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1.
Acta Pharmacol Sin ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39147900

RESUMEN

The pyroptosis of renal tubular epithelial cells leads to tubular loss and inflammation and then promotes renal fibrosis. The transcription factor Krüppel-like factor 4 (KLF4) can bidirectionally regulate the transcription of target genes. Our previous study revealed that sustained elevation of KLF4 is responsible for the transition of acute kidney injury (AKI) into chronic kidney disease (CKD) and renal fibrosis. In this study, we explored the upstream mechanisms of renal tubular epithelial cell pyroptosis from the perspective of posttranslational regulation and focused on the transcription factor KLF4. Mice were subjected to unilateral ureteral obstruction (UUO) surgery and euthanized on D7 or D14 for renal tissue harvesting. We showed that the pyroptosis of renal tubular epithelial cells mediated by both the Caspase-1/GSDMD and Caspase-3/GSDME pathways was time-dependently increased in UUO mouse kidneys. Furthermore, we found that the expression of the transcription factor KLF4 was also upregulated in a time-dependent manner in UUO mouse kidneys. Tubular epithelial cell-specific Klf4 knockout alleviated UUO-induced pyroptosis and renal fibrosis. In Ang II-treated mouse renal proximal tubular epithelial cells (MTECs), we demonstrated that KLF4 bound to the promoter regions of Caspase-3 and Caspase-1 and directly increased their transcription. In addition, we found that ubiquitin-specific protease 11 (USP11) was increased in UUO mouse kidneys. USP11 deubiquitinated KLF4. Knockout of Usp11 or pretreatment with the USP11 inhibitor mitoxantrone (3 mg/kg, i.p., twice a week for two weeks before UUO surgery) significantly alleviated the increases in KLF4 expression, pyroptosis and renal fibrosis. These results demonstrated that the increased expression of USP11 in renal tubular cells prevents the ubiquitin degradation of KLF4 and that elevated KLF4 promotes inflammation and renal fibrosis by initiating tubular cell pyroptosis.

2.
Int Immunopharmacol ; 140: 112830, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39096872

RESUMEN

High-concentration fluoride treatment is commonly used to prevent dental caries in the oral cavity, and fluorine-containing protective paint is used to alleviate common root sensitivity symptoms in patients with periodontitis after periodontal treatment. Recent studies have confirmed its safe use in normal oral environments. However, whether fluoride treatment affects the progression of periodontitis in an inflammatory microenvironment remains unclear. Immunometabolism is crucial for maintaining bone regeneration and repair in periodontitis, and the precise regulation of macrophage polarisation is crucial to this process. Fluoride can influence the immune microenvironment of bone tissue by regulating immune metabolic processes. Herein, we investigated the effects of high concentrations of sodium fluoride (NaF) on periodontal tissues. We examined the expression of osteogenic and M1/M2 macrophage polarisation markers and glucose metabolism in macrophages. RNA sequencing was used to study differentially expressed genes related to M1 polarisation and glucose metabolism in treated macrophages. The results showed that NaF indirectly affects human periodontal ligament cells (hPDLCs), aggravating bone loss, tissue destruction, and submandibular lymph node drainage. Furthermore, NaF promoted glycolysis in macrophages and M1 polarisation while inhibiting osteogenic differentiation. These findings suggest that NaF has a direct effect on hPDLCs. Moreover, we found that high concentrations of NaF stimulated M1 polarisation in macrophages by promoting glycolysis. Overall, these results suggest that M1 macrophages promote the osteoclastic ability of hPDLCs and inhibit their osteogenic ability, eventually aggravating periodontitis. These findings provide important insights into the mechanism of action of NaF in periodontal tissue regeneration and reconstruction, which is critical for providing appropriate recommendations for the use of fluoride in patients with periodontitis.


Asunto(s)
Macrófagos , Osteogénesis , Ligamento Periodontal , Periodontitis , Fluoruro de Sodio , Humanos , Periodontitis/tratamiento farmacológico , Periodontitis/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Animales , Células Cultivadas , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/patología , Osteogénesis/efectos de los fármacos , Masculino , Glucólisis/efectos de los fármacos , Ratones , Diferenciación Celular/efectos de los fármacos , Ratones Endogámicos C57BL
3.
Int Immunopharmacol ; 140: 112872, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39121605

RESUMEN

PURPOSE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC). METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0. RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs. CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Desoxicitidina , Gemcitabina , Compuestos de Fenilurea , Quinolinas , Humanos , Masculino , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/mortalidad , Femenino , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Persona de Mediana Edad , Anciano , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Estudios Retrospectivos , Infusiones Intraarteriales , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Arteria Hepática , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Compuestos Organoplatinos
4.
Fitoterapia ; 177: 106129, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39047846

RESUMEN

The classic Astragalus-Cassia twig drug pair has a long history of proven efficacy. However, a fewer studies on material basis of the Astragalus and Cassia twig decoction (ACD) was researched at present. The method of UPLC-Q-TOF-MS for classifying and identifying the main chemical components of ACD was established and the differences in composition between single decoction and co-decoction were compared by using HPLC-UV. The therapeutic role of ACD on type 2 diabetes (T2D) rats was investigated. Thirty-five compounds were resolved from the ACD. Fifteen compounds were deduced from the decoction of Astragalus, whereas nine compounds were identified from Cassia twig. Pairing of herbs make a significant effect on the chemical composition of herbal decoction. ACD can play a more obvious role in alleviating the symptoms of T2D rats, compared to the application of single herb.


Asunto(s)
Planta del Astrágalo , Animales , Cromatografía Líquida de Alta Presión , Ratas , Planta del Astrágalo/química , Masculino , Ratas Sprague-Dawley , Cassia/química , Medicamentos Herbarios Chinos/química , Espectrometría de Masas , Estructura Molecular , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico
5.
Waste Manag ; 187: 252-261, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39079253

RESUMEN

Desiccation-induced cracks in a compacted clay liner significantly deteriorate the hydraulic barrier performance of landfill covers. The present study explores the effects of polypropylene (PP) fiber reinforcement on the hydrological response and crack resistance of compacted steel slag (SS; 90 wt%) - bentonite (10 wt%) mixtures under drying and wetting cycles. Comprehensive tests were conducted to explore the impact of different fiber lengths (6-12 mm) and contents (0-0.4 % wt.%), including hydraulic conductivity tests for measuring the saturated hydraulic conductivity (ks), unconfined-penetration tests for measuring the tensile strength, small-sized plate tests for quantifying crack development, and large-sized bucket tests for studying the hydrological response and crack characteristics. Higher fiber contents and longer fiber lengths increased the ks-value of the specimens. For a 0.3 % fiber content, the tensile strength peaked for the 9-mm fiber. Consistently, the specimen reinforced with the 9-mm fibers exhibited significantly fewer cracks than those reinforced with the 6-mm and 12-mm fibers. It was because the 6-mm fibers had a shorter anchorage length, while the 12-mm fibers tended to agglomerate. The large-sized bucket tests showed that fiber reinforcement limited crack development significantly under wetting and drying cycles, reducing the rainfall infiltration by 40 % and enhancing the soil water retention capacity. Finally, a 0.3 wt% of 9-mm PP was recommended to reinforce the compacted SS-bentonite mixtures.


Asunto(s)
Bentonita , Polipropilenos , Acero , Polipropilenos/química , Bentonita/química , Acero/química , Resistencia a la Tracción , Hidrología , Desecación/métodos , Eliminación de Residuos/métodos
6.
Nano Lett ; 24(31): 9675-9682, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39058271

RESUMEN

Feeding silkworms with functional materials as additives to produce naturally modified silk is a facile, diverse, controllable, and environmentally friendly method with a low cost of time and investment. Among various additives, carbon dots (CDs) show unique advantages due to their excellent biocompatibility and fluorescence stability. Here, a new type of green fluorescent carbon dots (G-CDs) is synthesized with a high oil-water partition ratio of 147, a low isoelectric point of 5.16, an absolute quantum yield of 71%, and critically controlled surface states. After feeding with G-CDs, the silkworms weave light yellow cocoons whose green fluorescence is visible to the naked eye under UV light. The luminous silk is sewn onto the cloth to create striking patterns with beautiful fluorescence. Such G-CDs have no adverse effect on the survival rate and the life cycle of silkworms and enable their whole bodies to glow under UV light. Based on the strong fluorescence, chemical stability, and biological safety, G-CDs are found in the digestive tracts, silk glands, feces, cocoons, and even moth bodies. G-CDs accumulate in the posterior silk glands where fibroin protein is secreted, indicating its stronger combination with fibroin than sericin, which meets the requirements for practical applications.


Asunto(s)
Bombyx , Carbono , Puntos Cuánticos , Seda , Animales , Seda/química , Carbono/química , Puntos Cuánticos/química , Fibroínas/química , Rayos Ultravioleta , Fluorescencia , Colorantes Fluorescentes/química , Propiedades de Superficie
7.
Heliyon ; 10(11): e32091, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38933976

RESUMEN

Green and low-carbon development is an important part of global sustainable development. Green power trading provides strong support and assurance for promoting green and low-carbon development. Due to the long cycle of green power data chains and their susceptibility to malicious tampering, the integrity and traceability of data are difficult to guarantee. Therefore, this paper first proposes a security provenance model with enhanced relations based on the core structure of PROV and blockchain technology, which can securely capture provenance records, use the transfer time and number of transactions between various links in the traceability network as reasoning clues, realize the correlation tracing of the green electricity transfer process. Under the model, a traceability mechanism of green electricity is designed based on smart contracts. Trustworthy green electricity data collection is achieved through data filling and data verification techniques. Traceability query technique is adopted to achieve trustworthy traceability of green electricity. And the effectiveness of the proposed solution is demonstrated through simulation experiments.

8.
J Hazard Mater ; 476: 134984, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38943891

RESUMEN

As well known, surface discharge cold plasma has efficient inactivation ability and a variety of RONS are main active particles for inactivation, but their synergistic mechanism is still not clear. Therefore, surface discharge cold plasma system was applied to treat Pseudomonas fluorescens to study bacterial inactivation mechanism and energy benefit. Results showed that energy efficiency was directly proportional to applied voltage and inversely proportional to initial concentration. Cold plasma treatment for 20 min was inactivated by approximately > 4-log10Pseudomonas fluorescens and application of •OH and 1O2 scavengers significantly improved survival rate. In addition, •OH and 1O2 destroyed cell membrane structure and membrane permeability, which promoted diffusion of RONS into cells and affecting energy metabolism and antioxidant capacity, leading to bacterial inactivation. Furthermore, accumulation of intracellular NO and ONOOH was related to infiltration of exogenous RNS, while accumulation of •OH, H2O2, 1O2, O2- was the result of joint action of endogenous and exogenous ROS. Transcriptome analysis revealed that different RONS of cold plasma were responsible for Pseudomonas fluorescens inactivation and related to activation of intracellular antioxidant defense system and regulation of genes expression related to amino acid metabolism and energy metabolism, which promoting cellular process, catalytic activity and other biochemical pathways.


Asunto(s)
Gases em Plasma , Pseudomonas fluorescens , Especies Reactivas de Oxígeno , Pseudomonas fluorescens/metabolismo , Gases em Plasma/farmacología , Especies Reactivas de Oxígeno/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Microbiología del Agua , Viabilidad Microbiana/efectos de los fármacos
9.
Ultrason Sonochem ; 107: 106927, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38820934

RESUMEN

A novel technique was proposed for processing silkworm pupae by combining plasma- activated water (PAW) with ultrasound (US). The microbial diversity and quality characteristics of the silkworm pupae were also evaluated. The results of the microbial diversity analysis indicated that PAW combined with US treatment significantly reduced the relative abundance of Streptococcaceae, Leuconostocaceae, and Acetobacteraceae from 32%, 18% and 16% to 27%, 11% and 11%, respectively. Microstructural analysis demonstrated that the collapse of the internal structure of chitin in silkworm pupae facilitated the release of nutrients and flavour compounds including fatty acids, water-soluble proteins (WSP), amino acids, phenolics, and volatile compounds. Furthermore, the increase in antioxidant capacity and the decrease in catalase activity and malondialdehyde content confirmed the mechanism of quality change. These findings provide new insights into the possible mechanism of PAW combined with US to improve the quality of edible insects.


Asunto(s)
Bombyx , Pupa , Agua , Animales , Pupa/microbiología , Agua/química , Bombyx/química , Ondas Ultrasónicas , Fenómenos Químicos , Antioxidantes/química , Antioxidantes/farmacología , Biodiversidad
10.
Front Pharmacol ; 15: 1372401, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38803441

RESUMEN

Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The ß of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.

11.
J Transl Med ; 22(1): 477, 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38764038

RESUMEN

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a malignant tumor with a poor prognosis. Traditional treatments have limited effectiveness. Regulation of the immune response represents a promising new approach for OSCC treatment. B cells are among the most abundant immune cells in OSCC. However, the role of B cells in OSCC treatment has not been fully elucidated. METHODS: Single-cell RNA sequencing analysis of 13 tissues and 8 adjacent normal tissues from OSCC patients was performed to explore differences in B-cell gene expression between OSCC tissues and normal tissues. We further investigated the relationship between differentially expressed genes and the immune response to OSCC. We utilized tissue microarray data for 146 OSCC clinical samples and RNA sequencing data of 359 OSCC samples from The Cancer Genome Atlas (TCGA) to investigate the role of T-cell leukemia 1 A (TCL1A) in OSCC prognosis. Multiplex immunohistochemistry (mIHC) was employed to investigate the spatial distribution of TCL1A in OSCC tissues. We then investigated the effect of TCL1A on B-cell proliferation and trogocytosis. Finally, lentiviral transduction was performed to induce TCL1A overexpression in B lymphoblastoid cell lines (BLCLs) to verify the function of TCL1A. RESULTS: Our findings revealed that TCL1A was predominantly expressed in B cells and was associated with a better prognosis in OSCC patients. Additionally, we found that TCL1A-expressing B cells are located at the periphery of lymphatic follicles and are associated with tertiary lymphoid structures (TLS) formation in OSCC. Mechanistically, upregulation of TCL1A promoted the trogocytosis of B cells on dendritic cells by mediating the upregulation of CR2, thereby improving antigen-presenting ability. Moreover, the upregulation of TCL1A expression promoted the proliferation of B cells. CONCLUSION: This study revealed the role of B-cell TCL1A expression in TLS formation and its effect on OSCC prognosis. These findings highlight TCL1A as a novel target for OSCC immunotherapy.


Asunto(s)
Linfocitos B , Carcinoma de Células Escamosas , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Boca , Proteínas Proto-Oncogénicas , Estructuras Linfoides Terciarias , Humanos , Pronóstico , Neoplasias de la Boca/patología , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/inmunología , Estructuras Linfoides Terciarias/patología , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/metabolismo , Linfocitos B/metabolismo , Linfocitos B/inmunología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/metabolismo , Femenino , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Masculino , Persona de Mediana Edad , Línea Celular Tumoral , Proliferación Celular
12.
PLoS One ; 19(5): e0298864, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38753630

RESUMEN

Fibrotic remodeling is the primary driver of functional loss in chronic kidney disease, with no specific anti-fibrotic agent available for clinical use. Transglutaminase 2 (TG2), a wound response enzyme that irreversibly crosslinks extracellular matrix proteins causing dysregulation of extracellular matrix turnover, is a well-characterized anti-fibrotic target in the kidney. We describe the humanization and characterization of two anti-TG2 monoclonal antibodies (zampilimab [hDC1/UCB7858] and BB7) that inhibit crosslinking by TG2 in human in vitro and rabbit/cynomolgus monkey in vivo models of chronic kidney disease. Determination of zampilimab half-maximal inhibitory concentration (IC50) against recombinant human TG2 was undertaken using the KxD assay and determination of dissociation constant (Kd) by surface plasmon resonance. Efficacy in vitro was established using a primary human renal epithelial cell model of tubulointerstitial fibrosis, to assess mature deposited extracellular matrix proteins. Proof of concept in vivo used a cynomolgus monkey unilateral ureteral obstruction model of chronic kidney disease. Zampilimab inhibited TG2 crosslinking transamidation activity with an IC50 of 0.25 nM and Kd of <50 pM. In cell culture, zampilimab inhibited extracellular TG2 activity (IC50 119 nM) and dramatically reduced transforming growth factor-ß1-driven accumulation of multiple extracellular matrix proteins including collagens I, III, IV, V, and fibronectin. Intravenous administration of BB7 in rabbits resulted in a 68% reduction in fibrotic index at Day 25 post-unilateral ureteral obstruction. Weekly intravenous administration of zampilimab in cynomolgus monkeys with unilateral ureteral obstruction reduced fibrosis at 4 weeks by >50%, with no safety signals. Our data support the clinical investigation of zampilimab for the treatment of kidney fibrosis.


Asunto(s)
Fibrosis , Proteínas de Unión al GTP , Proteína Glutamina Gamma Glutamiltransferasa 2 , Insuficiencia Renal Crónica , Animales , Humanos , Masculino , Conejos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados/farmacología , Modelos Animales de Enfermedad , Fibrosis/tratamiento farmacológico , Proteínas de Unión al GTP/antagonistas & inhibidores , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/inmunología , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Macaca fascicularis , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/patología , Transglutaminasas/antagonistas & inhibidores , Transglutaminasas/metabolismo
13.
Phytomedicine ; 130: 155556, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38810552

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease that affects multiple organs and cause a wide range of severe clinical manifestations, including lupus nephritis (LN), which is a major risk factor for morbidity and mortality in individual with SLE. Ursolic acid (UA) is a natural compound with favorable anti-inflammatory properties and has been employed to treat multiple disease, including inflammatory diseases, diabetes, and Parkinson's disease. However, its therapeutic potential on LN and the underlying mechanisms remains unclear. PURPOSE: This aim of this study was to investigate the impact of UA on LN and its underlying mechanism. METHODS: MRL/lpr lupus-prone mouse model was used and UA was administered orally for 8 weeks. Dexamethasone was used as a positive control. After 8 weeks of administration, the spleen-to-body-weight ratio, renal function, urine albumin excretion, cytokines levels, and the deposition of immune complex were measured. The primary mouse glomerular mesangial cells (GMCs) and SV40-MES-13 were stimulated by lipopolysaccharide (LPS), either alone or in combination with nigericin, to establish an in vitro model. The activation of NLRP3 inflammasome were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence. RESULTS: Our results revealed that UA prominently alleviated LN in MRL/lpr lupus-prone mice, leading to a significant reduction in proteinuria production, infiltration of immune cells infiltration, and histopathological damage in the renal tissue. In addition, UA exerted inhibitory effects on the secretion of IL-1ß, IL-18, and caspase-1, pyroptosis, and ASC speck formation in primary mouse GMCs and SV40-MES-13 cells. Furthermore, UA facilitated the degradation of NLRP3 by suppressing SUMO1-mediated SUMOylation of NLRP3. CONCLUSION: UA possess a therapeutical effect on LN in MRL/lpr mice by enhancing the degradation of NLRP3 through inhibition of SUMO1-mediated SUMOylation of NLRP3. Our findings provide a basis for proposing UA as a potential candidate for the treatment of LN.


Asunto(s)
Inflamasomas , Nefritis Lúpica , Ratones Endogámicos MRL lpr , Proteína con Dominio Pirina 3 de la Familia NLR , Triterpenos , Ácido Ursólico , Animales , Triterpenos/farmacología , Nefritis Lúpica/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratones , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Células Mesangiales/efectos de los fármacos , Células Mesangiales/metabolismo , Antiinflamatorios/farmacología , Sumoilación/efectos de los fármacos
14.
Molecules ; 29(10)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38792209

RESUMEN

Ganoderma lucidum spore powder, valued for its nutritional and medicinal properties, contains polysaccharides crucial for its efficacy. However, the complex structural nature of these polysaccharides necessitates further investigation to fully realize their potential. This study aimed to investigate the effects of acid heat treatment on Ganoderma lucidum spore polysaccharides (GLSPs) to enhance their properties and application in antitumor activity. The GLSP was obtained via acid heat treatment, concentration, and centrifugal separation. This process led to a notable reduction in polysaccharide molecular weight, increasing water solubility and bioavailability. Analytical techniques including NMR spectroscopy and methylation analysis revealed a polysaccharide composition comprising four distinct monosaccharides, with molecular weights of 3291 Da (Mw) and 3216 Da (Mn). Six different linkage modes were identified, with a molar ratio of 1:5:2:3:4:3. In vivo experiments demonstrated the GLSP's significant inhibitory effect on the growth of four tumor models (sarcoma S180, Lewis lung cancer, liver cancer H22, and colon cancer C26) in mice, with no observed toxicity. These findings suggest the GLSP's potential as an antitumor therapeutic agent for clinical use.


Asunto(s)
Antineoplásicos , Reishi , Esporas Fúngicas , Animales , Reishi/química , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/farmacología , Línea Celular Tumoral , Peso Molecular
15.
Biomimetics (Basel) ; 9(5)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38786482

RESUMEN

To inhibit the deep conversion of partial oxidation products (POX-products) in C-H bonds' functionalization utilizing O2, 5-(4-(chloromethyl)phenyl)-10,15,20-tris(perfluorophenyl)porphyrin cobalt(II) and 5-(4-(chloromethyl)phenyl)-10,15,20-tris(perfluorophenyl)porphyrin copper(II) were immobilized on the surface of hybrid silica to conduct relay catalysis on the surface. Fluorocarbons with low polarity and heterogeneous catalysis were devised to decrease the convenient accessibility of polar POX-products to catalytic centers on the lower polar surface. Relay catalysis between Co and Cu was designed to utilize the oxidation intermediates alkyl hydroperoxides to transform more C-H bonds. Systematic characterizations were conducted to investigate the structure of catalytic materials and confirm their successful syntheses. Applied to C-H bond oxidation, not only deep conversion of POX-products was inhibited but also substrate conversion and POX-product selectivity were improved simultaneously. For cyclohexane oxidation, conversion was improved from 3.87% to 5.27% with selectivity from 84.8% to 92.3%, which was mainly attributed to the relay catalysis on the surface excluding products. The effects of the catalytic materials, product exclusion, relay catalysis, kinetic study, substrate scope, and reaction mechanism were also investigated. To our knowledge, a practical and novel strategy was presented to inhibit the deep conversion of POX-products and to achieve efficient and accurate oxidative functionalization of hydrocarbons. Also, a valuable protocol was provided to avoid over-reaction in other chemical transformations requiring high selectivity.

16.
Opt Express ; 32(4): 5117-5130, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439246

RESUMEN

Photon blockade (PB) is an important quantum phenomenon in cavity quantum electrodynamics (QED). Here, we investigate the PB effect in the simplest cavity QED systems (one cavity containing first a single atom and then two atoms), where only the atoms are weakly driven. Via the analytical calculation and numerical simulation, we show that the strong PB can be generated even with the weak-coupling regime at the total resonance. This blockade is ascribed to the two-photon absorption, which is fundamentally different from the conventional and unconventional blockade mechanisms. Therefore, our study provides an alternative approach to produce the PB in the atom-driven cavity QED system.

17.
J Clin Sleep Med ; 20(4): 555-564, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38059337

RESUMEN

STUDY OBJECTIVES: This study aimed to evaluate the safety and short-term effect of contemporaneous surgeries (bariatric surgery plus uvulopalatopharyngoplasty [UPPP]) in the treatment of morbid obesity comorbid with severe obstructive sleep apnea (OSA). METHODS: A retrospective cohort study was performed to identify patients with obesity and severe OSA who underwent laparoscopic sleeve gastrectomy (LSG) with or without UPPP surgeries between December 2019 and December 2021 in our center. Patients were divided into 2 groups according to different surgical methods (contemporaneous group [LSG with UPPP] vs LSG-only group). Data about surgical safety, OSA remission, and effectiveness of weight loss were collected and analyzed between the 2 groups before and 12 months after surgery. RESULTS: A total of 101 patients were included in this study (contemporaneous group [LSG with UPPP], n = 42 vs LSG only group, n = 59). There was no significant difference in surgical safety between the 2 groups, and both OSA and obesity were significantly improved at 12.5 ± 2.1 months postoperative follow-up. The apnea-hypopnea index decreased from 68.7 ± 30.4 events/h to 10.2 ± 7.0 events/h in the contemporaneous group (P < .001) and from 64.7 ± 26.2 events/h to 18.9 ± 9.8 events/h in the LSG group (P < .001). Moreover, the apnea-hypopnea index decreased to below 5 events/h in 50% of patients (21/42) in the contemporaneous group but only in 13.5% of patients in the LSG group (P < .001). In the LSG group 20 (34%) patients achieved a reduction in apnea-hypopnea index < 15 events/h and resolution of daytime sleepiness. CONCLUSIONS: Contemporaneous surgery (concurrent bariatric and UPPP surgeries) is feasible and an effective option for patients with obesity and severe OSA. However, our finding suggests that approximately a third of patients undergoing LSG with UPPP may not derive significant benefit from the UPPP portion of the contemporaneous surgical approach. CITATION: Yang C, Yu W, Yao K, et al. Concurrent laparoscopic sleeve gastrectomy with uvulopalatopharyngoplasty in the treatment of morbid obesity comorbid with severe obstructive sleep apnea: a retrospective cohort study. J Clin Sleep Med. 2024;20(4):555-564.


Asunto(s)
Laparoscopía , Obesidad Mórbida , Apnea Obstructiva del Sueño , Humanos , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/cirugía , Gastrectomía/métodos , Laparoscopía/métodos
18.
J Hazard Mater ; 465: 133066, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38042007

RESUMEN

Incorrect use of neonicotinoid pesticides poses a serious threat to human and pollinator health, as these substances are commonly present in bee products and even drinking water. To combat this threat, the study developed a new method of degrading the pesticide imidacloprid using surface discharge cold plasma oxidation technology. The study showed that this method achieved a very high efficiency of imidacloprid degradation of 91.4%. The main reactive oxygen species (H2O2, O3, ·OH, O2-, 1O2) effectively participated in the decomposition reaction of imidacloprid. Reactive oxygen species were more sensitive to the structure of the nitroimine group. Density functional theory (DFT) further explored the sites of reactive oxygen species attack on imidacloprid and revealed the process of energy change of attacking imidacloprid. In addition, a degradation pathway for imidacloprid was proposed, mainly involving reactive oxygen species chemisorption, a ring-opening intermediate, and complete cleavage of the nitroimine group structure. Model predictions indicated that acute oral and developmental toxicity were significantly reduced after cold plasma treatment, as confirmed by insect experiments. Animal experiments have shown that plasma treatment reduces imidacloprid damage to mice hippocampal tissue structure and inhibits the reduction of brain-derived neurotrophic factor content, thus revealing the detoxification mechanism of the body.


Asunto(s)
Insecticidas , Plaguicidas , Gases em Plasma , Humanos , Abejas , Animales , Ratones , Insecticidas/química , Especies Reactivas de Oxígeno , Estructura Molecular , Peróxido de Hidrógeno , Neonicotinoides/química , Nitrocompuestos/química , Nitrocompuestos/farmacología
19.
Food Chem ; 429: 136832, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37453333

RESUMEN

Based on the concept of circular economy, citrus peel was considered a valuable source of bioactive compounds for high-value foods. Electrohydrodynamic (EHD) drying is a novel technology appropriated for the dehydration of heat-sensitive products such as citrus peel. In current work, EHD drying of citrus peel was performed based on alternating current (AC) or direct current (DC) sources at various voltage levels (9, 18, 27, 36, and 45 kV). The effect of EHD on drying characteristics, water retention capacity, enzyme inactivation, phytochemical contents (phenolic compounds and carotenoids), and volatile compounds of citrus peel were evaluated and compared. Results showed that the drying time in the AC electric field was shorter compared to DC electric field at the same applied voltages due to the polarization layer formed by unipolar charges. The applied voltage determined electric field strength as well as the degree of tissue collapse and cell membrane rupture. EHD elucidated the transformation and degradation of phytochemicals including phenolic compounds, carotenoids, and volatile composition in proportion to the applied voltage. The findings indicate that EHD drying with AC improves drying behaviors, inactivates enzymes, and retains the phytochemical properties of citrus peel.


Asunto(s)
Citrus sinensis , Citrus , Citrus sinensis/química , Citrus/química , Extractos Vegetales/química , Carotenoides , Fenoles , Fitoquímicos
20.
Int J Mol Sci ; 24(14)2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37511053

RESUMEN

Gingival-derived mesenchymal stem cells (GMSCs) have strong self-renewal, multilineage differentiation, and immunomodulatory properties and are expected to be applied in anti-inflammatory and tissue regeneration. However, achieving the goal of using endogenous stem cells to treat diseases and even regenerate tissues remains a challenge. Resveratrol is a natural compound with multiple biological activities that can regulate stem cell immunomodulation when acting on them. This study found that resveratrol can reduce inflammation in human gingival tissue and upregulate the stemness of GMSCs in human gingiva. In cell experiments, it was found that resveratrol can reduce the expression of TLR4, TNFα, and NFκB and activate ERK/Wnt crosstalk, thereby alleviating inflammation, promoting the proliferation and osteogenic differentiation ability of GMSCs, and enhancing their immunomodulation. These results provide a new theoretical basis for the application of resveratrol to activate endogenous stem cells in the treatment of diseases in the future.


Asunto(s)
Encía , Periodontitis , Resveratrol , Humanos , Diferenciación Celular , Células Cultivadas , Encía/efectos de los fármacos , Sistema de Señalización de MAP Quinasas , Osteogénesis , Periodontitis/tratamiento farmacológico , Resveratrol/farmacología , Resveratrol/uso terapéutico
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