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1.
Am J Rhinol Allergy ; : 19458924221101218, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35746845

RESUMO

BACKGROUND: The pathophysiologic mechanisms of human chronic rhinosinusitis (CRS) are highly complex, and sinonasal colonization with pathogens is the first and most important step in this process. NLRP3, the main receptor activated by pathogen-associated molecular patterns (PAMPs), is associated with a variety of inflammatory diseases, including airway inflammation; however, the understanding of its role in CRS is limited. OBJECTIVE: By detecting the differential expression of the NLRP3 inflammasome and its downstream cytokines IL-1ß and IL-18 between CRS patients and controls, between different CRS phenotypes (CRSsNP and CRSwNP), between mucosal tissue and polyp tissue, and further its relationship with neutrophilic/eosinic infiltration, we aimed to elucidate the biological role of the NLRP3 inflammasome in the pathophysiologic mechanisms of CRS. METHODS: Fifteen cases in each control, CRSsNP, and CRSwNP groups (subdivided into mucosa tissue and polyp tissue) were included in this study. Differential expression of NLRP3/caspase-1 and its downstream cytokines IL-1ß and IL-18 was investigated, and its relationship with neutrophilic and eosinophilic infiltration was analyzed. Fluorescent immunohistochemistry (F-IHC) was used to assess NLRP3 and caspase-1 expression, RT-PCR was used for mRNA level quantitation, and western blotting was employed to analyze the protein concentrations. RESULTS: NLRP3 and cleaved caspase-1 were expressed at higher levels in both the CRSsNP and CRSwNP phenotypes than in the control nasal mucosa and at much higher levels in polyp tissue of CRSwNP (P < .05), which was in line with the expression of cleaved IL-1ß and cleaved IL-18 (P < .05). Higher expression of NLRP3 had a mild correlation with neutrophilic infiltration but highly correlated with eosinophilic infiltration (R = 0.607, P < .01). CONCLUSIONS: NLRP3 is involved in the pathogenesis of CRS, most likely by the NLRP3/caspase-1/IL-1ß and IL-18 response. It induced eosinophilic infiltration in CRSwNP, especially in polyp tissue. As for whether NLRP3 induces neutrophilic infiltration, further experiments are needed to confirm.

2.
Digit Health ; 8: 20552076221089794, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402000

RESUMO

Objectives: We aimed to construct a theoretical model and an observer-based measurement of shared decision making (SDM) in web-based pharmaceutical care consultation. Methods: We first constructed a theoretical model through analysis of SDM models and interviews with 24 key informants. Then, the initial measurement was formulated, and the content was evaluated by 16 key informants alone. A cross-sectional study was executed, where 300 provider-patient encounters were collected at the online platform 'Good Doctor Website', for reliability and validity assessment. Content validity was evaluated by appropriateness score, that is the median of 7-9 and without disagreement. Interrater reliability was evaluated by Spearman correlation coefficient using 30 out of 300 samples. Single indicator validity was tested by Pearson correlation analysis, and convergent validity was evaluated by the Multiple Indicators Multiple Causes (MIMIC) model using 300 samples. Results: Theoretical model constructed included four elements: 'comprehensive understanding of the patient's condition', 'exchanging ideas on medication options', 'achieving a medication plan', and 'providing decision support'. Measurement constructed included four dimensions and 19 items, and four dimensions were in accordance with four elements of the theoretical model. We found median scores of these dimensions and items were 7-9 and without disagreement, indicating good content validity. Spearman correlation coefficients of 19 items were greater than 0.750, suggesting good interrater reliability. Pearson coefficients between 19 items and their external variables were significant (p < 0.001), and MIMIC model results showed that the R 2 values of dimensions 1-4 were over 0.5, indicating good single indicator validity and convergent validity. Conclusions: Characteristics of web-based pharmaceutical care consultation, highlighting the importance of medication history, medication regimen, and detailed medication plan, were observed in the theoretical model. Measurement constructed had good reliability and validity and may be used by health policymakers to improve the quality of pharmaceutical care consultation online.

3.
Aging Clin Exp Res ; 34(2): 277-288, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34176086

RESUMO

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a poorly understood disorder, very common even after total hip arthroplasty (THA). It is widely considered that inflammation response play a role in the pathogenesis of POCD. AIMS: The aim of the present study was to investigate whether inflammation cytokine concentrations could serve as biomarkers for POCD in patients undergoing THA. METHODS: A systematic search of databases was conducted to retrieve publications measuring circulating inflammatory markers of patients with and without POCD after THA. Inflammatory markers identified in more than two studies were pooled. The standardized mean difference (SMD) and the 95% confidence interval (95% CI) were calculated for each outcome. Fail-safe N statistics was calculated to estimate possible publication bias. RESULTS: The pooled incidence rate of POCD after THA by combining 11 cohort studies was 31%. A total of five inflammatory markers, CRP, S-100B, IL-1ß, IL-6 and TNF-α, were assessed. Significantly higher pre-operative CRP (P = 0.012) and S-100B (P < 0.0001) as well as post-operative CPR (P = 0.005) and IL-6 (P < 0.0001) at 6 h were found in POCD compared with non-POCD patients undergoing THA. Fail-safe N statistics revealed that these results are robust. DISCUSSION: The current evidence suggests that some of the inflammatory markers, including CRP, S-100B, and IL-6, were correlated with the occurrence of POCD after THA. CONCLUSION: Monitor of inflammatory markers might help early diagnosis of POCD after THA and development of preventive strategies.


Assuntos
Artroplastia de Quadril , Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Artroplastia de Quadril/efeitos adversos , Biomarcadores , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório
4.
Food Chem ; 371: 131106, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34543925

RESUMO

Type 2 diabetes (T2D) is a metabolic disease characterized by hyperglycemia. Intake of dietary fiber is inversely associated with risks of T2D. Here, metabolomics and 16S rRNA gene sequencing were employed to investigate the effects of arabinoxylan on gut microbiota and their metabolites in type 2 diabetic rats. T2D increased the abundance of opportunistic pathogens (such as Desulfovibrio and Klebsiella) and the levels of 12α-hydroxylated bile acids and acylcarnitines (C3) in diabetic rats, which eventually contribute to insulin resistance and hyperglycemia. Supplementation with arabinoxylan promoted the growth of fiber-degrading bacteria to increase short-chain fatty acids (SCFAs), as well as decreased the abundance of opportunistic pathogens. Arabinoxylan treatment also decreased the concentrations of 12α-hydroxylated bile acids, and increased the levels of equol, indolepropionate, and eicosadienoic acid. This study indicated that the beneficial effects of arabinoxylan on T2D may be partially attributed to the modification of gut microbiota and related metabolites.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , RNA Ribossômico 16S , Ratos , Xilanos
5.
Synth Syst Biotechnol ; 6(4): 335-342, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34738044

RESUMO

The versatile photosynthetic α-proteobacterium Rhodobacter sphaeroides, has recently been extensively engineered as a novel microbial cell factory (MCF) to produce pharmaceuticals, nutraceuticals, commodity chemicals and even hydrogen. However, there are no well-characterized high-activity promoters to modulate gene transcription during the engineering of R. sphaeroides. In this study, several native promoters from R. sphaeroides JDW-710 (JDW-710), an industrial strain producing high levels of co-enzyme Q10 (Q10) were selected on the basis of transcriptomic analysis. These candidate promoters were then characterized by using gusA as a reporter gene. Two native promoters, P rsp _ 7571 and P rsp _ 6124 , showed 620% and 800% higher activity, respectively, than the tac promoter, which has previously been used for gene overexpression in R. sphaeroides. In addition, a P rsp _ 7571 -derived synthetic promoter library with strengths ranging from 54% to 3200% of that of the tac promoter, was created on the basis of visualization of red fluorescent protein (RFP) expression in R. sphaeroides. Finally, as a demonstration, the synthetic pathway of Q10 was modulated by the selected promoter T334* in JDW-710; the Q10 yield in shake-flasks increased 28% and the production reached 226 mg/L. These well-characterized promoters should be highly useful in current synthetic biology platforms for refactoring the biosynthetic pathway in R. sphaeroides-derived MCFs.

6.
Diagn Pathol ; 16(1): 90, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34629105

RESUMO

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern characterized by the intra-alveolar fibrin deposition and organizing pneumonia. Its clinical characteristics are still not well known and there is no consensus on treatment yet. CASE PRESENTATION: We report two female cases in their fifties diagnosed with AFOP confirmed by a second lung biopsy. Case 1 was idiopathic AFOP with manifestation of 6-week fever, dyspnea, and cough, while case 2 was secondary to systemic lupus erythematosus and fever was the major symptom. Their chest CT scans revealed bilateral multiple consolidations, predominantly in the lower lobes. Both cases were initially diagnosed with pneumonia, but did not improve after treatment with broad-spectrum antibiotics. In both cases, transbronchial biopsy and bronchoalveolar lavage fluid examination were inconclusive and the pathological diagnosis was confirmed by percutaneous lung biopsy. Both patients had a good clinical response to prednisone. CONCLUSIONS: We report two rare AFOP cases to highlight the importance of awareness of this disease. We further perform the most comprehensive review to date in AFOP, including 150 patients since 2002. Consolidation was the most common imaging pattern, followed by ground-glass opacity and nodules. A lung biopsy is required for a definitive diagnosis. Corticosteroids is recommended as the most effective therapy, but treatment options should depend on the etiology and disease severity.


Assuntos
Pneumonia em Organização Criptogênica/patologia , Pulmão/patologia , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Pneumonia em Organização Criptogênica/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Biópsia Guiada por Imagem , Pulmão/diagnóstico por imagem , Pulmão/efeitos dos fármacos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Neoplasma ; 68(6): 1257-1264, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34533031

RESUMO

This study was set out to determine the function of LAMC2 in laryngeal cancer (LC). Initially, we identified the expression of LAMC2 in LC cells and tissues using TCGA datasets, GEO datasets (GSE143224), qRT-PCR, and western blot. Besides, we analyzed the correlations between LAMC2 and clinicopathologic features in LC patients. The CCK-8 assays were performed to detect cell viability and the half-maximal inhibitory concentration of cetuximab (IC50) in LC cells. We explored the correlations between LAMC2 and EGFR and further explored the regulation mechanism of cetuximab in LC. This study identified a high expression of LAMC2 in LC cells and tissues. The expression levels of LAMC2 were associated with TNM classification, lymph node (LN) metastasis, differentiation, and overall survival (OS). LAMC2 significantly promoted cell proliferation and cell viability. Besides, cetuximab significantly inhibited LAMC2 expression levels. LAMC2 significantly reversed the effect of cetuximab suppressing cell proliferation in LC cells. In conclusion, LAMC2 may act as a novel anti-cancer target in LC.


Assuntos
Neoplasias Laríngeas , Linhagem Celular Tumoral , Proliferação de Células , Cetuximab/farmacologia , Humanos , Laminina , Neoplasias Laríngeas/tratamento farmacológico
8.
J Ethnopharmacol ; 281: 114522, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34391863

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Firstly prescribed in the ancient Chinese book Jingui Yaolue, Gancao Ganjiang decoction (GGD) is a traditional Chinese herbal formula that has been widely used to treat "atrophic lung disease". GGD is a popular and widely used traditional Chinese medicine. The decoction is extracted from the dried rhizomes and roots of Glycyrrhiza uralensis Fisch. and Zingiber officinale Roscoe (2:1). AIM OF STUDY: To investigate the therapeutic effect of idiopathic pulmonary fibrosis (IPF) of GGD, a bleomycin-induced IPF murine model was used in this study. MATERIALS AND METHODS: Mice were induced by bleomycin instillation and GGD was orally administered. Changes on mice weight were recorded during the experiment. Lung weight was recorded on days 14 and 28, and pulmonary index was calculated accordingly. Pathological evaluation, including fibrosis analysis of lung tissue, was assessed by H&E and Masson staining. The expression of PD-1, p-STAT3 and IL-17A were detected by immunohistochemistry (IHC). The expression of p-STAT3 in lung tissues of mice were detected by Western blot. The level of IL-17A in lung tissue were detected by ELISA. The expression of PD-1 in CD4+ T cells in peripheral blood of mice was detected by flow cytometry. The levels of hydroxyproline and TGF-ß1 in lung tissue were detected by ELISA. The expression of E-cadherin, vimentin and α-SMA in lung tissues of mice were detected by qRT-PCR and Western blot. RESULTS: GGD can increase body weight and reduce pulmonary index in mice with pulmonary fibrosis. As such, GGD can significantly improve the inflammatory and alleviate IPF in the lung tissue of mice. GGD treatment was capable of reducing the content of PD-1 in lung tissue as well as the expression of PD-1 in CD4+ T cells in peripheral blood. Likewise, GGD was able to reduce the content of p-STAT3, IL-17A and TGF-ß1. In addition, GGD stimulation could inhibit epithelial-mesenchymal transformation (EMT) by increasing the expression of E-cadherin and reducing vimentin and α-SMA, thus reducing extracellular matrix (ECM) deposition. CONCLUSION: Our results indicate that GGD positively affects IPF by regulating PD-1/TGF-ß1/IL-17A pathway.


Assuntos
Anti-Inflamatórios/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Bleomicina , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Caderinas/genética , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/patologia , Fatores Imunológicos/farmacologia , Interleucina-17 , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1 , Transdução de Sinais , Fator de Crescimento Transformador beta1 , Vimentina/genética
9.
Artigo em Inglês | MEDLINE | ID: mdl-34198296

RESUMO

OBJECTIVE: The objective of this study was to analyze the histopathologic changes in recurrent nasal polyps (NPs) in terms of tissue inflammatory cells infiltration and mucosal remodeling. METHODS: Thirty-five patients with primary NPs requiring a revision surgery during follow-up and a matched control group of 35 primary NP patients without recurrence were retrospectively enrolled. Histopathologic examination was performed of tissue inflammatory cells, subepithelial edema, epithelial cell hyperplasia, basement membrane thickness, and fibrosis. RESULTS: The mean eosinophil and neutrophil counts, proportions of eosinophil and neutrophil, as well as total inflammatory cell count were significantly higher in the recurrent group than those in the controls. Higher subepithelial edema was seen in the recurrent group. Within the recurrent group, the mean tissue eosinophil count and relative eosinophilia reduced from the first operation to revision surgery, whereas neutrophil count and proportion, and total inflammatory cell counts remained unchanged. Subepithelial edema and epithelial cell hyperplasia were significantly reduced after the first surgical procedure. CONCLUSION: NP recurrence is associated with higher inflammatory grade (especially in eosinophilia and neutrophilia). Surgical and corticoid treatments may have an impact on mucosal histopathologic changes but need further certification.

10.
Sheng Wu Gong Cheng Xue Bao ; 37(6): 2166-2180, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34227301

RESUMO

Bioactive peptides play important roles in promoting human health, such as lowering blood pressure, blood sugar and blood lipid, anti-obesity, and anti-cancer. Thus, exploring functional bioactive peptides and developing efficient production technologies are of crucial importance. Herein, we review the development of function discovery and production technology for natural bioactive peptides. Presently, the top-down and bottom-up approaches are mainly used for the function discovery and production of natural active peptides. The top-down approach includes the direct extraction and identification for functional discovery, and the direct extraction, enzymatic hydrolysis and microbial fermentation for production. The bottom-up approach includes the polypeptide modification and database mining for functional discovery, and the chemical synthesis, enzyme synthesis, recombinant expression and cell-free synthesis for production. The top-down approach is usually associated with complicated process, lower efficiency, higher cost, harder quality control, and uncertain functionality, while the bottom-up approach is more suitable for the development of peptide drugs but difficult to be used for functional foods. With the technology development of sequencing and mass spectrometry, it is easier to obtain the proteomic information of various organisms at the molecular level. Based on the proteomic information, the top-down and bottom-up approaches can be combined to overcome the disadvantages of using these two approaches alone, thus providing a new strategy for the rapid development and production of natural active peptides.


Assuntos
Peptídeos , Proteômica , Fermentação , Humanos , Espectrometria de Massas , Peptídeos/metabolismo , Tecnologia
11.
Neuroscience ; 469: 103-109, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34171408

RESUMO

The present study aimed to investigate the association between the serum SIRT1 protein and the severity of spinal cord injury (SCI) as well as the neurological recovery in mice. In this study, the wild-type (WT), Mx1-Cre+ SIRT1loxP/loxP (Mx1), and LCK-Cre+SIRT1loxP/loxP (LCK) mice were subjected to sham surgery, mild, moderate, or severe SCI, respectively. The serum was collected at intervals of 12 h, 1 day (d), 3 d, 5 d, 7 d, 10 d, 14 d, and 21 d after the injury. The locomotor function of all the animals was assessed using the Basso mouse scale (BMS) and the serum SIRT1 proteins were analyzed using enzyme-linked immunosorbent assay (ELISA). The results demonstrated that about 7-10 d after SCI, the levels of SIRT1 protein in the serum correlated significantly with the severity of the injury and at 28 d post-injury, there was a distant neurological recovery (BMS score). The serum SIRT1 concentration in both the Mx1 and LCK mice in the sham group was significantly reduced compared to that in the WT mice, and there was a delayed increase in the serum SIRT1 levels after injury. These findings indicate that the SIRT1 concentrations in the serum of the SCI mice closely correlated with the acute severity and neurological outcome.


Assuntos
Sirtuína 1 , Traumatismos da Medula Espinal , Animais , Camundongos , Recuperação de Função Fisiológica , Medula Espinal
12.
Front Cardiovasc Med ; 8: 690689, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124211

RESUMO

Background: The hemoglobin glycation index (HGI) has been proposed as a marker to quantify inter-individual variation in hemoglobin glycosylation. However, whether HGI is associated with an increased risk of diabetic complications independent of glycated hemoglobin (HbA1c) remains unclear. This meta-analysis aimed to determine the association between HGI and the risk of all cause mortality and composite cardiovascular disease (CVD). Methods: PubMed, and EMBASE databases were searched for related studies up to March 31, 2021. Observational studies reported associations between HGI levels and composite CVD and all cause mortality were included for meta-analysis. A random effect model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CI) for higher HGI. Results: A total of five studies, comprising 22,035 patients with type two diabetes mellitus were included for analysis. The median follow-up duration was 5.0 years. After adjusted for multiple conventional cardiovascular risk factors, an increased level of HGI was associated with a higher risk of composite CVD (per 1 SD increment: HR = 1.14, 95% CI = 1.04-1.26) and all cause mortality (per 1 SD increment: HR = 1.18, 95% CI = 1.05-1.32). However, when further adjusted for HbA1c, the association between HGI and risk of composite CVD (per 1 SD increment of HGI: HR = 1.01, 95% CI = 0.93-1.10) and all cause mortality (per 1 SD increment of HGI: HR = 1.03, 95% CI = 0.96-1.10) became insignificant. Conclusions: High HGI was associated with an increased risk of composite CVD and all cause mortality after adjustment for multiple conventional cardiovascular risk factors. However, the association was mainly mediating by the level of HbA1c.

13.
Front Psychiatry ; 12: 620489, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135780

RESUMO

Substance-related disorders are a group of medical conditions that affect a person's brain and behavior and lead to an inability to control the use of legal or illegal drug(s) or medication. Substance-related disorder is a serious public health and society problem worldwide. Genetic factors have been proven to have an important role. Researchers have carried out a lot of work in this field, and a large number of research results have been published in academic journals around the world. However, there are few overviews of research progress, presentation, and development trends in this field. In this study, a total of 636 articles related to genetic factors of substance-related disorders were retrieved from the Web of Science (WoS) database from 1997 to 2018, and the scientific literatures were analyzed by bibliometrics. The study found that the United States (US) has maintained a leading position in the field of research, with many core institutions and plenty of high-quality research results. Alcohol use disorder is still the most concerning issue in this field. Over the past 20 years, new techniques such as genome-wide association study (GWAS) based on high-throughput sequencing technology have replaced family studies, twin studies, and retrospective studies in this field. We believe that it is urgent to study the genetic factors of substance-related disorders, which can greatly deepen the understanding of the pathogenesis of substance-related disorders and may provide potential targets for precise treatment of such diseases.

14.
J Agric Food Chem ; 69(25): 7000-7015, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34139119

RESUMO

High intake of dietary fibers was found to be inversely associated with type-2 diabetes (T2D), whereas the difference among different dietary fibers on T2D remains unclear. Therefore, we have investigated the effects of different dietary fibers on T2D. Nine types of dietary fibers were used to investigate and evaluate their effects on type-2 diabetic rats via physiology, genomics, and metabolomics. We found that supplementation with ß-glucan, arabinogalactan, guar gum, apple pectin, glucomannan, and arabinoxylan significantly reduced the fasting blood glucose, whereas carrageenan, xylan, and xanthan gum did not affect glycemic control in diabetic rats. Also, bioactive dietary fibers (ß-glucan, arabinogalactan, guar gum, and apple pectin) associated with the increased butyric acid level and abundance of beneficial bacteria (Lachnobacterium, Parabacteroides, Faecalibacterium, Akkermansia, and some butyric acid-producing bacteria), as well as improved host metabolism by decreasing 12α-hydroxylated bile acids, acylcarnitines, and amino acids (leucine, phenylalanine, citrulline, etc.), thereby exert beneficial effects on T2D. It was also found that ß-glucan might attenuate insulin resistance via downregulation of Prevotella copri-mediated biosynthesis of branched-chain amino acids in T2D. Together, our study uncovered the effects of different dietary fibers on T2D, along with their potential mechanism.


Assuntos
Diabetes Mellitus Experimental , Microbioma Gastrointestinal , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Fibras na Dieta , Hipoglicemiantes , Prevotella , Ratos
15.
Carbohydr Polym ; 264: 118018, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33910741

RESUMO

The homeostasis between mitochondrial function and autophagy is crucial to the physiological activity of cancer cells, and its mechanism is conducive to the development of anti-tumor drugs. Here, we aimed to explore the effect and mechanism of Dendrobium officinale polysaccharide (DOP) on colon cancer cell line CT26. Our data showed that DOP significantly inhibited the proliferation of CT26 cells and elevated autophagy level. Moreover, DOP disrupted mitochondrial function through increasing reactive oxygen species (ROS) and reducing mitochondrial membrane potential (MMP), thereby impairing ATP biosynthesis, which activated AMPK/mTOR autophagy signaling. Intriguingly, the further experiments demonstrated that DOP-induced cytotoxicity, excessive autophagy and mitochondrial dysfunction were reversed after CT26 cells pretreated with antioxidant (N-acetyl-l-cysteine). Herein, these findings implied that DOP-induced mitochondrial dysfunction and cytotoxic autophagy repressed the propagation of CT26 cells via ROS-ATP-AMPK signaling, providing a new opinion for the study of antineoplastic drugs.


Assuntos
Autofagia/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Dendrobium/química , Mitocôndrias/efeitos dos fármacos , Polissacarídeos/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Acetilcisteína/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
17.
Plant Phenomics ; 2021: 6793457, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860277

RESUMO

Panax quinquefolium is a perennial herbaceous plant that contains many beneficial ginsenosides with diverse pharmacological effects. 24(R)-pseudoginsenoside F11 is specific to P. quinquefolium, a useful biomarker for distinguishing this species from other related plants. However, because of its nonconjugated property and the complexity of existing detection methods, this biomarker cannot be used as the identification standard. We herein present a stable 24(R)-pseudoginsenoside F11 fingerprint spectrum in the terahertz band, thereby proving that F11 can be detected and quantitatively analyzed via terahertz spectroscopy. We also analyzed the sample by high-performance liquid chromatography-triple quadrupole mass spectrometry. The difference between the normalized data for the two analytical methods was less than 5%. Furthermore, P. quinquefolium from different areas and other substances can be clearly distinguished based on these terahertz spectra with a standard principal component analysis. Our method is a fast, simple, and cost-effective approach for identifying and quantitatively analyzing P. quinquefolium.

18.
Biochem Biophys Res Commun ; 550: 30-36, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33677133

RESUMO

The extracellular matrix (ECM) degradation of nucleus pulposus cells (NPCs) is mainly induced by metalloproteinases (MMPs). Zn2+ is an essential component of MMPs, but the effect of Zn2+ importers in controlling ECM metabolism remains unclear. The purpose of this research was to identify the involvement of Zn2+ importers in ECM degradation induced by inflammatory stimuli and excessive mechanical stressing. In this study, NPCs from Sprague-Dawley (SD) rats were separated and cultured. FluoZin-3 AM staining was applied to detect [Zn2+]i in NPCs treated with Interleukin-1ß (IL-1ß) or cyclic tensile strain (CTS) with a Flexcell Strain Unit. We found that intracellular Zn2+ concentration ([Zn2+]i) elevated dramatically, and ZIP8 is the predominant Zn2+ importer among all importers in senescent NPCs. The [Zn2+]i and MMP expression level both increased in IL-1ß and CTS treated NPCs. Furthermore, the expression of ZIP8 was also markedly increased. However, knockdown of ZIP8 with siRNA alleviated ECM degradation induced by inflammatory stimuli and CTS. Both stimuli activated NF-κB signaling pathway, and knockdown of ZIP8 effectively inhibited NF-κB signaling pathway activation. In conclusion, knockdown of ZIP8 can alleviate NPCs' ECM degradation caused by inflammatory stimuli and excessive mechanical stressing.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Matriz Extracelular/metabolismo , NF-kappa B/metabolismo , Núcleo Pulposo/metabolismo , Transdução de Sinais , Animais , Proteínas de Transporte de Cátions/deficiência , Proteínas de Transporte de Cátions/genética , Colágeno Tipo II/metabolismo , Técnicas de Silenciamento de Genes , Inflamação/metabolismo , Masculino , Núcleo Pulposo/citologia , Ratos , Zinco/metabolismo
19.
Food Funct ; 12(6): 2617-2630, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33634806

RESUMO

Obesity is a chronic disease characterized by overweight resulting from fat accumulation, along with disturbance of metabolism and gut microbiota. Fermentation, as a green processing method, is beneficial for improving the nutrition capacity of food components. Polysaccharides are considered as one of the important components in food and are also potential supplements for anti-obesity treatment. This study aimed to investigate the anti-obesity effects of polysaccharides from fermented and non-fermented Momordica charantia L. with Lactobacillus plantarum NCU116 (FP and NFP) on obese rats by serum metabolomics and gut microbiota analysis. Metabolomics results revealed that abnormal lipid metabolism was formed due to obesity. The supplement of FP and NFP improved the glycerophospholipids, glycosphingolipids, and amino acid metabolism of the obese rats, which alleviated the hypercholesterolemia and overweight in rats. Furthermore, the disorder of gut microbiota was ameliorated by FP and NFP. FP promoted the growth of beneficial bacteria, such as phylum Firmicutes, Actinobacteria, and genera Anaerostipes, Coprococcus, Lactobacillus, and Bifidobacterium. FP also reduced several harmful bacteria belonging to the phylum Proteobacteria and genera Helicobacter. The positive correlation of the weight loss and lowering of serum lipids with the increased beneficial bacteria further elucidated that the anti-obesity effect of FP in obese rats is associated with the regulation of gut microbiota and serum metabolites. The results of this study could provide information for developing probiotic products in the future that may have beneficial effects on the prevention or treatment of obesity.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus plantarum , Momordica charantia/química , Polissacarídeos/farmacologia , Probióticos/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Fermentação , Lipídeos/sangue , Masculino , Doenças Metabólicas/metabolismo , Metaboloma/efeitos dos fármacos , Obesidade , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley
20.
J Agric Food Chem ; 69(8): 2632-2645, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33606525

RESUMO

Type 2 diabetes (T2D) is a worldwide epidemic associated with metabolic disorders and intestinal microbiota alterations. Polysaccharides have been considered to be beneficial to the prevention and alleviation of T2D. In the present study, ultra-performance liquid chromatography-triple-time-of-flight-based metabolomics and proteomics and 16S rRNA sequencing methods were employed to evaluate the effects of glucomannans from Dendrobium officinale stem, konjac, and Aloe vera leaves on host metabolism and intestinal microbiota regulation in type 2 diabetic rats and potential mechanisms. The metabolism of amino acids was significantly disturbed in the type 2 diabetic rats, especially the upregulated branched-chain amino acid (BCAA) metabolism. Host-derived BCAA metabolism was significantly decreased in type 2 diabetic rats. However, the levels of BCAAs in host circulation and gene abundance of BCAA biosynthesis in gut microbiota were significantly increased in diabetic rats, which suggested that the disturbed intestinal microbiota might be responsible for the increased circulation of BCAAs in T2D. Glucomannan treatment decreased the abundance of microbial BCAA biosynthesis-related genes and ameliorated the host BCAA metabolism. Also, glucomannan with a higher molecular weight and a lower ratio of mannose/glucose possessed better antidiabetic effects. In summary, the antidiabetic effects of glucomannans might be associated with the amelioration of BCAA metabolism by modulating intestinal microbiota.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Aminoácidos de Cadeia Ramificada , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Mananas , RNA Ribossômico 16S , Ratos
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