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1.
Artigo em Inglês | MEDLINE | ID: mdl-38401107

RESUMO

Objective: Parkinson's disease is a brain disorder that can cause mobility problems as well as mental health, sleep, pain and other health problems. To analyze the establishment of a platform for Parkinson's patients to cooperate with intelligent health education based on behavior change theory and the corresponding nursing measures. Methods: 80 patients with Parkinson's disease in the Affiliated Brain Hospital of Nanjing Medical University from October 2021 to September 2022 were selected and included in the conventional and wisdom education groups according to different health education methods, with 40 patients in each group. The conventional education group carried out routine health education and nursing. Based on routine health education and nursing, the wisdom education group established a smart health education platform based on behavior change theory. It implemented corresponding health education and nursing measures. The knowledge, belief and practice (KAP score), psychological status, self-efficacy [General self-efficacy scale (GSES) score], motor function [Parkinson's disease Uniform Scoring Scale (UPDRS) - III score], daily living ability (Barthel index), sleep quality (PSQI score), quality of life (QOL score), complication rate (pressure sores, constipation, bruises), and education satisfaction of the two groups were compared. Results: The KAP score of the wisdom education group after health education was higher than that of the conventional education group (P < .05); The SAS and SDS scores of the wisdom education group after health education were lower than those of the conventional education group (P < .05); The GSES score of the wisdom education group after health education was higher than that of the conventional education group (P < .05); The UPDRS - III score of the wisdom education group after health education was lower than that of the conventional education group, and the Barthel index was higher than that of the conventional education group, P < .05; The PSQI score of the wisdom education group after health education was lower than that of the conventional education group, and the QOL score was higher than that of the conventional education group, P < .05; The incidence of complications in the wisdom education group was lower than that in the conventional education group (P < .05); The satisfaction of the wisdom education group was higher than that of the conventional education group (P < .05). Conclusion: The establishment of an intelligent health education platform based on behavior change theory for Parkinson's patients and the implementation of corresponding health education and nursing measures can significantly improve the knowledge, belief, practice, and psychological status of patients. This will be helpful for those patients and clinicians. There are also limitations, such as little numbers of patients and no mechanisms.

2.
J Clin Gastroenterol ; 58(2): 120-130, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37682003

RESUMO

BACKGROUND: Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen in a pressurized chamber, increasing tissue oxygen levels and regulating inflammatory pathways. Mounting evidence suggests that HBOT may be effective for inflammatory bowel disease. Our systematic review and meta-analysis aimed to quantify the efficacy and safety of HBOT in fistulizing Crohn's disease (CD). METHODS: A systematic review was conducted using the EMBASE, Web of Science, Pubmed, and Cochrane Library databases according to the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" criteria. Study bias was assessed using the Cochrane Handbook guidelines. RESULTS: Sixteen studies with 164 patients were included in the analysis. For all fistula subtypes, the pooled overall clinical response was 87% (95% CI: 0.70-0.95, I2 = 0) and the pooled clinical remission was 59% (95% CI: 0.35-0.80, I2 = 0). The overall clinical response was 89%, 84%, and 29% for perianal, enterocutaneous, and rectovaginal fistulas, respectively. On meta-regression, hours in the chamber and the number of HBOT sessions were not found to correlate with clinical response. The pooled number of adverse events was low at 51.7 per 10,000 HBOT sessions for all fistula types (95% CI: 16.8-159.3, I2 = 0). The risk of bias was observed across all studies. CONCLUSION: HBOT is a safe and potentially effective treatment option for fistulizing CD. Randomized control trials are needed to substantiate the benefit of HBOT in fistulizing CD.


Assuntos
Doença de Crohn , Oxigenoterapia Hiperbárica , Feminino , Humanos , Doença de Crohn/terapia , Fístula/terapia , Oxigenoterapia Hiperbárica/efeitos adversos , Oxigênio/uso terapêutico , Resultado do Tratamento
3.
Medicine (Baltimore) ; 102(48): e36425, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050285

RESUMO

Lumbar disc herniation (LDH) is a common cause of pain in the lumbar spine and legs. While acupuncture has become the primary conservative treatment for LDH, some patients experience treatment failure and require surgery, causing substantial concern for clinicians. We developed an effective personalized clinical prediction model to identify the independent risk factors associated with acupuncture failure in patients with LDH. Our model aimed to predict the probability of surgery within 6 months of acupuncture failure in patients with LDH. A total of 738 patients with LDH who underwent acupuncture at 4 Chinese hospitals between January 2019 and October 2021 were selected. The patients were divided into training (n = 496) and validation (n = 242) cohorts. Seven predictive variables, including smoking, Oswestry Disability Index (ODI) score, lower-limb herniation, disc herniation type, lumbar spinal stenosis, lumbar lateral recess stenosis, and acupuncture frequency, were selected as risk factors using least absolute shrinkage and selection operato (LASSO) regression. A prediction model was developed using multivariate logistic regression analysis and a nomogram was constructed. The model exhibited good discrimination, with an area under the ROC curve (AUC) of 0.903 for the development cohort and 0.899 for the validation cohort. The Hosmer-Lemeshow goodness-of-fit test was a good fit for both cohorts (P = .956 for the development cohort; P = .513 for the validation cohort). Decision curve analysis (DCA) demonstrated that the threshold probabilities for the 2 cohorts ranged from > 4% and 5-95%, respectively. Therefore, the prediction model had a good net benefit. The nomogram established in this study, incorporating 7 risk factors, demonstrated a good predictive ability. It could predict acupuncture failure in LDH patients and the risk of surgery within 6 months, enabling physicians to conduct individualized treatment measures.


Assuntos
Terapia por Acupuntura , Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/terapia , Deslocamento do Disco Intervertebral/cirurgia , Prognóstico , Resultado do Tratamento , Modelos Estatísticos , Fatores de Risco , Vértebras Lombares/cirurgia , Nomogramas
4.
Nat Mater ; 22(7): 853-859, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37349395

RESUMO

III-nitride wide bandgap semiconductors are promising materials for modern optoelectronics and electronics. Their application has progressed greatly thanks to the continuous quality improvements of heteroepitaxial films grown on large-lattice-mismatched foreign substrates. But compared with bulk single crystals, there is still tremendous room for the further improvement of the material quality. Here we show a paradigm to achieve high-quality III-nitride heteroepitaxial films by the controllable discretization and coalescence of columns. By adopting nano-patterned AlN/sapphire templates with regular hexagonal holes, discrete AlN columns coalesce with uniform out-of-plane and in-plane orientations guaranteed by sapphire nitridation pretreatment and the ordered lateral growth of cleavage facets, which efficiently suppresses the regeneration of threading dislocations during coalescence. The density of dislocation etch pits in the AlN heteroepitaxial film reaches 3.3 × 104 cm-2, close to the present available AlN bulk single crystals. This study facilitates the growth of bulk-class quality III-nitride films featuring low cost and scalability.


Assuntos
Óxido de Alumínio , Eletrônica , Semicondutores , Software
5.
FASEB J ; 37(5): e22916, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37073611

RESUMO

Liver fibrosis is closely related to the proliferation and differentiation of liver progenitor cells (LPCs). Yes-associated protein (YAP) is a key effector molecule of the Hippo signaling pathway and plays an important role in regulating cell proliferation and liver homeostasis. However, its role in LPCs proliferation and differentiation during liver fibrosis are not well understood. Using immunohistochemistry, immunofluorescence staining, quantitative PCR and Western blotting, we discovered that LPCs expansion and enhanced YAP expression in LPCs in either choline-deficient, ethionine-supplemented (CDE) diet or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced fibrotic mice, as well as in patients with liver fibrosis. By injecting adeno-associated virus vectors under the transcriptional control of Lgr5 promoter, we found that targeted knockdown of YAP in LPCs attenuated the CDE/DDC diet-induced ductular reaction and liver fibrosis. Using EdU incorporation and Cell Counting Kit-8 assays, we demonstrated that YAP can modulate LPCs proliferation. Importantly, spleen transplantation of YAP-overexpressing LPCs improved their ability to differentiate into hepatocytes and alleviated carbon tetrachloride-induced liver fibrosis. Collectively, our findings indicate that LPCs expansion and differentiation during liver fibrosis could be modulated by YAP, further suggesting the possibility of manipulating YAP expression in LPCs as a potential treatment for chronic liver diseases.


Assuntos
Cirrose Hepática , Proteínas de Sinalização YAP , Animais , Camundongos , Cirrose Hepática/metabolismo , Fígado/metabolismo , Hepatócitos/patologia , Células-Tronco/patologia , Diferenciação Celular , Proliferação de Células
6.
Plants (Basel) ; 12(7)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37050142

RESUMO

Sustainable control of mosquitoes, vectors of many pathogens and parasites, is a critical challenge. Chemical insecticides are gradually losing their effectiveness because of development of resistance, and plant metabolites are increasingly being recognized as potential alternatives to chemical insecticides. This study aimed to analyze the main components of Perilla frutescens essential oil (PE-EO), investigate the specific activity of PE-EO as a botanical insecticide and mosquito repellent, and explore whether its main constituents are potential candidates for further research. The larvicidal activity assay showed that LC50 of PE-EO and 2-hexanoylfuran was 45 and 25 mg/L, respectively. In the ovicidal activity assay, both 120 mg/L PE-EO and 80 mg/L 2-hexanoylfuran could achieve 98% egg mortality. Moreover, PE-EO and 2-hexanoylfuran showed repellency and oviposition deterrence effects. Notably, 10% PE-EO maintained a high rate of protection for 360 min. Although PE-EO and its main component had certain toxic effects on zebrafish, no significant harmful effects were detected in human embryonic kidney cells. Therefore, perilla essential oil is an effective agent for mosquito control at several life stages and that its main component, 2-hexanoylfuran, is a potential candidate for developing novel plant biopesticides.

7.
N Engl J Med ; 388(13): 1191-1200, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36988594

RESUMO

BACKGROUND: Approximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis. METHODS: We conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. Patients were assigned (in a 1:1 ratio) to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All the patients received concomitant ciprofloxacin from weeks 1 to 4. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Other efficacy end points included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of ≥2 points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of ≤6 and a reduction from baseline of ≥3 points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings. RESULTS: Among the 102 patients who underwent randomization, the incidence of mPDAI-defined remission at week 14 was 31% (16 of 51 patients) with vedolizumab and 10% (5 of 51 patients) with placebo (difference, 21 percentage points; 95% confidence interval [CI], 5 to 38; P = 0.01). Differences in favor of vedolizumab over placebo were also seen with respect to mPDAI-defined remission at week 34 (difference, 17 percentage points; 95% CI, 0 to 35), mPDAI-defined response at week 14 (difference, 30 percentage points; 95% CI, 8 to 48) and at week 34 (difference, 22 percentage points; 95% CI, 2 to 40), and PDAI-defined remission at week 14 (difference, 25 percentage points; 95% CI, 8 to 41) and at week 34 (difference, 19 percentage points; 95% CI, 2 to 37). Serious adverse events occurred in 3 of 51 patients (6%) in the vedolizumab group and in 4 of 51 patients (8%) in the placebo group. CONCLUSIONS: Treatment with vedolizumab was more effective than placebo in inducing remission in patients who had chronic pouchitis after undergoing IPAA for ulcerative colitis. (Funded by Takeda; EARNEST ClinicalTrials.gov number, NCT02790138; EudraCT number, 2015-003472-78.).


Assuntos
Colite Ulcerativa , Fármacos Gastrointestinais , Pouchite , Proctocolectomia Restauradora , Adulto , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Ciprofloxacina/administração & dosagem , Ciprofloxacina/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/cirurgia , Pouchite/tratamento farmacológico , Pouchite/etiologia , Doença Crônica , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Proctocolectomia Restauradora/efeitos adversos , Método Duplo-Cego , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Administração Intravenosa , Quimioterapia Combinada
8.
J Exp Bot ; 73(22): 7285-7297, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-36112496

RESUMO

The majority of plant protein in the world's food supply is derived from soybean (Glycine max). Soybean is a key protein source for global animal feed and is incorporated into plant-based foods for people, including meat alternatives. Soybean protein content is genetically variable and is usually inversely related to seed oil content. ABI3-interacting protein 2 (AIP2) is an E3-RING ubiquitin ligase that targets the seed-specific transcription factor ABI3. Silencing both soybean AIP2 genes (AIP2a and AIP2b) by RNAi enhanced seed protein content by up to seven percentage points, with no significant decrease in seed oil content. The protein content enhancement did not alter the composition of the seed storage proteins. Inactivation of either AIP2a or AIP2b by a CRISPR-Cas9-mediated mutation increased seed protein content, and this effect was greater when both genes were inactivated. Transactivation assays in transfected soybean hypocotyl protoplasts indicated that ABI3 changes the expression of glycinin, conglycinin, 2S albumin, and oleosin genes, indicating that AIP2 depletion increased seed protein content by regulating activity of the ABI3 transcription factor protein. These results provide an example of a gene-editing prototype directed to improve global food security and protein availability in soybean that may also be applicable to other protein-source crops.


Assuntos
Sistemas CRISPR-Cas , Proteínas de Soja , Proteínas de Soja/genética , Sementes/genética , Fatores de Transcrição , Óleos de Plantas , Ubiquitina , Ligases
9.
Biochim Biophys Acta Mol Basis Dis ; 1868(11): 166510, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35926755

RESUMO

Previously, we reported that the nuclear translocation of Y-box binding protein 1 (YB-1) is induced by transforming growth factor-ß (TGF-ß) and promotes hepatic progenitor cells (HPCs) expansion. Here, we explored the mechanisms underlying YB-1 translocation and the impact of YB-1 on the epithelial-mesenchymal transition (EMT) in HPCs. YB-1flox/floxcre+/- (YB-1f/fcre+/-) mice and YB-1f/fcre-/- mice were fed with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or a choline-deficient, ethionine-supplemented (CDE) diet. Liver injury and fibrosis were assessed by performing hematoxylin and eosin (HE) and Masson staining. The expression of collagen and EMT-related markers (E-cadherin, N-cadherin, and Snail) was detected by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence analyses. Protein kinase B (AKT) expression in HPCs was silenced via RNA interference. Nuclear YB-1 expression in HPCs was detected via western blotting and immunofluorescence analyses. HPC proliferation was detected by immunofluorescence. Our results indicate that YB-1 transcriptionally regulated the biological behavior of HPCs. HPC-specific YB-1 knockout alleviated liver fibrosis in mice fed with DDC or CDE diet. YB-1 nuclear translocation promoted matrix metallopeptidase 9 transcription. YB-1 depletion in HPCs significantly dampened the EMT and inhibited AKT phosphorylation in vitro and in vivo. AKT knockdown compromised TGF-ß-induced YB-1 nuclear translocation, thereby inhibiting the EMT and HPC proliferation. EMT and AKT were highly activated in HPCs in cirrhotic livers. Collectively, our findings indicate that the loss of YB-1 suppressed EMT in HPCs and alleviated liver fibrosis in mice, and that AKT was essential for TGF-ß-induced YB-1 nuclear translocation and HPC proliferation.


Assuntos
Transição Epitelial-Mesenquimal , Proteínas Proto-Oncogênicas c-akt , Animais , Caderinas/metabolismo , Colina/metabolismo , Colágeno/metabolismo , Amarelo de Eosina-(YS)/metabolismo , Etionina/metabolismo , Hematoxilina/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Metaloproteases/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Células-Tronco/metabolismo , Fatores de Transcrição , Fator de Crescimento Transformador beta/metabolismo , Fatores de Crescimento Transformadores/metabolismo
10.
Dig Dis Sci ; 67(12): 5462-5471, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35290570

RESUMO

BACKGROUND: Endoscopic balloon dilation (EBD) has emerged as an alternative intervention to manage Crohn's disease (CD) strictures. We determined the cost-effectiveness of EBD versus resection surgery for patients with short (< 4-5 cm) primary or secondary/anastomotic small or large bowel strictures. METHODS: A microsimulation state-transition model analyzed the benefits and risks of EBD and resection surgery for patients with primary or anastomotic CD strictures. Our primary outcome was quality-adjusted life years (QALYs) over ten years, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (2021 $US) and incremental cost-effectiveness ratios (ICER) were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty. RESULTS: The EBD strategy cost $19,822 and resulted in 6.18 QALYs while the surgery strategy cost $41,358 and resulted in 6.37 QALYs. Surgery had an ICER of $113,332 per QALY, making EBD a cost-effective strategy. The median number of EBDs was 5 in the EBD strategy and 0 in the surgery strategy. The median number of surgeries was 2 in the surgery strategy and 1 in the EBD strategy. Of individuals who initially received EBD, 50.4% underwent subsequent surgery. One-way sensitivity analyses showed that the probabilities of requiring repeated interventions, surgery mortality (< 0.7%), and quality of life after interventions were the most influential model parameters. Probabilistic sensitivity analyses favored EBD in 50.9% of iterations. CONCLUSIONS: EBD is a cost-effective strategy for managing CD strictures. Differences in patient risk and quality of life after intervention impact cost-effectiveness. Intervention decisions should consider cost-effectiveness, patient risks, and quality of life.


Assuntos
Doença de Crohn , Humanos , Dilatação/métodos , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Doença de Crohn/complicações , Doença de Crohn/terapia , Análise Custo-Benefício , Qualidade de Vida , Endoscopia Gastrointestinal/métodos , Resultado do Tratamento
11.
Eur J Pharmacol ; 921: 174866, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35231468

RESUMO

The proliferation of hepatic progenitor cells (HPCs) contributes to liver regeneration and fibrogenesis during chronic liver injury; however, the mechanism modulating HPC proliferation remains unknown. Y-box binding protein-1 (YB-1) is a transcription factor that regulates the transcription of several genes and is highly expressed in liver injury. We explored the role of YB-1 in HPC proliferation and liver fibrosis. We detected increased expansion of HPCs and elevated levels of YB-1 in HPCs from patients with hepatitis B virus-related fibrosis and choline-deficient ethionine-supplemented or 5-diethoxycarbonyl-1,4-dihydrocollidine diet-induced mice compared with those in control groups. HPC-specific deletion of YB-1 using YB-1flox/flox; Foxl1-Cre+/- mice led to reduced HPC expansion and less collagen deposition in the liver tissues compared with that in Cre-/- mice. In cultured primary HPCs, YB-1 knockdown inhibited HPC proliferation. Further experiments indicated YB-1 negatively regulated p53 expression, and silencing of p53 blocked YB-1 knockdown-mediated inhibition of HPC proliferation. Collectively, YB-1 negatively regulates HPC proliferation and alleviates liver fibrosis by p53.


Assuntos
Cirrose Hepática , Células-Tronco , Fatores de Transcrição/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Animais , Proliferação de Células/genética , Etionina/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Regeneração Hepática/genética , Camundongos , Células-Tronco/metabolismo
12.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166290, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34662704

RESUMO

Hepatic fibrosis is characterized by excessive extracellular matrix deposition and ductular reactions, manifested as the expansion of hepatic progenitor cells (HPCs). We previously reported that the Y-box binding protein 1 (YB-1) in HPCs is involved in chronic liver injury. In this study, we constructed YB-1f/f Foxl1-Cre mice and investigated the role of YB-1 in HPC expansion in murine choline-deficient, ethionine-supplemented (CDE), and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) models. Liver injury and fibrosis were measured using hematoxylin and eosin (HE), Masson, and Sirius Red staining. HPC proliferation was detected using EdU and immunofluorescence (IF). Autophagic flow was measured by mCherry-GFP-LC3B staining and transmission electron microscopy (TEM). YB-1 expression was measured by immunofluorescence and western blotting. CUT & Tag analysis, chromatin immunoprecipitation, and RT-PCR were performed to explore the regulation of autophagy-related protein 7 (Atg7) transcription by YB-1. Our results indicated that liver injury was accompanied by high expression of YB-1, proliferative HPCs, and activated autophagy in the CDE and DDC models. YB-1f/f Cre+/- mice displayed less liver injury and fibrosis than YB-1f/f Cre-/- mice in the CDE and DDC models. YB-1 promoted proliferation and autophagy of HPCs in vitro and in vivo. Transforming growth factor-ß (TGF-ß) induced YB-1 nuclear translocation and facilitated the proliferation and autophagy of HPCs. YB-1 nuclear translocation promoted the transcription of Atg7, which is essential for TGF-ß/YB-1 mediated HPCs expansion in vitro and in vivo. In summary, YB-1 nuclear translocation induced by TGF-ß in HPCs promotes the proliferation and autophagy of HPCs and Atg7 participates in YB-1-mediated HPC-expansion and liver fibrosis.


Assuntos
Proteína 7 Relacionada à Autofagia/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Cirrose Hepática/genética , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta/genética , Animais , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Deficiência de Colina/induzido quimicamente , Deficiência de Colina/genética , Deficiência de Colina/patologia , Modelos Animais de Doenças , Etionina/toxicidade , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Piridinas/toxicidade , Células-Tronco/efeitos dos fármacos , Células-Tronco/patologia
13.
Mol Ther Nucleic Acids ; 26: 1364-1373, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34900395

RESUMO

Chronic liver disease (CLD) is currently a major health problem worldwide, which is accompanied by chronic liver injury and lack of clinically effective treatment; however, systematic characterization of chronic liver injury procedures at single-cell resolution is lacking. In the present study, we established chronic liver injury mouse models and conducted single-cell RNA sequencing (scRNA-seq), including choline-deficient, ethionine-supplemented (CDE) and 3,5-diethoxycarbonyl 1,4-dihydrocollidinen (DDC) mouse models. We captured in total 16,389 high-quality cells and identified 12 main cell types in scRNA-seq data. Macrophages and endothelial cells are the largest cell populations in our dataset. Transcriptional trajectory analysis revealed different expression patterns of cells between CDE and DDC models and identified potential liver injury markers, such as Ets1, Gda, Itgam, and Sparc. Differential analysis identified 25 and 152 differentially expressed genes in CDE and DDC macrophages, respectively. In addition, 413 genes were detected to exclusively express in specific pseudotime states of macrophages. These genes were found to participate in immune-related biological processes. Further cell-cell communication analysis found extensive receding of cell-cell interactions between different cell types in the liver injury process, especially in the DDC model. Our study characterized the single-cell transcriptional landscape in the process of chronic liver injury, promoting the understanding of the underlying molecular mechanisms and providing candidate clinical strategy for effective intervention of chronic liver diseases.

14.
J Tradit Chin Med ; 41(3): 381-389, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34114395

RESUMO

OBJECTIVE: To investigate the efficacy of celastrol treatment of hepatocellular carcinoma (HCC) cells in vitro and in vivo and to propose a mechanism of action. METHODS: A human HepG2 liver cancer cell line and a xenograft tumor model were used to investigate the effects of celastrol on HCC in vitro and in vivo. A CCK-8 kit was used to detect cell viability. Flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining were used to detect apoptosis. Western blotting and immunohistochemistry were used to detect the expression of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, cleaved-PARP, mammalian target of rapamycin (mTOR), and p-mTOR. Hematoxylin-eosin staining was used to observe the tissue morphology. RESULTS: Celastrol decreased the viability of HepG2 cells and induced apoptosis. Western blot assays indicated that celastrol up-regulated cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, and cleaved-PARP by inhibiting the phosphorylation of mTOR in HepG2 cells. Moreover, celastrol inhibited the tumor growth in a xenograft model. Celastrol also induced caspase-dependent apoptosis (up-regulation of cleaved-caspase- 3, -8, -9, and cleaved-PARP) and inhibited the activation of mTOR in vivo. CONCLUSION: Celastrol induces caspase-dependent apoptosis in HCC cells by inhibiting the activation of mTOR.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Triterpenos Pentacíclicos , Sirolimo , Serina-Treonina Quinases TOR/genética
15.
Inflamm Bowel Dis ; 27(7): 965-970, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32944766

RESUMO

BACKGROUND: Pouchitis can be a chronic complication of ileal pouch-anal anastomosis. We aimed to determine the efficacy and safety of hyperbaric oxygen therapy (HBOT) for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch. METHODS: This was a retrospective case series of adults with inflammatory bowel disease (IBD) who underwent ileal pouch-anal anastomosis and then developed CARP and received HBOT between January 2015 and October 2019. A modified Pouchitis Disease Activity Index (mPDAI) score was used to quantify subjective symptoms (0-6) and endoscopic findings (0-6) before and after HBOT. RESULTS: A total of 46 patients were included, with 23 (50.0%) being males with a mean age of 43.6 ± 12.9 years. The median number of HBOT sessions was 30 (range 10-60). There was a significant reduction in the mean mPDAI symptom subscore from 3.19 to 1.91 after HBOT (P < 0.05). The pre- and post-HBOT mean mPDAI endoscopy subscores for the afferent limb were 2.31 ± 1.84 and 0.85 ± 1.28 (P = 0.006); for the pouch body, 2.34 ± 1.37 and 1.29 ± 1.38 (P < 0.001); and for the cuff, 1.93 ± 1.11 and 0.63 ± 1.12 (P < 0.001), respectively. Transient side effects included ear barotrauma in 5 patients (10.9%) and hyperbaric myopic vision changes in 5 patients (10.9%). CONCLUSIONS: Despite minor adverse events, HBOT was well tolerated in patients with CARP and significantly improved symptoms and endoscopic parameters.


Assuntos
Colite Ulcerativa , Oxigenoterapia Hiperbárica , Pouchite , Proctocolectomia Restauradora , Adulto , Antibacterianos , Doença Crônica , Colite Ulcerativa/cirurgia , Bolsas Cólicas , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pouchite/etiologia , Pouchite/terapia , Proctocolectomia Restauradora/efeitos adversos , Estudos Retrospectivos
16.
Clin Gastroenterol Hepatol ; 19(6): 1288-1291, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32565291

RESUMO

Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for medically refractory ulcerative colitis. Pouch-related complications, such as pouchitis, cuffitis, or fistulae, occur in up to 50% of patients. Nearly 1 in 5 patients develop pouch-related complications refractory to medical therapy, including biologics. Hypoxia has been suggested as a trigger for these chronic refractory complications, and treating hypoxia may be of therapeutic benefit in this patient population. We investigated the effectiveness of hyperbaric oxygen therapy (HBOT) for patients with medically refractory pouch-related complications.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Oxigenoterapia Hiperbárica , Pouchite , Proctocolectomia Restauradora , Colite Ulcerativa/cirurgia , Humanos , Complicações Pós-Operatórias , Pouchite/terapia
17.
Environ Pollut ; 274: 115866, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33277062

RESUMO

Selenium (Se) and arsenic (As) are toxic contaminants in surface water and drinking water. The human body needs little quantity of Se, but too high dose is not allowed. Metal oxides such as iron oxides were used for adsorption or co-precipitation removal of As from water. However, the regeneration and stability problems of metals oxides sorbents are unsatisfactory , and there is not enough adsorbent for Se removal from water also. We developed the acrylic amine fiber (AAF) for adsorption reomval of Se and As from water and systematically studied the influenced factors. Batch experiments were conducted for investigating the adsorption edges, while column filtration tests were employed for dynamic application edges. At neutral pH, the Langmuir isotherm fittings gave the maximum adsorption capacities of As(V), As(III), Se(VI) and Se(IV) are 270.3, 40.5, 256.4, and 158.7 mg/g, respectively. Effects of co-existing inorganic anions on As(V) and Se(VI) adsorption using AAF gave the order of PO43- > SO42- > NO3- > SiO32-, while different organic acids obey the order of citric acid > oxalic acid > formic acid. Fourier transform infrared analysis showed the PO43- and SO42- competition mechanisms are electrostatic repulsions, while the competition of organic acids derived from acid-base reaction between the carboxyl group and the amino group. Column filtration and regeneration results showed that the spent AAF can be regenerated using 0.5 mol/L HCl solution and reused with no much decrease of adsorption capacity.


Assuntos
Arsênio , Selênio , Poluentes Químicos da Água , Purificação da Água , Adsorção , Aminas , Arsênio/análise , Humanos , Concentração de Íons de Hidrogênio , Cinética , Água , Poluentes Químicos da Água/análise
18.
Medicine (Baltimore) ; 99(22): e19923, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481364

RESUMO

BACKGROUND: Oxaliplatin can cause severe peripheral neurotoxicity, which is an important reason for clinical oxaliplatin reduction and cessation of treatment. Oxaliplatin induced peripheral neurotoxicity (OIPN) can cause paresthesia and dysesthesia, even affect the quality life of patients. So far, there are no recognized and effective measures to prevent OIPN. Huangqi Guizhi Wuwu decoction is a classical prescription of ancient Chinese medicine recorded in "the synopsis of the Golden Chamber," which can be used in the treatment of various neurotoxicity. However, there is a lack of large-scale and high-quality clinical studies on the prevention of OIPN by Huangqi Guizhi Wuwu decoction. The purpose of this study is to evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction on preventing OIPN. METHODS/DESIGN: This study is a randomized, controlled, double-blind, and multicenter clinical trial. Three hundred sixty patients will be randomly assigned into Huangqi Guizhi Wuwu decoction group and Huangqi Guizhi Wuwu decoction mimetic agent group. Patients will receive chemotherapy with FOLFOX of 8 cycles of 3 weeks with Traditional Chinese Medicine (TCM) for 6 months and 1-year follow-up. The primary outcome measure is the differences in the incidence of chronic neurotoxicity of grade 2 and above during and after treatment. The secondary outcome measure is the improvement in other symptoms associated with chemotherapy. Four methods will be used to evaluate the efficacy of neurotoxicity, including oxaliplatin specific toxicity grading standard (Levi classification); CTCAE4.02 version; EORTC QLQ-CIPN20 scale, EORTC QLQ C30 scale, and EORTC QLQ-CR29 scale are used at the same time; Electromyography. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Huangqi Guizhi Wuwu Decoction on preventing OIPN. TRIAL REGISTRATION: Clinical Trials.gov (Identifier: NCT04261920).


Assuntos
Antineoplásicos/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Método Duplo-Cego , Humanos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Fitoterapia
19.
Gastroenterol Rep (Oxf) ; 7(6): 455-458, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31857908

RESUMO

Anastomotic dehiscence and leak are dreaded complications after a colorectal resection and can often present with rectal bleeding and pelvic abscess or sepsis. Although most cases of bleeding after gastrointestinal anastomoses are minor and self-limited, major bleeding, as defined by hemodynamic instability or the need for blood transfusions, poses a significant challenge for management. Here we report a case in which a patient presenting with profuse rectal bleeding and pelvic hematoma secondary to a colorectal anastomotic leak was treated endoscopically with 50% dextrose spray then enema.

20.
Gene ; 716: 144034, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31377317

RESUMO

BACKGROUND: Outcome in adjuvant chemotherapy of gastric cancer (GC) has considerable stage-independent variability, which underscores the need for prognostic or predictive molecular markers. CHAF1A promotes tumor growth while its impact on chemotherapy outcome remains unknown. METHODS: CHAF1A protein expression was measured in independent discovery and validation sets that included 86 and 325 patients respectively who received fluoropyrimidines-based adjuvant chemotherapy after radical gastrectomy. The chemosensitizing effect of CHAF1A knockdown was investigated in vitro. Bioinformatics analysis based on RNA-seq and proteome data from public database was performed to investigate the potential mechanisms and further validation was conducted. RESULTS: In both the discovery and validation sets, CHAF1A expression level was an independent predictor for disease-free survival (HR = 4.25; 95% CI: 2.31-7.79; P < 0.001; and HR = 1.91; 95% CI: 1.03-3.54; P = 0.039, respectively) and overall survival (HR = 3.25; 95% CI: 1.75-6.05; P < 0.001; and HR = 2.42; 95% CI: 1.12-5.20; P = 0.024, respectively) in patients with non-cardia GC but not in those with cardia GC. In GC cells, CHAF1A knockdown significantly decreased the IC50 of 5-FU. Bioinformatics analyses indicated that CHAF1A correlated with folate metabolism and the expression of thymidylate synthetase (TS). Furthermore, CHAF1A knockdown significantly reduced TS expression in GC cells and CHAF1A positively correlated with TS protein expression in tumor tissues. Finally, ten proteins potentially relevant to the regulation of TS expression by CHAF1A were identified using online tools based on RNA-seq and proteome data. CONCLUSIONS: CHAF1A may impact adjuvant chemotherapy outcome of GC by regulating the expression of TS.


Assuntos
Antineoplásicos/uso terapêutico , Chaperonas de Histonas/metabolismo , Pirimidinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Timidilato Sintase/metabolismo , Idoso , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Fator 1 de Modelagem da Cromatina/metabolismo , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Ácido Fólico/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Timidilato Sintase/genética , Resultado do Tratamento
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