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1.
Nutr Neurosci ; : 1-15, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953237

RESUMO

OBJECTIVES: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting approximately 55 million individuals globally. Diagnosis typically occurs in advanced stages, and there are limited options for reversing symptoms. Preventive strategies are, therefore, crucial. Time Restricted Eating (TRE) or Time Restricted Feeding (TRF) is one such strategy. Here we review recent research on AD and TRE/TRF in addition to AD biomarkers and gut microbiota. METHODS: A comprehensive review of recent studies was conducted to assess the impact of TRE/TRF on AD-related outcomes. This includes the analysis of how TRE/TRF influences circadian rhythms, beta-amyloid 42 (Aß42), pro-inflammatory cytokines levels, and gut microbiota composition. RESULTS: TRE/TRF impacts circadian rhythms and can influence cognitive performance as observed in AD. It lowers beta-amyloid 42 deposition in the brain, a key AD biomarker, and reduces pro-ininflammatory cytokines. The gut microbiome has emerged as a modifiable factor in AD treatment. TRE/TRF changes the structure and composition of the gut microbiota, leading to increased diversity and a decrease in harmful bacteria. DISCUSSION: These findings underscore the potential of TRE/TRF as a preventive strategy for AD. By reducing Aß42 plaques, modulating pro-inflammatory cytokines, and altering gut microbiota composition, TRE/TRF may slow the progression of AD. Further research is needed to confirm these effects and to understand the mechanisms involved. This review highlights TRE/TRF as a promising non-pharmacological intervention in the fight against AD.

2.
Heliyon ; 10(12): e32836, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38948035

RESUMO

Introduction: This study examined the anti-inflammatory and antioxidant properties of Capparis spinosa L. (caper) in order to determine its medicinal potential in the treatment of acute colitis. Method: Sixty male rats were divided into six groups. After the experimental period, distal colonic extension was collected for determination of colonic damage, oxidative stress markers, along with antioxidant markers. The impact of altered levels of inflammatory cytokines in colon tissues on the underlying mechanisms examined. Results: The results showed that administering different doses of caper led to significant decreases in TNF-α and IL-6 levels when compared to the control colitis group (p < 0.001). Caper treatment effectively lowered elevated oxidative stress factors (MDA, NO, and MPO) compared to the control colitis group (p < 0.001). Caper treatment resulted in a significant increase in antioxidant factors (CAT, SOD, and GSH) compared with the control colitis group (p < 0.001).Significant improvements in tissue repair were observed in caper-treated groups compared to positives and control colitis (p < 0.001). Conclusion: The study highlights caper may be useful in the treatment of acute colitis due to its ameliorative effects on inflammation, oxidative stress, and tissue repair.

3.
Food Chem Toxicol ; 191: 114847, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964650

RESUMO

Prevention of anticancer drugs-induced cardiotoxicity remains an imperative area of oncology research as it continues to be a major challenge in cancer chemotherapy. This study was undertaken to investigate the protective effect of methanol extract of Morchella esculenta (ME) against cyclophosphamide (CP)-induced cardiotoxicity. Myocardial damage was assessed by biochemical and histopathological methods. Proinflammatory cytokines gene expression was determined by RT-PCR analysis. To assess the mitochondrial dysfunction, TCA cycle and electron transport chain complexes enzymes activities were determined. Chemical finger print of ME was accomplished by HPTLC. CP (200 mg/kg) treated animals showed elevation in cardiac injury markers which was attenuated by ME (p < 0.05). CP-induced decline of antioxidant status and expression of nuclear factor erythroid 2-related factor 2 were restored by ME. CP-induced expression of NF-ĸB, IL1-ß, IL-6, TNF-α, COX-2 and iNOS (p < 0.05) was attenuated by ME (500 mg/kg). Bioactive compounds namely, 5-eicosapentaenoicacid (C20H30O2), 8-hydroxyoctadecadienoic acid (C18H32O3), 4,4-dipo-zetacarotene (C30H44), CynarosideA (C21H32O10) present in the extract might be responsible for cardioprotection. The findings reveal the protective effect of ME against CP-induced cardiomyopathy.

4.
PeerJ ; 12: e17539, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952964

RESUMO

The association between sleep and the immune-endocrine system is well recognized, but the nature of that relationship is not well understood. Sleep fragmentation induces a pro-inflammatory response in peripheral tissues and brain, but it also activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing glucocorticoids (GCs) (cortisol in humans and corticosterone in mice). It is unclear whether this rapid release of glucocorticoids acts to potentiate or dampen the inflammatory response in the short term. The purpose of this study was to determine whether blocking or suppressing glucocorticoid activity will affect the inflammatory response from acute sleep fragmentation (ASF). Male C57BL/6J mice were injected i.p. with either 0.9% NaCl (vehicle 1), metyrapone (a glucocorticoid synthesis inhibitor, dissolved in vehicle 1), 2% ethanol in polyethylene glycol (vehicle 2), or mifepristone (a glucocorticoid receptor antagonist, dissolved in vehicle 2) 10 min before the start of ASF or no sleep fragmentation (NSF). After 24 h, samples were collected from brain (prefrontal cortex, hypothalamus, hippocampus) and periphery (liver, spleen, heart, and epididymal white adipose tissue (EWAT)). Proinflammatory gene expression (TNF-α and IL-1ß) was measured, followed by gene expression analysis. Metyrapone treatment affected pro-inflammatory cytokine gene expression during ASF in some peripheral tissues, but not in the brain. More specifically, metyrapone treatment suppressed IL-1ß expression in EWAT during ASF, which implies a pro-inflammatory effect of GCs. However, in cardiac tissue, metyrapone treatment increased TNF-α expression in ASF mice, suggesting an anti-inflammatory effect of GCs. Mifepristone treatment yielded more significant results than metyrapone, reducing TNF-α expression in liver (only NSF mice) and cardiac tissue during ASF, indicating a pro-inflammatory role. Conversely, in the spleen of ASF-mice, mifepristone increased pro-inflammatory cytokines (TNF-α and IL-1ß), demonstrating an anti-inflammatory role. Furthermore, irrespective of sleep fragmentation, mifepristone increased pro-inflammatory cytokine gene expression in heart (IL-1ß), pre-frontal cortex (IL-1ß), and hypothalamus (IL-1ß). The results provide mixed evidence for pro- and anti-inflammatory functions of corticosterone to regulate inflammatory responses to acute sleep loss.


Assuntos
Glucocorticoides , Metirapona , Camundongos Endogâmicos C57BL , Mifepristona , Privação do Sono , Animais , Masculino , Metirapona/farmacologia , Privação do Sono/metabolismo , Privação do Sono/tratamento farmacológico , Camundongos , Mifepristona/farmacologia , Glucocorticoides/farmacologia , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Corticosterona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/antagonistas & inibidores , Receptores de Glucocorticoides/genética
5.
Biogerontology ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970715

RESUMO

The intestinal barrier weakens and chronic gut inflammation occurs in old age, causing age-related illnesses. Recent research shows that low-molecular-weight heparin (LMWH), besides anticoagulation, also has anti-inflammatory and anti-apoptotic effects, protecting the intestinal barrier. This study aims to analyze the effect of LMWH on the intestinal barrier of old male rodents. This study assigned Sprague-Dawley male rats to four groups: young (3 months), young + LMWH, old (20 months), and old + LMWH. The LMWH groups received 1 mg/kg LMWH via subcutaneous injection for 7 days. Optical and transmission electron microscopy (TEM) were used to examine morphological changes in intestinal mucosa due to aging. Intestinal permeability was measured using fluorescein isothiocyanate (FITC)-dextran. ELISA kits were used to measure serum levels of IL-6 and IL-1ß, while Quantitative RT-PCR detected their mRNA levels in intestinal tissues. Western blotting and immunohistochemistry (IHC) evaluated the tight junction (TJ) protein levels such as occludin, zonula occludens-1 (ZO-1), and claudin-2. Western blotting assessed the expression of the apoptosis marker cleaved caspase 3, while IHC was used to detect LGR5+ intestinal stem cells. The intestinal permeability of aged rats was significantly higher than that of young rats, indicating significant differences. With age, the protein levels of occludin and ZO-1 decreased significantly, while the level of claudin-2 increased significantly. Meanwhile, our study found that the levels of IL-1ß and IL-6 increased significantly with age. LMWH intervention effectively alleviated age-related intestinal barrier dysfunction. In aged rats treated with LMWH, the expression of occludin and ZO-1 proteins in the intestine increased, while the expression of claudin-2 decreased. Furthermore, LMWH administration in aged rats resulted in a decrease in IL-1ß and IL-6 levels. LMWH also reduced age-related cleaved caspase3 expression, but IHC showed no difference in LGR5+ intestinal stem cells between groups. Research suggests that LMWH could potentially be a favorable therapeutic choice for age-related diseases associated with intestinal barrier dysfunction, by protecting TJ proteins, reducing inflammation, and apoptosis.

6.
Cancers (Basel) ; 16(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39001432

RESUMO

The reorganization of the cell cytoskeleton and changes in the content of cell adhesion molecules are crucial during the metastatic spread of tumor cells. Colorectal cancer (CRC) cells express high SMAD7, a protein involved in the control of CRC cell growth. In the present study, we evaluated whether SMAD7 regulates the cytoskeleton reorganization and dynamics in CRC. Knockdown of SMAD7 with a specific antisense oligonucleotide (AS) in HCT116 and DLD1, two human CRC cell lines, reduced the migration rate and the content of F-ACTIN filaments. A gene array, real-time PCR, and Western blotting of SMAD7 AS-treated cells showed a marked down-regulation of the X-linked inhibitor of apoptosis protein (XIAP), a member of the inhibitor of apoptosis family, which has been implicated in cancer cell migration. IL-6 and IL-22, two cytokines that activate STAT3, enhanced XIAP in cancer cells, and such induction was attenuated in SMAD7-deficient cells. Finally, in human CRC, SMAD7 mRNA correlated with XIAP expression. Our data show that SMAD7 positively regulates XIAP expression and migration of CRC cells, and suggest a mechanism by which SMAD7 controls the architecture components of the CRC cell cytoskeleton.

7.
Mol Biol Rep ; 51(1): 814, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008163

RESUMO

Periodontitis is a severe gum infection that begins as gingivitis and can lead to gum recession, bone loss, and tooth loss if left untreated. It is primarily caused by bacterial infection, which triggers inflammation and the formation of periodontal pockets. Notably, periodontitis is associated with systemic health issues and has been linked to heart disease, diabetes, respiratory diseases, adverse pregnancy outcomes, and cancers. Accordingly, the presence of chronic inflammation and immune system dysregulation in individuals with periodontitis significantly contributes to the initiation and progression of various cancers, particularly oral cancers. These processes promote genetic mutations, impair DNA repair mechanisms, and create a tumor-supportive environment. Moreover, the bacteria associated with periodontitis produce harmful byproducts and toxins that directly damage the DNA within oral cells, exacerbating cancer development. In addition, chronic inflammation not only stimulates cell proliferation but also inhibits apoptosis, causes DNA damage, and triggers the release of pro-inflammatory cytokines. Collectively, these factors play a crucial role in the progression of cancer in individuals affected by periodontitis. Further, specific viral and bacterial agents, such as hepatitis B and C viruses, human papillomavirus (HPV), Helicobacter pylori (H. pylori), and Porphyromonas gingivalis, contribute to cancer development through distinct mechanisms. Bacterial infections have systemic implications for cancer development, while viral infections provoke immune and inflammatory responses that can lead to genetic mutations. This review will elucidate the link between periodontitis and cancers, particularly oral cancers, exploring their underlying mechanisms to provide insights for future research and treatment advancements.


Assuntos
Neoplasias Bucais , Periodontite , Humanos , Periodontite/complicações , Periodontite/microbiologia , Neoplasias Bucais/microbiologia , Neoplasias Bucais/genética , Animais , Inflamação/complicações , Porphyromonas gingivalis/patogenicidade
8.
J Inflamm Res ; 17: 4443-4452, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006492

RESUMO

Objective: Pro-inflammatory cytokines mediate the course of rosacea, anxiety, and depression through various means such as immunity and inflammation. This study aims to further explore the relationship between rosacea, anxiety, and depression through changes in the levels of pro-inflammatory cytokines. Methods: 280 rosacea patients were included in the rosacea group, divided into: rosacea without mental disorders, rosacea with anxiety, rosacea with depression, and rosacea with combined anxiety and depression. The mental control group included 210 anxiety and depression patients, divided into: anxiety, depression, and combined anxiety and depression. The healthy control group consisted of 70 healthy individuals. Serum specimens were collected and ELISA was used to detect major pro-inflammatory cytokines. CEA, IGA, GFSS, RosaQoL, HAMA, and HAMD-24 were used for the diagnosis and severity assessment of rosacea and anxiety and depression. Results: This study primarily used the Chi-Square test, Kruskal-Wallis H-test, generalized linear model, and binary logistic regression to evaluate the data. IL-1ß, IL-17, and IL-8 levels in rosacea patients and anxiety/depression patients were higher than those in the healthy population (P<0.001), and TNF-α levels in rosacea patients were higher than those in the healthy population (P<0.001). There was an interaction between rosacea, anxiety, and depression in terms of IL-1ß, IL-17, and IL-8 levels (P<0.001). Elevated levels of IL-1ß, IL-17, and IL-8 are positively correlated with anxiety and depression in rosacea (all P<=0.05). Conclusion: It was confirmed that the elevated levels of IL-1ß, IL-17, and IL-8 are positively correlated with the onset of anxiety and depression in rosacea. The interaction of the above inflammatory factors suggests a possible common inflammatory mechanism in the coexistence of rosacea and mental disorders. TNF-α only increased in patients with rosacea, combined with the skin-to-mental irreversible phenomenon, indicating that this cytokine may be a key and potential therapeutic target for the onset of rosacea.

9.
Biomark Med ; : 1-10, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011671

RESUMO

Aim: ITIH4 has anti-inflammatory properties toward eosinophilic/neutrophilic inflammation. This study aimed to explore clinical value of ITIH4 in childhood asthma. Materials & methods: Serum ITIH4 and inflammatory cytokines were determined in 120 childhood asthma patients by enzyme-linked immunosorbent assay. Results: In the entire and acute exacerbation patients, ITIH4 positively associated with IFN-γ, but negatively related to proinflammatory cytokines. ITIH4 was lowest in patients with acute exacerbation, followed by chronic persistent, and highest in clinical remission. By receiver-operating characteristic analysis, ITIH4 potentially estimated acute exacerbation asthma risk. Moreover, ITIH4 negatively related to exacerbation severity in acute exacerbation patients. Conclusion: Serum ITIH4 negatively links with Th2 cell signature cytokine, proinflammatory cytokines, exacerbation risk and severity in childhood asthma.


[Box: see text].

10.
J Neuroimmunol ; 393: 578398, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-39002186

RESUMO

The classification of autoimmune encephalitis (AE) is based on the presence of different types of antibodies. Currently, the clinical manifestations and treatment regimens of patients with all types of AE exhibit similarities. However, the presence of immunological distinctions among different types of AE remains uncertain. In this study, we prospectively collected clinical data, as well as blood and cerebrospinal fluid (CSF) samples from patients diagnosed with MOG antibody-associated disease (MOGAD) or GFAP astrocytopathy (GFAP-A), in order to assess changes in inflammatory biomarkers such as immunoglobulin oligoclonal bands, cytokines in serum and CSF, as well as peripheral blood lymphocyte subtypes within different subsets. To further distinguish the immune response in patients with MOGAD and GFAP-A from that of healthy individuals, we prospectively recruited 20 hospitalized patients diagnosed with AE. Among them, 15 (75%) tested positive for MOG antibodies, 4 (20%) tested positive for GFAP antibodies, and 1 (5%) tested positive for both MOG and GFAP antibodies. These patients were then followed up for a period of 18 months. Compared to healthy controls (HC), AE patients exhibited elevated levels of MIP-1beta, SDF-1alpha, IL-12p70, IL-5, IL-1RA, IL-8 and decreased levels of IL-23, IL-31, IFN-alpha, IL-7, TNF-beta and TNF-alpha in serum. The CSF of AE patients showed increased levels of IL-1RA, IL-6 and IL-2 while decreased levels of RANTES, IL-18,IL-7,TNF-beta,TNF-alpha,RANTES,Eotaxin,and IL-9. The level of MCP-1 in the CSF of GFAP-A patients was found to be lower compared to that of MOGAD patients, while RANTES levels were higher. And the levels of IL-17A, Eotaxin, GRO-alpha, IL-8, IL-1beta, MIP-1beta were higher in the CSF of patients with epilepsy. The presence of intrathecal immune responses is also observed in patients with spinal muscular atrophy (SMA). However, no biomarker was found to be associated with disease severity in patients with AE. Among the 17 patients, recovery was observed, while 2 patients experienced persistent symptoms after an 18-month follow-up period. Additionally, within one year of onset, 8 patients had a single recurrence. Therefore, the immunological profiles of MOGAD and GFAP-A patients differ from those of normal individuals, and the alterations in cytokine levels may also exhibit a causal association with the clinical presentations, such as seizure.

11.
Front Immunol ; 15: 1380889, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979412

RESUMO

Background: Mounting evidence suggests a connection between inflammatory cytokines and adhesive capsulitis (AC). However, the specific systemic inflammatory cytokines contributing to AC have not been clearly identified. This study employed Mendelian randomization (MR) to explore the causal relationships between 41 inflammatory cytokines and AC. Methods: In this bidirectional, two-sample MR analysis, genetic variations associated with AC were derived from a comprehensive genome-wide association study (GWAS). The inflammatory cytokines data were sourced from a GWAS summary involving 8,293 healthy participants. The primary MR method employed was inverse variance weighting, supplemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier for sensitivity analysis. Heterogeneity was assessed using Cochran's Q test, and the MR results were validated using the leave-one-out method. Results: Elevated levels of interferon gamma-induced protein 10 (IP-10) (odds ratio (OR) = 1.086, 95% confidence interval (CI) = 1.002-1.178) and regulated on activation, normal T cell expressed and secreted (RANTES) (OR = 1.107, 95% CI = 1.026-1.195) were linked to an increased risk of AC. Increased levels of stromal cell-derived factor-1 alpha (SDF-1α) (OR = 0.879, 95% CI = 0.793-0.974) and tumor necrosis factor-alpha (TNF-α) (OR = 0.911, 95% CI = 0.831-0.999) were associated with a reduced AC risk. Moreover, genetically predicted AC exhibited associations with elevated cutaneous T cell attracting (CTACK) levels (OR = 1.202, 95% CI = 1.007-1.435) and diminished levels of interleukin-17 (IL-17) (OR = 0.678, 95% CI = 0.518-0.888) and interleukin-5 (IL-5) (OR = 0.786, 95% CI = 0.654-0.944), as confirmed through inverse-variance weighted (IVW) methods. Conclusion: The present study successfully establishes a causal association between genetically proxied circulating levels of IP-10, RANTES, SDF-1α, and TNF-α and the risk of AC. Additionally, AC contributes to an increase in CTACK and a decrease in IL-17 and IL-5. This significant finding not only enhances the understanding of the pathogenesis of AC but also holds promise for the development of effective clinical management strategies.


Assuntos
Bursite , Citocinas , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Citocinas/sangue , Citocinas/genética , Bursite/genética , Predisposição Genética para Doença , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/sangue
12.
Front Psychiatry ; 15: 1417213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979494

RESUMO

Introduction: Schizophrenia (SCZ) is a severe psychiatric disorder whose pathophysiology remains elusive. Recent investigations have underscored the significance of systemic inflammation, particularly the impact of circulating inflammatory proteins, in SCZ. Methods: This study explores the potential causal association between certain inflammatory proteins and SCZ. Bidirectional Mendelian randomization (MR) analyses were conducted utilizing data from expansive genome-wide association studies (GWAS). Data regarding circulating inflammatory proteins were sourced from the GWAS Catalog database, encompassing 91 inflammatory cytokines. SCZ-related data were derived from the Finngen database, incorporating 47,696 cases and 359,290 controls. Analytical methods such as inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode were employed to evaluate the association between inflammatory cytokines and SCZ. Sensitivity analyses were also performed to affirm the robustness of the results. Results: Following FDR adjustment, significant associations were observed between levels of inflammatory cytokines, including Fibroblast Growth Factor 5 (OR = 1.140, 95%CI = 1.045, 1.243, p = 0.003, FDR=0.015), C-C Motif Chemokine 4 (OR = 0.888, 95%CI = 0.816, 0.967, p = 0.006, FDR = 0.015), C-X-C Motif Chemokine 1 (OR = 0.833, 95%CI = 0.721, 0.962, p = 0.013, FDR = 0.064), and C-X-C Motif Chemokine 5 (OR = 0.870, 95%CI = 0.778, 0.973, p = 0.015, FDR = 0.074), and the risk of SCZ. Conclusion: Our results from MR analysis suggest a potential causal link between circulating inflammatory cytokines and SCZ, thereby enriching our understanding of the interactions between inflammation and SCZ. Furthermore, these insights provide a valuable foundation for devising therapeutic strategies targeting inflammation.

13.
Cytokine ; 181: 156686, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38991382

RESUMO

Liver injury, a major global health issue, stems from various causes such as alcohol consumption, nonalcoholic steatohepatitis, obesity, diabetes, metabolic syndrome, hepatitis, and certain medications. The liver's unique susceptibility to ischemia and hypoxia, coupled with the critical role of the gut-liver axis in inflammation, underscores the need for effective therapeutic interventions. The study highlights E2's interaction with estrogen receptors (ERs) and its modulation of the Toll-like receptor 4 (TLR4) signaling pathway as key mechanisms in mitigating liver injury. Activation of TLR4 leads to the release of pro-inflammatory cytokines and chemokines, exacerbating liver inflammation and injury. E2 down-regulates TLR4 expression, reduces oxidative stress, and inhibits pro-inflammatory cytokines, thereby protecting the liver. Both classic (ERα and ERß) and non-classic [G protein-coupled estrogen receptor (GPER)] receptors are influenced by E2. ERα is particularly crucial for liver regeneration, preventing liver failure by promoting hepatocyte proliferation. Furthermore, E2 exerts anti-inflammatory, antioxidant, and anti-apoptotic effects by inhibiting cytokines such as IL-6, IL-1ß, TNF-α, and IL-17, and by reducing lipid peroxidation and free radical damage. The article calls for further clinical research to validate these findings and to develop estrogen-based treatments for liver injuries. Overall, the research emphasizes the significant potential of E2 as a therapeutic agent for liver injuries. It advocates for extensive clinical studies to validate E2 hepatoprotective properties and develop effective estrogen-based treatments.

14.
Artigo em Inglês | MEDLINE | ID: mdl-39021185

RESUMO

OBJECTIVE: Bushen Zhuyun Decoction (BSZY), a traditional Chinese herbal prescription has shown promising effects on gynecological infertility, but the mechanism for endometrial receptivity is still unclear. This study aimed to investigate the regulatory effects of BSZY on endometrial receptivity, which plays a key role in colonization of embryo, and its regulatory mechanisms associated with NF- κB/NLRP3 pathway. METHODS: SD rats at reproductive age with affected endometrial receptivity was established using mifepristone (RU486), and the regulatory effects of BSZY on endometrial receptivity were evaluated by H&E staining, and changes in sex hormones by ELISA and Western blot. Moreover, human endometrial RL95-2 cells were treated with H2O2, and inflammatory cytokines in rats and RL95-2 cells were analyzed by ELISA. The activation of NF-κB/NLRP3 signaling pathway in RL95-2 cells were characterized using immunofluorescence and Western blot. Mitochondrial morphology and function in RL95-2 cells were observed by transmission electron microscope and cell mitochondrial stress test. RESULTS: BSZY increased uterine endometrial thickness and attenuate histopathological changes induced by RU486. BSZY can regulate endometrial estrogen receptor and progesterone receptor, and the levels of sex hormones and inflammatory cytokines in pregnant rats. BSZY-containing serum also showed strong anti-inflammatory and cytoprotective effects in vitro. In addition, BSZY-containing serum inhibited the activation of NF-κB/NLRP3 signaling pathway, and improve mitochondrial morphology and function in RL95-2 cells. CONCLUSION: BSZY can improve endometrial receptivity, potentially by improving mitochondrial morphology and function to inhibit the activation of NF-κB/NLRP3 signaling pathway in endometrial cells, thus regulate inflammation to improve endometrial receptivity.

15.
Animal Model Exp Med ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39021318

RESUMO

BACKGROUND: Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge. It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comorbidities. We have explored the impact of an Ayurvedic medicine, Fevogrit, in an endotoxin (lipopolysaccharide)-induced fever model in Wistar rats. METHODS: Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography (UHPLC) platform. For the in-vivo study, fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide (LPS), obtained from Escherichia coli. The animals were allocated to normal control, disease control, Paracetamol treated and Fevogrit treated groups. The rectal temperature of animals was recorded at different time points using a digital thermometer. At the 6-h time point, levels of TNF-α, IL-1ß and IL-6 cytokines were analyzed in serum. Additionally, the mRNA expression of these cytokines was determined in hypothalamus, 24 h post-LPS administration. RESULTS: UHPLC analysis of Fevogrit revealed the presence of picroside I, picroside II, vanillic acid, cinnamic acid, magnoflorine and cordifolioside A, as bioactive constituents with known anti-inflammatory properties. Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals. The levels and gene expression of TNF-α, IL-1ß and IL-6 in serum and hypothalamus, respectively, was also significantly reduced by Fevogrit treatment. CONCLUSION: The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.

16.
J Biochem Mol Toxicol ; 38(7): e23760, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953502

RESUMO

Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and neurological diseases. This research was designed to measure several biochemical parameters in the brain tissue of CP-applied rats to investigate the impact of combined CUR-PP administration. The study evaluated six groups of eight rats: Group 1 was the control; Groups 2 and 3 were administered 200 or 300 mg/kg CUR-PP via oral gavage; Group 4 received only 200 mg/kg CP on day 1; Groups 5 and 6 received CP + CUR-PP for 7 days. Data from all parameters indicated that CP caused brain damage. Phosphorylated TAU (pTAU), amyloid-beta peptide 1-42 (Aß1-42), glutamate (GLU), and gamma amino butyric acid (GABA) parameters were the same in Groups 4, 5, and 6. On the other hand, 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), interleukin-6 (IL-6), nuclear factor kappa beta (NF-kß), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels in the CP + CUR-PP groups were lower than those in the CP group (p < 0.05). However, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) parameters were higher in the CP + CUR-PP groups compared to the CP group (p < 0.05). It is thought that the similarity of Groups 5 and 6 with Group 4 in Aß1-42, pTAU, GLU, and GABA parameters hinder the determination of treatment protection however, they might have a therapeutic effect if the applied dose or study duration were changed. This study attempted to evaluate the effects of a CUR-PP combination on CP-induced brain damage in rats by measuring biochemical parameters and performing histopathological examinations. Based on the findings, this CUR-PP combination could be considered an alternative medicine option in cases with conditions similar to those evaluated in this study.


Assuntos
Alcaloides , Benzodioxóis , Lesões Encefálicas , Curcumina , Ciclofosfamida , Piperidinas , Alcamidas Poli-Insaturadas , Animais , Alcamidas Poli-Insaturadas/farmacologia , Benzodioxóis/farmacologia , Curcumina/farmacologia , Piperidinas/farmacologia , Alcaloides/farmacologia , Ratos , Ciclofosfamida/toxicidade , Ciclofosfamida/efeitos adversos , Masculino , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Lesões Encefálicas/prevenção & controle , Ratos Wistar , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Estresse Oxidativo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia
17.
Front Mol Neurosci ; 17: 1391189, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962804

RESUMO

This investigation aims to elucidate the novel role of Stromal Interaction Molecule 1 (STIM1) in modulating store-operated calcium entry (SOCE) and its subsequent impact on inflammatory cytokine release in T lymphocytes, thereby advancing our understanding of trigeminal neuralgia (TN) pathogenesis. Employing the Gene Expression Omnibus (GEO) database, we extracted microarray data pertinent to TN to identify differentially expressed genes (DEGs). A subsequent comparison with SOCE-related genes from the Genecards database helped pinpoint potential target genes. The STRING database facilitated protein-protein interaction (PPI) analysis to spotlight STIM1 as a gene of interest in TN. Through histological staining, transmission electron microscopy (TEM), and behavioral assessments, we probed STIM1's pathological effects on TN in rat models. Additionally, we examined STIM1's influence on the SOCE pathway in trigeminal ganglion cells using techniques like calcium content measurement, patch clamp electrophysiology, and STIM1- ORAI1 co-localization studies. Changes in the expression of inflammatory markers (TNF-α, IL-1ß, IL-6) in T cells were quantified using Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) in vitro, while immunohistochemistry and flow cytometry were applied in vivo to assess these cytokines and T cell count alterations. Our bioinformatic approach highlighted STIM1's significant overexpression in TN patients, underscoring its pivotal role in TN's etiology and progression. Experimental findings from both in vitro and in vivo studies corroborated STIM1's regulatory influence on the SOCE pathway. Furthermore, STIM1 was shown to mediate SOCE-induced inflammatory cytokine release in T lymphocytes, a critical factor in TN development. Supportive evidence from histological, ultrastructural, and behavioral analyses reinforced the link between STIM1-mediated SOCE and T lymphocyte-driven inflammation in TN pathogenesis. This study presents novel evidence that STIM1 is a key regulator of SOCE and inflammatory cytokine release in T lymphocytes, contributing significantly to the pathogenesis of trigeminal neuralgia. Our findings not only deepen the understanding of TN's molecular underpinnings but also potentially open new avenues for targeted therapeutic strategies.

18.
Fish Shellfish Immunol ; 152: 109756, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38992802

RESUMO

Fish skin plays an important role in defending against pathogens in water, primarily through the secretion of skin mucus containing various immune-related factors. Local immune responses in the skin activate systemic immune responses by inflammatory cytokines. However, it remains unclear whether immune responses in the skin occur after systemic immune responses caused by pathogen invasion into the fish body. This study aimed to clarify the relationship between systemic immune responses and skin responses after intraperitoneal injection of formalin-killed cells (FKC) of Vibrio anguillarum. Although systemic inflammatory responses were observed in the spleen after injection, expression changes in the skin did not show significant differences. In contrast, expression of hemoglobin subunit genes significantly increased in the skin after FKC injection, suggesting that erythrocytes infiltrate extravascularly.

19.
Vitam Horm ; 125: 1-29, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38997161

RESUMO

Advanced glycation end products (AGEs) are a heterogeneous group of potentially harmful molecules that can form as a result of a non-enzymatic reaction between reducing sugars and proteins, lipids, or nucleic acids. The total body pool of AGEs reflects endogenously produced AGEs as well as exogeneous AGEs that come from sources such as diet and the environment. Engagement of AGEs with their cellular receptor, the receptor for advanced glycation end products (RAGE), which is expressed on the surface of various cell types, converts a brief pulse of cellular activation to sustained cellular dysfunction and tissue destruction. The AGEs/RAGE interaction triggers a cascade of intracellular signaling pathways such as mitogen-activated protein kinase/extracellular signal-regulated kinase, phosphoinositide 3-kinases, transforming growth factor beta, c-Jun N-terminal kinases (JNK), and nuclear factor kappa B, which leads to the production of pro-inflammatory cytokines, chemokines, adhesion molecules, and oxidative stress. All these events contribute to the progression of several chronic diseases. This chapter will provide a comprehensive understanding of the dynamic roles of AGEs in health and disease which is crucial to develop interventions that prevent and mitigate the deleterious effects of AGEs accumulation.


Assuntos
Produtos Finais de Glicação Avançada , Receptor para Produtos Finais de Glicação Avançada , Transdução de Sinais , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Transdução de Sinais/fisiologia , Estresse Oxidativo/fisiologia
20.
BMC Complement Med Ther ; 24(1): 260, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987758

RESUMO

BACKGROUND: The Pro-inflammatory mediators such as prostaglandin E2, nitric oxide and TNF-α are the key players in the stimulation of the inflammatory responses. Thus, the pro-inflammatory mediators are considered to be potential targets for screening nutraceutical with anti-inflammatory activity. METHODS: In this context, we explored the anti-inflammatory potency of seagrass extract with western blot (Bio-Rad) analysis by using LPS induced RAW macrophages as in-vitro models, western blot analysis, In-silico methods using Mastero 13.0 software. RESULTS: The anti-inflammatory activity of Seagrass was demonstrated through down regulation of Pro-inflammatory markers such as Cyclooxygenase-2, induced Nitric oxide synthase and prostaglandin E synthase-1. The results were validated by docking the phytochemical constituents of seagrass namely Isocoumarin, Hexadecanoic acid, and Cis-9 Octadecenoic acid, 1,2 Benzene dicarboxylic acid and beta-sitosterol with TNF-alpha, COX-2, iNOS and PGES-1. CONCLUSION: The methanolic extract of seagrass Halophila beccarii is a potential nutraceutical agent for combating against inflammation with a significant anti-inflammatory activity.


Assuntos
Anti-Inflamatórios , Suplementos Nutricionais , Extratos Vegetais , Camundongos , Anti-Inflamatórios/farmacologia , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Biomarcadores , Alismatales/química , Inflamação/tratamento farmacológico , Ciclo-Oxigenase 2/metabolismo
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