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1.
Bioact Mater ; 21: 499-510, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36185744

RESUMO

Acute myeloid leukemia (AML) remains a most lethal hematological malignancy, partly because of its slow development of targeted therapies compared with other cancers. PLK1 inhibitor, volasertib (Vol), is among the few molecular targeted drugs granted breakthrough therapy status for AML; however, its fast clearance and dose-limiting toxicity greatly restrain its clinical benefits. Here, we report that transferrin-guided polymersomes (TPs) markedly augment the targetability, potency and safety of Vol to AML. Vol-loaded TPs (TPVol) with 4% transferrin exhibited best cellular uptake, effective down-regulation of p-PLK1, p-PTEN and p-AKT and superior apoptotic activity to free Vol in MV-4-11 leukemic cells. Intravenous injection of TPVol gave 6-fold higher AUC than free Vol and notable accumulation in AML-residing bone marrow. The efficacy studies in orthotopic MV-4-11 leukemic model demonstrated that TPVol significantly reduced leukemic cell proportions in periphery blood, bone marrow, liver and spleen, effectively enhanced mouse survival rate, and impeded bone loss. This transferrin-guided nano-delivery of molecular targeted drugs appears to be an interesting strategy towards the development of novel treatments for AML.

2.
Talanta ; 251: 123738, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35921743

RESUMO

Natural products, especially alkaloids, are one of the most valuable, potential drug leads in drug discovery. As an efficient tool for complex samples, two-dimensional liquid chromatography (2D-LC) has become a powerful means of analysis and separation of natural alkaloids. Method development of 2D-LC is of great importance because it helps to enhance the selectivity, resolution and peak capacity of a separation system. However, due to the diversity of the nature and subclasses of natural alkaloids, peak tailing occurs frequently, making alkaloid separation complicated and time-consuming. To conquer such difficulties, we proposed a guide for column selection and combination in 2D-LC so as to improve the alkaloid separation. Based on a comprehensive evaluation of applicability and orthogonality of several columns, this guide would provide a simple but clear starting point for column selection of 2D-LC method development. The evaluation included seven columns to involve most separation mechanisms reported in alkaloid separation, and 49 natural alkaloid standards of various subclasses and natures. Detailed studies of peak shapes of every column were carried out as well, providing useful references to better understand the peak tailing issues of some analytes on specific columns. Subsequently, a 2D-LC method was developed using our guide to isolate an alkaloid sample from U. rhynchophylla, generating symmetrical peaks and a high orthogonality of 80.3%. Further, this evaluation process would help to have a quick understanding when a new stationary phase is designed.


Assuntos
Alcaloides , Produtos Biológicos , Alcaloides/análise , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida/métodos , Descoberta de Drogas , Padrões de Referência
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 284: 121825, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36081192

RESUMO

Raman spectroscopy and stimulated Raman scattering (SRS) were used to investigate the hydrogen bonding (HB) network in 1,2-propanediol (1,2-PD)-water binary solutions. Abnormal changes in hydrogen bonds (HBs) were detected when V1,2-PD (volume fraction of the1,2-PD) was 0.4. In the case of Raman spectroscopy, the HB strength of water is weakened and then strengthened with the increase of 1,2-PD volume fraction. In the case of SRS, two new peaks at 3283 cm-1 and 3319 cm-1 were appeared, which demonstrated the appearance of ice-like structures near the methyl group and the weakening of HBs. Based on these phenomena, the HB structure of this binary system underwent a transition from H2O-H2O to H2O-1,2-PD when the V1,2-PD was 0.4 as V1,2-PD increased. This work serves as a reference value for the study of HB networks in alcohol-water binary solutions.


Assuntos
Propilenoglicol , Análise Espectral Raman , Ligação de Hidrogênio , Gelo , Análise Espectral Raman/métodos , Água/química
4.
Food Chem ; 399: 133999, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36037688

RESUMO

Melastoma dodecandrum Lour. (MDL) extracts have shown potent α-glucosidase inhibitory activity, suggesting MDL might be a good source of α-glucosidase inhibitors. The aim of the study was to identify compounds in MDL extracts with α-glucosidase inhibitory activities and evaluate their effect on postprandial blood glucose as well as elucidating the underlying mechanisms of inhibition. A total of 34 polyphenols were identified in MDL fruits, among which 10 anthocyanins and three proanthocyanidin derivatives were discovered for the first time. Dosing mice with MDL extracts (100 mg/kg body weight, by gavage) was associated with a significantly decrease in postprandial blood glucose concentrations after oral administration of maltose. The most potent α-glucosidase inhibitor was identified as casuarictin (IC50 of 0.21 µg/mL). Casuarictin bound competitively to α-glucosidase, occupying not only the catalytic site but also forming strong hydrogen bonds with α-glucosidase residues. Therefore, casuarictin derived from MDL fruits might be used as novel α-glucosidase inhibitor in functional foods or other dietary products.


Assuntos
Inibidores de Glicosídeo Hidrolases , Melastomataceae , Animais , Antocianinas , Glicemia/metabolismo , Frutas/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Melastomataceae/metabolismo , Camundongos , Extratos Vegetais/química , alfa-Glucosidases/metabolismo
5.
Biomater Sci ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317535

RESUMO

Smart nanomaterials with stimuli-responsive imaging enhancement have been widely developed to meet the requirements of accurate cancer diagnosis. However, these imaging nanoenhancers tend to be always on during circulation, which significantly increases the background signal when assessing the imaging performance. To improve unfavorable signal-to-noise ratios, an effective way is to shield the noise signal of these nanoprobes in non-targeted areas. Fortunately, there is a natural mutual shielding effect between some imaging nanomaterials, which provides the possibility of designing engineered nanomaterials with imaging quenching between two different components at the beginning. Once in the tumor microenvironment, the two components will present activated dual-mode imaging ability because of their separation, designated as two-way imaging tuning. This review highlights the design and mechanism of a series of engineered nanomaterials with two-way imaging tuning and their latest applications in the fields of cancer magnetic resonance imaging, fluorescence imaging, and their combination. The challenges and future directions for the improvement of these engineered nanomaterials towards clinical transformation are also discussed. This review aims to introduce the special constraint relationships of imaging components and provide scientists with simpler and more efficient nanoplatform construction ideas, promoting the development of engineered nanomaterials with two-way imaging tuning in cancer theranostics.

6.
Inflamm Res ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329130

RESUMO

BACKGROUND: Rosacea, a chronic inflammatory disorder of the facial skin, is effectively treated by intense pulsed light (IPL). OBJECTIVE: To explore the potential molecular mechanism underlying the photobiomodulation effect of IPL for rosacea treatment. METHODS: Skin samples from patients with rosacea were subjected to histological and immunohistological staining. Ten patients were followed up after IPL treatment using the VISIA® skin analysis system, and the severity was assessed. In vivo, skin changes in mice with rosacea-like inflammation induced by intradermal injection of 320 µM LL-37 with or without IPL treatment were evaluated using L*a*b colorimetry as well as histological and immunological staining. In vitro, LL-37-stimulated mast cells (MCs) with or without IPL treatment were evaluated for protein expression of matrix metalloproteinase (MMP)-9, kallikrein-related peptidase 5 (KLK5), and cathelicidin using western blotting and qRT-PCR. RESULTS: Profound infiltration of inflammatory cells and evident MC degranulation were found in rosacea skin lesions. The expression of rosacea-related biomarkers and inflammatory cytokines was higher in lesional areas than in non-lesional areas, as demonstrated via immunochemical staining. In all patients, rosacea severity reduced after IPL therapy. In vivo, IPL alleviated inflammation in mice with rosacea-like inflammation, as demonstrated by the significantly decreased MMP-9, KLK5, and cathelicidin expression and reduced percentage of degranulating MCs. In vitro, IPL decreased MMP-9, KLK5, and cathelicidin expression in P815 cells, reducing the release of inflammatory cytokines and inhibiting rosacea-like inflammatory reactions. CONCLUSION: The photobiomodulation effect of IPL for rosacea treatment may inhibit MC degranulation and alleviate inflammatory reactions.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36330602

RESUMO

Double hydrosilylation of alkynes represents a straightforward method to synthesize bis(silane)s, yet it is challenging if α-substituted vinylsilanes act as the intermediates. Here, a cobalt-catalyzed regiodivergent double hydrosilylation of arylacetylenes is reported for the first time involving this challenge, accessing both vicinal and geminal bis(silane)s with exclusive regioselectivity. Various novel bis(silane)s containing Si-H bonds can be easily obtained. The gram-scale reactions could be performed smoothly. Preliminarily mechanistic studies demonstrated that the reactions were initiated by cobalt-catalyzed α-hydrosilylation of alkynes, followed by cobalt-catalyzed ß-hydrosilylation of the α-vinylsilanes to deliver vicinal bis(silane)s, or hydride-catalyzed α-hydrosilylation to give geminal ones. Notably, these bis(silane)s can be used for the synthesis of high-refractive-index polymers (nd up to 1.83), demonstrating great potential utility in optical materials.

8.
Int J Anal Chem ; 2022: 9229970, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36317051

RESUMO

In this paper, a novel fingerprint method was established for the quality control of Rana chensinensis eggs (RE) by high-performance liquid chromatography (HPLC). Cluster analysis and principal component analysis were performed. Besides, the antitussive effect of RE was explored. The analysis was achieved on a Kromasil 100-5C18 (4.6 mm × 250 mm, 5 µm) column by gradient elution using methanol-0.1% phosphoric acid solution as the mobile phase. The influence of RE on cough latent periods and cough times of mice was investigated via an ammonia cough-inducing experiment. The validated HPLC method was precise, reproducible, and stable. The HPLC fingerprints of 10 batches of RE samples displayed 31 well-resolved common peaks in the chromatogram. Three of these peaks were identified and assigned to 1-methyl hydantoin, estradiol, and 4-cholestene-3-one. The similarities of 10 batches of samples were more than 0.95. RE from different origins could be classified into three groups via SPSS 23.0 software, suggesting RE samples from various provinces (Jilin, Liaoning, and Heilongjiang) can be well distinguished via the established method. High dose and middle dose of the RE group can significantly prolong the cough latent periods of mice (P < 0.05 or P < 0.01) and inhibit the cough times of mice (P < 0.01), indicating RE had a good antitussive effect. HPLC fingerprint combined with multicomponent determination can be an efficient and useful method for monitoring the quality of RE. This study also provided a more comprehensive strategy for the quality evaluation of RE.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36327068

RESUMO

The government-led Chinese economic development system determines that local government competition is a significant factor affecting the economic low-carbon transition. Driving an economic development mode with green technology innovation as the core is the critical path to realizing an economic low-carbon transition. Consequently, it is of significant practical relevance to investigate the impact of local government competition and green technology innovation on the economic low-carbon transition under the government-led Chinese economic development system. This paper systematically explores the nexus between green technology innovation and economic low-carbon transition in terms of local government competition perspective using the system generalized method of moments, panel threshold model, and geographically weighted regression on the basis of a dataset of 30 provincial administrative areas in China from a period of 2006-2019. The results indicate that green technology innovation significantly promotes the economic low-carbon transition. Local government competition not only significantly dampens the economic low-carbon transition but also considerably inhibits the positive effect of green technology innovation on the economic low-carbon transition. A significant N-shaped association is evident between green technology innovation and the economic low-carbon transition when green technology innovation is applied as a threshold, while such association is insignificant when local government competition is used as a threshold. Compared with high-competition intensity areas, green technology innovation promotes economic low-carbon transition weaker in low- competition intensity areas, while local government competition inhibits economic low-carbon transition stronger. However, local government competition significantly inhibits the positive effect of green technology innovation on the economic low-carbon transition in low-competition intensity areas, while insignificant in high-competition intensity areas. The geographically weighted regression technique as a whole also verified the above results. Therefore, policymakers should not only increase research and development investment in green technologies, but also develop a regionally linked low-carbon emission reduction system to avoid ineffective competition among governments to facilitate the earlier fulfillment of the "dual carbon" goal.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36334141

RESUMO

PURPOSE: Treatment of chronic lateral ankle instability (CLAI) with poor remnant quality is challenging. The aim of the present study was to evaluate clinical results and complications of anatomic reconstruction of the lateral ligaments using allograft tendon and suspensory fixation in the treatment of such patients. METHODS: One hundred and eight patients with CLAI, who were treated surgically using anatomic reconstruction with allograft tendon and suspensory fixation between April 2016 and January 2018 at our hospital, were retrospectively analysed. None of the patients had sufficient ligament remnants for the modified Broström procedure during the intraoperative evaluation. Eighteen patients were excluded. Seventeen patients were lost to follow-up and 73 patients completed the study. The mean duration of instability symptoms was 39.1 months (range, 6-480 months). The mean follow-up time was 57.5 months (range, 48-69 months). Clinical results were evaluated using the Karlsson scoring scale, American Orthopaedic Foot and Ankle Society-Ankle and Hindfoot (AOFAS-AH) score, visual analogue scale (VAS), patients' subjective satisfaction, and incidence of complications. Mechanical stability was evaluated using the varus talar tilt angle (TTA) and anterior talar displacement (ATD). RESULTS: The AOFAS-AH scores significantly improved from 67.7 ± 8.5 points to 89.8 ± 9.5 (p < 0.001). The Karlsson scoring scales evolved from 58.8 ± 16.5 to 88.4 ± 11.2 (p < 0.001). VAS scores significantly decreased from 2.9 ± 1.3 to 1.1 ± 1.0 (p < 0.001). On stress radiographs, TTA decreased from 15.1 ± 2.5 degrees to 5.8 ± 2.1 degrees (p < 0.001), whereas ATD reduced from 13.4 ± 2.9 mm to 5.7 ± 1.5 mm (p < 0.001). Patients' subjective satisfaction indicated 46 excellent, 20 good, 5 fair, and 2 bad results. Postoperatively, 15 cases (20.5%) did not achieve complete relief of discomfort or swelling, 9 cases (12.3%) experienced joint stiffness or decreased range of motion, and 6 cases (8.2%) had soft tissue irritation. Residual instability and reoperation are rare. Allograft rejection or wound infection was not observed. CONCLUSION: For the CLAI patients with poor remnant quality, anatomic reconstruction of the lateral ligaments using allograft tendon and suspensory fixation is an effective procedure, while the top three complications in incidence were residual discomfort, joint stiffness, and soft tissue irritation. LEVELS OF EVIDENCE: Level IV, retrospective case series.

11.
Blood ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322932

RESUMO

Transferrin receptor 1 (TFR1) performs a critical role in cellular iron uptake. Hepatocyte TFR1 is also proposed to influence systemic iron homeostasis by interacting with the hemochromatosis protein HFE to regulate hepcidin production. Here, we generated hepatocyte Tfrc knockout mice (Tfrcfl/fl;Alb-Cre+), either alone or together with Hfe knockout or ß-thalassemia, to investigate to what extent hepatocyte TFR1 function depends on HFE, whether hepatocyte TFR1 impacts hepcidin regulation by serum iron and erythropoietic signals, and the contribution of hepatocyte TFR1 to hepcidin suppression and iron overload in ß-thalassemia. Compared to Tfrcfl/fl;Alb-Cre- controls, Tfrcfl/fl;Alb-Cre+ mice displayed reduced serum and liver iron; mildly reduced hematocrit, mean cell hemoglobin, and mean cell volume; increased erythropoietin and erythroferrone; and unchanged hepcidin levels that were inappropriately high relative to serum iron, liver iron, and erythroferrone levels. However, ablation of hepatocyte Tfrc had no impact on iron phenotype in Hfe knockout mice. Tfrcfl/fl;Alb-Cre+ mice also displayed a greater induction of hepcidin by serum iron compared with Tfrcfl/fl;Alb-Cre- controls. Finally, although acute erythropoietin injection similarly reduced hepcidin in Tfrcfl/fl;Alb-Cre+ and Tfrcfl/fl;Alb-Cre- mice, ablation of hepatocyte Tfrc in a mouse model of ß-thalassemia intermedia ameliorated hepcidin deficiency and liver iron loading. Together, our data suggest that the major nonredundant function of hepatocyte TFR1 in iron homeostasis is to interact with HFE to regulate hepcidin. This regulatory pathway is modulated by serum iron and contributes to hepcidin suppression and iron overload in murine ß-thalassemia.

12.
Obesity (Silver Spring) ; 30(11): 2242-2255, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36321273

RESUMO

OBJECTIVE: Elevation of energy expenditure through an increase of brown adipose tissue (BAT) thermogenesis is regarded as one of the most promising ways to prevent obesity development. The preoptic area (POA) of the hypothalamus is a critical area for control of BAT thermogenesis. However, the intracellular signaling cascades in the POA for regulation of BAT thermogenesis are poorly understood. METHODS: Phosphorylation proteomics (phosphoproteomics) and bioinformatics approaches were used to disclose numerous hypothalamic signaling pathways involved in the regulation of BAT thermogenesis. Conditional manipulation of the p38α gene in mouse POA was performed by stereotaxic injection of adeno-associated virus 9 vector to explore the role of p38α in BAT thermogenesis. RESULTS: Multiple hypothalamic signaling pathways were triggered by cold exposure, especially the mitogen-activated protein kinase (MAPK) signaling pathway. The p38α activation, but not extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK), in the hypothalamus was significantly decreased during cold exposure. p38α deficiency in the POA dramatically elevated energy expenditure owing to a marked increase in BAT thermogenesis, resulting in significantly decreased body weight gain and fat mass. Overexpression of p38α in the POA led to a dramatic increase in weight gain. CONCLUSIONS: These results demonstrate that p38α in the POA exacerbates obesity development, at least in part owing to a decrease in BAT thermogenesis.


Assuntos
Tecido Adiposo Marrom , Área Pré-Óptica , Camundongos , Animais , Tecido Adiposo Marrom/metabolismo , Área Pré-Óptica/metabolismo , Termogênese/fisiologia , Obesidade/metabolismo , Metabolismo Energético/fisiologia , Aumento de Peso
13.
Cartilage ; : 19476035221137726, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36377077

RESUMO

BACKGROUND: The intra-articular injection of mesenchymal stem cell (MSC)-derived exosomes has already been proved to reverse osteoarthritic cartilage degeneration. Pulsed electromagnetic field (PEMF) has been found to regulate the biogenic function of MSCs. However, the effect of PEMF on MSC-derived exosomes has not yet been characterized. The aim of this study was to elucidate the regulatory role of different frequencies of PEMF in promoting the osteoarthritic cartilage regeneration of MSC-derived exosomes. METHODS: The adipose tissue-derived MSCs (AMSCs) were extracted from the epididymal fat of healthy rats and further exposed to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. The chondrocytes were treated with interlukin-1ß (IL-1ß) and the regenerative effect of co-culturing with PEMF-exposed AMSC-derived exosomes was assessed via Western blot, quantitative polymerase chain reaction, and ELISA assays. A rat model of osteoarthritis was established by anterior cruciate ligament transection (ACLT) surgery and received 4 times intra-articular injection of PEMF-exposed AMSC-derived exosomes once a week. After 8 weeks, the knee joint specimens of rats were collected for micro-computed tomography and histologic analyses. RESULTS: PEMF-exposed AMSC-derived exosomes could be endocytosed with IL-1ß-induced chondrocytes. Compared with the AMSC-derived exosomes alone, the PEMF-exposed AMSC-derived exosomes substantially suppressed the inflammation and extracellular matrix degeneration of IL-1ß-induced chondrocytes as shown by higher expression of transcripts and proteins of COL2A1, SOX9, and ACAN and lower expression of MMP13 and caspase-1. Of these, the 75-Hz PEMF presented a more significant inhibitive effect than the 15-Hz and 45-Hz PEMFs. Furthermore, the intra-articular injection of 75-Hz PEMF-exposed exosomes could obviously increase the number of tibial epiphyseal trabeculae, lead to a remarkable decrease in Osteoarthritis Research Society International score, and upregulate the COL2A1 and ACAN protein level of the degenerated cartilage. CONCLUSION: The present study demonstrated that PEMF stimulation could effectively promote the regeneration effects of AMSC-derived exosomes on osteoarthritic cartilage. Compared with other frequency parameters, the PEMF at a frequency of 75 Hz showed a superior positive effect on AMSC-derived exosomes in suppressing the IL-1ß-induced chondrocyte inflammation and extracellular matrix catabolism, as well as the osteoarthritic cartilage degeneration.

14.
J Nat Prod ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36367222

RESUMO

Cladoxanthones A (1) and B (2), two xanthone-derived metabolites featuring a new spiro[cyclopentane-1,2'-[3,9a]ethanoxanthene]-2,4',9',11'(4a'H)-tetraone skeleton, were isolated from cultures of the ascomycete fungus Cladosporium sp., together with the known mangrovamide J (3). Their structures were elucidated primarily by NMR experiments. The absolute configurations of 1 and 2 were assigned by X-ray crystallography using Cu Kα radiation. Compound 1 could be generated from the hypothetical precursors related to α-methylene ketone and dihydro-xanthone via a Diels-Alder reaction, while 2 could be an oxidative coupling product resulting from 1 and 3. Compounds 1 and 2 showed weakly cytotoxic effects.

15.
Front Plant Sci ; 13: 1029722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352878

RESUMO

In the Atractylodes lancea (A. lancea)-maize intercropping system, maize can promote the growth of A. lancea, but it is unclear whether this constitutes an aboveground or belowground process. In this study, we investigated the mechanisms of the root system interaction between A. lancea and maize using three different barrier conditions: no barrier (AI), nylon barrier (AN), and plastic barrier (AP) systems. The biomass, volatile oil concentration, physicochemical properties of the soil, and rhizosphere microorganisms of the A. lancea plant were determined. The results showed that (1) the A. lancea - maize intercropping system could promote the growth of A. lancea and its accumulation of volatile oils; (2) a comparison of the CK, AI, and AP treatments revealed that it was the above-ground effect of maize specifically that promoted the accumulation of both atractylon and atractylodin within the volatile oils of A. lancea, but inhibited the accumulation of hinesol and ß-eudesmol; (3) in comparing the soil physicochemical properties of each treatment group, intercropping maize acidified the root soil of A. lancea, changed its root soil physicochemical properties, and increased the abundance of the acidic rhizosphere microbes of A. lancea at the phylum level; (4) in an analysis of rhizosphere microbial communities of A. lancea under different barrier systems, intercropping was found to promote plant growth-promoting rhizobacteria (PGPR) enrichment, including Streptomyces, Bradyrhizobium, Candidatus Solibacter, Gemmatirosa, and Pseudolabrys, and the biomass of A. lancea was significantly influenced by PGPR. In summary, we found that the rhizosphere soil of A. lancea was acidified in intercropping with maize, causing the accumulation of PGPR, which was beneficial to the growth of A. lancea.

16.
Food Funct ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36385382

RESUMO

The association between dietary meat consumption habits and neurodegenerative cognitive impairment (NCI) has been made but recent studies have reported controversial results. Herein, we have systematically explored associations between meat consumption and NCI risk. PubMed, Embase, and MEDLINE databases were explored for data sources of primary studies. Twenty-four prospective cohort studies that met the selection criteria, involving over 500 000 participants from 11 countries, were included. Relative risks (RRs) were pooled using random-effects model meta-analysis, and a dose-response analysis was conducted using a 2-stage generalized least-squares trend program. The results showed that total meat (RRs 1.14; 95% CI: 1.04-1.24), fish (RRs 0.87; 95% CI: 0.78-0.98), and poultry (RRs 0.88; 95% CI: 0.80-0.98) intake was significantly associated with NCI risk but red meat (RRs 1.03; 95% CI: 0.92-1.16) showed a non-significant association. Subgroup analysis further demonstrated a significant association between total meat consumption and the risk of NCI, especially for total processed meat (RRs 1.67; 95% CI, 1.46-1.92) and processed red meat (RRs 1.22; 95% CI, 1.11-1.34). Each additional 50 g day-1 intake of total meat (RRs 1.03; 95% CI: 1.00-1.05) and processed meat (RRs 1.12; 95% CI: 1.08-1.17) increased the risk of NCI. In contrast, a 50 g day-1 increment of fish (RRs 0.97; 95% CI: 0.94-0.99) and poultry (RRs 0.948; 95% CI: 0.90-0.99) intake was associated with lower NCI risk. This study provided evidence for further understanding the relationship between the type and amount of meat intake and the occurrence of NCI.

17.
Nutrients ; 14(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36364726

RESUMO

Exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn's disease (CD). This study aims to depict EEN's modification of bile acid (BA) metabolism in pediatric CD and explores the effect of the EEN-enriched BA in inhibiting the inflammatory response. The twelve enrolled pediatric CD patients showed BA dysmetabolism, represented by decreased levels of fecal secondary and unconjugated BAs as determined by UPLC-TQMS, which were accompanied by gut microbiota dysbiosis and reduced BA-metabolizing bacteria including Eubacterium and Ruminococcus genera, assessed by shotgun metagenomic sequencing. EEN treatment induced remission in these patients at eight weeks, and nine patients remained in stable remission for longer than 48 weeks. EEN improved BA dysmetabolism, with some enriched BAs, including hyocholic acid (HCA), α-muricholic acid (αMCA), strongly associated with decreased severity of CD symptoms. These BAs were significantly correlated with the increased abundance of certain bacteria, including Clostridium innocuum and Hungatella hathewayi, which express 3ß-hydroxysteroid dehydrogenase and 5ß-reductase. HCA could suppress TNF-α production by CD4+ T cells in the peripheral blood mononuclear cells (PBMCs) of CD patients. Moreover, intraperitoneal injection of HCA could attenuate dextran sulfate sodium (DSS)-induced mouse colitis. Our data suggests that BA modification may contribute to the EEN-induced remission of pediatric CD.


Assuntos
Nutrição Enteral , Microbiota , Camundongos , Animais , Indução de Remissão , Leucócitos Mononucleares , Bactérias , Anti-Inflamatórios , Ácidos e Sais Biliares
18.
Ren Fail ; 44(1): 1915-1923, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36369936

RESUMO

BACKGROUND: Patients with persistent nephrotic-range proteinuria have a high risk of kidney dysfunction and cardiovascular events. Recently, the maintenance of proteinuria remission has been demonstrated to reduce the risk of kidney endpoint. However, the effect of remission duration on cardiovascular outcomes remains unclear. METHODS: This study enrolled 982 patients with primary nephrotic syndrome who had achieved clinical remission. Remission duration was defined as the maintenance time (months) of the first remission. Arteriosclerotic cardiovascular disease (ASCVD) and kidney dysfunction (ESKD or eGFR reduction >50%) were the endpoints. Survival curves, Cox regression models, restricted cubic spline analysis were used and the cutoff time points were determined. RESULTS: During the 38.3 months of follow-up, 161 (16.4%) patients developed ASCVD (51.3 per 1000 patient-years) and 52 (5.3%) patients developed kidney dysfunction (15.3 per 1000 patient-years). Multivariate analysis showed that remission duration was an independently protective factor to ASCVD, in which each one-year extension associated with a 15% reduction of the risk (HR, 0.854; 95% CI, 0.776 ∼ 0.940, p = .001). The initial time point was seven months for remission to present the protective effect to ASCVD and the maximum time point was 36 months. Remission duration was also an independently protective factor to kidney dysfunction. This effect was shown from the beginning of remission and reached the maximum at 26 months. CONCLUSIONS: The maintenance of proteinuria remission was crucial for the improvement of cardiovascular and kidney outcomes in nephrotic syndrome patients.


Assuntos
Sistema Cardiovascular , Síndrome Nefrótica , Humanos , Síndrome Nefrótica/complicações , Rim , Proteinúria/complicações , Modelos de Riscos Proporcionais
19.
Exp Hematol Oncol ; 11(1): 96, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352455

RESUMO

Acute graft-versus-host disease (aGVHD), especially intestinal aGVHD, is one of the most severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) has been applied to the treatment of intestinal steroid-refractory aGVHD (SR-aGVHD). Ruxolitinib is the first drug recommended for SR-aGVHD. Here, we reported the outcome data from 21 patients who had received the combined treatment of FMT with ruxolitinib as a salvage treatment in intestinal SR-aGVHD after HSCT. The overall response rate on day 28 was 71.4% (95% CI 50.4-92.5%), including 10 patients with complete responses. The durable overall response at day 56 in responders was 80%. GVHD relapse rate was 33.3% in responders. The levels of inflammatory cytokines as well as T cells and NK cells activation declined. The diversity of the intestinal microbiota was improved in responders. Viral reactivations and severe cytopenia were the major adverse events (61.9% and 81% respectively). The estimated 6-month overall survival was 57.1% (95% CI: 35.9-78.3%), while event-free survival was 52.4% (95% CI: 21.7%-64.1%). Collectively, FMT with ruxolitinib could be an effective treatment for intestinal SR-aGVHD after HSCT.Trial registration: ClinicalTrials.gov identifier: NCT03148743.

20.
Mol Biol Rep ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352181

RESUMO

AIM: Lysine-Specific Demethylase 1 (LSD1) inhibitors have been developed and reached the clinic, but its effect in combination with cytotoxic chemotherapy is unclear. Here, we investigated the anti-tumor effect of LSD1 inhibitor GSK-LSD1 and its anti-tumor effect with the DNA damage drug doxorubicin (DOX) in gastric cancer (GC) cells. METHODS: Cells were treated with different concentrations of GSK-LSD1 to examine the anti-tumor effect versus cell viability by MTT and cell cycle arrest by flow cytometry. To explore whether LSD1 inhibitors can increase the anti-tumor effect of DNA damage drugs, cells were treated with DOX for 48 h after pretreatment with GSK-LSD1 for 48 h. Cell viability was detected by MTT and apoptosis-related proteins were examined by Western blot. Furthermore, anti-tumor efficacy of combination GSK-LSD1 with DOX was also measured in MGC-803 xenografts model in nude mice. RESULTS: The results showed that LSD1 was highly expressed in GC cell lines. Inhibition of LSD1 has a weak effect on cell viability and cell cycle. Moreover, LSD1 inhibitors pretreatment could significantly increase the anti-tumor effect of DOX. Further study found that inhibition of LSD1 can significantly enhance DOX-induced the apoptosis, accompanied by down-regulation of antiapoptotic Bcl-2 expression and up-regulation of proapoptotic Bax expression. We also confirmed that inhibition of LSD1 can sensitize the anti-tumor effect of DOX in vivo. CONCLUSION: Our findings suggest that the LSD1 inhibitor GSK-LSD1 has a weak inhibitory effect on the viability and cell cycle of GC cells, but can enhance the sensitivity of DOX.

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