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1.
CNS Drugs ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573471

RESUMO

BACKGROUND: Percutaneous endoscopic transforaminal discectomy (PETD) is an effective method for treating lumbar disc herniation, and is typically performed under local anesthesia. However, inadequate analgesia during the procedure remains a concern, prompting the search for a medication that can provide optimal pain control with minimal impact on the respiratory and circulatory systems. OBJECTIVES: The aim of this study was to observe the effects of different doses of esketamine combined with dexmedetomidine on reducing visual analog scale (VAS) scores during surgical interventions. METHODS: One hundred two patients who underwent PETD were randomly divided into a control group (group C: normal saline + dexmedetomidine), an E1 group (0.1 mg kg-1 esketamine + dexmedetomidine), and an E2 group (0.2 mg kg-1 esketamine + dexmedetomidine). The primary outcome was the maximum visual analogue scale (VAS) (score: 0 = no pain and 10 = worst pain) at six time points. The secondary outcomes included the Assessment of Alertness/Sedation Scale (OAA/S) score and mean arterial pressure (BP), heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) at 11 time points. The incidence of adverse reactions during and 24 h after the operation and patient satisfaction with the anesthesia were also recorded. RESULTS: Compared with those in group C, the VAS scores of patients in groups E1 and E2 were lower at T6, T7, and T9 (P < 0.05). From T4 to T10, the OAA/S scores of the E1 and E2 groups were both lower than those of group C (P < 0.05), and at the T4-T6 time points, the OAA/S score of the E2 group was lower than that of group E1 (P < 0.05). At T4 and T5, the HR and BP of patients in groups E1 and E2 were greater than those in group C (P < 0.05). Compared with those in group C, the incidences of intraoperative illusion, floating sensation, postoperative dizziness, and hyperalgesia in groups E1 and E2 were significantly greater (P < 0.01). There was no significant difference in patient RR, SpO2, or postoperative satisfaction with anesthesia among the three groups (P > 0.05). CONCLUSION: The combination of esketamine and dexmedetomidine can reduce VAS scores during certain stages of this type of surgery; it has minimal impact on respiration and circulation. However, this approach is associated with increased incidences of postoperative dizziness and psychiatric side effects, which may also affect patients' compliance with surgical instructions from medical staff. Patient satisfaction was not greater with dexmedetomidine combined with esketamine than with dexmedetomidine alone. TRIAL REGISTRATION: http://www.chictr.org.cn . Identifier: ChiCTR2300068206. Date of registration: 10 February 2023.

2.
Int J Biol Macromol ; 268(Pt 2): 131816, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38677682

RESUMO

Paeoniae Radix alba is used in Traditional Chinese Medicine for the treatment of gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In the current study, the yield of Paeoniae Radix alba polysaccharide (PRP) was significantly increased with optimal ultrasound-assisted extraction compared to hot water extraction. Further, an acidic polysaccharide (PRP-AP) was isolated from PRP after chromatographic separation and was characterized as a typical pectic polysaccharide with side chains of arabinogalactans types I and II. Moreover, it showed antioxidant effects on LPS-induced damage on IPEC-J2 cells determined by qRT-PCR and ELISA, including decreasing the pro-inflammatory factors' expressions and increasing the antioxidant enzymes activities, which was shown to be related to the Nrf2/Keap1 pathway modulated by PRP-AP. The metabolites change (such as itaconate, cholesterol sulfate, etc.) detected by untargeted metabolomic analysis in cells was also shown to be modulated by PRP-AP, and these metabolites were further utilized and protected cells damaged by LPS. These results revealed the cellular active mechanism of the macromolecular PRP-AP on protecting cells, and supported the hypothesis that PRP-AP has strong benefits as an alternative dietary supplement for the prevention of intestinal oxidative stress by modulating cellular metabolism.

3.
Medicine (Baltimore) ; 102(46): e36087, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37986302

RESUMO

RATIONALE: Actinobacillus ureae (A. ureae) is an unusual commensal of human respiratory flora, rarely causing human infection. The predisposing factors, identification, clinical features, and antibiotic therapy of A. ureae are seldomly reported. Herein, we present a case of 64-year-old man affected by A. ureae pneumonia after intracranial surgery. PATIENT CONCERNS AND DIAGNOSES: A 64-year-old male was admitted with vomiting, drowsiness, and a severe disturbance of consciousness and was later diagnosed with cerebral hemorrhage by computed tomography images. After a craniocerebral surgery, the patient suffered from intractable pneumonia, experiencing treatment failure with multiple anti-bacterial agents. Sputum culture yield pure colonies of A. ureae, confirmed by matrix-assisted laser desorption/ionization time of flight and 16S rRNA gene sequencing. INTERVENTIONS: Minocycline (100 mg p.o. per 12 hours) with a course of 15 days was administrated for this patient. OUTCOMES: The respiratory symptoms, presenting as intermittent coughing with purulent and yellowish sputum, were gone. A 3-month follow-up examination showed a complete resolution of radiological findings. LESSONS: Clinically, the actual incidence of A. ureae pneumonia may be higher than that we generally recognized, and clinicians should consider A. ureae as a possible etiologic agent in patients with predispositions. Currently, A. ureae may be susceptible to penicillin, ampicillin, and third-generation cephalosporins. Other antibacterial agents, such as tetracycline, amoxicillin/clavulanic acid, and aminoglycosides also respond well and can be a choice in the treatment of A. ureae infections.


Assuntos
Infecções por Actinobacillus , Actinobacillus , Pneumonia , Masculino , Humanos , Pessoa de Meia-Idade , RNA Ribossômico 16S , Infecções por Actinobacillus/diagnóstico , Infecções por Actinobacillus/tratamento farmacológico , Infecções por Actinobacillus/microbiologia , Antibacterianos/uso terapêutico , Pneumonia/complicações
4.
Chem Biol Drug Des ; 102(4): 815-827, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37500510

RESUMO

Diaminodichoroplatinum (DDP) resistance of tumor cells is the culprit of nasopharyngeal carcinoma (NPC) treatment failure. MicroRNA-577 is lowly expressed in NPC tissues, but relevant mechanism is poorly studied. Therefore, this study investigated the role of microRNA-577 in NPC cells with DDP resistance and its mechanism. DDP-resistant NPC cells were established by treatment with DDP at increased concentrations (2, 4, 6, 8, or 10 µg/mL). MicroRNA-577 and EIF5A2 mRNA expressions were detected by qRT-PCR. Cell biological behaviors were assessed via cell function experiments. Expressions of epithelial mesenchymal transformation (EMT)-related proteins were quantified by western blot. The targeting relationship between eukaryotic translation initiation factor 5A2 (EIF5A2) and microRNA-577 was verified through dual-luciferase reporter assay. The tumor volume and weight were measured after subcutaneous tumorigenesis in mice. As observed from the results, microRNA-577 expression was reduced in NPC cells and DDP-resistant NPC cells. Up-regulated microRNA-577 suppressed the malignant behaviors and EMT of DDP-resistant NPC cells, and facilitated cell apoptosis. MicroRNA-577 targeted EIF5A2, and overexpressed EIF5A2 reversed the above effects of up-regulated microRNA-577 on DDP-resistant NPC cells. Besides, EIF5A2 positively regulated TGF-ß signaling pathway, and TGF-ß treatment offset the promoting effects of EIF5A2 silencing on apoptosis of DDP-resistant NPC cells. Up-regulated microRNA-577 suppressed the proliferation of DDP-resistant NPC cells, and down-regulated the levels of EIF5A2 and TGF-ß as well as EMT in vivo. Collectively, microRNA-577/EIF5A2 axis hinders the EMT progression through the blockage of TGF-ß signaling pathway, so as to inhibit the proliferation of DDP-resistant NPC.


Assuntos
MicroRNAs , Neoplasias Nasofaríngeas , Animais , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fator de Iniciação de Tradução Eucariótico 5A
5.
Cell Cycle ; 22(13): 1544-1562, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37287276

RESUMO

This study investigated the underlying mechanism of miR-18a-5p regulating the proliferation, invasion, and metastasis of nasopharyngeal carcinoma (NPC) cells in vitro and in vivo to indicate the pathogenesis of NPC. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was utilized to determine miR-18a-5p expression level in NPC tissues and cell lines. Besides, 2,5-diphenyl-2 H-tetrazolium bromide (MTT) and colony formation assays were employed to detect the effect of miR-18a-5p expression level on NPC cell proliferation. Wound healing and Transwell assays were utilized to detect the effect of miR-18a-5p on NPC cell invasion and migration. The expression levels of epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin, and E-cadherin) were identified by Western blot assay. After collecting exosomes from CNE-2 cells, it was found that exosomal miR-18a-5p secreted from NPC cells promoted NPC cell proliferation, migration, invasion, and EMT, whereas inhibition of miR-18a-5p expression level led to the opposite results. The dual-luciferase reporter assay showed that BTG anti-proliferation factor 3 (BTG3) was the target gene of miR-18a-5p, and BTG3 could overturn the effect of miR-18a-5p on NPC cells. Xenograft mouse model of NPC nude mice showed that miR-18a-5p promoted NPC growth and metastasis in vivo. This study revealed that exosomal miR-18a-5p derived from NPC cells promoted angiogenesis via targeting BTG3 and activating the Wnt/ß-catenin signaling pathway.


Assuntos
MicroRNAs , Neoplasias Nasofaríngeas , Humanos , Animais , Camundongos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , MicroRNAs/metabolismo , Transição Epitelial-Mesenquimal/genética , Via de Sinalização Wnt/genética , Camundongos Nus , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Nasofaríngeas/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Ciclo Celular/metabolismo
6.
Genes Genomics ; 45(9): 1211-1226, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37301776

RESUMO

BACKGROUND: Glioma is the most common and devastating form of malignant brain tumor, with a poor prognosis. Extracellular matrix (ECM) organization is a crucial determinant of glioma invasion and progression. However, the clinical significance of ECM organization in glioma patients remains unclear. OBJECTIVE: To evaluate the prognostic value of ECM organization-related genes in glioma patients and identify potential therapeutic targets. METHODS: Bulk RNA-sequencing and corresponding clinical data for patients with glioma were downloaded from TCGA and GEO databases. Differentially expressed ECM organization genes were identified, and an ECM organization-related gene prognostic model was then generated. Furthermore, the prognostic model has validated in the Chinese Glioma Genome Atlas (CGGA) dataset. The role of TIMP1 in glioma cells by using various functional assays revealed their underlying mechanism in vitro. RESULTS: We identified and validated a nine-gene signature (TIMP1, SERPINE1, PTX3, POSTN, PLOD3, PDPN, LOXL1, ITGA2, and COL8A1) related to ECM organization as a robust prognostic biomarker for glioma. Time-dependent ROC curve analysis confirmed the specificity and sensitivity of the signature. The signature was closely related to an immunosuppressive phenotype, and its combination with immune checkpoints served as a good predictor for patients' clinical outcomes. Notably, single-cell RNA sequencing analysis revealed high expression of TIMP1 in astrocytes and oligodendrocyte progenitor cells in glioma patients. Last, we show that TIMP1 regulates glioma cell growth and invasion via the AKT/GSK3ß signaling pathway. CONCLUSION: This study provides promising insights into predicting glioma prognosis and identifying a potential therapeutic target in TIMP1.


Assuntos
Matriz Extracelular , Genes Reguladores , Glioma , Inibidor Tecidual de Metaloproteinase-1 , Humanos , Biomarcadores , Glioma/genética , Prognóstico , Inibidor Tecidual de Metaloproteinase-1/genética
7.
Cell Biol Int ; 47(9): 1589-1599, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37309064

RESUMO

Macrophage-derived foam cell formation is critical for the initiation and development of atherosclerosis, which contributes to atherosclerotic cardiovascular disease (ASCVD). Glutathione peroxidase 4 (GPX4), a crucial ferroptosis regulator, protects cells from excessive oxidative stress by neutralizing lipid peroxidation. However, the role of macrophage GPX4 in foam cell formation remains unknown. We reported that oxidized low-density lipoprotein (oxLDL) upregulated GPX4 expression in macrophages. Using the Cre-loxP system, we generated myeloid cell-specific Gpx4 knockout (Gpx4myel-KO ) mice. Bone marrow-derived macrophages (BMDMs) were isolated from WT and Gpx4myel-KO mice and incubated with modified low-density lipoprotein (LDL). We found that Gpx4 deficiency promoted foam cell formation and increased the internalization of modified LDL. Mechanistic studies unveiled that Gpx4 knockout upregulated scavenger receptor type A and LOX-1 expression and downregulated ABCA1 and ABCG1 expression. Collectively, our study lends a novel insight into the role of GPX4 in suppressing macrophage-derived foam cell formation and suggests GPX4 as a promising therapeutic target to interfere with atherosclerosis-related diseases.


Assuntos
Aterosclerose , Células Espumosas , Camundongos , Animais , Células Espumosas/metabolismo , Macrófagos/metabolismo , Lipoproteínas LDL/metabolismo , Receptores Depuradores/metabolismo , Aterosclerose/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
8.
Front Cell Infect Microbiol ; 13: 1103909, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37009501

RESUMO

Helicobacter pylori is believed to induce gastropathy; however, the exact pathogenic molecules involved in this process have not been elucidated. Duodenal ulcer promoting gene A (DupA) is a virulence factor with a controversial role in gastric inflammation and carcinogenesis. To explore and confirm the function of DupA in gastropathy from the perspective of the microbiome, we investigated the microbial characteristics of 48 gastritis patients through 16S rRNA amplicon sequencing. In addition, we isolated 21 H. pylori strains from these patients and confirmed the expression of dupA using PCR and qRT-PCR. Bioinformatics analysis identified diversity loss and compositional changes as the key features of precancerous lesions in the stomach, and H. pylori was a characteristic microbe present in the stomach of the gastritis patients. Co-occurrence analysis revealed that H. pylori infection inhibits growth of other gastric inhabiting microbes, which weakened the degradation of xenobiotics. Further analysis showed that dupA+ H. pylori were absent in precancerous lesions and were more likely to appear in erosive gastritis, whereas dupA- H. pylori was highly abundant in precancerous lesions. The presence of dupA in H. pylori caused less disturbance to the gastric microbiome, maintaining the relatively richness of gastric microbiome. Overall, our findings suggest that high dupA expression in H. pylori is correlated with a high risk of erosive gastritis and a lower level of disturbance to the gastric microbiome, indicating that DupA should be considered a risk factor of erosive gastritis rather than gastric cancer.


Assuntos
Úlcera Duodenal , Gastrite , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Úlcera Gástrica , Humanos , RNA Ribossômico 16S/genética , Neoplasias Gástricas/genética
9.
Pathol Res Pract ; 244: 154056, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36989847

RESUMO

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is a type of keratinizing squamous cell malignancy. Ubiquitination, a common protein posttranslational modification, participates in cancer development. This study sought to investigate the mechanism of F-box and WD repeat domain containing 7 (FBXW7) in NPC cell proliferation in vivo and in vitro. METHODS: FBXW7, Homeobox A10 (HOXA10), and bone morphogenetic protein-2 (BMP2) expression levels in NPC tissues and cells were detected by RT-qPCR and Western blotting. Cell proliferation was assessed by cell counting kit-8 and colony formation assays. The binding of FBXW7 to HOXA10 and HOXA10 ubiquitination level were detected via co-immunoprecipitation and ubiquitination assay. Cells were treated with MG132 (the proteasome inhibitor), followed by the determination of HOXA10 ubiquitination and protein levels. The binding of HOXA10 to BMP2 was testified via dual-luciferase and chromatin immunoprecipitation assays. Collaborative experiments were performed to confirm the role of HOXA10 or BMP2 in FBXW7-mediated NPC cell proliferation. Xenograft tumor assay was performed to confirm the role of FBXW7/HOXA10/BMP2 in vivo. RESULTS: FBXW7 was under-expressed, while HOXA10 and BMP2 were up-expressed in NPC tissues and cells. FBXW7 overexpression restricted NPC cell proliferation. Mechanically, FBXW7 bound to HOXA10 to promote ubiquitination-based degradation of HOXA10 and further reduced the binding of HOXA10 to the BMP2 promoter and inhibited BMP2 transcription. Overexpression of HOXA10 or BMP2 attenuated the role of FBXW7 overexpression in inhibiting NPC cell proliferation. FBXW7 overexpression reduced Ki67 positive rate and repressed tumor growth. CONCLUSION: FBXW7 overexpression promoted HOXA10 ubiquitination-based degradation and further inhibited BMP2 transcription, consequently restricting NPC cell proliferation in vitro and in vivo.


Assuntos
Proteína 7 com Repetições F-Box-WD , Neoplasias Nasofaríngeas , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteína 7 com Repetições F-Box-WD/genética , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/patologia , Ubiquitinação
10.
Front Neurol ; 13: 1036750, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530622

RESUMO

Background: Fat Mass and Obesity-Associated (FTO) and the Melanocortin-4 Receptor (MC4R) genes are strongly associated with obesity, an established risk factor for stroke. We aimed to assess the associations between rs17817449 at the FTO and rs6567160 at the MC4R and the risk of stroke events in middle-aged and older Chinese people. Materials and methods: Study data were obtained from the Guangzhou Biobank Cohort Study; a total of 148 participants with a self-reported history of stroke and an equal volume of age- and sex-matched participants were selected as the cases and the controls in a case-control study; a total of 13,967 participants at the first follow-up and all participants with fatal stroke (up to April 2021) were included in a retrospective cohort study. Conditional logistic regression and the Cox proportional hazards regression analyses were used to assess the associations of the two genetic loci with the risk of stroke events. Results: After adjusting for age, sex, education, job, smoking, alcohol consumption, body mass index, physical activity, hypertension, diabetes, and dyslipidemia, rs17817449 and rs6567160 shared minor alleles G and C, respectively, in the case-control analyses. The genotypes GG+GT of rs17817449 at the FTO were significantly associated with a decreased risk of fatal stroke occurrence, with fatal all strokes having an adjusted hazard ratio (aHR) of 0.71 (95% confidence intervals (CI) 0.52-0.97, P = 0.04) and fatal ischemic stroke having an aHR of 0.64 (95% CI 0.41-1.00, P = 0.05), when the genotype TT was taken as a reference and a series of multiplicities were adjusted; the risk of fatal all strokes was lowered by dyslipidemia (aHR = 0.63, 95% CI 0.39-1.00, P = 0.05) and non-diabetes (aHR = 0.68, 95% CI 0.46-0.99, P = 0.049) in the retrospective cohort analyses. Significances were observed neither in the associations between rs6567160 and the risk of stroke events nor in an interaction between rs17817449 and rs6567160 in the two-stage analyses. Conclusion: The G allele of rs17817449 at the FTO, not rs6567160 at the MC4R, was associated with a decreased risk of fatal stroke occurrence; its functional role in stroke should be explored in relatively healthy middle-aged to older Chinese people.

11.
Biomed Pharmacother ; 150: 113012, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35658246

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant tumor highly prevalent in Southeast Asia. The distant metastasis and disease recurrence are still unsolved clinical problems. In recent years, traditional Chinese medicine (TCM) monomers have become significantly attractive due to their advantages. Using high throughput drug sensitivity screening, we identified gambogic acid (GA) as a common TCM monomer displaying multiple anti-NPC effects. GA could effectively inhibit the proliferation of low differentiated cells and highly metastatic cells in NPC via inducing apoptosis and G2/M cell cycle arrest. In addition, GA obviously repressed the abilities of cell clone, migration, invasion, angiogenesis and represented satisfied synergistic effects combined with chemotherapy. Importantly, we found the elevated immune checkpoint CD47 stimulated after chemotherapy was dramatically impaired by GA treatment. Mechanically, the network pharmacology analyses unraveled that the oncogenic signaling pathways including STATs were rewired by GA treatment. Taken together, our study reveals a molecular basis and provides a rationale for GA application as the treatment regime in NPC therapy in future.


Assuntos
Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Monitorização Imunológica , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Xantonas
12.
J Ethnopharmacol ; 295: 115446, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35675860

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Angelica sinensis, has been commonly used in gynecology for centuries, and is normally applied divided into different parts in various clinical applications. At present, the majority of existing studies focus on the volatile oil and ferulic acid extracted from different parts of A. sinensis, but there is a dearth of scientific information on its water-soluble polysaccharides. AIM OF THE STUDY: The structures of polysaccharides from plants, have been reported contributing to multiple pharmacological activities such as anti-oxidative, anti-inflammatory, anti-tumor and liver protection. Therefore, the focus of this study was on its anti-oxidative and anti-inflammatory activities in vitro, which would be based on the various polysaccharides with distinct structures obtained from different parts of the A. sinensis root. MATERIALS AND METHODS: Four parts of A. sinensis root were separated according to the Chinese Pharmacopoeia: head, body, tail and whole body. Crude polysaccharides were obtained by water extraction and ethanol precipitation method, and were further fractionated by DEAE Sepharose chromatographic column and gel filtration. The comparison of ASPs from different root parts were performed, including chemical compositions determined by colorimetric analysis, monosaccharide compositions measured by high performance liquid chromatography (HPLC), glycosidic linkage units determined by methylation and gas chromatography-mass spectrometry (GC-MS), organic functional groups determined by FT-IR, molecular weight (Mw) demarcated by gel permeation chromatography, and the viscosities and solubilities were measured according to method published in the previous report with minor modification. In vitro biological activities of APSs were compared on lipopolysaccharide (LPS)-induced inflammatory and oxidative stress models on IPEC-J2 cells. RESULTS: Four purified polysaccharides, ASP-H-AP, ASP-B-AP, ASP-T-AP and ASP-Hb-AP from the root of A. sinensis, were obtained, and consisted of various contents of protein and the polyphenol. They were possibly pectic polysaccharides with a long homogalacturonan region as the main backbone and ramified with rhamnogalacturonan I region, but they were differed by subregions and the relative contents of glycosidic units. The Mw of four pectic polysaccharides were ranged from 67.9-267.7 kDa. The infrared spectrum also showed that the four polysaccharide fractions contained the characteristic peaks of polysaccharides. Their distinct primary structure could lead to a variety of biological activities. In vitro biological assays suggested that four polysaccharide fractions can protect IPEC-J2 cells against the LPS-induced inflammation by down-regulating inflammation factors and related genes on IPEC-J2 cells. These polysaccharides also could alleviate oxidative stress on IPEC-J2 cells by up-regulating the gene and protein expressions of antioxidant enzymes. It was concluded that ASP-H-AP possessed better anti-inflammatory and anti-oxidative effects, while those of ASP-T-AP was relatively poor among the four polysaccharide fractions. CONCLUSION: All results indicated that the structure of pectic polysaccharides from different root parts of A. sinensis differed, which lead to their distinct anti-inflammatory and anti-oxidative activities. This may also be one of the factors why different parts of A. sinensis showed various pharmacological activities and applied independently in traditional use. In addition, it would be valuable for further studies on structure-activity relationship of polysaccharides obtained by different root parts of A. sinensis.


Assuntos
Angelica sinensis , Angelica sinensis/química , Anti-Inflamatórios/farmacologia , Inflamação , Lipopolissacarídeos , Polissacarídeos/química , Polissacarídeos/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química
13.
Food Funct ; 12(21): 10828-10841, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34617945

RESUMO

In this study, the Nelumbo nucifera leaf polysaccharide (NNLP) was isolated by hot water extraction and ethanol precipitation. DEAE anion exchange chromatography and gel filtration were further performed to obtained the purified fraction NNLP-I-I, the molecular weight of which was 16.4 kDa. The monosaccharide composition analysis and linkage units determination showed that the fraction NNLP-I-I was a pectic polysaccharide. In addition, the NMR spectra analysis revealed that NNLP-I-I mainly consisted of a homogalacturonan backbone and rhamnogalacturonan I, containing a long HG region and short RG-I region, with AG-II and 1-3 linked rhamnose as side chains. The biological studies demonstrated that NNLP-I-I displayed antioxidant properties through mediating the Nrf2-regulated intestinal cellular antioxidant defense, which could protect cultured intestinal cells from oxidative stress and improve the intestinal function of aged mice.


Assuntos
Antioxidantes/farmacologia , Nelumbo/química , Pectinas/farmacologia , Folhas de Planta/química , Animais , Antioxidantes/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Malondialdeído , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Pectinas/química , Superóxido Dismutase , Suínos
14.
Pain Physician ; 24(4): E433-E441, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34213868

RESUMO

BACKGROUND: More evidence is required to support that computerized tomography navigation percutaneous spinal endoscopy in the treatment of highly migrated lumbar disc herniation is a more minimally invasive surgery than open discectomy . OBJECTIVE: To quantitatively evaluate the efficacy and minimal invasiveness of computerized tomography navigation percutaneous spinal endoscopy and open discectomy in highly migrated lumbar disc herniation. STUDY DESIGN: A prospective randomized study. SETTING: First Affiliated Hospital of Gannan Medical College. METHODS: From August 2016 to February 2020, 68 patients with highly migrated lumbar disc herniation had undergone discectomy. Thirty-five of them randomly received computerized tomography (CT) navigation percutaneous spinal endoscopy at the pain department (CT navigation percutaneous spinal endoscopy group), and 33 patients received open discectomy at the orthopedics department (open discectomy group). The Visual Analog Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and modified MacNab criteria were applied to evaluate the clinical situations pre- and post-operation. The serum concentrations of IL-6, TNF-alpha, creatine phosphokina (CPK), and C-reactive protein (CRP) in the 2 groups were quantitatively measured. RESULTS: The postoperative VAS scores of the back and lower extremity were lower than those pre-operation in both groups, while the VAS score of back pain in the open discectomy group was significantly higher than that in the CT navigation percutaneous spinal endoscopy group at one week post-operation (P < 0.01). The postoperative JOA scores were significantly higher than those pre-operation in both groups. The serum concentrations of IL-6, TNF-alpha, CPK, and CRP in the open discectomy group were higher than those in the computerized tomography navigation percutaneous spinal endoscopy group postoperatively (P < 0.01). LIMITATIONS: This is a single-center randomized study and with the limitation of the sample size. CONCLUSION: CT navigation percutaneous spinal endoscopy is a more minimally invasive surgery than open discectomy.Certificate number for the medical institution conducting the clinical trials for humans in China: 934.


Assuntos
Discotomia Percutânea , Dor nas Costas , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Prospectivos , Tomografia Computadorizada por Raios X
15.
J Sci Food Agric ; 101(14): 6043-6052, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33857333

RESUMO

BACKGROUND: Codonopsis pilosula and Codonopsis tangshen are plants widely used in traditional Chinese medicine. Two pectic polysaccharides from the roots of C. pilosula and C. tangshen named as CPP-1 and CTP-1 were obtained by boiling water extraction and column chromatography. RESULTS: The core structures of both CPP-1 and CTP-1 comprise the long homogalacturonan region (HG) as the backbone and the rhamnogalacturonan I (RG-I) region as the side chains. CPP-1 has methyl esterified galacturonic acid units and a slightly lower molecular weight than CTP-1. Biological testing suggested that CPP-1 and CTP-1 can protect IPEC-J2 cells against the H2 O2 -induced oxidative stress by up-regulating nuclear factor-erythroid 2-related factor 2 and related genes in IPEC-J2 cells. The different antioxidative activities of polysaccharides from different source of C. pilosula may be result of differences in their structures. CONCLUSION: All of the results indicated that pectic polysaccharides CPP-1 and CTP-1 from different species of C. pilosula roots could be used as a potential natural antioxidant source. These findings will be valuable for further studies and new applications of pectin-containing health products. © 2021 Society of Chemical Industry.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Codonopsis/química , Pectinas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Linhagem Celular , Humanos , Fator de Transcrição NF-E2/genética , Fator de Transcrição NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pectinas/farmacologia , Raízes de Plantas/química
16.
Pain Physician ; 24(2): E203-E210, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33740357

RESUMO

BACKGROUND: Percutaneous full-endoscopic surgery was recently developed for the treatment of cervical foraminal stenosis and posterolateral disc herniation. However, there are no studies involving endoscopic surgery to treat cervical spondylotic myelopathy (CSM). OBJECTIVES: To observe the safety, feasibility, and efficacy of posterolateral full-endoscopic ventral decompression (PLEVD) via computed tomography (CT)-guided surgery in patients with single-level CSM. STUDY DESIGN: A prospective cohort study. SETTING: The First Affiliated Hospital of Gannan Medical College. METHODS: From May 2018 to August 2019, 21 patients with single-level CSM underwent CT-guided PLEVD. The posterolateral angle was measured during surgery. The neurologic condition was evaluated via the Japanese Orthopaedic Association (JOA) score and recovery rate, and a Visual Analog Scale (VAS) was used to measure pain relief. The maximum spinal canal diameter (MSCD) was measured on pre- and postoperative CT images. RESULTS: The mean length of follow-up was 11.3 ± 5.3 months. The average posterolateral angle was 36.0° ± 5.6°. The mean VAS score of limbs significantly decreased after surgery. The mean JOA score improved during the follow-up period. Nineteen of the 21 patients achieved good or excellent outcomes, and 2 patients had fair outcomes according to the JOA score 6 months after surgery. The average MSCD was enlarged from 0.55 ± 0.15 cm preoperatively to 1.02 ± 0.18 cm postoperatively. LIMITATIONS: This study was nonrandomized and provides only preliminary clinical results for single-level CSM. CONCLUSION: Under appropriate indications, PLEVD under CT guidance is an available and safe technique for treating single-level CSM.


Assuntos
Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/métodos , Doenças da Medula Espinal/cirurgia , Adulto , Idoso , Vértebras Cervicais/diagnóstico por imagem , Endoscopia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Doenças da Medula Espinal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Escala Visual Analógica
17.
Int J Biol Macromol ; 175: 473-480, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33571586

RESUMO

Platycodonis Radix is widely used as homology of medicine and food in China; polysaccharides are thought to be one of its functional constituents. In this study, a pectic polysaccharide, PGP-I-I, was obtained from the root of the traditional medicine plant Platycodon grandiflorus through ion exchange chromatography and gel filtration. This was characterized being mainly composed of 1,5-α-L-arabinan and both arabinogalactan type I (AG-I) and II chains linked to rhamnogalacturonan I (RG-I) backbone linked to longer galacturonan chains. In vitro bioactivity study showed that PGP-I-I could restore the intestinal cellular antioxidant defense under the condition of hydrogen peroxide (H2O2) treatment through promoting the expressions of cellular antioxidant genes and protect against oxidative damages.


Assuntos
Pectinas/química , Platycodon/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular , Cromatografia em Gel , Cromatografia por Troca Iônica , Carboidratos da Dieta , Galactanos/química , Peróxido de Hidrogênio , Extratos Vegetais/química , Raízes de Plantas/química , Polissacarídeos/química , Suínos
18.
JCI Insight ; 6(3)2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290273

RESUMO

Current treatments for pneumonia (PNA) are focused on the pathogens. Mortality from PNA-induced acute lung injury (PNA-ALI) remains high, underscoring the need for additional therapeutic targets. Clinical and experimental evidence exists for potential sex differences in PNA survival, with males having higher mortality. In a model of severe pneumococcal PNA, when compared with male mice, age-matched female mice exhibited enhanced resolution characterized by decreased alveolar and lung inflammation and increased numbers of Tregs. Recognizing the critical role of Tregs in lung injury resolution, we evaluated whether improved outcomes in female mice were due to estradiol (E2) effects on Treg biology. E2 promoted a Treg-suppressive phenotype in vitro and resolution of PNA in vivo. Systemic rescue administration of E2 promoted resolution of PNA in male mice independent of lung bacterial clearance. E2 augmented Treg expression of Foxp3, CD25, and GATA3, an effect that required ERß, and not ERα, signaling. Importantly, the in vivo therapeutic effects of E2 were lost in Treg-depleted mice (Foxp3DTR mice). Adoptive transfer of ex vivo E2-treated Tregs rescued Streptococcus pneumoniae-induce PNA-ALI, a salutary effect that required Treg ERß expression. E2/ERß was required for Tregs to control macrophage proinflammatory responses. Our findings support the therapeutic role for E2 in promoting resolution of lung inflammation after PNA via ERß Tregs.


Assuntos
Estradiol/farmacologia , Receptor beta de Estrogênio/metabolismo , Pneumonia Pneumocócica/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Transferência Adotiva , Animais , Modelos Animais de Doenças , Estradiol/metabolismo , Receptor beta de Estrogênio/deficiência , Receptor beta de Estrogênio/genética , Feminino , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/metabolismo , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/patologia , Fatores Sexuais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
19.
J Sci Food Agric ; 101(6): 2491-2499, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33063324

RESUMO

BACKGROUND: Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. RESULTS: It was confirmed that the neutral polymers CPPN and CTPN were ß-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. CONCLUSION: The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.


Assuntos
Antioxidantes/química , Codonopsis/química , Medicamentos de Ervas Chinesas/química , Frutanos/química , Inulina/química , Prebióticos/análise , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Codonopsis/classificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Frutanos/isolamento & purificação , Frutanos/farmacologia , Humanos , Inulina/isolamento & purificação , Inulina/farmacologia , Lactobacillus/efeitos dos fármacos , Lactobacillus/crescimento & desenvolvimento , Estresse Oxidativo/efeitos dos fármacos , Polimerização
20.
Cell Cycle ; 19(22): 3004-3017, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33092435

RESUMO

Nasopharyngeal carcinoma is a malignant tumor that not only negatively affects the physical and mental health but also the quality of life of the patients. Growth arrest-specific transcript 5 (GAS5) is a common long-chain non-coding RNA (lncRNA) that has been reported to participate in the development of various cancers. However, the biological functions of lncRNA GAS5 in the occurrence and development of nasopharyngeal carcinoma are elusive. The expression of lncRNA GAS5 in nasopharyngeal carcinoma and normal samples were analyzed. Bioinformatic tool was utilized to predict the potential function of lncRNA in nasopharyngeal carcinoma. Transplanted mice were used for in vivo experiments. We observed that the expression of lncRNA GAS5 was upregulated in nasopharyngeal carcinoma tissues and cells. Down-regulation of lncRNA GAS5 inhibited the proliferation and promoted apoptosis of nasopharyngeal carcinoma cells. The expression of miR-4465 was down regulated in nasopharyngeal carcinoma tissues and cells. LncRNA GAS5 could directly bind to miR-4465 and regulated the expression of miR-4465. It was further confirmed that miR-4465 could directly bind with COX2 and inhibit the expression of COX2. Down-regulation of lncRNA GAS5 suppressed tumor growth, promoted the expression levels of miR-18a-5p and suppressed the expression of COX2 in vivo. LncRNA GAS5 regulated nasopharyngeal carcinoma malignancy through targeting miR-4465 and modulating COX2. The GAS5/miR-4465/COX2 axis in nasopharyngeal carcinoma pathogenesis was confirmed, which would provide a new therapeutic target for nasopharyngeal carcinoma.


Assuntos
Ciclo-Oxigenase 2/metabolismo , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Adulto , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , RNA Longo não Codificante/genética , Transdução Genética , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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