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1.
Zhonghua Gan Zang Bing Za Zhi ; 32(4): 354-362, 2024 Apr 20.
Artículo en Chino | MEDLINE | ID: mdl-38733191

RESUMEN

Objective: To observe the therapeutic effect of Shengsan Jiedu Huayu decoction in alleviating inflammatory liver injury in rats with acute-on-chronic liver failure (ACLF) and its effect on the activation intensity for the NLRP3 signaling pathway. Methods: 63 SD rats were randomly divided into a blank group, a model group, and low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction (7.29 g/kg/d, 14.58 g/kg/d, and 29.16 g/kg/d). The ACLF rat model was replicated using carbon tetrachloride combined with d-galactosamine and lipopolysaccharide. Different dose gradients of the Shengsan Jiedu Huayu decoction were used for a five-day intervention treatment, and then rat serum and tissue samples were collected. A biochemical analyzer was used to detect the serum levels of ALT, AST, and TBIL in rats. ELISA was used to detect serum IL-18 and IL-1ß content. HE staining was used to observe histomorphological changes in liver tissue. Immunohistochemistry was used to detect GSDMD expression in liver tissue. Western blot and PCR were used to detect NLRP3, Caspase1, ASC, TLR4, IL-1ß, IL-18 protein, and mRNA expression levels.The groups were compared using analysis of variance and the rank-sum test. Results: Compared with the blank group, the model group's rat liver tissue was severely injured. Serum levels of ALT, AST, and TBIL, inflammatory factors IL-1ß and IL-18, and the GSDMD protein expression level, NLRP3 expression level, TLR4, caspase 1, ASC, IL-1ß, IL-18 protein, and mRNA (P<0.01) were all significantly increased in the model than the blank group (P<0.01). Additionally, compared with the model group, the low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction had improved liver tissue injury in ACLF rats, while the serum levels of ALT, AST, TBIL, IL-1ß, IL-18, liver tissue GSDMD protein, NLRP3, TLR4, caspase 1, and ASC expressions were all lower in the different dose gradients of the Shengsan Jiedu Huayu decoction than the model group, with the most evident reduction in the high-dose group (P<0.01). Conclusion: Shengsan Jiedu Huayu decoction can weaken the activation intensity of the NLRP3 signaling pathway, alleviate liver tissue pathological injury, reduce inflammatory factor release, and alleviate inflammatory liver injury in ACLF rats.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Medicamentos Herbarios Chinos , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas Sprague-Dawley , Transducción de Señal , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Insuficiencia Hepática Crónica Agudizada/etiología , Medicamentos Herbarios Chinos/farmacología , Ratas , Transducción de Señal/efectos de los fármacos , Masculino , Interleucina-18/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Interleucina-1beta/metabolismo , Receptor Toll-Like 4/metabolismo , Proteínas Portadoras/metabolismo
2.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38731838

RESUMEN

The effect of dietary supplementation with sodium butyrate, ß-glucan and vitamins (A, D3, E, K, C) on breeding indicators and immune parameters of juvenile African catfish was examined. The fish were fed with unenriched (group C) and enriched feed with a variable proportion of sodium butyrate/ß-glucan, and constant content of vitamins (W1-W3). After the experiment, blood and the middle gut were collected. The microbiome of the gut was determined using Next Generation Sequencing (NGS). Liver tissue was collected for determination of expression of immune-related genes (HSP70, IL-1ß, TNFα). W2 and W3 were characterized by the most favorable values of breeding indicators (p < 0.05). The highest blood cortisol concentration was in group C (71.25 ± 10.45 ng/mL), and significantly the lowest in W1 (46.03 ± 7.01 ng/ mL) (p < 0.05). The dominance of Cetobacterium was observed in all study groups, with the largest share in W3 (65.25%) and W1 (61.44%). Gene expression showed an increased number of HSP70 genes in W1. IL-1ß and TNFα genes peaked at W3. The W3 variant turns out to be the most beneficial supplementation, due to the improvement of breeding and immunological parameters. The data obtained can be used to create a preparation for commercial use in the breeding of this species.


Asunto(s)
Ácido Butírico , Bagres , Suplementos Dietéticos , Microbioma Gastrointestinal , Hidrocortisona , Vitaminas , beta-Glucanos , Animales , beta-Glucanos/farmacología , beta-Glucanos/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Ácido Butírico/farmacología , Bagres/inmunología , Bagres/genética , Bagres/microbiología , Hidrocortisona/sangre , Vitaminas/farmacología , Vitaminas/administración & dosificación , Alimentación Animal , Proteínas HSP70 de Choque Térmico/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo
3.
Arch Dermatol Res ; 316(5): 156, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734816

RESUMEN

Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1ß and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1ß, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1ß expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1ß (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1ß, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1ß, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68+ macrophages secreting GSDMD, ASC and IL-1ß in moderate and severe AD. Cutaneous macrophages, early detected in moderate AD, have its role in the disease inflammatory mechanisms. Our study indicates a canonical activation pathway of inflammasomes, reinforced by the chronic status of inflammation in AD. The analysis of the inflammasome complex evidenced an imbalance in its regulation, with increased expression of the evaluated components, which is remarkably in severe AD, emphasizing its relevance as potential disease biomarkers and targets for immunomodulatory interventions.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD , Caspasa 1 , Dermatitis Atópica , Inflamasomas , Interleucina-18 , Interleucina-1beta , Péptidos y Proteínas de Señalización Intracelular , Macrófagos , Proteína con Dominio Pirina 3 de la Familia NLR , Proteínas de Unión a Fosfato , Humanos , Inflamasomas/metabolismo , Inflamasomas/inmunología , Proteínas Adaptadoras de Señalización CARD/metabolismo , Dermatitis Atópica/inmunología , Dermatitis Atópica/metabolismo , Dermatitis Atópica/patología , Macrófagos/metabolismo , Macrófagos/inmunología , Interleucina-1beta/metabolismo , Masculino , Femenino , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Adulto , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-18/metabolismo , Caspasa 1/metabolismo , Piel/patología , Piel/inmunología , Piel/metabolismo , Índice de Severidad de la Enfermedad , Persona de Mediana Edad , Antígenos de Diferenciación Mielomonocítica/metabolismo , Adulto Joven , Proteínas Reguladoras de la Apoptosis/metabolismo , Antígenos CD/metabolismo , Proteínas NLR/metabolismo , Estudios de Casos y Controles , Epidermis/inmunología , Epidermis/metabolismo , Epidermis/patología , Gasderminas , Molécula CD68 , Proteínas de Unión al ADN
4.
BMC Musculoskelet Disord ; 25(1): 375, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734632

RESUMEN

BACKGROUND: Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear. METHODS: Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1ß and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays. RESULTS: The results indicate that both IL-1ß and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues' inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1ß and IL-6 with minimal side effects. CONCLUSION: These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.


Asunto(s)
Ácidos Grasos Insaturados , Interleucina-1beta , Imagen por Resonancia Magnética , Membrana Sinovial , Sinovitis , Lesiones de Menisco Tibial , Lesiones de Menisco Tibial/tratamiento farmacológico , Lesiones de Menisco Tibial/metabolismo , Sinovitis/tratamiento farmacológico , Sinovitis/metabolismo , Sinovitis/patología , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Humanos , Ácidos Grasos Insaturados/farmacología , Ácidos Grasos Insaturados/metabolismo , Ácidos Grasos Insaturados/uso terapéutico , Masculino , Interleucina-1beta/metabolismo , Animales , Interleucina-6/metabolismo , Femenino , Meniscos Tibiales/efectos de los fármacos , Meniscos Tibiales/metabolismo , Ratones , Modelos Animales de Enfermedad
5.
J Agric Food Chem ; 72(19): 10923-10935, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38691832

RESUMEN

This study aimed to explore the ameliorative effects and potential mechanisms of Huangshan Umbilicaria esculenta polysaccharide (UEP) in dextran sulfate sodium-induced acute ulcerative colitis (UC) and UC secondary liver injury (SLI). Results showed that UEP could ameliorate both colon and liver pathologic injuries, upregulate mouse intestinal tight junction proteins (TJs) and MUC2 expression, and reduce LPS exposure, thereby attenuating the effects of the gut-liver axis. Importantly, UEP significantly downregulated the secretion levels of TNF-α, IL-1ß, and IL-6 through inhibition of the NF-κB pathway and activated the Nrf2 signaling pathway to increase the expression levels of SOD and GSH-Px. In vitro, UEP inhibited the LPS-induced phosphorylation of NF-κB P65 and promoted nuclear translocation of Nrf2 in RAW264.7 cells. These results revealed that UEP ameliorated UC and SLI through NF-κB and Nrf2-mediated inflammation and oxidative stress. The study first investigated the anticolitis effect of UEP, suggesting its potential for the treatment of colitis and colitis-associated liver disease.


Asunto(s)
Colitis , Sulfato de Dextran , Factor 2 Relacionado con NF-E2 , FN-kappa B , Polisacáridos , Animales , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/administración & dosificación , Sulfato de Dextran/efectos adversos , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Humanos , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/metabolismo , Células RAW 264.7 , FN-kappa B/metabolismo , FN-kappa B/genética , Ratones Endogámicos C57BL , Sustancias Protectoras/farmacología , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/inmunología , Estrés Oxidativo/efectos de los fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/inmunología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/inducido químicamente , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Mucina 2/genética , Mucina 2/metabolismo
6.
FASEB J ; 38(9): e23637, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38720403

RESUMEN

Vascular smooth muscle cell (VSMC) plasticity is fundamental in uterine spiral artery remodeling during placentation in Eutherian mammals. Our previous work showed that the invasion of trophoblast cells into uterine myometrium coincides with a phenotypic change of VSMCs. Here, we elucidate the mechanism by which trophoblast cells confer VSMC plasticity. Analysis of genetic markers on E13.5, E16.5, and E19.5 in the rat metrial gland, the entry point of uterine arteries, revealed that trophoblast invasion is associated with downregulation of MYOCARDIN, α-smooth muscle actin, and calponin1, and concomitant upregulation of Smemb in VSMCs. Myocardin overexpression or knockdown in VSMCs led to upregulation or downregulation of contractile markers, respectively. Co-culture of trophoblast cells with VSMCs decreased MYOCARDIN expression along with compromised expression of contractile markers in VSMCs. However, co-culture of trophoblast cells with VSMCs overexpressing MYOCARDIN inhibited their change in phenotype, whereas, overexpression of transactivation domain deleted MYOCARDIN failed to elicit this response. Furthermore, the co-culture of trophoblast cells with VSMCs led to the activation of NFκß signaling. Interestingly, despite producing IL-1ß, trophoblast cells possess only the decoy receptor, whereas, VSMCs possess the IL-1ß signaling receptor. Treatment of VSMCs with exogenous IL-1ß led to a decrease in MYOCARDIN and an increase in phosphorylation of NFκß. The effect of trophoblast cells in the downregulation of MYOCARDIN in VSMCs was reversed by blocking NFκß translocation to the nucleus. Together, these data highlight that trophoblast cells direct VSMC plasticity, and trophoblast-derived IL-1ß is a key player in downregulating MYOCARDIN via the NFκß signaling pathway.


Asunto(s)
Interleucina-1beta , Músculo Liso Vascular , Miocitos del Músculo Liso , FN-kappa B , Proteínas Nucleares , Transducción de Señal , Transactivadores , Trofoblastos , Animales , Trofoblastos/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citología , Transactivadores/metabolismo , Transactivadores/genética , Ratas , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Transducción de Señal/fisiología , FN-kappa B/metabolismo , Femenino , Miocitos del Músculo Liso/metabolismo , Interleucina-1beta/metabolismo , Embarazo , Técnicas de Cocultivo , Ratas Sprague-Dawley , Células Cultivadas , Plasticidad de la Célula/fisiología , Calponinas
7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(4): 296-302, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38710513

RESUMEN

Objective To evaluate the effects of heme oxygenase-1 (HO-1) gene deletion on immune cell composition and inflammatory injury in lung tissues of mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods C57BL/6 wild-type (WT) mice and HO-1 conditional-knockout (HO-1-/-) mice on the same background were randomly divided into four groups (n=5 in every group): WT control group, LPS-treated WT group, HO-1-/- control group and LPS-treated HO-1-/- group. LPS-treated WT and HO-1-/- groups were injected with LPS (15 mg/kg) through the tail vein to establish ALI model, while WT control group and HO-1-/- control group were injected with an equivalent volume of normal saline through the tail vein, respectively. Twelve hours later, the mice were sacrificed and lung tissues from each group were collected for analysis. Histopathological alterations of lung tissues were assessed by HE staining. The levels of mRNA expression of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 were determined by PCR. The percentages of neutrophils (CD45+CD11b+Ly6G+Ly6C-), total monocytes (CD45+CD11b+Ly6Chi), pro-inflammatory monocyte subsets (CD45+CD11b+Ly6ChiCCR2hi) and total macrophages (CD45+CD11b+F4/80+), M1 macrophage (CD45+CD11b+F4/80+CD86+), M2 macrophage (CD45+CD11b+F4/80+CD206+), total T cells (CD45+CD3+), CD3+CD4+ T cells, CD3+CD8+ T cells and myeloid suppressor cells (MDSCs, CD45+CD11b+Gr1+) were detected by flow cytometry. Results Compared with the corresponding control groups, HE staining exhibited increased inflammation in the lung tissues of both LPS-treated WT and HO-1-/- model mice; mRNA expression levels of TNF-α, IL-1ß and IL-6 were up-regulated; the proportions of neutrophils, total monocytes, pro-inflammatory monocyte subsets, MDSCs and total macrophages increased significantly. The percentage of CD3+, CD3+CD4+ and CD3+CD8+ T cells decreased significantly. Under resting-state, compared with WT control mice, the proportion of neutrophils, monocytes and pro-inflammatory monocyte subset increased in lung tissues of HO-1-/- control mice, while the proportion of CD3+ and CD3+CD8+ T cells decreased. Compared with LPS-treated WT mice, the mRNA expression levels of TNF-α and IL-1ß were up-regulated in lung tissues of LPS-treated HO-1-/- mice; the proportion of total monocytes, pro-inflammatory monocyte subsets, M1 macrophages and M1/M2 ratio increased greatly; the percentage of CD3+CD8+ T cells decreased significantly. Conclusion The deletion of HO-1 affects the function of the lung immune system and aggravates the inflammatory injury after LPS stimulation in ALI mice.


Asunto(s)
Lesión Pulmonar Aguda , Hemo-Oxigenasa 1 , Lipopolisacáridos , Pulmón , Ratones Endogámicos C57BL , Ratones Noqueados , Animales , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/patología , Pulmón/patología , Pulmón/inmunología , Pulmón/metabolismo , Ratones , Lipopolisacáridos/efectos adversos , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Masculino , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Inflamación/genética , Inflamación/inducido químicamente , Inflamación/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo
8.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(4): 319-326, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38710516

RESUMEN

Objective To investigate the impact of the cannabinoid receptor agonist arachidonyl-2'-chloroethylamide (ACEA) on cognitive function in mice with sepsis-associated encephalopathy (SAE). Methods C57BL/6 mice were randomly divided into artificial cerebrospinal fluid (ACSF) and lipopolysaccharide (LPS) groups. The SAE model was established by intraventricular injection of LPS. The severity of sepsis in mice was assessed by sepsis severity score (MSS) and body mass changes. Behavioral paradigms were used to evaluate motor ability (open field test) and cognitive function (contextual fear conditioning test, Y-maze test). To evaluate the effects of ACEA intervention on SAE, mice were randomly assigned to ACSF group, ACEA intervention combined with ACSF group, LPS group, and ACEA intervention combined with LPS group. The dosage of ACEA intervention was 1.5 mg/kg. Real-time quantitative PCR was used to measure the mRNA expression levels of interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α) in mouse hippocampal tissues. Western blot analysis was used to assess the protein levels of IL-6 and TNF-α in the hippocampus. Nissl staining was performed to examine neuronal damage in the CA1 region of the mouse hippocampus. Behavioral paradigms were again employed to evaluate motor ability and cognitive function. Results Three days after intraventricular LPS injection, mice exhibited significant cognitive dysfunction, confirming SAE modeling. Compared to the control group, the LPS group showed significant increases in mRNA of inflammatory factors such as IL-6, TNF-α, and IL-1ß, together with significant increases in IL-6 and TNF-α protein levels in the hippocampus, a decrease in Nissl bodies in the CA1 region, and significant cognitive dysfunction. Compared to the LPS group, the ACEA intervention group showed a significant decrease in the mRNA of IL-6, TNF-α, and IL-1ß, a significant reduction in IL-6 and TNF-α protein levels, an increase in Nissl bodies, and improved cognitive function. Conclusion ACEA improves cognitive function in SAE mice by inhibiting the expression levels of inflammatory factors IL-6 and TNF-α.


Asunto(s)
Ácidos Araquidónicos , Ratones Endogámicos C57BL , Encefalopatía Asociada a la Sepsis , Animales , Encefalopatía Asociada a la Sepsis/tratamiento farmacológico , Encefalopatía Asociada a la Sepsis/metabolismo , Ratones , Masculino , Ácidos Araquidónicos/farmacología , Agonistas de Receptores de Cannabinoides/farmacología , Lipopolisacáridos/efectos adversos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB1/agonistas , Cognición/efectos de los fármacos , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/metabolismo
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(4): 327-332, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38710517

RESUMEN

Objective To investigate the liver injury induced by chronic intermittent hypoxia (CIH) activation of NOD-like receptor pyrin domain containing protein 1 (NLRP1) inflammasome. Methods C57BL/6 male mice were randomly divided into control group and CIH group. Mice in CIH group were put into CIH chamber for molding (8 hours a day for 4 weeks). After 4 weeks of molding, liver tissue cells was observed by HE staining, and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of mice were detected by kit. The levels of reactive oxygen species (ROS) in liver tissue were detected by dihydroethidine (DHE). The expression and localization of NLRP1, apoptosis speck-like protein containing a caspase activation and recruiting domain (ASC) and caspase-1 were detected by immunohistochemical staining. The protein expressions of NLRP1, ASC, caspase-1, interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) were detected by Western blot analysis. The serum levels of IL-1ß and TNF-α were detected by ELISA. Results Compared with the control group, the CIH group exhibited significant pathological changes in hepatocytes. Hepatocytes showed signs of rupture and necrosis, accompanied by inflammatory cell aggregation. Furthermore, the levels of ALT, AST, ROS, IL-1ß and TNF-α were elevated, along with increased protein expressions of NLRP1, ASC, caspase-1, IL-1ß and TNF-α. Conclusion CIH causes liver injury by activating NLRP1 inflammasome.


Asunto(s)
Caspasa 1 , Hipoxia , Inflamasomas , Interleucina-1beta , Hígado , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno , Animales , Masculino , Inflamasomas/metabolismo , Hipoxia/metabolismo , Hipoxia/complicaciones , Especies Reactivas de Oxígeno/metabolismo , Hígado/metabolismo , Hígado/patología , Caspasa 1/metabolismo , Interleucina-1beta/metabolismo , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Alanina Transaminasa/sangre , Proteínas Adaptadoras de Señalización CARD/metabolismo , Aspartato Aminotransferasas/sangre , Hepatopatías/etiología , Hepatopatías/metabolismo , Hepatopatías/patología
10.
PLoS One ; 19(5): e0302906, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38718039

RESUMEN

Osteoarthritis is the most prevalent type of degenerative arthritis. It is characterized by persistent pain, joint dysfunction, and physical disability. Pain relief and inflammation control are prioritised during osteoarthritis treatment Mume Fructus (Omae), a fumigated product of the Prunus mume fruit, is used as a traditional medicine in several Asian countries. However, its therapeutic mechanism of action and effects on osteoarthritis and articular chondrocytes remain unknown. In this study, we analyzed the anti-osteoarthritis and articular regenerative effects of Mume Fructus extract on rat chondrocytes. Mume Fructus treatment reduced the interleukin-1ß-induced expression of matrix metalloproteinase 3, matrix metalloproteinase 13, and a disintegrin and metalloproteinase with thrombospondin type 1 motifs 5. Additionally, it enhanced collagen type II alpha 1 chain and aggrecan accumulation in rat chondrocytes. Furthermore, Mume Fructus treatment regulated the inflammatory cytokine levels, mitogen-activated protein kinase phosphorylation, and nuclear factor-kappa B activation. Overall, our results demonstrated that Mume Fructus inhibits osteoarthritis progression by inhibiting the nuclear factor-kappa B and mitogen-activated protein kinase pathways to reduce the levels of inflammatory cytokines and prevent cartilage degeneration. Therefore, Mume Fructus may be a potential therapeutic option for osteoarthritis.


Asunto(s)
Cartílago Articular , Condrocitos , Interleucina-1beta , FN-kappa B , Osteoartritis , Extractos Vegetales , Animales , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Interleucina-1beta/metabolismo , Ratas , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , FN-kappa B/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Osteoartritis/patología , Extractos Vegetales/farmacología , Prunus/química , Ratas Sprague-Dawley , Regulación hacia Abajo/efectos de los fármacos , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/genética , Colágeno Tipo II/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/genética , Frutas/química , Agrecanos/metabolismo , Proteína ADAMTS5/metabolismo , Proteína ADAMTS5/genética , Células Cultivadas , Masculino , Sistema de Señalización de MAP Quinasas/efectos de los fármacos
11.
Mol Biol Rep ; 51(1): 643, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38727775

RESUMEN

BACKGROUND: Baicalein is the main active flavonoid in Scutellariae Radix and is included in shosaikoto, a Kampo formula used for treating hepatitis and jaundice. However, little is known about its hepatoprotective effects against hepatic ischemia-reperfusion injury (HIRI), a severe clinical condition directly caused by interventional procedures. We aimed to investigate the hepatoprotective effects of baicalein against HIRI and partial hepatectomy (HIRI + PH) and its potential underlying mechanisms. METHODS AND RESULTS: Male Sprague-Dawley rats received either baicalein (5 mg/kg) or saline intraperitoneally and underwent a 70% hepatectomy 15 min after hepatic ischemia. After reperfusion, liver and blood samples were collected. Survival was monitored 30 min after hepatic ischemia and hepatectomy. In interleukin 1ß (IL-1ß)-treated primary cultured rat hepatocytes, the influence of baicalein on inflammatory mediator production and the associated signaling pathway was analyzed. Baicalein suppressed apoptosis and neutrophil infiltration, which are the features of HIRI + PH treatment-induced histological injury. Baicalein also reduced the mRNA expression of the proinflammatory cytokine tumor necrosis factor-α (TNF-α). In addition, HIRI + PH treatment induced liver enzyme deviations in the serum and hypertrophy of the remnant liver, which were suppressed by baicalein. In the lethal HIRI + PH treatment group, baicalein significantly reduced mortality. In IL-1ß-treated rat hepatocytes, baicalein suppressed TNF-α and chemokine mRNA expression as well as the activation of nuclear factor-kappa B (NF-κB) and Akt. CONCLUSIONS: Baicalein treatment attenuates HIRI + PH-induced liver injury and may promote survival. This potential hepatoprotection may be partly related to suppressing inflammatory gene induction through the inhibition of NF-κB activity and Akt signaling in hepatocytes.


Asunto(s)
Apoptosis , Modelos Animales de Enfermedad , Flavanonas , Hepatectomía , Hepatocitos , Interleucina-1beta , Hígado , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Flavanonas/farmacología , Flavanonas/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Hepatectomía/métodos , Masculino , Ratas , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Apoptosis/efectos de los fármacos , Interleucina-1beta/metabolismo , FN-kappa B/metabolismo , Sustancias Protectoras/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo
12.
Sci Rep ; 14(1): 10178, 2024 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702410

RESUMEN

The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been associated with worse outcomes from severe traumatic brain injury (TBI). The NLRP3 inflammasome is also strongly associated with other pro-inflammatory conditions, such as obesity. Little is known about the potential effect of mild TBI (mTBI) on the NLRP3 inflammasome and the extent to which modifying factors, such as obesity, may augment the inflammatory response to mTBI. The purpose of this study was to evaluate the association of NLRP3 inflammasome proteins with obese body mass index (BMI ≥ 30) within 24 h of mTBI after presenting to a level 1 trauma center emergency department. This is a secondary analysis of prospectively enrolled patients with mTBI who presented to the emergency department of one U.S. Level 1 trauma center from 2013 to 2018 (n = 243). A series of regression models were built to evaluate the association of NLRP3 proteins obtained from blood plasma within 24 h of injury and BMI as well as the potential interaction effect of higher BMI with NLRP3 proteins (n = 243). A logistic regression model revealed a significant association between IL-18 (p < 0.001) in mTBI patients with obese BMI compared to mTBI patients with non-obese BMI (< 30). Moderation analyses revealed statistically significant interaction effects between apoptotic speck-like protein (ASC), caspase-1, IL-18, IL-1ß and obese BMI which worsened symptom burden, quality of life, and physical function at 2 weeks and 6 months post-injury. Higher acute concentrations of IL-1ß in the overall cohort predicted higher symptoms at 6-months and worse physical function at 2-weeks and 6-months. Higher acute concentrations of IL-18 in the overall cohort predicted worse physical function at 6-months. In this single center mTBI cohort, obese BMI interacted with higher acute concentrations of NLRP3 inflammasome proteins and worsened short- and long-term clinical outcomes.


Asunto(s)
Índice de Masa Corporal , Conmoción Encefálica , Inflamasomas , Interleucina-18 , Proteína con Dominio Pirina 3 de la Familia NLR , Obesidad , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Femenino , Obesidad/complicaciones , Inflamasomas/metabolismo , Adulto , Persona de Mediana Edad , Conmoción Encefálica/complicaciones , Conmoción Encefálica/sangre , Interleucina-18/sangre , Interleucina-18/metabolismo , Estudios Prospectivos , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Caspasa 1/metabolismo
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 739-747, 2024 Apr 20.
Artículo en Chino | MEDLINE | ID: mdl-38708508

RESUMEN

OBJECTIVE: To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of Sidaxue at low, moderate and high doses (10, 20, and 40 g/kg, respectively) for 21 days, with Tripterygium glycosides (GTW) as the positive control, on swelling in the hind limb plantar regions by arthritis index scoring. Pathologies in joint synovial membrane of the rats were observed with HE staining, and serum TNF-α and IL-1ß levels were detected with ELISA. The expressions of NF-κB p65, matrix metalloproteinase 1 (MMP1), MMP2 and MMP9 at the mRNA and protein levels in the synovial tissues were detected using real-time PCR and Western blotting. Network pharmacology analysis was conducted to identify the important target proteins in the pathways correlated with the therapeutic effects of topical Sidaxue treatment for RA, and the core target proteins were screened by topological analysis. RESULTS: Treatment with GTW and Sidaxue at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, improved cartilage and bone damage and reduced neovascularization in CIA rats (P<0.05), and the effects of Sidaxue showed a dose dependence. Both GTW and Sidaxue treatments significantly lowered TNF-α, IL-1ß, NF-κB p65, MMP1, MMP2, and MMP9 mRNA and protein expressions in the synovial tissues of CIA rats (P<0.05). Network pharmacological analysis identified MMPs as the core proteins associated with topical Sidaxue treatment of RA. CONCLUSION: Sidaxue alleviates articular bone and cartilage damages and reduces synovial neovascularization in CIA rats possibly by downregulating MMPs via the TNF-α/IL-1ß/NF-κB-MMP1, 2, 9 signaling pathway, and MMPs probably plays a key role in mediating the effect of Sidaxue though the therapeutic pathways other than oral administration.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Medicamentos Herbarios Chinos , Metaloproteinasa 1 de la Matriz , Ratas Sprague-Dawley , Membrana Sinovial , Factor de Necrosis Tumoral alfa , Animales , Ratas , Artritis Reumatoide/tratamiento farmacológico , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Metaloproteinasa 1 de la Matriz/metabolismo , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Tripterygium/química , Factor de Transcripción ReIA/metabolismo
14.
Wiad Lek ; 77(3): 497-505, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38691792

RESUMEN

OBJECTIVE: Aim: The aim of this research is to clarify the potential effect of CDDO-EA against experimentally sepsis induced lung injury in mice. PATIENTS AND METHODS: Materials and Methods: Mice have divided into four groups: Sham group CLP group, Vehicle-treatment group, CDDO-EA-treated group: mice in this group received CDDO-EA 2mg/kg intraperitoneally, 1hr before CLP, then the animals were sacrificed 24hr after CLP. After exsAngpuinations, tissue samples of lung were collected, followed by markers measurement including, TNF-α, IL-1ß, VEGF, MPO, caspase11, Angp-1and Angp-2 by ELISA, gene expression of TIE2 and VE-cadherin by qRT-PCR, in addition to histopathological study. RESULTS: Results: A significant elevation (p<0.05) in TNF-α, IL-1ß, MPO, ANGP-2, VEGF, CASPASE 11 in CLP and vehicle groups when compared with sham group. CDDO-EA group showed significantly lower levels p<0.05, level of ANGP-1 was significantly lower p<0.05 in the CLP and vehicle groups as compared with the sham group. Quantitative real-time PCR demonstrated a significant decrement in mRNA expression of TIE2&ve-cadherin genes p<0.05 in sepsis & vehicle. CONCLUSION: Conclusions: CDDO-EA has lung protective effects due to its anti-inflammatory and antiAngpiogenic activity, additionally, CDDO-EA showes a lung protective effect as they affect tissue mRNA expression of TIE2 and cadherin gene. Furthermore, CDDO-EA attenuate the histopathological changes that occur during polymicrobial sepsis thereby lung protection effect.


Asunto(s)
Lesión Pulmonar Aguda , Modelos Animales de Enfermedad , Endotoxemia , Sepsis , Animales , Ratones , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Endotoxemia/metabolismo , Sepsis/complicaciones , Sepsis/metabolismo , Masculino , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Pulmón/patología , Pulmón/metabolismo , Interleucina-1beta/metabolismo
15.
J Med Virol ; 96(5): e29643, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38695269

RESUMEN

Severe pneumonia caused by respiratory viruses has become a major threat to humans, especially with the SARS-CoV-2 outbreak and epidemic. The aim of this study was to investigate the universal molecular mechanism of severe pneumonia induced by multiple respiratory viruses and to search for therapeutic strategies targeting this universal molecular mechanism. The common differential genes of four respiratory viruses, including respiratory syncytial virus (RSV), rhinovirus, influenza, and SARS-CoV-2, were screened by GEO database, and the hub gene was obtained by Sytohubba in Cytoscape. Then, the effect of hub genes on inflammasome and pyrodeath was investigated in the model of RSV infection in vitro and in vivo. Finally, through virtual screening, drugs targeting the hub gene were obtained, which could alleviate severe viral pneumonia in vitro and in vivo. The results showed that CMPK2 is one of the hub genes after infection by four respiratory viruses. CMPK2 activates the inflammasome by activating NLRP3, and promotes the releases of inflammatory factors interleukin (IL)-1ß and IL-18 to induce severe viral pneumonia. Z25 and Z08 can reduce the expression level of CMPK2 mRNA and protein, thereby inhibiting NLRP3 and alleviating the development of severe viral pneumonia. In conclusion, the inflammatory response mediated by CMPK2 is the common molecular mechanism of severe pneumonia induced by viral infection, and Z25 and Z08 can effectively alleviate viral infection and severe pneumonia through this mechanism.


Asunto(s)
Inflamasomas , Piroptosis , Piroptosis/efectos de los fármacos , Humanos , Animales , Inflamasomas/metabolismo , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Interleucina-18/metabolismo , Interleucina-18/genética , SARS-CoV-2 , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/virología
16.
Nutrients ; 16(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38732595

RESUMEN

While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets impacts intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate-dextran (FITC-dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC-dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.


Asunto(s)
Colitis , Colon , Sulfato de Dextran , Dieta Cetogénica , Grasas de la Dieta , Modelos Animales de Enfermedad , Fluoresceína-5-Isotiocianato/análogos & derivados , Ratones Endogámicos C57BL , Animales , Colitis/inducido químicamente , Colitis/dietoterapia , Masculino , Ratones , Grasas de la Dieta/efectos adversos , Colon/patología , Colon/metabolismo , Permeabilidad , Proteínas de Uniones Estrechas/metabolismo , Interleucina-1beta/metabolismo , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ácidos Grasos , Dextranos
17.
Ulus Travma Acil Cerrahi Derg ; 30(5): 309-315, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38738674

RESUMEN

BACKGROUND: This study aimed to evaluate the histopathological and biochemical effects of ketamine on penile tissues following ischemia-reperfusion injury induced by priapism. METHODS: Twenty-four male rats were randomized into three groups. Group 1 served as the control group. Group 2 underwent the priapism model to induce ischemia-reperfusion injury. Group 3, the treatment group, experienced a similar ischemia-reperfusion model as Group 2; additionally, 50 mg/kg of ketamine was administered intraperitoneally just before reperfusion. Blood biochemical analyses and penile histopathological evaluations were performed. RESULTS: In Group 3, significant improvements were observed in all histopathological scores, including desquamation, edema, inflammation, and vasocongestion compared to Group 2 (p<0.001). Blood biochemical analyses showed that the malondialdehyde (MDA) levels were recorded as 10 in Group 2, with a significant decrease in Group 3 (p=0.013). Similarly, proinflammatory cytokine levels, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were found to be suppressed in Group 3 compared to Group 2 (p=0.003, p=0.022, and p=0.028, respectively). Antioxidant enzyme activities, such as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), were higher in Group 3 compared to Group 2 (p=0.016 and p=0.024, respec-tively). CONCLUSION: Ketamine is an effective anesthetic agent in alleviating the effects of penile ischemia-reperfusion injury.


Asunto(s)
Modelos Animales de Enfermedad , Ketamina , Malondialdehído , Pene , Priapismo , Daño por Reperfusión , Animales , Ketamina/administración & dosificación , Ketamina/farmacología , Ketamina/uso terapéutico , Masculino , Priapismo/tratamiento farmacológico , Priapismo/etiología , Ratas , Pene/efectos de los fármacos , Pene/irrigación sanguínea , Pene/patología , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Malondialdehído/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Distribución Aleatoria , Anestésicos Disociativos/administración & dosificación , Interleucina-1beta/metabolismo , Interleucina-1beta/sangre
18.
Mol Biol Rep ; 51(1): 655, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739285

RESUMEN

BACKGROUND: There is limited data regarding the hazardous effect of gentamicin (GM) on the uterus and whether or not vinpocetine (Vinpo) ameliorates it. The present study aimed to identify the possible protective effect of Vinpo in GM-induced uterine injury in rats. METHODS: Female rats were assorted in control-group, Vinpo-group, GM-group, and Vinpo plus GM group. Serum and uterine GM concentration were measured. Uterine oxidative stress parameters besides inflammatory and apoptotic biomarkers were evaluated. Uterine histopathological examination and interlukin-1beta (IL-1ß) immune-histochemical study were detected. RESULTS: GM significantly increased uterine oxidative stress, inflammatory and apoptotic biomarkers. Histopathological picture of uterine damage and increased IL-1ß immunoexpression were detected. Vinpo significantly ameliorated the distributed GM concentration, oxidative stress, inflammatory and apoptotic biomarkers with a prompt improvement in histopathological picture and a decrease in IL-1ß immunoexpression. CONCLUSION: Vinpo protective effect against GM-induced uterine injury involves modulation of inflammasome/caspase-1/IL-1ß signaling pathway.


Asunto(s)
Caspasa 1 , Gentamicinas , Inflamasomas , Interleucina-1beta , Estrés Oxidativo , Transducción de Señal , Útero , Alcaloides de la Vinca , Animales , Femenino , Interleucina-1beta/metabolismo , Alcaloides de la Vinca/farmacología , Ratas , Caspasa 1/metabolismo , Gentamicinas/efectos adversos , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Útero/efectos de los fármacos , Útero/metabolismo , Útero/patología , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos
19.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732100

RESUMEN

The use of temporary resin for provisional restorations is a fundamental step to maintain the position of prepared teeth, to protect the pulpal vitality and the periodontal health as well as the occlusion. The present study aimed at evaluating the biological effects of two resins used in dentistry for temporary restorations, Coldpac (Yates Motloid) and ProTemp 4™ (3M ESPE ™), and their eluates, in an in vitro model of human gingival fibroblasts (hGFs). The activation of the inflammatory pathway NFκB p65/NLRP3/IL-1ß induced by the self-curing resin disks was evaluated by real-time PCR, Western blotting and immunofluorescence analysis. The hGFs adhesion on resin disks was investigated by means of inverted light microscopy and scanning electron microscopy (SEM). Our results suggest that hGF cells cultured in adhesion and with eluate derived from ProTemp 4™ (3M ESPE ™) resin evidenced a downregulation in the expression of the inflammatory mediators such as NFκB p65, NLRP3 and IL-1ß compared to the cells cultured with Coldpac (Yates Motloid) after 24 h and 1 week of culture. Furthermore, the cells cultured with ProTemp 4™ (3M ESPE ™) after 24 h and 1 week of culture reported a higher cell viability compared to the cells cultured with Coldpac (Yates Motloid), established by MTS cell analysis. Similar results were obtained when hGFs were placed in culture with the eluate derived from ProTemp 4™ (3M ESPE ™) resin which showed a higher cell viability compared to the cells cultured with eluate derived from Coldpac (Yates Motloid). These results highlighted the lower pro-inflammatory action and improved cell biocompatibility of ProTemp 4™ (3M ESPE ™), suggesting a better performance in terms of cells-material interaction.


Asunto(s)
Resinas Compuestas , Fibroblastos , Encía , Interleucina-1beta , Polimetil Metacrilato , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Encía/citología , Resinas Compuestas/farmacología , Resinas Compuestas/química , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacología , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Células Cultivadas , Factor de Transcripción ReIA/metabolismo , Adhesión Celular/efectos de los fármacos
20.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732106

RESUMEN

Type 2 diabetes (T2D) is characterized by muscle metabolic dysfunction that exercise can minimize, but some patients do not respond to an exercise intervention. Myokine secretion is intrinsically altered in patients with T2D, but the role of myokines in exercise resistance in this patient population has never been studied. We sought to determine if changes in myokine secretion were linked to the response to an exercise intervention in patients with T2D. The participants followed a 10-week aerobic exercise training intervention, and patients with T2D were grouped based on muscle mitochondrial function improvement (responders versus non-responders). We measured myokines in serum and cell-culture medium of myotubes derived from participants pre- and post-intervention and in response to an in vitro model of muscle contraction. We also quantified the expression of genes related to inflammation in the myotubes pre- and post-intervention. No significant differences were detected depending on T2D status or response to exercise in the biological markers measured, with the exception of modest differences in expression patterns for certain myokines (IL-1ß, IL-8, IL-10, and IL-15). Further investigation into the molecular mechanisms involving myokines may explain exercise resistance with T2D; however, the role in metabolic adaptations to exercise in T2D requires further investigation.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ejercicio Físico , Fibras Musculares Esqueléticas , Entrenamiento de Fuerza , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Masculino , Ejercicio Físico/fisiología , Persona de Mediana Edad , Femenino , Fibras Musculares Esqueléticas/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/sangre , Citocinas/metabolismo , Citocinas/sangre , Interleucina-8/metabolismo , Interleucina-8/sangre , Interleucina-10/metabolismo , Interleucina-10/sangre , Anciano , Interleucina-15/metabolismo , Interleucina-15/sangre , Terapia por Ejercicio/métodos , Contracción Muscular , Músculo Esquelético/metabolismo , Mioquinas
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