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1.
Phytomedicine ; 128: 155378, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38507851

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a type of immune-mediated condition associated with intestinal homeostasis. Our preliminary studies disclosed that Cichorium intybus L., a traditional medicinal plant, also known as Chicory in Western countries, contained substantial phenolic acids displaying significant anti-inflammatory activities. We recognized the potential of harnessing Chicory for the treatment of IBD, prompting a need for in-depth investigation into the underlying mechanisms. METHODS: On the third day, mice were given 100, 200 mg/kg of total phenolic acids (PA) from Chicory and 200 mg/kg of sulfasalazine (SASP) via gavage, while dextran sodium sulfate (DSS) concentration was 2.5 % for one week. The study measured and evaluated various health markers including body weight, disease activity index (DAI), colon length, spleen index, histological score, serum concentrations of myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD), lipid oxidation (MDA), and inflammatory factors. We evaluated the TRP family and the NLRP3 inflammatory signaling pathways by Western blot, while 16S rDNA sequencing was used to track the effects of PA on gut microbes. RESULTS: It was shown that PA ameliorated the weight loss trend, attenuated inflammatory damage, regulated oxidative stress levels, and repaired the intestinal barrier in DSS mice. Analyses of Western blots demonstrated that PA suppressed what was expressed of transient receptor potential family TRPV4, TRPA1, and the expression of NLRP3 inflammatory signaling pathway, NLRP3 and GSDMD. In addition, PA exerted therapeutic effects on IBD by regulating gut microbiota richness and diversity. Meanwhile, the result of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis showed that gut microbiota was mainly related to Membrane Transport, Replication and Repair, Carbohydrate Metabolism and Amino Acid Metabolism. CONCLUSION: PA derived from Chicory may have therapeutic effects on IBD by regulating the TRPV4/NLRP3 signaling pathway and gut microbiome. This study provides new insights into the effects of phenolic acids from Chicory on TRP ion channels and gut microbiota, revealing previously unexplored modes of action.


Assuntos
Cichorium intybus , Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Hidroxibenzoatos , Raízes de Plantas , Transdução de Sinais , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Cichorium intybus/química , Transdução de Sinais/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Colite/tratamento farmacológico , Colite/induzido quimicamente , Raízes de Plantas/química , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Colo/efeitos dos fármacos , Colo/metabolismo , Extratos Vegetais/farmacologia , Sulfassalazina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Canais de Cátion TRPV/metabolismo
2.
Am J Chin Med ; 52(1): 1-33, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38351701

RESUMO

Obesity is a common metabolic syndrome that causes a significant burden on individuals and society. Conventional therapies include lifestyle interventions, bariatric surgery, and pharmacological therapies, which are not effective and have a high risk of adverse events. Acupuncture is an effective alternative for obesity, it modulates the hypothalamus, sympathetic activity and parasympathetic activity, obesity-related hormones (leptin, ghrelin, insulin, and CCK), the brain-gut axis, inflammatory status, adipose tissue browning, muscle blood flow, hypoxia, and reactive oxygen species (ROS) to influence metabolism, eating behavior, motivation, cognition, and the reward system. However, hypothalamic regulation by acupuncture should be further demonstrated in human studies using novel techniques, such as functional MRI (fMRI), positron emission tomography (PET), electroencephalogram (EEG), and magnetoencephalography (MEG). Moreover, a longer follow-up phase of clinical trials is required to detect the long-term effects of acupuncture. Also, future studies should investigate the optimal acupuncture therapeutic option for obesity. This review aims to consolidate the recent improvements in the mechanism of acupuncture for obesity as well as discuss the future research prospects and potential of acupuncture for obesity.


Assuntos
Terapia por Acupuntura , Obesidade , Humanos , Obesidade/etiologia , Terapia por Acupuntura/métodos , Tecido Adiposo , Imageamento por Ressonância Magnética/métodos
3.
J Vis Exp ; (200)2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37902367

RESUMO

The increase of circulating galactose-deficient IgA1 (Gd-IgA1) is caused by excessive activation of IgA-positive secretory cells in the process of mucosal immune responses, which is a critical link in the pathogenesis of IgA nephropathy (IgAN). Peyer's patch, the prominent place where B lymphocytes are transformed into IgA-secreting plasma cells, is the primary source of IgA. In addition, the lower expression of core 1ß-1,3-galactosyltransferase (C1GalT1) and its molecular chaperone, C1GalT1-specific molecular chaperone (Cosmc), is related to abnormal glycosylation of IgA1 in IgAN patients. Our clinical experience shows that Dioscoreae Nipponicae Rhizoma's (DNR) herbal medicine can relieve proteinuria and hematuria and improve renal function in IgAN patients. Dioscin (DIO) is one of the main active ingredients of DNR, which has various pharmacological activities. This study explores DIO's possible mechanism in treating IgAN.The IgAN model mouse was established by mucosal immune induction. The mice were divided into the control, model, and DIO gavage groups. The glomerular IgA deposition in mice, renal pathological changes, and B cell markers CD20 and CXCR5 expression in Peyer's patch were detected by immunofluorescence and immunohistochemistry. After lipopolysaccharide (LPS) stimulation, DIO's effects on DAKIKI cells proliferation, IgA and Gd-IgA1 secretion, C1GalT1, and Cosmc expression were studied by cell counting kit-8 (CCK-8) assay, enzyme-linked immunosorbent assay (ELISA) test, quantitative real-time polymerase chain reaction (QRT-PCR), and western blotting (WB). In in vivo studies, IgA deposition accompanied by glomerular mesangial hyperplasia and increased expression of CD20 and CXCR5 in Peyer's patch in the IgAN model mouse was alleviated by DIO. In vitro studies showed 0.25 µg/mL to 1.0 µg/mL DIO inhibited LPS-induced DAKIKI cell proliferation, IgA and Gd-IgA1 secretion, and up-regulated the mRNA and protein expression of C1GalT1 and Cosmc. This study demonstrates that DIO may reduce Gd-IgA1 production by inhibiting excessive activation of IgA-secreting cells and up-regulating C1GALT1/Cosmc expression.


Assuntos
Glomerulonefrite por IGA , Humanos , Animais , Camundongos , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/genética , Lipopolissacarídeos/farmacologia , Imunoglobulina A/metabolismo , Chaperonas Moleculares/metabolismo , Galactose/metabolismo
4.
Nat Prod Res ; 37(3): 508-513, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34546825

RESUMO

In this study, ethylenediaminetetraacetic acid (EDTA) disodium was first chosen as catalyst to convert psoralenoside (PO) to psoralen (PSO) for increasing the extraction yield of PSO. An efficient continuous system for synchronous transformation and extraction of PSO from fig leaves applying microwave-assisted EDTA disodium (MAE-EDTA) was developed. The optimal MAE-EDTA condition was obtained: EDTA disodium concentration of 0.07 mol·L-1, ethanol volume fraction of 56%, extraction time of 16 min, and extraction temperature of 70 °C by single factor experiments and response surface method (RSM). Under the optimal condition, the yield of PSO reached 27.24 mg·g-1. Compared with microwave-assisted ethanol extraction (MAE) and reflux extraction (RE), the yield of PSO by MAE-EDTA is 2.03-fold higher than RE and 1.70-fold higher than MAE. Therefore, MAE-EDTA is an efficient method for extracting PSO from fig leaves, and it might provide references for the extraction of PSO from other medicinal plants.


Assuntos
Ficus , Ficusina , Ácido Edético , Etanol , Folhas de Planta
5.
Int J Mol Sci ; 23(23)2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36499158

RESUMO

Neural-tube defects (NTDs) are one type of the most serious birth defects. Studies have shown that inositol deficiency is closely related to the occurrence of NTDs. Bone morphogenetic protein (BMP)-mediated Smad signaling pathways have been implicated in neurogenesis and neural-tube closure. However, the role of the BMP/Smad pathway in inositol-deficiency-induced NTDs remains unclear. Inositol-deficiency models in C57 mice and mouse neural stem cells (mNSCs) were induced with Li2CO3 treatment or inositol withdrawal. The role of the BMP/Smad pathway in the regulation of cell proliferation and the development of NTDs was determined utilizing qRT-PCR, HE staining, Western blot, immunostaining, MTT assay, EdU staining, and flow cytometry. The intraperitoneal injection of Li2CO3 at Embryonic Day 7.5 induced the occurrence of NTDs. The mRNA levels of Bmp2, Bmp4, Smad1, Smad5, Smad8 and Runx2, the phosphorylation of Smad1/5/8, and the nuclear translocation of Runx2 were significantly increased in NTD embryonic brain tissues and mNSCs exposed to Li2CO3 or an inositol-free medium, which were suppressed by BMP receptor selective inhibitor LDN-193189. The Li2CO3-induced phosphorylation of Smad1/5/8 was inhibited by inositol supplementation. Cell proliferation was significantly promoted by Li2CO3 exposure or the absence of inositol in mNSCs, which was reversed by LDN-193189. These results suggest that the activation of the BMP/Smad signaling pathway might play an important role in the development of NTDs induced by maternal Li2CO3 exposure via inositol deficiency.


Assuntos
Células-Tronco Neurais , Defeitos do Tubo Neural , Camundongos , Animais , Carbonato de Lítio/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Transdução de Sinais/fisiologia , Proteína Smad1/genética , Proteína Smad1/metabolismo
6.
Plant Cell Physiol ; 63(7): 967-980, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35536598

RESUMO

Plant High-affinity K+ transporters/K+ uptake permeases/K+ transporters (HAK/KUP/KT) transporters have been predicted as membrane H+-K+ symporters in facilitating K+ uptake and distribution, while their role in seed production remains to be elucidated. In this study, we report that OsHAK26 is preferentially expressed in anthers and seed husks and located in the Golgi apparatus. Knockout of either OsHAK26 or plasma membrane located H+-K+ symporter gene OsHAK1 or OsHAK5 in both Nipponbare and Dongjin cultivars caused distorted anthers, reduced number and germination rate of pollen grains. Seed-setting rate assay by reciprocal cross-pollination between the mutants of oshak26, oshak1, oshak5 and their wild types confirmed that each HAK transporter is foremost for pollen viability, seed-setting and grain yield. Intriguingly, the pollens of oshak26 showed much thinner wall and were more vulnerable to desiccation than those of oshak1 or oshak5. In vitro assay revealed that the pollen germination rate of oshak5 was dramatically affected by external K+ concentration. The results suggest that the role of OsHAK26 in maintaining pollen development and fertility may relate to its proper cargo sorting for construction of pollen walls, while the role of OsHAK1 and OsHAK5 in maintaining seed production likely relates to their transcellular K+ transport activity.


Assuntos
Oryza , Fertilidade , Regulação da Expressão Gênica de Plantas , Proteínas de Membrana Transportadoras/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pólen/genética , Pólen/metabolismo , Potássio/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-34956376

RESUMO

Although bone marrow mesenchymal stem cells (BMMSCs) are effective in treating chronic bacterial prostatitis (CBP), the homing of BMMSCs seems to require ultrasound induction. Dihydroartemisinin (DHA) is an important derivative of artemisinin (ART) and has been previously reported to alleviate inflammation and autoimmune diseases. But the effect of DHA on chronic prostatitis (CP) is still unclear. This study aims to clarify the efficacy and mechanism of DHA in the treatment of CBP and its effect on the accumulation of BMMSCs. The experimental CBP was produced in C57BL/6 male mice via intraurethrally administered E. coli solution. Results showed that DHA treatment concentration-dependently promoted the accumulation of BMMSCs in prostate tissue of CBP mice. In addition, DHA and BMMSCs cotreatment significantly alleviated inflammation and improved prostate damage by decreasing the expression of proinflammatory factors such as TNF-α, IL-1ß, and chemokines CXCL2, CXCL9, CXCL10, and CXCL11 in prostate tissue of CBP mice. Moreover, DHA and BMMSCs cotreatment displayed antioxidation property by increasing the production of glutathione peroxidase (GSH-Px), SOD, and decreasing malondialdehyde (MDA) expression. Mechanically, DHA and BMMSCs cotreatment significantly inhibited the expression of TGFß-RI, TGFß-RII, phosphor (p)-Smad2/3, and Smad4 in a dose-dependent manner while stimulated Smad7 expression in the same manner. In conclusion, our findings provided evidence that DHA effectively eliminated inflammatory and oxidative stress against prostate injury, and this effect involved the TGF-ß/Smad signaling pathway in CBP.

8.
Bioorg Chem ; 114: 105222, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34375196

RESUMO

Seven new diterpenoids, eupholenes A-G (1-7), including two presegetanes (1 and 2), four jatrophanes (3-6), and one paraliane (7), along with 19 known analogues (8-26) were obtained by anti-liver fibrosis bioassay-guided isolation of Euphorbia sieboldiana. Their structures were elucidated by extensive spectroscopic data analyses, chemical methods, ECD calculations, and single-crystal X-ray diffractions. Euphorbesulin A (10), a presegetane diterpenoid (5/9/5 ring system), was identified as a promising anti-liver fibrosis agent that could inhibit the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagen I in TGF-ß1-stimulated LX-2 cells at a micromolar level. Mechanistic study revealed that 10 suppressed liver fibrosis via inhibition of TGF-ß/Smad signaling pathway, and its potential target was TGF-ß type I receptor. These findings suggested that presegetane diterpenoid could serve as a new type of structural motif in future anti-liver fibrosis drug development.


Assuntos
Diterpenos/farmacologia , Euphorbia/química , Cirrose Hepática/tratamento farmacológico , Extratos Vegetais/farmacologia , Proteínas Smad/antagonistas & inibidores , Fator de Crescimento Transformador beta/antagonistas & inibidores , Células Cultivadas , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo
9.
Chin J Integr Med ; 27(9): 643-648, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34105098

RESUMO

Monoclonal gammopathy of renal significance (MGRS) is a pathological state which presents with a spectrum of renal lesions. MGRS is characterized by pathogenic monoclonal immunoglobulins or light chains produced by a premalignant plasma cell or B cell clone. In view of inadequate understanding in the past, the low detection rate of MGRS often results in poor outcomes and reduces quality of life of patients. Thus, MGRS stands for a group of clinical refractory renal diseases. To date, no standard treatment strategy for MGRS is available. Current consensus suggests a clone-directed approach that aims to eradicate the offending clone, but its long-term prognosis is not clear. In this article, we discuss the diagnostic methods, highlight treatment advances, and introduce integrated Chinese and Western medicine in the management of MGRS.


Assuntos
Nefropatias , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , China , Humanos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/terapia , Qualidade de Vida
10.
J Pharm Biomed Anal ; 201: 114090, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33933704

RESUMO

A comprehensive method for the evaluation of Acanthopanax senticosus (AS) was established by the quantitative analysis of multiple components by single marker (QAMS), fingerprint, similarity analysis (SA), hierarchical cluster analysis (HCA), and factor analysis (FA) based on high performance liquid chromatography (HPLC). A total of 27 common peaks were identified in the standard fingerprint of 20 batches of AS from different regions in China, of which 8 peaks were identified as protocatechuic acid, syringin, chlorogenic acid, caffeic acid, eleutheroside E, hyperoside, isofrqxidin, and acacetin, and the concentrations of these eight components were determined simultaneously by QAMS. The results showed that the QAMS method was effective and feasible compared with the external standard method (ESM) (RD < 3.3 %, P ≤ 0.01). Sample 1 (S1) was used as the reference chromatogram, the similarity of other samples was between 0.765 and 0.968. Through HCA, AS could be mainly divided into two production areas, the north Liaoning (including Liaoning) and the south Liaoning areas. Furthermore, FA showed that the quality of AS in the north Liaoning area was better than that in the south Liaoning area. In summary, the method established in this study can comprehensively and systematically evaluate quality differences in AS samples, and may be used to help to improve the quality control of AS.


Assuntos
Medicamentos de Ervas Chinesas , Eleutherococcus , China , Cromatografia Líquida de Alta Pressão , Análise de Dados , Medicamentos de Ervas Chinesas/análise
11.
Zhongguo Zhen Jiu ; 41(2): 149-52, 2021 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-33793110

RESUMO

OBJECTIVE: To observe the clinical therapeutic effect of electroacupuncture (EA) combined with tamsulosin hydrochloride sustained release capsule on chronic prostatitis (CP) of damp and heat stasis. METHODS: A total of 70 patients with CP of damp and heat stasis were randomized into an acupuncture plus medication group (35 cases, 4 cases dropped off) and a medication group (35 cases, 5 cases dropped off). In the medication group, tamsulosin hydrochloride sustained release capsule was given orally, 0.2 mg a time, once each night. On the basis of treatment in the medication group, EA was applied at Guanyuan (CV 4), Sanyinjiao (SP 6) and Yinglingquan (SP 9), with disperse-dense wave, 5 mA in intensity for 30 min. Treatment for 30 days was as one course, and totally 3 courses were required in both groups. Before treatment, 1, 2, 3 months into treatment and at the follow-up of 2 months after treatment, the TCM syndrome score and National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score were observed, and the clinical efficacy was evaluated in both groups. RESULTS: Compared before treatment, the TCM syndrome scores of 3 months into treatment and follow-up were decreased in the acupuncture plus medication group (P<0.01), and were lower than those in the medication group (P<0.05). Compared before treatment, the NIH-CPSI scores of 3 months into treatment and follow-up were decreased in both groups (P<0.01), and those in the acupuncture plus medication group were lower than the medication group (P<0.05). The total effective rate was 90.3% (28/31) in the acupuncture plus medication group, which was superior to 80.0% (24/30) in the medication group (P<0.05). CONCLUSION: Acupuncture combined with medication can improve the clinical symptoms in patients with CP of damp and heat stasis, and its therapeutic effect is superior to simple western medication.


Assuntos
Terapia por Acupuntura , Prostatite , Pontos de Acupuntura , Doença Crônica , Temperatura Alta , Humanos , Masculino , Prostatite/tratamento farmacológico , Resultado do Tratamento
12.
Chinese Journal of Cardiology ; (12): 340-344, 2021.
Artigo em Chinês | WPRIM | ID: wpr-941284

RESUMO

Objective: To investigate the safety and efficacy of ultrafiltration on diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance. Methods: This was a single-center randomized controlled trial. A total of 148 heart failure patients with reduced ejection fraction admitted to the Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region from June 2010 to June 2020 were enrolled in this study, and these patients were randomly divided (ratio 1:1) into the ultrafiltration group (n=74) and the control group (n=74). All patients were treated with diuretics, cardiotonic, vasodilator and other comprehensive drugs according to relevant guidelines. After grouping, the patients in the control group were treated with standard treatment plan, while patients in the ultrafiltration group were treated with ultrafiltration on top of standard therapy. Diuretic drugs were discontinued during ultrafiltration, and intravenously furosemide (40 mg) was given immediately and 24 hours after the end of ultrafiltration. Clinical data including gender, age, complicated diseases, New York Heart Association (NYHA) function classification, etc. were collected. Effectiveness indicators include urine volume (the first 12-hour and 24-hour urine volume and the second 24-hour urine volume after using diuretic), body weight and dyspnea severity score. Safety indicators include systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration and the number of deaths before and after intervention. Results: Two patients in the control group died due to worsening heart failure after randomization and were excluded in this study, 146 patients were finally analyzed (72 patients in the control group and 74 patients in the ultrafiltration group). There were 93 males, and the age was (68.3±11.2) years. There was no significant difference between patients in the ultrafiltration group and the control group in gender, age, body weight, course of disease, dyspnea severity score, NYHA function classification Ⅲ/Ⅳ, the proportion of patients with severe edema of both lower limbs, the proportion of patients with complicated diseases, and basic medication (all P>0.05). After using diuretics, the urine volume of the first 12-hour and 24-hour and the second 24-hour were significantly higher in the ultrafiltration group than in the control group (all P<0.05). Body weight decreased significantly after ultrafiltration treatment as compared with that before intervention in the ultrafiltration group (P<0.05). Compared with the control group, the dyspnea severity score was significantly improved in the ultrafiltration group (P<0.05). There was no significant difference in systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration of patients between ultrafiltration group and control group before and after intervention (all P>0.05). During the clinical diagnosis and treatment, 2 male patients in the control group died, and the cause of death was aggravation of basic diseases complicated with acute heart failure and cardiogenic shock. There was no death in the ultrafiltration group, and there were no obvious clinical adverse events during and after ultrafiltration. Conclusion: Ultrafiltration therapy is safe and can improve diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance.


Assuntos
Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Diuréticos/uso terapêutico , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Ultrafiltração
13.
Clin Cancer Res ; 26(18): 5007-5018, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32611647

RESUMO

PURPOSE: To evaluate the prognostic value of posttreatment fibrosis in human PDAC patients, and to compare a type I collagen targeted MRI probe, CM-101, to the standard contrast agent, Gd-DOTA, for their abilities to identify FOLFIRINOX-induced fibrosis in a murine model of PDAC. EXPERIMENTAL DESIGN: Ninety-three chemoradiation-treated human PDAC samples were stained for fibrosis and outcomes evaluated. For imaging, C57BL/6 and FVB mice were orthotopically implanted with PDAC cells and FOLFIRINOX was administered. Mice were imaged with Gd-DOTA and CM-101. RESULTS: In humans, post-chemoradiation PDAC tumor fibrosis was associated with longer overall survival (OS) and disease-free survival (DFS) on multivariable analysis (OS P = 0.028, DFS P = 0.047). CPA increased the prognostic accuracy of a multivariable logistic regression model comprised of previously established PDAC risk factors [AUC CPA (-) = 0.76, AUC CPA (+) = 0.82]. In multiple murine orthotopic PDAC models, FOLFIRINOX therapy reduced tumor weight (P < 0.05) and increased tumor fibrosis by collagen staining (P < 0.05). CM-101 MR signal was significantly increased in fibrotic tumor regions. CM-101 signal retention was also increased in the more fibrotic FOLFIRINOX-treated tumors compared with untreated controls (P = 0.027), consistent with selective probe binding to collagen. No treatment-related differences were observed with Gd-DOTA imaging. CONCLUSIONS: In humans, post-chemoradiation tumor fibrosis is associated with OS and DFS. In mice, our MR findings indicate that translation of collagen molecular MRI with CM-101 to humans might provide a novel imaging technique to monitor fibrotic response to therapy to assist with prognostication and disease management.


Assuntos
Carcinoma Ductal Pancreático/terapia , Quimiorradioterapia Adjuvante , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Pâncreas/patologia , Neoplasias Pancreáticas/terapia , Idoso , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Colágeno/análise , Colágeno/metabolismo , Intervalo Livre de Doença , Feminino , Fibrose , Fluoruracila/administração & dosagem , Seguimentos , Compostos Heterocíclicos/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Masculino , Camundongos , Pessoa de Meia-Idade , Imagem Molecular/métodos , Sondas Moleculares/administração & dosagem , Recidiva Local de Neoplasia/prevenção & controle , Compostos Organometálicos/administração & dosagem , Oxaliplatina/administração & dosagem , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Trials ; 21(1): 31, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907076

RESUMO

BACKGROUND: IgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie formula (YQF; a compound recipe of Chinese medicinal herbs) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we have designed a prospective double-blind randomized placebo-controlled trial. METHODS/DESIGN: The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until study completion (3 years). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment, or death due to chronic kidney disease (CKD) during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR slope, ml/min per 1.73 m2 per year), which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria < 0.5 g/day) at weeks 24, 36, and 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated at week 48. Safety monitoring and assessment will be undertaken during the study. DISCUSSION: The TCM-WINE study will evaluate the effects and safety of YQF combined therapy compared with immunosuppression monotherapy on the basis of the optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective, and safe Chinese characteristic therapy for high-risk IgAN patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03418779. Registered on 18 June 2018.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/administração & dosagem , Falência Renal Crônica/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/mortalidade , Glomerulonefrite por IGA/patologia , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/imunologia , Falência Renal Crônica/patologia , Falência Renal Crônica/terapia , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Substituição Renal/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
15.
Nat Prod Res ; 34(19): 2729-2736, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30887848

RESUMO

Chemical investigation of the aerial parts of Mikania micrantha led to the isolation of eight sesquiterpenoids and ten diterpenoids, including five cadinane sesquiterpenoids (1-5), three bisabolene sesquiterpenoids (6 - 8), nine ent-kaurane diterpenoids (9-17), and an abietane diterpenoid (18). Among them, 1 - 3 are new and feature a rare lactone or furan ring derived from C-6 isopropyl group side chain. Compound 18 was isolated from genus Mikania for the first time, and was also the first example of abietane-type diterpenoids from this plant. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HRESIMS, and ECD). All compounds were examined for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophage cells, and compound 18 exhibited pronounced inhibition on NO production (IC50 = 11.04 µM), being comparable to the positive control, quercetin (IC50 = 11.15 µM).


Assuntos
Abietanos/isolamento & purificação , Diterpenos do Tipo Caurano/isolamento & purificação , Mikania/química , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Animais , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/antagonistas & inibidores , Células RAW 264.7 , Ácidos Tri-Iodobenzoicos
16.
Stress ; 23(1): 105-115, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31418329

RESUMO

Transcendental meditation (TM) is effective in alleviating stress and anxiety and promoting well-being. While the underlying biological mechanisms of TM are not yet fully explored, the hypothalamic-pituitary-adrenal (HPA) axis represents an index providing important clues embodying the stress system cascade. In this pilot study, young adults were randomly assigned to TM training followed by 8 weeks of meditation practice or a wait-list control condition. TM was conducted over 8 weeks. Thirty-four young adult participants were randomized; 27 participants completed the HPA outcome assessments (41% male). To assess HPA axis functioning, salivary samples to assess cortisol awakening response (CAR) that were collected in the morning, both at baseline and at week-4. Salivary cortisol in the context of a social stressor using the Trier Social Stress Test (TSST) was collected at week-8. The results indicate that participants who were randomly assigned to TM had lower awakening salivary cortisol levels and a greater drop in CAR from baseline to week-4 than the control group. There were no significant differences in HPA axis functioning in the context of the TSST. Primary limitations of this randomized controlled trial were the small sample size, the use of a wait-list as opposed to an active control, and the limited scope of HPA axis assessments. The results of this pilot study provide tentative evidence that TM may impact biological stress system functioning and suggests that this may be a worthwhile avenue to continue to examine. It will also be useful to extend these findings to a broader array of meditative and mindful practices, particularly for those who are experiencing more distress.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Meditação/psicologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/terapia , Ansiedade/psicologia , Feminino , Humanos , Hidrocortisona , Masculino , Atenção Plena , Projetos Piloto , Saliva , Estresse Psicológico/psicologia , Adulto Jovem
17.
Artigo em Chinês | WPRIM | ID: wpr-873098

RESUMO

Objective::To establish a scientific and reasonable grade evaluation standard for Polygoni Multiflori Caulis. Method::The quality constant method was used to conduct a grade evaluation study on Polygoni Multiflori Caulis. A total of 16 batches of samples were collected from Chinese herbal slices enterprises and medicinal materials markets. By measuring its appearance traits (average quality and average thickness of the decoction pieces) and the intrinsic quality indicators (content of 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-D-glucoside), then its quality constant and percentage quality constant were calculated comprehensively, finally, the grades of Polygoni Multiflori Caulis were classified by quality constant method. Result::The quality constant of 16 batches of the decoction pieces was 0.054-0.417, and the percentage quality constant was 12.98-100.00.If these samples were divided into three grades, the quality constant shall be ≥0.334 for the first-grade decoction pieces, the quality constant shall be <0.334 and ≥0.209 for the second-grade decoction pieces, while for the third-grade decoction pieces, the quality constant shall be <0.209. Conclusion::The grade evaluation method based on quality constant can overcome the shortcomings of traditional evaluation method for decoction pieces, and can realize scientific, objective and simple classification of Polygoni Multiflori Caulis. This study enriches the research data of modern grade evaluation of Polygoni Multiflori Caulis, and provides reference for grade evaluation and market circulation of other decoction pieces.

18.
Chin J Integr Med ; 25(3): 163-167, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30815804

RESUMO

Chronic kidney disease (CKD) is a clinical syndrome with a series of clinical manifestations and metabolic disorders caused by many diseases, which are characterized by progressive deterioration or irreversible damage of renal structures and functions. With the progress of epidemiological research, CKD has brought about huge economic and psychological burdens. There is a considerable risk of cardiovascular events or death than progression to end-stage renal disease for patients. Particular attentions should be paid to the new goals of reducing cardiovascular events and all-cause mortality. It is important to analyze the etiology and pathogenesis according to patients' ages, regions, primary disease as well as different stages of disease, and choose the appropriate therapeutic strategies accordingly. In clinical practice, due to the uncertainty of therapeutic effects of modern medicine based on the risk factors, it is necessary to use Chinese medicine (CM) to delay the disease progression and reduce comorbidities. Turbid toxin and blood stasis are two critical pathological factors worthy of concerns in the theory of CM. In addition, appropriate use of CM may help improve the quality of life of patients with CKD.


Assuntos
Medicina Tradicional Chinesa , Insuficiência Renal Crônica/tratamento farmacológico , Hemostasia , Humanos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/prevenção & controle
19.
FASEB J ; 33(4): 4688-4702, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30592646

RESUMO

Folate deficiency in early development leads to disturbance in multiple processes, including neurogenesis during which fibroblast growth factor (FGF) pathway is one of the crucial pathways. Whether folic acid (FA) directly affects FGF pathways to influence neurodevelopment and the possible mechanism remains unclear. In this study, we presented evidence that in human FA-insufficient encephalocele, the FGF pathway was interfered. Furthermore, in Brachyury knockout mice devoid of such T-box transcription factors regulating embryonic neuromesodermal bipotency and a key component of FGF pathway, change in expression of Brachyury downstream targets, activator Fgf8 and suppressor dual specificity phosphatase 6 was detected, along with the reduction in expression of other key FGF pathway genes. By using a FA-deficient cell model, we further demonstrated that decrease in Brachyury expression was through alteration in hypermethylation at the Brachyury promoter region under FA deficiency conditions, and suppression of Brachyury promoted the inactivation of the FGF pathway. Correspondingly, FA supplementation partially reverses the effects seen in FA-deficient embryoid bodies. Lastly, in mice with maternal folate-deficient diets, aberrant FGF pathway activity was found in fetal brain dysplasia. Taken together, our findings highlight the effect of FA on FGF pathways during neurogenesis, and the mechanism may be due to the low expression of Brachyury gene via hypermethylation under FA-insufficient conditions.-Chang, S., Lu, X., Wang, S., Wang, Z., Huo, J., Huang, J., Shangguan, S., Li, S., Zou, J., Bao, Y., Guo, J., Wang, F., Niu, B., Zhang, T., Qiu, Z., Wu, J., Wang, L. The effect of folic acid deficiency on FGF pathway via Brachyury regulation in neural tube defects.


Assuntos
Proteínas Fetais/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Deficiência de Ácido Fólico/metabolismo , Ácido Fólico/uso terapêutico , Defeitos do Tubo Neural/tratamento farmacológico , Defeitos do Tubo Neural/metabolismo , Proteínas com Domínio T/metabolismo , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Imunoprecipitação da Cromatina , Encefalocele/metabolismo , Feminino , Deficiência de Ácido Fólico/fisiopatologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regiões Promotoras Genéticas , Transdução de Sinais/efeitos dos fármacos , Sulfitos/farmacologia
20.
Artigo em Chinês | WPRIM | ID: wpr-773176

RESUMO

To establish a quality constant evaluation system of Alismatis Rhizoma decoction pieces,in order to provide reference for regulating the market circulation of this decoction pieces. A total of 18 batches of Alismatis Rhizoma decoction pieces were collected from different pharmaceutical factories,and the morphological parameters of each sample were tested. The content of alisol B 23-acetate in Alismatis Rhizoma decoction pieces was determined by HPLC in the 2015 edition of Chinese Pharmacopoeia,and the parameters such as quality constant and relative quality constant were calculated. The quality constant range of 18 batches of Alismatis Rhizoma decoction pieces was 0. 390-2. 076. If 18 batches of Alismatis Rhizoma decoction pieces were divided into 3 grades,taking 80% of the maximum quality constant as first grade,50% to 80% as second grade,and the rest as third grade,then the quality constant of firstgrade samples was ≥1. 66,the quality constant of second-grade samples was ≥1. 04 and <1. 66,and the quality constant of third-grade samples was <1. 04. The established quality constant evaluation method is objective and feasible,which can be used to classify the grade of Alismatis Rhizoma decoction pieces and provide a reference method to control the quality of this decoction pieces.


Assuntos
Alisma , Química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Padrões de Referência , Controle de Qualidade , Rizoma , Química
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