set up with 0.9 % NaCl in a laminar flow hood with MP contamination precautions. Various volumes of 0.9 % NaCl passed through the system, some with a volumetric pump. Fluid filtered with Anodisc filters washed with isopropyl alcohol. The IV cannula was immersed in Mili-Q water for 72 h to simulate vein conditions. Subsequently, the water was filtered and washed. Optical photothermal infrared (O-PTIR) microspectroscopy is used to examine filters for MP particles. All filters examined from the IV infusion system contained MP particles, including MPs from the polymer materials used in the manufacture of the IV delivery systems (polydimethylsiloxane, polypropylene, polystyrene, and polyvinyl chloride) and MP particles arising from plastic resin additives (epoxy resin, polyamide resin, and polysiloxane-containing MPs). The geometric mean from the extrapolated result data indicated that approximately 0.90 MP particles per mL of 0.9 % NaCl solution can be administered through a conventional IV infusion system in the absence of a volumetric pump. However, with the implementation of a pump, this value may increase to 1.57 particles per mL. Notably, over 72 h, a single cannula was found to release approximately 558 MP particles including polydimethylsiloxane, polysiloxane-containing MPs, polyamide resin, and epoxy resin. Routine IV infusion systems release microplastics. MP particles are also released around IV cannulas, suggesting transfer into the circulatory system during standard IV procedures.


Assuntos
Microplásticos , Microplásticos/análise , Espectrofotometria Infravermelho , Monitoramento Ambiental/métodos , Infusões Intravenosas , Humanos , Plásticos/análise
14.
Food Funct ; 15(9): 4954-4969, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38602356

RESUMO

Overdose of Acetaminophen (APAP) is a major contributor to acute liver injury (ALI), a complex pathological process with limited effective treatments. Emerging evidence links lipid peroxidation to APAP-induced ALI. Cynarin (Cyn), a hydroxycinnamic acid derivative, exhibits liver protective effects, but whether it mitigates APAP-induced ALI is unclear. Our aim was to verify the protective impact of Cyn on APAP-induced ALI and elucidate the molecular mechanisms governing this process. Herein, the regulation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) interaction was determined to be a novel mechanism underlying this protective impact of Cyn against APAP-induced ALI. Nrf2 deficiency increased the severity of APAP-induced ALI and lipid peroxidation and counteracted the protective effect of Cyn against this pathology. Additionally, Cyn promoted the dissociation of Nrf2 from Keap1, enhancing the nuclear translocation of Nrf2 and the transcription of downstream antioxidant proteins, thereby inhibiting lipid peroxidation. Molecular docking demonstrated that Cyn bound competitively to Keap1, and overexpression of Keap1 reversed Nrf2-activated anti-lipid peroxidation. Additionally, Cyn activated the adenosine monophosphate-activated protein kinase (AMPK)/sirtuin (SIRT)3 signaling pathway, which exhibits a protective effect on APAP-induced ALI. These findings propose that Cyn alleviates APAP-induced ALI by enhancing the Keap1/Nrf2-mediated lipid peroxidation defense via activation of the AMPK/SIRT3 signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Proteína 1 Associada a ECH Semelhante a Kelch , Peroxidação de Lipídeos , Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Acetaminofen/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Camundongos , Masculino , Proteínas Quinases Ativadas por AMP/metabolismo , Sirtuína 3/metabolismo , Sirtuína 3/genética , Camundongos Endogâmicos C57BL , Humanos , Ácidos Cumáricos/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos
15.
Int J Biol Macromol ; 267(Pt 2): 131462, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614163

RESUMO

The rapid development of the industry has led to the destruction of the earth's ozone layer, resulting in an increasingly serious problem of excessive ultraviolet radiation. Exploring effective measures to address these problems has become a hot topic. Lignin shows promise in the design and preparation of anti-ultraviolet products due to its inherent properties. However, it is important to investigate way to enhance the reactivity of lignin and determine its application form in related products. In this study, phenolic reactions with tea polyphenols were conducted through acid-catalyzed conversion, utilizing organic solvent lignin as the primary material. The phenolic hydroxyl content of the original lignin increased significantly by 218.8 %, resulting in notable improvements in UV resistance and oxidation resistance for phenolic lignin. Additionally, micro-nanocapsule emulsions were formed using phenolic lignin particles as surfactants through ultrasonic cavitation with small-molecule sunscreens. A bio-based sunscreen was prepared with phenolated lignin micro-nanocapsules as the active ingredient, achieving an SPF 100.2 and demonstrating excellent stability. The sunscreen also exhibited strong antioxidant properties and impermeability, ensuring user safety. This research offers a current solution for improving the application of lignin in sunscreens while also broadening the potential uses of plant-based materials in advanced functional products.


Assuntos
Lignina , Oxirredução , Polifenóis , Protetores Solares , Chá , Raios Ultravioleta , Lignina/química , Polifenóis/química , Catálise , Chá/química , Protetores Solares/química , Protetores Solares/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Ácidos/química
16.
Front Neurosci ; 18: 1349781, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560048

RESUMO

Background and objectives: Glioblastoma (GBM) and brain metastasis (MET) are the two most common intracranial tumors. However, the different pathogenesis of the two tumors leads to completely different treatment options. In terms of magnetic resonance imaging (MRI), GBM and MET are extremely similar, which makes differentiation by imaging extremely challenging. Therefore, this study explores an improved deep learning algorithm to assist in the differentiation of GBM and MET. Materials and methods: For this study, axial contrast-enhanced T1 weight (ceT1W) MRI images from 321 cases of high-grade gliomas and solitary brain metastasis were collected. Among these, 251 out of 270 cases were selected for the experimental dataset (127 glioblastomas and 124 metastases), 207 cases were chosen as the training dataset, and 44 cases as the testing dataset. We designed a new deep learning algorithm called SCAT-inception (Spatial Convolutional Attention inception) and used five-fold cross-validation to verify the results. Results: By employing the newly designed SCAT-inception model to predict glioblastomas and brain metastasis, the prediction accuracy reached 92.3%, and the sensitivity and specificity reached 93.5 and 91.1%, respectively. On the external testing dataset, our model achieved an accuracy of 91.5%, which surpasses other model performances such as VGG, UNet, and GoogLeNet. Conclusion: This study demonstrated that the SCAT-inception architecture could extract more subtle features from ceT1W images, provide state-of-the-art performance in the differentiation of GBM and MET, and surpass most existing approaches.

17.
Biochem Genet ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635014

RESUMO

Chronic rhinosinusitis without nasal polyps (CRSsNP) is a CRS phenotype. However, the mechanisms of CRSsNP remains unclear. Differentially expressed genes (DEGs) were obtained from the GSE36830 and GSE198950 datasets through the GEO2R tool. The six hub genes were screened by the protein-protein interaction (PPI) network analysis and Cytoscape software. Then we constructed the mouse models of CRS and verified the expression levels of hub genes by reverse transcription quantitative PCR (RT-qPCR). Hematoxylin-eosin (HE) staining was employed to observe pathological alterations in mouse tissues. Casepase-3 expression was detected by immunohistochemistry (IHC). The levels of TNF-α, IL-12, IL-6, IL-1ß, LDH, and IL-18 were evaluated using enzyme-linked immunosorbent assay (ELISA). Pyroptosis-related protein expressions were measured by western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were performed to assess the proliferation and apoptosis of lipopolysaccharide (LPS)-induced NP69 cells. Six hub DEGs were identified. The expression levels of IRF4, IKZF1, and CD79A were obviously increased in CRSsNP, while those of ADH6, ADH1A, and LDHC were significantly decreased. IRF4 knockdown attenuated the pathologic features of CRSsNP. IRF4 knockdown reduced levels of the TNF-α, IL-12, IL-6 IL-1ß, LDH, and IL-18 as well as the proteins expression of Casepase-1, GSDMD, and NLRP3 both in vivo and in vitro, implying that inflammation and pyroptosis were inhibited. IRF4 knockdown hinders the development of CRSsNP by inhibiting the inflammatory response and NLRP3/Caspase-1/GSDMD-mediated pyroptosis, which offers novel promising treatment strategies for clinical intervention.

18.
World J Clin Cases ; 12(11): 1974-1979, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38660558

RESUMO

BACKGROUND: This case of gestational gingival tumor is huge and extremely rare in clinical practice. As the growth location of this gingival tumor is in the upper anterior tooth area, it seriously affects the pregnant woman's speech and food, causing great pain to the patient. The use of Nd:YGA water mist laser to remove the gingival tumor resulted in minimal intraoperative bleeding, minimal adverse reactions, and good postoperative healing, which is worthy of clinical promotion and application. CASE SUMMARY: The patient, a pregnant woman, reported a large lump in her mouth on the first day of postpartum treatment. Based on medical history and clinical examination, the diagnosis was diagnosed as gestational gingival tumor. Postoperative pathological biopsy also confirmed this diagnosis. The use of Nd:YAG water mist laser to remove the tumor resulted in minimal intraoperative bleeding, clear surgical field of view, short surgical time, and good postoperative healing. CONCLUSION: In comparison to traditional surgery, Nd:YAG water mist laser surgery is minimally invasive, minimizes cell damage, reduces bleeding, ensures a clear field of vision, and virtually eliminates postoperative edema, carbonization, and the risk of cross infection. It has unique advantages in oral soft tissue surgery for pregnant patients. Therefore, the clinical application of Nd:YAG water mist laser for the treatment of gestational gingival tumors is an ideal choice.

19.
Technol Cancer Res Treat ; 23: 15330338241241935, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564315

RESUMO

Hepatocellular carcinoma (HCC), partly because of its complexity and high heterogeneity, has a poor prognosis and an extremely high mortality rate. In this study, mRNA sequencing expression profiles and relevant clinical data of HCC patients were gathered from different public databases. Kaplan-Meier survival curves as well as ROC curves validated that OLA1|CLEC3B was an independent predictor with better predictive capability of HCC prognosis compared to OLA1 and CLEC3B separately. Further, the cell transfection experiment verified that knockdown of OLA1 inhibited cell proliferation, facilitated apoptosis, and improved sensitivity of HCC cells to gemcitabine. In this study, the prognostic model of HCC composed of OLA1/CLEC3B genes was constructed and verified, and the prediction ability was favorable. A higher level of OLA1 along with a lower level of CEC3B is a sign of poor prognosis in HCC. We revealed a novel gene pair OLA1|CLEC3B overexpressed in HCC patients, which may serve as a promising independent predictor of HCC survival and an approach for innovative diagnostic and therapeutic strategies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Prognóstico , Neoplasias Hepáticas/genética , Apoptose/genética , Proliferação de Células/genética , Adenosina Trifosfatases , Proteínas de Ligação ao GTP
20.
Clin Nucl Med ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38620003

RESUMO

ABSTRACT: We report 18F-FDG PET/CT appearances of intracholecystic papillary neoplasm (ICPN) in the gallbladder neck and duct of a 74-year-old woman with a history of hepatitis B cirrhosis. The lesion presented with a large and sessile soft mass in the neck and duct of gallbladder with obvious glucose metabolism on PET/CT images, which was confirmed pathologically as ICPN (gastric foveolar type) with high-grade intraepithelial neoplasia. ICPN localized in the gallbladder neck and duct is extremely rare, and is easily misdiagnosed as gallbladder carcinoma. Our report aids in the application of PET/CT in the differential diagnosis of ICPN and guiding early surgery.

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