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1.
Adv Healthc Mater ; : e2400125, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38513154

RESUMO

Microglia-mediated inflammation is involved in the pathogenesis of Alzheimer's disease (AD), whereas human fibroblast growth factor 21 (hFGF21) has demonstrated the ability to regulate microglia activation in Parkinson's disease, indicating a potential therapeutic role in AD. However, challenges such as aggregation, rapid inactivation, and the blood-brain barrier hinder its effectiveness in treating AD. This study develops targeted delivery of hFGF21 to activated microglia using BV2 cell membrane-coated PEGylated liposomes (hFGF21@BCM-LIP), preserving the bioactivity of hFGF21. In vitro, hFGF21@BCM-LIP specifically targets Aß1-42-induced BV2 cells, with uptake hindered by anti-VCAM-1 antibody, indicating the importance of VCAM-1 and integrin α4/ß1 interaction in targeted delivery to BV2 cells. In vivo, following subcutaneous injection near the lymph nodes of the neck, hFGF21@BCM-LIP diffuses into lymph nodes and distributes along the meningeal lymphatic vasculature and brain parenchyma in amyloid-beta (Aß1-42)-induced mice. Furthermore, the administration of hFGF21@BCM-LIP to activated microglia improves cognitive deficits caused by Aß1-42 and reduces levels of tau, p-Tau, and BACE1. It also decreases interleukin-6  (IL-6) and tumor necrosis factor-α (TNF-α) release while increasing interleukin-10 (IL-10) release both in vivo and in vitro. These results indicate that hFGF21@BCM-LIP can be a promising treatment for AD, by effectively crossing the blood-brain barrier and targeting delivery to brain microglia via the neck-meningeal lymphatic vasculature-brain parenchyma pathways.

2.
Fitoterapia ; 174: 105833, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301935

RESUMO

Five new steroidal saponins, paripolins D-H (1-5), and 6 known compounds (6-11) were isolated from the aerial parts of Paris polyphylla var. yunnanensis. The structures of 1-5 were determined using spectroscopic analyses in conjunction with acid hydrolysis. It is for the first time to report the 12-hydroxysteroidal saponins from the genus Paris. The effect of all isolated compounds on blood coagulation was determined in vitro using the plasma recalcification time method. Compounds 1 and 2 showed potent procoagulant activity, and 5-11 exhibited significant anticoagulant activity.


Assuntos
Liliaceae , Saponinas , Liliaceae/química , Rizoma/química , Estrutura Molecular , Saponinas/farmacologia , Saponinas/química , Coagulação Sanguínea
3.
Front Immunol ; 14: 1251648, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37809069

RESUMO

Background and objectives: The relationship between the tumor microenvironment and the network of key signaling pathways in cancer plays a key role in the occurrence and development of tumors. Tumor-associated macrophages (TAMs) are important inflammatory cells in the tumor microenvironment and play an important role in tumorigenesis and progression. Macrophages in malignant tumors, mainly the M2 subtype, promote tumor progression by producing cytokines and down-regulating anti-inflammatory immune responses. Several articles have investigated the effect of macrophages on the sensitivity of cancer chemotherapeutic agents, but few such articles have been reported in cholangiocarcinoma, so we investigated the effect of M2 macrophage on the sensitivity of cholangiocarcinoma cells to Lenvatinib compared to M1. Methods: THP-1 monocytes were polarized to M0 macrophage by phorbol 12-myristate 13-acetate (PMA) and then induced to differentiate into M1 and M2 macrophages by LPS, IFN-γ and IL-4 and IL-13, respectively. Macrophages and cholangiocarcinoma cells were co-cultured prior to 24 hours of Lenvatinib administration, cancer cell apoptosis was detected by western-blot, FACS analysis of Annexin V and PI staining. Furthermore, we use xCELLigence RTCA SP Instrument (ACEA Bio-sciences) to monitor cell viability of Lenvatinib administration in co-culture of cholangiocarcinoma cells and macrophages. After tumorigenesis in immunodeficient mice, Lenvatinib was administered, and the effects of M2 on biological characteristics of cholangiocarcinoma cells were investigated by immuno-histochemistry. Results: mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1 derived macrophages, which provided a successful and efficient model of monocyte polarization to TAMs. Lenvatinib-induced apoptosis of cholangiocarcinoma cells was significantly reduced when co-cultured with M2 macrophage, whereas apoptosis of cholangiocarcinoma cells co-cultured with M1 macrophage was increased. In the CDX model, Lenvatinib-induced cancer cell apoptosis was markedly reduced, and proliferative cells increased in the presence of M2 macrophages. Angiogenesis related factors was significantly increased in cholangiocarcinoma cells co-cultured with M2. Conclusion: Compared with M1, M2 macrophages can inhibit the anti-tumor effect of Lenvatinib on cholangiocarcinoma through immune regulation, which may be related to the tumor angiogenesis factor effect of M2 macrophage.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Animais , Camundongos , Macrófagos , Colangiocarcinoma/metabolismo , Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos , Carcinogênese/metabolismo , Microambiente Tumoral
4.
BMC Neurosci ; 24(1): 51, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749547

RESUMO

BACKGROUND/AIMS: Early diagnosis of Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with non-invasive imaging modalities benefiting is crucial to guarantee prompt treatments decision-making and good prognosis for patients. The present study aimed to explore the correlation of MRI features with brain metabolism characteristics of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and to describe the metabolic patterns in Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis at acute and subacute phases. Twenty-four patients with anti-NMDAR encephalitis confirmed by serum and/or CSF tests at acute and subacute phases, 9 females and 15 males, with an age range of 6-80 years, were enrolled in this retrospective study as encephalitis group. 18F-FDG PET and MRI findings of all patients were investigated and interpreted with visual analysis. Chi-square test was performed to compare the diagnostic sensitivity between MRI and PET. Independent sample t-test was used to compare the standardized uptake value ratio (SUVR) of each ROI between the encephalitis group and control group, which consisted of 24 healthy volunteers of the same age and gender. RESULTS: There was no statistical difference in the diagnostic sensitivity between FDG PET (23/24, 95.83%) and MRI (18/24, 75.00%) in anti-NMDAR encephalitis patients (P > 0.05). Three categories of abnormalities shown on T2 FLAIR, including shallow of sulci and swelling of brain tissue, increased signal in the sulci, increased signal on brain gray matter or adjacent white matter presented hypermetabolism on PET, excepting increased signal in brain linear structure with hypometabolism of the basal ganglia on PET. We identified 19 brain regions with hypermetabolism and 16 brain regions with hypometabolism that exhibited statistically significant changes in SUVRs between anti-NMDAR encephalitis group and control group (FDR P < 0.05). CONCLUSION: Anteroposterior glucose metabolism gradient (frontal-temporal/parietal-occipital) is proved to be a typical pattern of anti-NMDAR encephalitis at the acute and subacute phases in both visual and statistical testing. Interestingly, the pattern is also commonly found in the anterior and posterior portions of the parietal lobe and cingular cortex, which may be a potential indicator for the diagnosis of this disorder. In addition, MRI is an important and reliable neuroimaging modality to assist in the correct evaluation of activity changes on individual 18F-FDG PET.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Feminino , Masculino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico por imagem , Fluordesoxiglucose F18 , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética
5.
Arch Med Sci ; 19(4): 976-986, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560735

RESUMO

Introduction: This meta-analysis was performed to analyze the clinical presentation, magnetic resonance imaging (MRI) characteristics, and the management of lymphocytic hypophysitis (LYH). Material and methods: Four different databases were searched from January 2010 to December 2020, two researchers independently conducted literature screening, data extraction, and quality evaluation. We used a random effects meta-analysis to calculate summary relative risks with 95% CI. Results: This meta-analysis showed that the percentage of women among LYH patients was 78%. LYH was associated with pregnancy in 15% of female patients, with headache (49%) and symptoms of central diabetes insipidus (CDI) (45%) being the most frequent presentation. In 24% of LYH patients, there was an association with another autoimmune disease. The incidence of secondary hypogonadism, secondary hypoadrenalism, secondary hypothyroidism, and growth hormone deficit was 54%, 49%, 43%, and 22%, respectively. Pituitary contrast enhancement (63%), symmetrical pituitary enlargement (60%), thickening of the pituitary stalk (58%), sella mass or suprasellar extension (58%), and loss of posterior pituitary hyperintensity (50%) were typical MRI findings. Regarding LYH treatment, the percentage of patients who had observation or hormone replacement, steroid therapy, and surgery was 43%, 36%, and 34%, respectively. Conclusions: It is of great significance to fully understand the clinical characteristics of lymphocytic hypophysitis, reduce missed diagnosis and misdiagnosis, avoid unnecessary surgery and maintain normal pituitary function.

6.
Mol Genet Genomic Med ; 11(10): e2228, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37455597

RESUMO

BACKGROUND AND PURPOSE: Lafora disease (LD) is a very rare autosomal recessive disorder manifesting primarily as fatal, congenital, and neurodegenerative epilepsies. We aimed to describe the MRI characteristics due to gene mutations in a Chinese pedigree with LD. METHODS: Whole-exome sequencing, muscle biopsy, pedigree analysis, and MRI analysis were conducted. Five family members (two of whom were affected by LD) were whole-genome sequenced. Longitudinal changes in brain MRI volumes were analyzed by Freesurfer. RESULTS: We identified a new intron heterozygous mutation in the EMP2A gene c.71 (exon 1) G>A in a Chinese LD pedigree that was characterized by refractory seizures, progressive vision impairment, and declines in motor and cognitive functions. The patient suffered generalized tonic-clonic seizures since the age of 15 years and had severe forms of progressive myoclonic seizure. She eventually died after being admitted to the intensive care unit due to status epilepticus at the age of 24 years. Period acid Schiff staining showed positive polyglucosan particles in muscle biopsy specimens. Regions of atrophy in the whole brain, and especially in the hippocampus, were detected. CONCLUSIONS: We identified a new heterozygous mutation (c.71+1G>A) in a Chinese LD pedigree, which broadens the mutation spectrum of LD genes. We found that the patient exhibited brain volumetric atrophy along with rapidly worsening symptoms. These results contribute to our understanding of LD.

8.
Oncologist ; 28(11): e995-e1004, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37265056

RESUMO

BACKGROUND: The disease burden of pancreatic cancer in East Asia is at a high level, but the epidemiological characteristics of pancreatic cancer in the region have not been systematically studied. METHOD: Joinpoint analysis was used to identify average annual percentage change (AAPC) and annual percentage change (APC) in mortality. Age-period-cohort models were used to analyze age-period cohort effects across countries. Bayesian age-period-cohort (BAPC) analysis was used to project the burden of disease for 2020-2030. RESULTS: Pancreatic cancer mortality in males in Japan (2012-2019, APC = -0.97) and Korea (2012-2019, APC = -0.91) has shown a decreasing trend since 2012 (P < .05). However, China (2016-2019, APC = 3.21), Mongolia (2015-2.019, APC = 2.37), and North Korea (2012-2019, APC = 0.47) showed a significant increase in pancreatic cancer in both genders (P < .05). Risk factors for pancreatic cancer in East Asia remained largely stable between 2010 and 2019. Mortality of pancreatic cancer due to smoking began to decline in areas with high socio-demographic index (SDI), and mortality of pancreatic cancer due to high body mass index and high fasting plasma glucose increased with SDI. The age-standardized mortality for pancreatic cancer in Chinese males is expected to exceed that of Japan and South Korea by 2030, but the disease burden of pancreatic cancer in Japan and South Korea remains at extremely high levels. CONCLUSION: Economically developed countries are beginning to show a decreasing trend in the burden of pancreatic cancer disease, and developing countries are experiencing a rapid increase in the age-standardized death rate (ASDR) of pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Feminino , Humanos , Masculino , Teorema de Bayes , Ásia Oriental , Japão , Fatores de Risco , Anos de Vida Ajustados por Qualidade de Vida
9.
Phytochemistry ; 212: 113729, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37247765

RESUMO

Twenty-five grayanane diterpenoids including six undescribed compounds (craibiodenoside A-F), were isolated from the leaves of Craibiodendron yunnanense W. W. Smith. The structures of the isolated compounds were determined by 1D-NMR, 2D-NMR, and HR-ESI-MS spectrometric analyses. All compounds were evaluated for their anti-inflammatory activities by inhibiting the release of interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells. The results demonstrated that three undescribed compounds craibiodenoside A, B, F, and three known compounds could inhibit the release of IL-6 significantly. In addition, the antinociceptive activities of compounds were assessed using acetic acid-induced writhing test. Craibiodenoside D, grayanoside D, and rhodojaponins VI exhibited notable antinociceptive activities. Specifically, rhodojaponins VI exhibited antinociceptive activity with the inhibition percentage of 87.6%.


Assuntos
Diterpenos , Ericaceae , Analgésicos/farmacologia , Analgésicos/química , Interleucina-6 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Ericaceae/química , Espectroscopia de Ressonância Magnética , Diterpenos/farmacologia , Diterpenos/química
10.
Reprod Sci ; 30(1): 301-308, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35851684

RESUMO

Cervical cancer is a complex polygenic disease, and the interaction between single-nucleotide polymorphisms (SNPs) may lead to differences in the incidence and susceptibility of cervical cancer. In this study, we explored whether three potentially functional SNPs-rs59661306, rs257847, and rs637442 with reference/alternative alleles A/G, C/T, and T/G, respectively-in chr5q14 were related to cervical cancer risk in a Chinese population. A total of 703 samples were collected, including 215 patients with cervical cancer and 488 normal controls. The SNP genotyping was determined by using polymerase chain reaction-restriction fragment length polymorphism. There was an association between the AG rs59661306 genotype or the GG rs59661306 genotype and cervical cancer risk, and the percentage of cancer patients with the A/G rs59661306 genotype plus the percentage of cancer patients with the G/G rs59661306 genotype (AG + GG) was significantly higher than the percentage of AG + GG healthy women in the control group. There was no association between either the rs257847 or the rs637442 and cervical cancer risk. Genotype analysis showed that the genotype CT of rs257847 in combination with the AG, GG, and AG + GG genotypes of rs59661306 were associated with a higher cervical cancer risk, and that the genotypes TG and TG + GG of rs637442 in combination with the AG and AG + GG genotypes of rs59661306 were also associated with a higher cervical cancer risk. These findings indicate that rs59661306, rs257847, and rs637442 may be susceptible loci for cervical cancer. Our study advances the understanding of SNPs that are responsible for cervical cancer susceptibility.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Predisposição Genética para Doença , População do Leste Asiático , Genótipo , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Frequência do Gene
11.
Biochimie ; 206: 49-60, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36244578

RESUMO

Colorectal cancer (CRC) raises concerns to people because of its high recurrence and metastasis rate, diagnosis challenges, and poor prognosis. Various studies have shown the association of altered autophagy with tumorigenesis, tumor-stroma interactions, and resistance to cancer therapy in CRC. Autophagy is a highly conserved cytosolic catabolic process in eukaryotes that plays distinct roles in CRC occurrence and progression. In early tumorigenesis, autophagy may inhibit tumor growth through diverse mechanisms, whereas it exhibits a tumor promoting function in CRC progression. This different functions of autophagy in CRC occurrence and progression make developing therapies targeting autophagy complicated. In this review, we discuss the classification and process of autophagy as well as its dual roles in CRC, functions in the tumor microenvironment, cross-talk with apoptosis, and potential usefulness as a CRC therapeutic target.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/metabolismo , Apoptose , Carcinogênese , Transformação Celular Neoplásica , Autofagia , Microambiente Tumoral
12.
Cancer Med ; 12(4): 4363-4364, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36533542

RESUMO

AIM: After reading the article by Ivan K. Poon et al. Certain issues regarding the methodology must be addressed. RESULT: First, it was not sufficient using only sensitivity and specificity. Second, we think the receiver operator characteristic curve (ROC) as well as the index of area under curve (AUC) could better be demonstrated in this, it was not sufficient using only sensitivity and specificity. Second, we think the receiver operator characteristic curve (ROC) as well as the index of area under curve (AUC) could better be demonstrated in this article for a more comprehensive understanding of this diagnostic test accuracy when comparing different tests. CONCLUSION: With using more comprehensive indexes including Youden's index, LR and AUC, the conclusions of Ivan K. Poon and his colleagues would be sodified.


Assuntos
Derrame Pleural Maligno , Derrame Pleural , Humanos , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia , Curva ROC , Derrame Pleural/diagnóstico , Pleura/patologia , Sensibilidade e Especificidade , Biópsia
13.
Acta Biomater ; 157: 467-486, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460288

RESUMO

Diabetic wounds are challenging to heal due to complex pathogenic abnormalities. Routine treatment with acid fibroblast growth factor (aFGF) is widely used for diabetic wounds but hardly offers a satisfying outcome due to its instability. Despite the emergence of various nanoparticle-based protein delivery approaches, it remains challenging to engineer a versatile delivery system capable of enhancing protein stability without the need for complex preparation. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and Epigallocatechin-3-gallate (EGCG) was constructed and applied in the healing of diabetic wounds. First, the binding patterns of EGCG and aFGF were predicted by molecular docking analysis. Then, the characterizations demonstrated that AE-NPs displayed higher stability in hostile conditions than free aFGF by enhancing the binding activity of aFGF to cell surface receptors. Meanwhile, the AE-NPs also had a powerful ability to scavenge reactive oxygen species (ROS) and promote angiogenesis, which significantly accelerated full-thickness excisional wound healing in diabetic mice. Besides, the AE-NPs suppressed the early scar formation by improving collagen remodeling and the mechanism was associated with the TGF-ß/Smad signaling pathway. Conclusively, AE-NPs might be a potential and facile strategy for stabilizing protein drugs and achieving the scar-free healing of diabetic wounds. STATEMENT OF SIGNIFICANCE: Diabetic chronic wound is among the serious complications of diabetes that eventually cause the amputation of limbs. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and EGCG was constructed. The EGCG not only acted as a carrier but also possessed a therapeutic effect of ROS scavenging. The AE-NPs enhanced the binding activity of aFGF to cell surface receptors on the cell surface, which improved the stability of aFGF in hostile conditions. Moreover, AE-NPs significantly accelerated wound healing and improved collagen remodeling by regulating the TGF-ß/Smad signaling pathway. Our results bring new insights into the field of polyphenol-containing nanoparticles, showing their potential as drug delivery systems of macromolecules to treat diabetic wounds.


Assuntos
Diabetes Mellitus Experimental , Camundongos , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Fator 1 de Crescimento de Fibroblastos/farmacologia , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio , Cicatrização , Cicatriz , Colágeno/farmacologia , Fator de Crescimento Transformador beta/farmacologia
14.
Front Bioeng Biotechnol ; 11: 1343177, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38188493

RESUMO

Primary liver cancer (PLC) is one of the most commonly diagnosed cancers worldwide and a leading cause of cancer-related deaths. However, traditional liver cancer models fail to replicate tumor heterogeneity and the tumor microenvironment, limiting the study and personalized treatment of liver cancer. To overcome these limitations, scientists have introduced three-dimensional (3D) culture models as an emerging research tool. These 3D models, utilizing biofabrication technologies such as 3D bioprinting and microfluidics, enable more accurate simulation of the in vivo tumor microenvironment, replicating cell morphology, tissue stiffness, and cell-cell interactions. Compared to traditional two-dimensional (2D) models, 3D culture models better mimic tumor heterogeneity, revealing differential sensitivity of tumor cell subpopulations to targeted therapies or immunotherapies. Additionally, these models can be used to assess the efficacy of potential treatments, providing guidance for personalized therapy. 3D liver cancer models hold significant value in tumor biology, understanding the mechanisms of disease progression, and drug screening. Researchers can gain deeper insights into the impact of the tumor microenvironment on tumor cells and their interactions with the surrounding milieu. Furthermore, these models allow for the evaluation of treatment responses, offering more accurate guidance for clinical interventions. In summary, 3D models provide a realistic and reliable tool for advancing PLC research. By simulating tumor heterogeneity and the microenvironment, these models contribute to a better understanding of the disease mechanisms and offer new strategies for personalized treatment. Therefore, 3D models hold promising prospects for future PLC research.

15.
Front Oncol ; 12: 1036710, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439477

RESUMO

Background: Clinically, few patients with locally advanced cervical cancer (LACC) are insensitive to neoadjuvant chemotherapy (NACT). Recent studies have reported that circulating microRNAs (miRNAs) may be involved in the response to NACT. The aim of this study was to discover the potential miRNAs that can predict the response to NACT in LACC. Methods: Pair-matched blood samples of 39 LACC patients before and after receiving NACT were collected. Seven paired samples were used for microRNA microarray analysis. Targeted miRNAs were selected by bioinformatics analysis and were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). All 39 patients were assigned into either the responders group or the non-responders group after NACT. The predictive performance of selected microRNA was evaluated by sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve. Results: A total of 17 miRNAs downregulated before NACT and upregulated after NACT were selected according to microarray analysis in our previous study, and miR-326 and miR-376a-3p were selected for further exploration. According to the responses and the evaluation criteria, 25 patients reached partial response (PR) and 14 patients remained stable. Further qRT-PCR analysis showed that miR-326 significantly downregulated before NACT and upregulated after NACT in 12 responders (p = 0.02). The expression of miR-376a-3p showed no statistical difference before and after NACT in these 12 responders. Then, miR-326 provided an AUC-ROC of 0.75 (p = 0.04) in the discrimination between the responders and non-responders groups. The cutoff value of ROC for miR-326 to predict the response of NACT was <0.023, the sensitivity was 88.89%, and the specificity was 50%. Conclusions: The expression of miR-326 significantly upregulated after NACT in responders. miR-326 may be a biomarker for predicting the response to NACT in LACC patients. The results may optimize individualized treatments for LACC patients.

16.
Chin Herb Med ; 14(4): 554-562, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36405054

RESUMO

Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1ß and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.

17.
J Neuroimmunol ; 373: 578000, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36410057

RESUMO

This study aimed to investigate prognostic significance and brain metabolic mechanism of hyponatremia in anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis. After adjusting for confounders, patients with moderate and severe hyponatremia had significantly increased risk of poor functional outcome and sequelae of seizures. In addition, serum sodium was negatively correlated with normalized ratio of the standardized uptake value of medial temporal lobe (MTL), basal ganglia (BG), and hypothalamus on positron emission tomography (PET) and which was further validated using voxel-wise analysis, suggesting an extra-hypothalamus (BG and MTL) localization for hyponatremia.


Assuntos
Encefalite , Glioma , Hiponatremia , Humanos , Prognóstico , Hiponatremia/diagnóstico por imagem , Leucina
18.
Biomed Res Int ; 2022: 3002353, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119929

RESUMO

lncRNAs and mRNA are closely associated with hypertensive renal damage, and Astragalus membranaceus and Salvia miltiorrhiza (AS) have a therapeutic effect; however, the mechanism of AS to ameliorate hypertensive renal damage through the co-expression network of lncRNA-mRNA was unclear. In this study, we investigated the role of AS regulated the coexpression network of lncRNA-mRNA in improving hypertensive renal damage. Sixteen 24-week old spontaneous hypertensive rats (SHRs) were randomly divided into model group (M) and drug intervention group (AS, 5.9 g/kg), 8 Wistar Kyoto rats (WKY) of the same age as normal group (N). The treatment of rats was 4 weeks. Detecting the change of blood pressure, renal pathology and renal function related indicators, and lncRNA and mRNA sequencing and joint analysis was performed on the kidney. AS reduced blood pressure; decreased urine NAG, urine mALB, serum CysC, and IL-6; and improved renal pathology compared with group M. Simultaneously, AS reversed the disordered expression of 178 differential expression (DE) mRNAs and 237 DE-lncRNAs in SHRs, and their joint analysis showed that 13 DE-mRNAs and 32 DE-lncRNAs were coexpressed. Further analysis of 13 coexpressed DE-mRNAs showed negative regulation of blood pressure and fatty acid beta-oxidation was highly enriched in GO pathways, PPAR signaling pathway was highly enriched in KEGG pathways, and the verification related to these pathways was also highly consistent with the sequence. AS can alleviate hypertensive renal damage through the coexpression network of lncRNA-mRNA, of which coexpressed 13 DE-mRNAs and 32 DE-lncRNAs were the important targets, and the pathway negative regulation of blood pressure, fatty acid beta-oxidation, and PPAR signaling pathway play a major regulatory role.


Assuntos
Hipertensão , RNA Longo não Codificante , Salvia miltiorrhiza , Animais , Astragalus propinquus , Ácidos Graxos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Interleucina-6 , Rim/metabolismo , Receptores Ativados por Proliferador de Peroxissomo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR
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