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1.
Front Nutr ; 11: 1386361, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832098

RESUMO

Background: Patients with nasopharyngeal carcinoma are notably susceptible to high nutritional risks. If not addressed, this susceptibility can lead to malnutrition, resulting in numerous adverse clinical outcomes. Despite the significance of this issue, there is limited comprehensive research on the topic. Objective: The objective of our study was to identify nutritional risk factors in patients with nasopharyngeal carcinoma. Methods: For this cross-sectional study, we recruited a total of 377 patients with nasopharyngeal carcinoma. The Nutritional Risk Screening 2002 tool was used to assess their nutritional risk. These patients were divided into a well-nourished group (n = 222) and a nutritional risk group (n = 155). Potential risk factors were screened out using univariate analysis (p < 0.1). These factors were subsequently analyzed with multivariate logistic regression analysis (p < 0.05) to identify the nutritional risk factors for these patients. Results: Our findings indicated that increasing age (OR = 1.085, 95%CI: 1.053-1.117, p < 0.001), high number of radiation treatments (OR = 1.103, 95%CI: 1.074-1.132, p < 0.001), low BMI (OR = 0.700, 95%CI: 0.618-0.793, p < 0.001), and low albumin levels (OR = 0.852, 95%CI: 0.789-0.921, p < 0.001) are significant nutritional risk factors in patients with nasopharyngeal carcinoma. Conclusion: Increasing age, high number of radiation treatments, low BMI, and low albumin levels are significant nutritional risk factors in patients with nasopharyngeal carcinoma.

2.
Plant J ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606539

RESUMO

The Phyllanthaceae family comprises a diverse range of plants with medicinal, edible, and ornamental value, extensively cultivated worldwide. Polyploid species commonly occur in Phyllanthaceae. Due to the rather complex genomes and evolutionary histories, their speciation process has been still lacking in research. In this study, we generated chromosome-scale haplotype-resolved genomes of two octoploid species (Phyllanthus emblica and Sauropus spatulifolius) in Phyllanthaceae family. Combined with our previously reported one tetraploid (Sauropus androgynus) and one diploid species (Phyllanthus cochinchinensis) from the same family, we explored their speciation history. The three polyploid species were all identified as allopolyploids with subgenome A/B. Each of their two distinct subgenome groups from various species was uncovered to independently share a common diploid ancestor (Ancestor-AA and Ancestor-BB). Via different evolutionary routes, comprising various scenarios of bifurcating divergence, allopolyploidization (hybrid polyploidization), and autopolyploidization, they finally evolved to the current tetraploid S. androgynus, and octoploid S. spatulifolius and P. emblica, respectively. We further discuss the variations in copy number of alleles and the potential impacts within the two octoploids. In addition, we also investigated the fluctuation of metabolites with medical values and identified the key factor in its biosynthesis process in octoploids species. Our study reconstructed the evolutionary history of these Phyllanthaceae species, highlighting the critical roles of polyploidization and hybridization in their speciation processes. The high-quality genomes of the two octoploid species provide valuable genomic resources for further research of evolution and functional genomics.

3.
Support Care Cancer ; 32(4): 256, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546900

RESUMO

BACKGROUND: For patients with nasopharyngeal carcinoma (NPC), the incidence of malnutrition is quite high, and malnutrition has severe effects on NPC patients. However, there is currently no recognized gold standard or specific nutritional assessment tool available to assess malnutrition in NPC patients. Our objective was to develop and verify a new nomogram model for NPC patients. METHODS: Data were collected from NPC patients. To evaluate risk factors for malnutrition, univariate and multivariate logistic regression analyses were used. Based on the risk factors, a new nomogram model was developed. The efficacy of the model was evaluated and validated. RESULTS: Logistic regression analysis showed that age ≥ 65 years, the number of chemotherapy cycles completed ≥ 1, a high total radiation dose received, low body mass index (BMI), low albumin, and low chloride were the risk factors. The assessment effect of the new model was good by evaluation and validation; it can be used as an assessment tool for malnutrition in NPC patients. CONCLUSIONS: Age ≥ 65 years, completing ≥ 1 chemotherapy cycles, a high total radiation dose received, low BMI, low albumin, and low chloride levels are risk factors for malnutrition in NPC patients. The assessment effect of the new model, developed based on these risk factors, is good, and it can be used as an assessment tool for malnutrition in NPC patients.


Assuntos
Desnutrição , Neoplasias Nasofaríngeas , Humanos , Idoso , Carcinoma Nasofaríngeo/patologia , Nomogramas , Neoplasias Nasofaríngeas/radioterapia , Cloretos/uso terapêutico , Fatores de Risco , Desnutrição/epidemiologia , Desnutrição/etiologia , Albuminas
4.
Nutrition ; 116: 112199, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37722250

RESUMO

OBJECTIVES: It is necessary to construct an evaluation index for patients with nasopharyngeal carcinoma during peri-radiotherapy to provide a reference for the evaluation of the quality of nutritional management of patients with nasopharyngeal carcinoma during peri-radiotherapy. The aim of this study was to construct a set of scientific, comprehensive, and feasible indicators for evaluating the quality of nutrition management in patients with nasopharyngeal carcinoma during peri-radiotherapy to provide a unified reference basis for objective nutritional evaluation of these patients during the peri-radiotherapy period and to provide insights to the clinical treatment and care of these patients. METHODS: A multidisciplinary research team was set up from December 2021 to April 2022. We took the three-dimensional quality structure model as the theoretical framework; based on the literature review, the first draft of the nutrition management quality evaluation index for patients with nasopharyngeal carcinoma during peri-radiotherapy was formed by a semi-structured interview. The Delphi correspondence method was used to survey 18 experts from 12 cities in China. The multidimensional analytical hierarchy process was used to determine the evaluation index and weight of nutrition management quality of patients with nasopharyngeal carcinoma during peri-radiotherapy. RESULTS: The effective questionnaire recovery rates of the two rounds of letters were 90.005% and 100%, respectively, and the expert authority coefficients were 0.906 and 0.918, respectively. The Kendall harmony coefficients of the two rounds of letters were 0.271 to 0.313 and 0.309 to 0.349, respectively. The nutrition management quality evaluation index of patients with nasopharyngeal carcinoma during peri-radiotherapy was constructed and included 3 first-level indexes, 10 second-level indexes, and 71 third-level indexes. CONCLUSION: The evaluation index of the nutrition management quality of patients with nasopharyngeal carcinoma during peri-radiotherapy is scientific and reliable, and it may have a certain guiding significance for nurses to evaluate the quality of nutrition management of these patients during this period.


Assuntos
Neoplasias Nasofaríngeas , Avaliação Nutricional , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , China
5.
Phytochemistry ; 213: 113771, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37352949

RESUMO

Herein, 13 previously undescribed neo-clerodane diterpenoids (1-13) and 27 known analogs (14-40) were isolated from the aerial parts of Scutellaria barbata. Absolute configurations of undescribed compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of experimental and circular dichroism. All isolates were evaluated for the inhibition of nitric oxide generation induced by lipopolysaccharide in RAW 264.7 macrophages. Compound 36 was found to be the most active with an IC50 value of 10.6 µM. Structure-activity relations of these neo-clerodane diterpenoids revealed that the α, ß-unsaturated-γ-lactone moiety with an exocyclic conjugated double bond was necessary for maintaining and increasing its activity. Further mechanistic studies show that compound 36 suppressed nitric oxide synthase enzymes (iNOS) expression without affecting iNOS activity. Additionally, compound 36 suppresses NF-κB signaling by inhibiting IκBα phosphorylation.


Assuntos
Diterpenos Clerodânicos , Scutellaria , Estrutura Molecular , Diterpenos Clerodânicos/farmacologia , Diterpenos Clerodânicos/química , Scutellaria/química , Lipopolissacarídeos/farmacologia , Macrófagos , Óxido Nítrico
6.
Support Care Cancer ; 31(5): 251, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37036536

RESUMO

OBJECTIVE: This study is to explore the effect of the Plan-Do-Check-Act (PDCA) cycle on the nutritional management of patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 100 NPC patients were randomly divided into a control group and a PDCA group, with 50 patients in each group. The control group adopted a routine nutritional management strategy, and the PDCA group adopted a PDCA cycle management strategy. The body weight, body mass index (BMI), hemoglobin, serum prealbumin, serum albumin, the Patient-Generated Subjective Global Assessment (PG-SGA) score, the Nutrition Risk Screening 2002 (NRS-2002) score, the incidence rate of nutritional risk, the grade of malnutrition, and the grade of oral mucositis were compared between the two groups. RESULTS: The body weight, BMI, and serum prealbumin in the PDCA group were higher than those in the control group, and the difference was statistically significant (p < 0.05). The NRS2002 score and PG-SGA score in the PDCA group were lower than those in the control group, and the differences were statistically significant (p < 0.05). The incidence of nutritional risk, the grade of malnutrition, and the grade of oral mucositis were less in the PDCA group than those in the control group (p < 0.05). There was no significant difference in hemoglobin and serum albumin between the two groups (p > 0.05). CONCLUSION: The PDCA cycle can improve body weight, BMI, and serum prealbumin in NPC patients. It can reduce the NRS2002 score, the PG-SGA score, the incidence of nutritional risk, the severity of malnutrition, and the severity of oral mucositis in NPC patients.


Assuntos
Desnutrição , Neoplasias Nasofaríngeas , Estomatite , Humanos , Pré-Albumina , Avaliação Nutricional , Carcinoma Nasofaríngeo/terapia , Estado Nutricional , Desnutrição/etiologia , Desnutrição/prevenção & controle , Peso Corporal , Albumina Sérica , Neoplasias Nasofaríngeas/terapia , Hemoglobinas , Estomatite/complicações
7.
Int J Mol Sci ; 24(5)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36901746

RESUMO

Glucokinase-maturity onset diabetes of the young (GCK-MODY) is a kind of rare diabetes with low incidence of vascular complications caused by GCK gene inactivation. This study aimed to investigate the effects of GCK inactivation on hepatic lipid metabolism and inflammation, providing evidence for the cardioprotective mechanism in GCK-MODY. We enrolled GCK-MODY, type 1 and 2 diabetes patients to analyze their lipid profiles, and found that GCK-MODY individuals exhibited cardioprotective lipid profile with lower triacylglycerol and elevated HDL-c. To further explore the effects of GCK inactivation on hepatic lipid metabolism, GCK knockdown HepG2 and AML-12 cell models were established, and in vitro studies showed that GCK knockdown alleviated lipid accumulation and decreased the expression of inflammation-related genes under fatty acid treatment. Lipidomic analysis indicated that the partial inhibition of GCK altered the levels of several lipid species with decreased saturated fatty acids and glycerolipids including triacylglycerol and diacylglycerol, and increased phosphatidylcholine in HepG2 cells. The hepatic lipid metabolism altered by GCK inactivation was regulated by the enzymes involved in de novo lipogenesis, lipolysis, fatty acid ß-oxidation and the Kennedy pathway. Finally, we concluded that partial inactivation of GCK exhibited beneficial effects in hepatic lipid metabolism and inflammation, which potentially underlies the protective lipid profile and low cardiovascular risks in GCK-MODY patients.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/genética , Ácidos Graxos , Glucoquinase/metabolismo , Hepatócitos/metabolismo , Inflamação/complicações , Metabolismo dos Lipídeos , Mutação , Triglicerídeos
8.
Int J Hematol ; 117(3): 428-437, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36378406

RESUMO

BACKGROUND/OBJECTIVE: Cryopreservation of grafts is not common practice in allogeneic hematopoietic stem cell transplant (HSCT) recipients. However, our center had to use cryopreserved cells for allogeneic HSCT during the COVID-19 pandemic to avoid delays in transplantation due to uncertainty regarding patient and donor exposures. STUDY DESIGN: We retrospectively evaluated post-transplant engraftment and survival outcomes of adult patients who received cryopreserved versus fresh allografts during the COVID-19 pandemic. RESULTS: Fifty-five patients with hematologic malignancies received either cryopreserved (n = 34) or fresh (n = 21) allogeneic HSCT using peripheral blood stem cells between January 2020 and December 2020. At a median follow-up time of 15 months, cryopreserved allograft recipients had significantly lower overall survival (OS) (p = 0.02). They also experienced significantly delayed neutrophil (p = 0.01) and platelet engraftments (p < 0.0001), as well as higher red blood cell transfusion-dependence after day + 60 (67.6% vs. 28.6%; p = 0.01). Significantly more cryopreserved allograft recipients received donor lymphocyte infusion than fresh allograft recipients (35.3% vs. 4.8%, p = 0.01). Neither relapse-free survival nor non-relapse mortality differed significantly between the two groups. CONCLUSION: Cryopreservation of allografts in combination with post-transplant cyclophosphamide may negatively affect engraftment and OS outcomes in HSCT recipients.


Assuntos
COVID-19 , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Adulto , Humanos , Estudos Retrospectivos , Pandemias , Recidiva Local de Neoplasia/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ciclofosfamida/uso terapêutico , Criopreservação , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle
9.
Front Pharmacol ; 13: 1045235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467062

RESUMO

Aims: Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs). Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4. Results: Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups versus placebo or standard diabetes therapies (SMD: -1.21; 95% CI: -1.91, -0.52, p < 0.001). The effects of CRP (SMD: 0.25; 95% CI: -0.47, -0.03, p = 0.02) and leptin (SMD: -0.22; 95% CI: -0.43, -0.01, p = 0.04) were reduced, and the effects of adiponectin were improved (SMD: 0.28; 95% CI: 0.15, 0.41, p < 0.001) in placebo-controlled studies. PAI-1 levels were significantly reduced in studies controlled for diabetes therapies (SMD: -0.38; 95% CI: -0.61, -0.15, p = 0.001). Conclusion: This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.

11.
J Immunother ; 45(9): 389-395, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36066505

RESUMO

Immune checkpoint inhibitors (ICIs) can cause a variety of immune-related adverse events (irAEs). The coronavirus disease 2019 (COVID-19) is associated with increased amounts of pro-inflammatory cytokines, which may affect the outcome of irAEs. Data are limited regarding the impact of COVID-19 on irAEs in ICI-treated cancer patients. Hence, in this study, we retrospectively analyzed ICI-treated adult patients with malignant solid tumors at a single institution between August 2020 and August 2021. Patients who had the most recent ICI treatment over 1-month before or after the positive COVID-19 test were excluded from the study. For the COVID-19 positive group, only the irAEs that developed after COVID-19 infection were considered as events. A total of 579 patients were included in our study, with 46 (7.9%) in the COVID-19 positive group and 533 (92.1%) in the COVID-19 negative group. The baseline characteristics of patients in the 2 groups were similar. With a median follow-up of 331 days (range: 21-2226), we noticed a nonsignificant higher incidence of all-grade irAEs in the COVID-19 positive group (30.4% vs. 19.9%, P =0.18). The incidence of grade 3 and 4 irAEs was significantly higher in the COVID-19 positive group (10.9% vs. 3.2%, P =0.02). Multivariate analysis confirmed the association between COVID-19 infection and increased risk of severe irAE development (odds ratio: 1.08, 95% confidence interval: 1.02-1.14, P =0.01). Our study suggested that COVID-19 may pose a risk of severe irAEs in cancer patients receiving ICIs. Close monitoring and possibly delaying ICI administration could be considered when cancer patients are infected with COVID-19.


Assuntos
Antineoplásicos Imunológicos , COVID-19 , Neoplasias , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Citocinas , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Estudos Retrospectivos
12.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(2): 181-186, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-36031579

RESUMO

Objective: To investigate the effects of berberine on glucose and lipid metabolism, sex hormone binding protein, adiponectin (LPS), NF-κB and MAPK signaling pathways in polycystic ovary syndrome (PCOS) model rats. Methods: Female SD rats were randomly divided into control group, PCOS model group, berberine (0.216 g/kg) group, metformin (0.135 g/kg) group and Dyne-35 (0.18 mg/kg) group, 10 rats in each group. The rats in PCOS model group were treated with letrozole 1 mg.kg-1 by ig for 3 weeks. After 28 days of drug intervention, the body constitution, ovarian and uterine indexes of the rats were detected, and the changes in the number of ovarian follicles were observed by HE staining. The levels of serum sex hormone, glucose and insulin, triglyceride and cholesterol, sex hormone-binding protein and adiponectin were determined by ELISA, and the protein expressions of p38-MAPK, C-Jun and NF-κB in ovarian tissues were determined by Western blot. Results: Compared with control group, body weight of model group was increased (P<0.05), and uterine index was decreased (P<0.05); The number of follicles was increased (P<0.05). Serum levels of luteinizing hormone (LH), testosterone (T) and LH/FSH ratio were increased (P<0.05), follicular estrogen (FSH) level was decreased (P<0.05), total cholesterol (TC), triglyceride (TG), fasting insulin and insulin index (HOMA) were increased (P< 0.05). The content of sex hormone binding protein (SHBG) was decreased and the content of adiponectin (LPS) was increased (P<0.05). The protein expressions of p38-MAPK, c-Jun and NF-κB in ovarian tissue were up-regulated (P<0.05). Compared with model group, in berberine group, the uterine index and the number of secondary follicles were increased(P<0.05), the serum levels of luteinizing hormone (LH) , testosterone (T) and the ratio of LH/FSH were decreased (P<0.05), and the protein expression levels of p38-MAPK and NF-κB in ovarian tissue were down-regulated (P<0.05), which were similar to those of Dyne-35 group. Berberine significantly decreased serum triglyceride (TG), insulin level and insulin index (P<0.05), increased serum SHBG level and decreased serum LPS level (P<0.05), which were similar to those of metformin. Conclusion: Berberine can regulate sex hormone disorder and insulin resistance (IR) in PCOS rats by down-regulating the expressions of p38-MAPK and NF-κB protein in ovarian tissues and decreasing the serum content of LPS.


Assuntos
Berberina , Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , Transdução de Sinais , Adiponectina , Animais , Berberina/farmacologia , Colesterol , Feminino , Hormônio Foliculoestimulante , Glucose , Hormônios Esteroides Gonadais , Insulina , Lipopolissacarídeos , Hormônio Luteinizante , NF-kappa B , Síndrome do Ovário Policístico/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Testosterona , Triglicerídeos
13.
SN Compr Clin Med ; 4(1): 193, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36043120

RESUMO

Cancer patients are a vulnerable population in the current coronavirus disease 2019 (COVID-19) outbreak. The impact of immune checkpoint inhibitors (ICIs) on the outcomes of COVID-19 infection in cancer patients remains largely unclear. We retrospectively investigated all solid cancer patients who received at least one cycle of ICIs at a single institution between August 2020 and August 2021. All stage IV solid cancer patients who were on or ceased ICI treatment when diagnosed with COVID-19 were eligible. All COVID-19 infections were confirmed by RT-PCR. Risk factors for hospitalization, severe symptoms, and death were analyzed. A total of 56 patients were included in our study. Twenty (35.7%) patients require hospitalization, 12 (21.4%) developed severe symptoms, and 10 (17.9%) died from COVID-19 infection. ICI treatment was interrupted in 37 patients (66.1%), 24 of whom (64.9%) had treatment resumed. Eight (80%) COVID-19-related death occurred in unvaccinated individuals. Reinfection occurred in seven patients (12.5%), and three of them died from their second COVID-19 infection. Factors associated with hospitalization were high Charlson comorbidity score (OR 1.56, 95% CI 1.10-2.23, p = 0.01) and lymphocyte ≤ 1500 mm3 (OR 10.05, 95% CI 2.03-49.85, p = 0.005). Age, chemoimmunotherapy, and ICI treatment duration were not associated with increased risk of hospitalization, severe symptoms, or COVID-19-related mortality. ICI therapy does not impose an increased risk for severe COVID-19 infection in stage IV cancer patients. Vaccination should be encouraged among this population. Clinicians should be cognizant of a potential worse outcome in COVID-19-reinfected patients.

14.
BMJ Case Rep ; 15(6)2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35667697

RESUMO

Primary breast lymphoma (PBL) is an uncommon type of breast malignancy. Its clinical presentation and radiographic findings are non-specific and overlap with breast carcinoma. The treatment of PBL differs significantly from breast carcinomas. Here we present a middle-aged woman who presented with an enlarging palpable right breast mass. Mammogram showed breast imaging-reporting and data system 4 findings. Breast mass biopsy pathology confirmed diffuse large B cell lymphoma. Although uncommon, clinicians should be cognisant of the possibility of PBL when patients present with a breast mass. Accurate diagnosis is essential to avoid unnecessary mastectomies.


Assuntos
Neoplasias da Mama , Linfoma Difuso de Grandes Células B , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/patologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Mamografia , Mastectomia , Pessoa de Meia-Idade
15.
Front Cell Dev Biol ; 9: 766815, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796178

RESUMO

Nutritional microenvironment determines the specification of progenitor cells, and lipid availability was found to modulate osteogenesis in skeletal progenitors. Here, we investigated the implications of lipid scarcity in the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) and the role of low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor transducing canonical Wnt/beta-catenin signals, in BMSC lipid uptake during osteogenesis. The osteogenic differentiation of murine BMSCs was suppressed by lipid scarcity and partially rescued by additional fatty acid treatment with oleate. The enhancement of osteogenesis by oleate was found to be dosage-dependent, along with the enhanced activation of beta-catenin and Wnt target genes. Conditional knockout (CKO) of Lrp5 gene in murine mesenchymal lineage using Lrp5 fl/fl ;Prrx1-cre mice led to decreased bone quality and altered fat distribution in vivo. After Lrp5 ablation using adenoviral Cre-recombinase, the accumulation of lipid droplets in BMSC cytoplasm was significantly reduced, and the osteogenesis of BMSCs was suppressed. Moreover, the impaired osteogenesis due to either lipid scarcity or Lrp5 ablation could be rescued by recombinant Wnt3a protein, indicating that the osteogenesis induced by Wnt/beta-catenin signaling was independent of LRP5-mediated lipid uptake. In conclusion, lipid scarcity suppresses BMSC osteogenic differentiation. LRP5 plays a role in the uptake of lipids in BMSCs and therefore mediates osteogenic specification.

16.
J Nanobiotechnology ; 19(1): 209, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256779

RESUMO

BACKGROUND: The therapeutic potential of exosomes derived from stem cells has attracted increasing interest recently, because they can exert similar paracrine functions of stem cells and overcome the limitations of stem cells transplantation. Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) have been confirmed to promote osteogenesis and angiogenesis. The magnetic nanoparticles (eg. Fe3O4, γ-Fe2O3) combined with a static magnetic field (SMF) has been commonly used to increase wound healing and bone regeneration. Hence, this study aims to evaluate whether exosomes derived from BMSCs preconditioned with a low dose of Fe3O4 nanoparticles with or without the SMF, exert superior pro-osteogenic and pro-angiogenic activities in bone regeneration and the underlying mechanisms involved. METHODS: Two novel types of exosomes derived from preconditioned BMSCs that fabricated by regulating the contents with the stimulation of magnetic nanoparticles and/or a SMF. Then, the new exosomes were isolated by ultracentrifugation and characterized. Afterwards, we conducted in vitro experiments in which we measured osteogenic differentiation, cell proliferation, cell migration, and tube formation, then established an in vivo critical-sized calvarial defect rat model. The miRNA expression profiles were compared among the exosomes to detect the potential mechanism of improving osteogenesis and angiogenesis. At last, the function of exosomal miRNA during bone regeneration was confirmed by utilizing a series of gain- and loss-of-function experiments in vitro. RESULTS: 50 µg/mL Fe3O4 nanoparticles and a 100 mT SMF were chosen as the optimum magnetic conditions to fabricate two new exosomes, named BMSC-Fe3O4-Exos and BMSC-Fe3O4-SMF-Exos. They were both confirmed to enhance osteogenesis and angiogenesis in vitro and in vivo compared with BMSC-Exos, and BMSC-Fe3O4-SMF-Exos had the most marked effect. The promotion effect was found to be related to the highly riched miR-1260a in BMSC-Fe3O4-SMF-Exos. Furthermore, miR-1260a was verified to enhance osteogenesis and angiogenesis through inhibition of HDAC7 and COL4A2, respectively. CONCLUSION: These results suggest that low doses of Fe3O4 nanoparticles combined with a SMF trigger exosomes to exert enhanced osteogenesis and angiogenesis and that targeting of HDAC7 and COL4A2 by exosomal miR-1260a plays a crucial role in this process. This work could provide a new protocol to promote bone regeneration for tissue engineering in the future.


Assuntos
Indutores da Angiogênese/farmacologia , Osso e Ossos/efeitos dos fármacos , Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/metabolismo , Osteogênese/efeitos dos fármacos , Animais , Regeneração Óssea/efeitos dos fármacos , Diferenciação Celular , Movimento Celular , Proliferação de Células , Colágeno Tipo IV/metabolismo , Biologia Computacional , Exossomos , Histona Desacetilases/metabolismo , Humanos , Campos Magnéticos , Masculino , Ratos , Cicatrização
17.
World J Clin Oncol ; 12(4): 282-289, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33959481

RESUMO

BACKGROUND: Sarcomatoid carcinoma is a rare subtype of non-small-cell lung cancer, commonly associated with locally advanced disease, early metastasis, and poor prognosis. Tongue metastasis from lung cancer is a rare condition that may occur in advanced stage of the disease. CASE SUMMARY: The patient was a 70-year-old female with a history of resected pulmonary sarcomatoid carcinoma (PSC) who presented with subacute tongue swelling, imparting the clinical impression of a lingual abscess. However, histologic examination of the partial glossectomy revealed a high-grade, poorly differentiated spindle and epithelioid carcinoma consistent with metastatic PSC. CONCLUSION: Although uncommon, clinicians should be cognizant of the possibility of a metastatic process to the tongue mimicking a benign or inflammatory process. A high index of suspicion for metastatic disease should be maintained when tongue swelling is observed in patients with a known history of PSC.

18.
Endocr Pract ; 27(8): 776-782, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33991656

RESUMO

OBJECTIVE: Genetic detection for the diagnosis of maturity-onset diabetes of the young (MODY) in China has low sensitivity and specificity. Better gene detection is urgently needed to distinguish testing subjects. We proposed to use numerous and weighted clinical traits as key indicators for reasonable genetic testing to predict the probability of MODY in the Chinese population. METHODS: We created a prediction model based on data from 306 patients, including 140 patients with MODY, 84 patients with type 1 diabetes (T1D), and 82 patients with type 2 diabetes (T2D). This model was evaluated using receiver operating characteristic curves. RESULTS: Compared with patients with T1D, patients with MODY had higher C-peptide levels and negative antibodies, and most patients with MODY had a family history of diabetes. Different from T2D, MODY was characterized by lower body mass index and younger diagnostic age. A clinical prediction model was established to define the comprehensive probability of MODY by a weighted consolidation of the most distinguishing features, and the model showed excellent discrimination (areas under the curve of 0.916 in MODY vs T1D and 0.942 in MODY vs T2D). Further, high-sensitivity C-reactive protein, glycated hemoglobin A1c, 2-h postprandial glucose, and triglyceride were used as indicators for glucokinase-MODY, while triglyceride, high-sensitivity C-reactive protein, and hepatocellular adenoma were used as indicators for hepatocyte nuclear factor 1-α MODY. CONCLUSION: We developed a practical prediction model that could predict the probability of MODY and provide information to identify glucokinase-MODY and hepatocyte nuclear factor 1-α MODY. These results provide an advanced and more reasonable process to identify the most appropriate patients for genetic testing.


Assuntos
Diabetes Mellitus Tipo 2 , China/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Humanos , Modelos Estatísticos , Mutação , Prognóstico
19.
Basic Clin Pharmacol Toxicol ; 129(1): 61-71, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33834601

RESUMO

Cantharidin (CTD) is a promising anticancer drug; however, its dosage is limited by hepatotoxicity. We previously showed that Astragalus polysaccharides (APS) effectively improved chemical liver injury. In this study, we established a CTD-induced subacute liver injury mouse model and examined the effects of APS on weight, liver indexes, histopathology, serum biochemical indexes and liver metabolism. Compared with the control group, mice in the CTD model group had obvious liver damage, which was partially prevented by APS. Metabolomics demonstrated that CTD caused liver damage mainly by regulating glycerophospholipid metabolism, ABC transporter pathways and choline metabolism in cancer in vivo. APS regulated primary bile acid biosynthesis and glycerophospholipid metabolism, thus decreasing the liver damage caused by CTD. This study revealed the protective mechanism of APS against CTD-induced liver injury from the perspective of metabolomics. The results provide an important basis for analysing the mechanism of CTD-induced liver toxicity and for assessing clinical treatment options to reduce CTD liver toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Astrágalo/química , Cantaridina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Polissacarídeos/administração & dosagem , Transportadores de Cassetes de Ligação de ATP/análise , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Antineoplásicos/administração & dosagem , Cantaridina/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colina/análise , Colina/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Modelos Animais de Doenças , Glicerofosfolipídeos/análise , Glicerofosfolipídeos/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Metabolômica/métodos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Espectrometria de Massas em Tandem/métodos
20.
Int J Nanomedicine ; 15: 7979-7993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116513

RESUMO

BACKGROUND: Both magnetic nanoparticles (MNPs) and exosomes derived from bone mesenchymal stem cells (BMSC-Exos) have been reported to improve wound healing. In this study, novel exosomes (mag-BMSC-Exos) would be fabricated from BMSCs with the stimulation of MNPs and a static magnetic field (SMF) to further enhance wound repair. METHODS: Mag-BMSC-Exos, namely, exosomes derived from BMSCs preconditioned with Fe3O4 nanoparticles and a SMF, together with BMSC-Exos were both first isolated by ultracentrifugation, respectively. Afterwards, we conducted in vitro experiments, including scratch wound assays, transwell assays, and tube formation assays, and established an in vivo wound healing model. The miRNA expression profiles were compared between BMSC-Exos and mag-BMSC-Exos to detect the potential mechanism of improving wound healing. At last, the function of exosomal miR-21-5p during wound healing was confirmed by utilizing a series of gain- and loss-of-function experiments in vitro. RESULTS: The optimal working magnetic condition was 50 µg/mL Fe3O4 nanoparticles combined with 100 mT SMF. In vitro, mag-BMSC-Exo administration promoted proliferation, migration and angiogenesis to a greater extent than BMSC-Exo administration. Local transplantation of mag-BMSC-Exos into rat skin wounds resulted in accelerated wound closure, narrower scar widths and enhanced angiogenesis compared with BMSC-Exo transplantation. Notably, miR-21-5p was found to be highly enriched in mag-BMSC-Exos and served as a critical mediator in mag-BMSC-Exo-induced regulatory effects through inhibition of SPRY2 and activation of the PI3K/AKT and ERK1/2 signaling pathways. CONCLUSION: Mag-BMSC-Exos can further enhance wound healing than BMSC-Exos by improving angiogenesis and fibroblast function, and miR-21-5p upregulation in mag-BMSC-Exos might be the potential mechanism. This work offers an effective and promising protocol to improve wound healing in clinic.


Assuntos
Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Campos Magnéticos , Nanopartículas de Magnetita , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Regulação para Cima , Cicatrização , Animais , Fibroblastos/citologia , Fibroblastos/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas do Tecido Nervoso/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos
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