Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.175
Filtrar
1.
Aging (Albany NY) ; 132021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33795523

RESUMO

Human Mesenchymal stem cells (hMSCs) are multi-potential cells which are widely used in cell therapy. However, the frequently emerged senescence and decrease of differentiation capabilities limited the broad applications of MSC. Several strategies such as small molecules treatment have been widely studied and used to improve the stem characteristics bypassing the senescence but the exact mechanisms for them to reduce senescence have not been fully studied. In this study, hMSCs were treated by rapamycin, oltipraz, metformin, and vitamin C for the indicated time and these cells were subjected to senescence evaluation and trilineage differentiation. Furthermore, transcriptomics and lipidomics datasets of hMSCs after drug treatment were analyzed to interpret biological pathways responsible for their anti-senescence effects. Although four drugs exhibited significant activities in promoting MSC osteogenic differentiation, metformin is the optimal drug to promote trilineage differentiation. GO terms illustrated that the anti-aging effects of drugs were mainly associated with cellular senescence, mitotic and meiosis process. Biosynthesis of phosphatidylcholines (PC) and phosphatidylethanolamine (PE) were inhibited whereas production of phosphatidylinositols (PIs) and saturated fatty acids (SFA)/ mono-unsaturated fatty acids (MUFA) conversion was activated. Medium free fatty acids (FFA) was increased in hMSCs with different anti-aging phenotypes. Therefore, we established a comprehensive method in assessing drug intervention based on the results of transcriptomics and lipidomics. The method can be used to study different biological phenotypes upon drug intervention in MSC which will extend the clinical application of hMSCs.

2.
Clin Nucl Med ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795592

RESUMO

ABSTRACT: Langerhans cell histiocytosis (LCH) is a rare proliferative histiocytic disorder. It mainly occurs in the pediatric population, whereas it is rarely reported in adults. Herein, we reported a case of a patient with isolated rib LCH, which showed elevated 18F-FDG uptake. Our case showed that 18F-FDG PET/CT can be a potential tool in the evaluation of LCH.

3.
Clin Nucl Med ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33826568

RESUMO

ABSTRACT: A 59-year-old woman with newly diagnosed pulmonary nodules underwent both 18F-FDG and 68Ga-FAPI PET/CT. Both studies showed similarly increased uptake in pneumonia. However, only 68Ga-FAPI PET/CT showed increased uptake in splenic hemangioma, whereas FDG uptake in the splenic lesion is low. Our case illustrates that splenic hemangioma can also reveal increased FAPI activity.

4.
Clin Nucl Med ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33826570

RESUMO

ABSTRACT: 68Ga-labeled quinoline-based fibroblast activation protein inhibitors (68Ga-FAPIs) has been used in the evaluation of a variety of malignancies. We report the case of a patient with rib plasmacytoma, which showed elevated 68Ga-FAPI activity. This case indicated fibroblast activation protein overexpression and some degree of fibrosis in the plasmacytoma lesion. Therefore, 68Ga-FAPI can be a potential tracer in the evaluation of plasmacytoma.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 316-321, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812393

RESUMO

OBJECTIVE: To investigate the efficacy and safety of micro-transplantation in acute myeloid leukemia (AML). METHODS: The clinical data of 13 adult AML patients who received micro-transplantation as consolidation therapy from July 2014 to October 2019 was retrospectively analyzed, and the adverse reactions and efficacy of micro-transplantation were followed up. RESULTS: Eight patients received micro-transpantation were still in complete remission, 5 patients relapsed after micro-transplantation, 1 of them received umbilical cord blood micro-transplantation after remission by reinduction, and all of the 13 patients have survived till now. The median overall survival time was 13 months, and the median relapse-free survival time was 12 months. All 13 patients developed grade 2-4 hematological adverse reactions. The median recovery time of neutrophils and platesets was 13 (11-15) and 15 (13-17) days, respectively. None of the 13 patients developed acute or chronic graft versus host disease. Twelve patients suffered from different infections, however, there were no serious organ function injury complications happened. CONCLUSION: The micro-transplomtation of HLA-incompatible stem cells derived from peripheral blood or umbilical and blood is an effective regimen for the consolidation therapy of AML, especially for the patients suffered from low and moderate risk of AML or the aged AML patients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Idoso , Quimioterapia de Consolidação , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do Tratamento
6.
Mar Drugs ; 19(4)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807472

RESUMO

We have accomplished a 10-step (longest linear) total synthesis of nannocystin A on a four hundred milligram scale. The previously reported Kobayashi vinylogous Mukaiyama aldol reaction to connect C4 and C5 was unreproducible during the scaling up process. A more convenient and cost-efficient Keck asymmetric vinylogous aldol reaction was employed to improve this transformation.

7.
World J Surg Oncol ; 19(1): 99, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823871

RESUMO

BACKGROUND: The American Society of Colon and Rectal Surgeons is suggesting laparoscopic surgeries for colorectal cancer. Conventional perioperative procedures like long preoperative fasting and bowel procedures are not useful and harmful to patients undergoing surgeries for colorectal cancer. The objectives of the study were to compare surgery outcomes, hospital stays, and survival of patients who received fast-track (laparoscopy/open) surgical procedure followed by chemotherapy against those who received conventional (laparoscopy/open) surgical procedure followed by chemotherapy for colorectal cancer. METHODS: The study analyzes the outcomes of a total of 542 colorectal cancer (preoperative biopsies stage II or III) patients submitted to surgery and adjuvant chemotherapy. The study cohort is retrospectively subdivided in 4 groups submitted to open or laparoscopic resection with or without fast-track protocol appliance and two different chemotherapy regimens. Patients who ended up being TNM stage I have not received the adjuvant chemotherapy. RESULTS: The fast-track surgical procedure had shorter total hospital stays and postoperative hospital stays than the conventional surgical procedures. Flatus resumption time, the time until first defecation, and intraoperative blood loss were shorter for the fast-track surgical procedures than the conventional surgical procedures. Those surgery outcomes were also shorter for the fast-track laparoscopy than the open fast-track. Resumption of a fluid diet and ambulation onset time were shorter for the fast-track surgical procedures than the conventional surgical procedures. The surgical checkpoints that were compliance by patient of fast-track surgeries were significantly fewer than those of the conventional surgeries. Clinically significant difference for QLQ-C30/CR38 score after chemotherapy was reported between patients who received open conventional surgeries and those patients who received fast-track laparoscopy (59.63 ± 2.26 score/patient vs. 71.67 ± 5.19 score/patient). There were no significant differences for the number of patients with any grade adverse effects (p = 0.431) or with grade 3-4 adverse effects (p = 0.858), and the disease-free and overall survival among cohorts. CONCLUSIONS: The fast-track surgical procedure is effective and safe even in a multidisciplinary scenario as colorectal cancer treatment in which surgery is only a part of management. LEVEL OF EVIDENCE: III: Technical efficacy stage: 4.

8.
Sci Rep ; 11(1): 7591, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33828166

RESUMO

The relevance of pregestational body mass index (BMI) on adverse pregnancy outcomes remained unclear in Southwest China. This study aimed to investigate the overall and age-category specific association between pre-gestational BMI and gestational diabetes mellitus (GDM), preeclampsia, cesarean delivery, preterm delivery, stillbirth, macrosomia, and small-for-gestational age (SGA) or large-for-gestational age (LGA) neonates in Southwest China. Furthermore, it explores the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. 51,125 Chinese singleton pregnant women were recruited as study subjects. Multiple logistic regression models were used to examine the influence of pre-pregnancy BMI on adverse pregnancy outcomes. Gradient boosting machine was used to evaluate the relative importance of influence of pregravid BMI and maternal age on pregnancy outcomes. It is found that women who were overweight or obese before pregnancy are at higher risk of adverse pregnancy outcomes except for SGA neonates, while pre-pregnancy underweight is a protective factor for GDM, preeclampsia, cesarean delivery, macrosomia and LGA, but not SGA. Younger mothers are more susceptible to GDM and macrosomia neonates, while older mothers are more prone to preeclampsia. Pre-pregnancy BMI has more influence on various pregnancy outcomes than maternal age. To improve pregnancy outcomes, normal BMI weight as well as relatively young maternal ages are recommended for women in child-bearing age.

9.
Chin J Integr Med ; 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33837482

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS: A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS: The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION: The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

10.
Artigo em Inglês | MEDLINE | ID: mdl-33829416

RESUMO

PURPOSE: Renal fibrosis is a pathological state in the progression of chronic kidney disease. Early detection and treatment are vital to prolonging patient survival. Renal puncture examination is the gold standard for renal fibrosis, but it has several limitations. This study aims to evaluate the diagnostic performance of a novel PET radiotracer, [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04, which specifically images fibroblast activation protein (FAP) expression for renal fibrosis. METHODS: All patients underwent renal puncture before receiving [68Ga]Ga-FAPI-04 PET/CT imaging. They then underwent [68Ga]Ga-FAPI-04 PET/CT and immunochemistry examinations. The data obtained were analyzed. RESULTS: The [68Ga]Ga-FAPI-04 PET/CT examination results demonstrated that almost all patients (12/13) exhibited increased radiotracer uptake. The maximum standardized uptake value (SUVmax) in patients with mild, moderate, and severe fibrosis was 3.92 ± 1.50, 5.98 ± 1.6, and 7.67 ± 2.23, respectively. CONCLUSION: Compared with renal puncture examination, non-invasive imaging of FAP expression through [68Ga]Ga-FAPI-04 PET/CT quickly demonstrates bilateral kidney conditions with high sensitivity. [68Ga]Ga-FAPI-04 PET/CT can facilitate the evaluation of disease progression, diagnosis, and the development of a treatment plan.

11.
Anat Sci Educ ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33829672

RESUMO

Dental anatomy is an integrated, core fundamental dental course, which prepares students for all future clinical dental courses. This study aimed to build up an online dental learning platform of micro-computed tomography-based three-dimensional (3D) tooth models with pulp cavity, and to further evaluate its effectiveness for dental anatomy education using a cohort study. First, ninety-six extracted permanent teeth were scanned by micro-computed tomography and the enamel, dentine, and pulp cavity of each was distinguished by different grey-scale intensities using Mimics software. Three-dimensional images allowed further discrimination and insights into permanent three-rooted premolars, central tip, and dental diseases including deep caries and wedge-shaped defects. Furthermore, a second mesiobuccal canal (MB2) in maxillary permanent molar teeth and Vertucci type III root canal configuration in mandibular anterior teeth could be detected using the 3D analytical tool. A digitized 3D tooth model learning platform was implemented. Lastly, two groups of dental students were assessed to evaluate the effect of 3D models on dental anatomy education. Participants in the Digital group were allowed to use the online dental learning platform freely after class, while the participants in the Traditional group were not. Assessment quizzes showed that participants' scores improved in the Digital group with the use of the learning platform compared with scores in the Traditional group. A questionnaire survey indicated that the participants had a positive attitude towards the 3D models. Thus, adding digital 3D resources to a traditional curriculum may have a positive effect on academic achievements.

12.
J Med Chem ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33829783

RESUMO

The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was recently implicated as a synthetic lethal target in cancers with deletion of the methylthioadenosine phosphorylase (MTAP) gene, which is adjacent to the CDKN2A tumor suppressor and codeleted with CDKN2A in approximately 15% of all cancers. Previous attempts to target MAT2A with small-molecule inhibitors identified cellular adaptations that blunted their efficacy. Here, we report the discovery of highly potent, selective, orally bioavailable MAT2A inhibitors that overcome these challenges. Fragment screening followed by iterative structure-guided design enabled >10 000-fold improvement in potency of a family of allosteric MAT2A inhibitors that are substrate noncompetitive and inhibit release of the product, S-adenosyl methionine (SAM), from the enzyme's active site. We demonstrate that potent MAT2A inhibitors substantially reduce SAM levels in cancer cells and selectively block proliferation of MTAP-null cells both in tissue culture and xenograft tumors. These data supported progressing AG-270 into current clinical studies (ClinicalTrials.gov NCT03435250).

13.
Clin Nucl Med ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33782279

RESUMO

ABSTRACT: Solitary non-Hodgkin lymphoma of the trachea is extremely rare. Herein, we reported a case of solitary laryngotracheal lymphoma in a 55-year-old man. He complained of cough, tachypnea, and dyspnea. 18F-FDG PET/CT showed a hypermetabolic lesion in the subglottic larynx and upper cervical trachea. The subsequent histology and immunohistochemistry of the laryngotracheal lesion tissue confirmed the diagnosis of non-Hodgkin lymphoma (mucosa-associated lymphatic tissue lymphoma).

14.
Clin Nucl Med ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33782317

RESUMO

ABSTRACT: 68Ga-FAPI PET/CT has been used in the evaluation of a variety of malignancies. An increasing number of case studies on FAPI uptake in nonmalignant diseases is also gaining support and enthusiasm. We present a case of asymptomatic chronic cholecystitis and degenerative osteophyte detected incidentally by 68Ga-FAPI PET/CT.

16.
Genes Genomics ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33779948

RESUMO

BACKGROUND: The activation of macrophages and the release of inflammatory cytokines are the main reasons for the progress of systemic lupus erythematosus (SLE). MicroRNA (miRNA)-124 is involved in the regulation of macrophages and is a key regulator of inflammation and immunity. OBJECTIVE: To explore whether paeoniflorin (PF) regulates the biological functions of macrophages depends on miR-124. METHODS: RT-PCR, WB, ELISA, CCK-8 and flow cytometry were used to evaluate that PF regulated the biological functions of THP-1 cells through miR-124. RESULTS: PF significantly inhibited the proliferation while promotes the apoptosis of THP-1 cells, and inhibited the release of IL-6, TNF-α and IL-1ßin THP-1 cells. RT-PCR results shown that PF up-regulated the expression of miR-124 in THP-1 cells. Functional recovery experiments showed that compared with the LPS + mimic-NC group, LPS + miR-124 mimic significantly inhibited the proliferation and the release of IL-6, TNF-α and IL-1ß, but promoted the apoptosis of THP-1 cells. In addition, compared with the LPS + PF + inhibitor-NC group, LPS + PF + miR-124 inhibitor significantly promoted the proliferation and the release of IL-6, TNF-α and IL-1ß, but inhibited the apoptosis of THP-1 cells. CONCLUSIONS: By down-regulating miR-124, PF inhibits the proliferation and inflammation of THP-1 cells, and promotes the apoptosis of THP-1 cells.

17.
Cardiovasc Res ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757117

RESUMO

AIMS: Acute aortic dissection (AAD) is a life-threatening disease with high morbidity and mortality. Previous studies have showed that vascular smooth muscle cell (VSMC) phenotype switching modulates vascular function and AAD progression. However, whether an endogenous signaling system that protects AAD progression exists, remains unknown. Our aim is to investigate the role of Anxa1 in VSMC phenotype switching and the pathogenesis of AAD. METHODS AND RESULTS: We first assessed Anxa1 expression levels by immunohistochemical staining in control aorta and AAD tissue from mice. A strong increase of Anxa1 expression was seen in the mouse AAD tissues. In line with these findings, micro-CT scan results indicated that Anxa1 plays a role in the development of AAD in our murine model, with systemic deficiency of Anxa1 markedly progressing AAD. Conversely, administration of Anxa1 mimetic peptide, Ac2-26, rescued the AAD phenotype in Anxa1-/- mice. Transcriptomic studies revealed a novel role for Anxa1 in VSMC phenotype switching, with Anxa1 deficiency triggering the synthetic phenotype of VSMCs via down-regulation of the JunB/MYL9 pathway. The resultant VSMC synthetic phenotype rendered elevated inflammation and enhanced matrix metalloproteinases (MMPs) production, leading to augmented elastin degradation. VSMC-restricted deficiency of Anxa1 in mice phenocopied VSMC phenotype switching and the consequent exacerbation of AAD. Finally, our studies in human AAD aortic specimens recapitulated key findings in murine AAD, specifically that the decrease of Anxa1 is associated with VSMC phenotype switch, heightened inflammation, and enhanced MMP production in human aortas. CONCLUSIONS: Our findings demonstrated that Anxa1 is a novel endogenous defender that prevents acute aortic dissection by inhibiting vascular smooth muscle cell phenotype switching, suggesting that Anxa1 signaling may be a potential target for AAD pharmacological therapy. TRANSLATIONAL PERSPECTIVE: Our studies herein may lead to a paradigm shift for pharmacologic therapy towards acute aortic dissection. Through careful examination of the pathological changes that occur during AAD onset in experimental animal models, we demonstrated that VSMC phenotype switching plays a critical role in the development of AAD. Inhibition of VSMC phenotype switching and its attendant impacts on aortic function may be a viable approach for future treatment. Toward that end, our studies highlighted the protective benefit of Anxa1 and its mimetic peptide Ac2-26 in AAD through prevention of the switching of VSMC to a synthetic phenotype.

18.
Cancer Med ; 10(7): 2268-2285, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33660378

RESUMO

In this study, we developed a long noncoding RNA (lncRNA)-based prognostic signature for stratification of patients with head a nd neck squamous cell carcinoma (HNSCC). In total, 493 HNSCC samples obtained from the Cancer Genome Atlas database were divided into training and testing cohorts (3:2 ratio). We identified 3913 immune-related lncRNAs in the HNSCC training cohort by Pearson correlation analysis; only seven were independently associated with overall survival and were used to develop an immune-related lncRNA prognostic signature (IRLPS) grouping of HNSCC patients into high- and low-IRLPS subgroups. Univariate and multivariate Cox analyses revealed that low-IRLPS patients had a better prognosis in all the cohorts, which was retained after stratification by sex, grade, and HPV status. Although the TNM stage was also an independent prognostic factor, the IRLPS had a better discriminability with higher AUC at the 3- and 5-year follow-ups in all cohorts. Low-IRLPS samples had more immune cell infiltration and were enriched in immune-related pathways, while high- IRLPS samples were enriched in metabolic pathways. A nomogram constructed including age, TNM stage, and IRLPS showed good calibration. Thus, IRLPS improves the prognostic prediction and also distinguishes different tumor microenvironment (TME) in HNSCC patients.

19.
Plant Physiol ; 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33787923

RESUMO

Sex determination is a crucially important developmental event that is pervasive throughout nature and enhances the adaptation of species. Among plants, cucumber (Cucumis sativus L.) can generate both unisexual and bisexual flowers, and the sex type is mainly controlled by several 1-aminocyclopropane-1-carboxylic acid synthases (CsACSs). However, the regulatory mechanism of these synthases remains elusive. Here, we used gene expression analysis, protein-DNA interaction assays, and transgenic plants to study the function of a gynoecium-specific gene, ETHYLENE RESPONSE FACTOR31 (CsERF31), in female flower differentiation. We found that in a predetermined female flower, ethylene signaling activates CsERF31 by CsEIN3, and then CsERF31 stimulates CsACS2, which triggers a positive feedback loop to ensure female rather than bisexual flower development. A similar interplay is functionally conserved in melon (Cucumis melo L.). Knockdown of CsERF31 by RNAi causes defective bisexual flowers to replace female flowers. Ectopic expression of CsERF31 suppresses stamen development and promotes pistil development in male flowers, demonstrating that CsERF31 functions as a sex switch. Taken together, our data confirm that CsERF31 represents the molecular link between female-male determination and female-bisexual determination, and provide mechanistic insight into how ethylene promotes female flowers, rather than bisexual flowers, in cucumber sex determination.

20.
Plant Physiol ; 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33744968

RESUMO

Sex determination is a crucially important developmental event that is pervasive throughout nature and enhances the adaptation of species. Among plants, cucumber (Cucumis sativus L.) can generate both unisexual and bisexual flowers, and the sex type is mainly controlled by several 1-aminocyclopropane-1-carboxylic acid (ACC) synthases. However, the regulatory mechanism of these synthases remains elusive. Here, we used gene expression analysis, protein-DNA interaction assays and transgenic plants to study the function of a gynoecium-specific gene, ETHYLENE RESPONSE FACTOR31 (CsERF31), in female flower differentiation. We found that in a predetermined female flower, ethylene signalling activates CsERF31 by CsEIN3, and then CsERF31 stimulates CsACS2, which triggers a positive feedback loop to ensure female rather than bisexual flower development. A similar interplay is functionally conserved in melon (Cucumis melo L.). Knockdown of CsERF31 by RNAi causes defective bisexual flowers to replace female flowers. Ectopic expression of CsERF31 suppresses stamen development and promotes pistil development in male flowers, demonstrating that CsERF31 functions as a sex switch. Taken together, our data confirm that CsERF31 represents the molecular link between female-male determination and female-bisexual determination, and provide mechanistic insight into how ethylene promotes female flowers, rather than bisexual flowers, in cucumber sex determination.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...