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1.
J Cell Mol Med ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452765

RESUMO

Myomesin-1 (encoded by MYOM1 gene) is expressed in almost all cross-striated muscles, whose family (together with myomesin-2 and myomesin-3) helps to cross-link adjacent myosin to form the M-line in myofibrils. However, little is known about its biological function, causal relationship and mechanisms underlying the MYOM1-related myopathies (especially in the heart). Regrettably, there is no MYMO1 knockout model for its study so far. A better and further understanding of MYOM1 biology is urgently needed. Here, we used CRISPR/Cas9 gene-editing technology to establish an MYOM1 knockout human embryonic stem cell line (MYOM1-/- hESC), which was then differentiated into myomesin-1 deficient cardiomyocytes (MYOM1-/- hESC-CMs) in vitro. We found that myomesin-1 plays an important role in sarcomere assembly, contractility regulation and cardiomyocytes development. Moreover, myomesin-1-deficient hESC-CMs can recapitulate myocardial atrophy phenotype in vitro. Based on this model, not only the biological function of MYOM1, but also the aetiology, pathogenesis, and potential treatments of myocardial atrophy caused by myomesin-1 deficiency can be studied.

2.
Stem Cell Res Ther ; 12(1): 48, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422132

RESUMO

INTRODUCTION: Spinal cord injury (SCI) is a neurological, medically incurable disorder. Human pluripotent stem cells (hPSCs) have the potential to generate neural stem/progenitor cells (NS/PCs), which hold promise in the treatment of SCI by transplantation. In our study, we aimed to establish a chemically defined culture system using serum-free medium and ascorbic acid (AA) to generate and expand long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) differentiated from hPSCs effectively and stably. METHODS: We induced human embryonic stem cells (hESCs)/induced PSCs (iPSCs) to neurospheres using a newly established in vitro induction system. Moreover, lt-NES cells were derived from hESC/iPSC-neurospheres using two induction systems, i.e., conventional N2 medium with gelatin-coated plates (coated) and N2+AA medium without pre-coated plates (AA), and were characterized by reverse transcription polymerase chain reaction (RT-PCR) analysis and immunocytochemistry staining. Subsequently, lt-NES cells were induced to neurons. A microelectrode array (MEA) recording system was used to evaluate the functionality of the neurons differentiated from lt-NES cells. Finally, the mechanism underlying the induction of lt-NES cells by AA was explored through RNA-seq and the use of inhibitors. RESULTS: HESCs/iPSCs were efficiently induced to neurospheres using a newly established induction system in vitro. lt-NES cells derived from hESC/iPSC-neurospheres using the two induction systems (coated vs. AA) both expressed the neural pluripotency-associated genes PAX6, NESTIN, SOX1, and SOX2. After long-term cultivation, we found that they both exhibited long-term expansion for more than a dozen generations while maintaining neuropluripotency. Moreover, the lt-NES cells retained the ability to differentiate into general functional neurons that express ß-tubulin at high levels. We also demonstrated that AA promotes the generation and long-term expansion of lt-NES cells by promoting collagen synthesis via the MEK-ERK1/2 pathway. CONCLUSIONS: This new chemically defined culture system was stable and effective regarding the generation and culture of lt-NES cells induced from hESCs/iPSCs using serum-free medium combined with AA. The lt-NES cells induced under this culture system maintained their long-term expansion and neural pluripotency, with the potential to differentiate into functional neurons.

3.
Hum Vaccin Immunother ; : 1-8, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270487

RESUMO

Meningococcal serogroups A and C cause significant numbers of cases in China. The Sanofi Pasteur meningococcal polysaccharide A + C vaccine (Men-AC) was licensed in China in 1995. Immunogenicity and safety of a single dose of Men-AC against a similar marketed vaccine, the Lanzhou Institute serogroups A and C vaccine (Lanzhou-AC), were evaluated in children 2 to 6 y of age. Antibody titers were determined before and on Day 30 after vaccination using a serum bactericidal assay using baby rabbit complement (SBA-BR). Immunogenicity endpoints included rates of seroconversion (postvaccination antibody titers ≥4-fold higher) and seroprotection (postvaccination titers ≥1:8). Unsolicited systemic adverse events (AEs) within 30 minutes after vaccination, solicited injection site and systemic reactions between Days 0 and 7, unsolicited non-serious AEs within 30 d, and serious adverse events (SAEs) throughout were recorded. Seroconversion rates against serogroups A and C were 97.0% (95% confidence interval [CI], 94.5-98.6) and 94.7% (95% CI, 91.6-97.0), respectively, in the Men-AC group and 97.7% (95% CI, 95.4-99.1) and 94.8% (95% CI, 91.7-97.0), respectively, in the Lanzhou-AC group, while seroprotection rates were 98.0% (95% CI, 95.8-99.3) and 97.0% (95% CI, 94.5-98.6), respectively, in the Men-AC group and 99.0% (95% CI, 97.2-99.8) and 96.8% (95% CI, 94.1-98.4), respectively, in the Lanzhou-AC group. Non-inferiority of Men-AC with regard to immunogenicity was demonstrated since the lower bounds of the 95% CIs of the differences in rates between the two groups were > -5% for both serogroups. Both vaccines were well tolerated.

4.
Front Cell Dev Biol ; 8: 585879, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195237

RESUMO

Ras associated with diabetes (RAD) is a membrane protein that acts as a calcium channel regulator by interacting with cardiac L-type Ca2 + channels (LTCC). RAD defects can disrupt intracellular calcium dynamics and lead to cardiac hypertrophy. However, due to the lack of reliable human disease models, the pathological mechanism of RAD deficiency leading to cardiac hypertrophy is not well understood. In this study, we created a RRAD -/- H9 cell line using CRISPR/Cas9 technology. RAD disruption did not affect the ability and efficiency of cardiomyocytes differentiation. However, RAD deficient hESC-CMs recapitulate hypertrophic phenotype in vitro. Further studies have shown that elevated intracellular calcium level and abnormal calcium regulation are the core mechanisms by which RAD deficiency leads to cardiac hypertrophy. More importantly, management of calcium dysregulation has been found to be an effective way to prevent the development of cardiac hypertrophy in vitro.

5.
Org Biomol Chem ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180084

RESUMO

Hypsampsone A (1) and hyperhexanone F (2), two novel seco-polycyclic polyprenylated acylphloroglucinols, were isolated from Hypericum sampsonii. Hypsampsone A (1) features the first spirocyclic system fused with 5/6/5/5 tetracyclic skeleton. Hyperhexanone F (2) represents the second novel 1,2-seco-bicyclo[3.3.1]-PPAP skeleton. Their structures were established by extensive spectroscopic analysis, computer-assisted structure elucidation software, and calculated electronic circular dichroism spectra. A plausible biogenetic pathway of 1 was also proposed. Compounds 1 and 2 showed moderate multidrug resistance reversal activity to adriamycin (ADR) resistant cancer cell lines, HepG2/ADR and MCF-7/ADR, with the fold-reversals ranging from 16 to 38 at noncytotoxic concentration of 10 µM.

6.
Food Funct ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33237069

RESUMO

Benefitting from the versatility and biocompatibility of food sourced materials, the construction of hybrid structures via their molecular interplay generates novel platforms with unexpected properties. In this work, two hydrophobic biomolecules were co-assembled into water-soluble amphiphiles at pH 7 by a facile pH-cycle approach. Wheat gluten proteins (WPs) and shellac were dissolved together at pH 12 followed by a one-step adjustment to pH 7, yielding nanospheres with a protein recovery over 90%. Structural characterization evidenced that shellac stiffened the protein backbones that were resistant against thermodynamically-favored folding. The reactions were proven to be initiated between the protein secondary structures and shellac, forming a relatively unfolded three-dimensional conformation during the acid-induced co-assembly. Silybin was employed as a hydrophobic bioactive model and was entrapped following the same procedure as the hybrid assembly, with a maximum loading of 102 mg g-1 hybrid. The bioavailability of silybin loaded in shellac-WP co-assemblies was improved as assessed by cell proliferation assays, due to the improved dispersity and cell internalization of the co-assemblies. The preparation method based on a simple pH manipulation may be applied to encapsulate various hydrophobic bioactive compounds, apart from the silybin explored in this study.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33072159

RESUMO

Background: Vitamin D (VitD) can regulate immune responses and maternal VitD-deficiency can affect immune responses in the offspring. This study aimed at investigating the effects of maternal VitD-deficiency during pregnancy on Treg and Breg responses in offspring mice with house dust mite (HDM)-induced allergic airway inflammation. Methods: Female BALB/c mice were randomized and fed with normal chow or VitD-deficient diet until their offspring weaned. The offspring mice were fed with normal chow and injected with vehicle or HDM to induce allergic airway inflammation. The levels of serum 25(OH)D, cytokines and infiltrate numbers as well as percentages of Tregs and Bregs in the bronchoalveolar lavage fluid (BALF) were analyzed. The relative levels of VitD receptor (VDR), VitD-binding protein (VDBP), Cytochromes P450 (CYP) 27b1, and CYP24A1 mRNA transcripts in the lungs of different groups of mice were measured. Results: Maternal VitD-deficiency significantly reduced serum 25(OH)D levels in offspring mice. VitD-deficiency significantly increased the relative levels of VDR, VDBP and CYP27B1 mRNA transcripts, but decreased CYP24A1 expression in the lungs of mice. In comparison with the control mice, significantly elevated levels of pro-inflammatory cytokines, increased numbers of lymphocytes and eosinophils, but decreased levels of anti-inflammatory cytokines were detected in the BALF of VitD-deficient mice. VitD-deficiency significantly increased the frequency of Th1, Th2, Th9, Th17 cells, but decreased regulatory T (Tregs) and B cells (Bregs) in the BALF of mice with allergic airway inflammation. Conclusion: Maternal VitD-deficiency lowed serum 25(OH)D levels and enhanced HDM-induced allergic airway inflammation in the offspring by impairing Breg and Treg responses.

8.
Ann N Y Acad Sci ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009679

RESUMO

Aeromonas veronii is an important zoonotic and aquatic pathogen. An increasing number of reports indicate that it has caused substantial economic losses in the aquaculture industry, in addition to threatening human health. However, little is known about its pathogenesis. Exploration of new virulence factors of A. veronii would be helpful for further understanding its pathogenesis. Hence, we comparatively analyzed the proteomes of virulent, attenuated, and avirulent strains of A. veronii using tandem mass tag (TMT) protein labeling and found numerous proteins either up- or downregulated in the virulent strain. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins (DEPs) were involved mainly in pathways associated with bacterial chemotaxis and microbial metabolism in diverse environments. Furthermore, the expression levels of lysine decarboxylase, endoribonuclease, maltoporin, pullulanase, and aerolysin were positively correlated with the virulence of the strains, suggesting that their function may be closely related to the virulence of A. veronii. The results of qRT-PCR and multiple reaction monitoring for some DEPs were consistent with the results of TMT protein labeling. These results suggest that these DEPs may be novel potential virulence factors and will help to further understand the pathogenesis of A. veronii.

9.
Zhen Ci Yan Jiu ; 45(8): 671-5, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32869580

RESUMO

OBJECTIVE: To investigate the clinical effect of acupuncture combined with western medicine in the treatment of children with abdominal Henoch-Schonlein purpura with spleen-stomach damp-heat syndrome. METHODS: A total of 60 children with abdominal Henoch-Schonlein purpura with spleen-stomach damp-heat syndrome were randomly divided into treatment group and control group, with 30 patients in each group. The patients in the control group were given Hydroprednisone 2 mg•kg-1•d-1, and in addition to the treatment in the control group, those in the treatment group were given acupuncture at Tianshu (ST25), Neiguan (PC6), Zusanli (ST36), Zhongwan (CV12), Qihai (CV6), and Sanyinjiao (SP6) once a day, with a needle retaining time of 15 minutes. Both groups were treated for 7 days. The scores of abdominal pain, hematochezia, hematemesis, vomiting, poor appetite, abdominal distension, purpura, occult blood in stool, and abdominal ultrasound were determined before and after treatment, and the time to the disappearance of abdominal pain was observed. Clinical outcome was evaluated. RESULTS: The treatment group had a significantly higher effective rate than the control group [96.7% (29/30) vs 80.0% (24/30), P<0.05]. Both groups had significant reductions in the scores of abdominal pain, hematochezia, hematemesis, poor appetite, abdominal distension, purpura, occult blood and abdominal ultrasound and the total score after treatment (P<0.05), and compared with the control group after treatment, the treatment group had significantly lower scores of abdominal pain, poor appetite, abdominal distension, and abdominal ultrasound and total score (P<0.05). The treatment group had a significantly shorter time to disappea-rance of abdominal pain than the control group (P<0.05). CONCLUSION: Acupuncture combined with western medicine has a better clinical effect than western medicine alone in the treatment of abdominal Henoch-Schonlein purpura with spleen-stomach damp-heat syndrome and can significantly improve clinical symptoms and signs and shorten the time to disappearance of abdominal pain.


Assuntos
Terapia por Acupuntura , Púrpura de Schoenlein-Henoch , Criança , Temperatura Alta , Humanos , Púrpura de Schoenlein-Henoch/terapia , Estômago , Resultado do Tratamento
10.
Toxicon ; 187: 223-231, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32971099

RESUMO

Snake venom metalloproteinases (SVMPs) are an important component in viperid and crotalid venoms, and these SVMPs play important and versatile roles in the pathogenesis of snakebite envenoming. The SVMPs from elapid venoms are not well elucidated compared with those from viperid and crotalid venoms. Atrase B is a nonhemorrhagic P-III SVMP purified from the Naja atra venom, which possesses a weak fibrinogenolytic activity. In this paper, the activity and mechanism of atrase B against platelet aggregation and blood coagulation were investigated. The in vitro assay showed that atrase B remarkably inhibited ristocetin- and thrombin-induced platelet aggregation by cleavage of the platelet membrane glycoprotein Ib, and the coagulation of normal human plasma, which may be caused by inhibiting coagulation factor VIII predominantly. When atrase B was intravenously injected into rats at doses of 0.05 and 0.30 mg/kg, the activated partial thromboplastin and the thrombin times were significantly prolonged in a dose-dependent manner. Similarly, the fibrinogen level decreased, but only a high dose of atrase B showed remarkable activity against platelet aggregation. Results suggested that anticoagulation was a more important function of atrase B compared with its activity against platelet aggregation. These results indicated that atrase B may play an important role in the anticoagulant properties of Naja atra venom. In addition, atrase B may be a potent anticoagulant agent because its effectiveness in vivo against platelet aggregation and blood coagulation.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Venenos Elapídicos/toxicidade , Metaloproteases/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Animais , Humanos , Ratos
11.
Dalton Trans ; 49(37): 13167-13175, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32936157

RESUMO

Inorganic borate compounds exhibit significant diversity in their structure types, which are associated with interesting optical and magnetic properties. In our work, a new rare-earth polyborate Na3GdB8O15 was prepared with an infinite one-dimensional (1D) broad-banded framework of [B8O15]∞ running along the a-axis, in which large Gd3+ and Na+ ions reside to ensure cohesion and neutrality of the structure. The basic fundamental building block (FBB) of [B8O15]∞ is B16O32, which is composed of five BO3 and three BO4 groups and can be written as 5Δ3□: 〈2Δ□〉-〈Δ2□〉〈2Δ□〉. First principle studies reveal that Na3GdB8O15 is an indirect bandgap semiconductor and the optical absorption at 280 nm originates from the O2-→ Gd3+ transition. Solid solutions of Na3Gd1-xCexB8O15 and Na3Gd0.98-yYyCe0.02B8O15 were prepared and exhibited a bluish violet emissive luminescence by near-UV excitation due to the 5d1→ 4f1 transition of Ce3+. Substitution of Gd3+ by Y3+ enhanced the luminescence efficiency and significantly improved the thermal stability. At 423 K, the luminescence intensity of Na3Gd0.58Y0.4Ce0.02B8O15 remained 77% of that at 298 K. We hypothesize that Na3GdB8O15 is a potential inorganic luminescent host matrix.

12.
J Oncol ; 2020: 9327512, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774373

RESUMO

Background: The prognosis of patients with hepatocellular carcinoma (HCC) is poor, with 60% to 70% of patients developing recurrence and metastasis within five years of radical resection. Alpha-fetoprotein (AFP) plays a significant role in predicting the recurrence and metastasis of HCC after surgery. However, its role in modulating tumor immunity has not been investigated. Our objective was to examine the effect of AFP on the expression of B7 family and activation of the NF-κB (P65) pathway in HCC. Methods: We generated human hepatoma SMMC-7721 cell lines with or without recombinant AFP transfection (AFPup and control groups). Colony formation assay, Transwell invasion assay, and wound healing assay were used to detect the function of AFP. Liver cancer xenografts were made in BALB/c nude male mice (N = 6 per group). After 28 days of inoculation, the expression of immune genes in the HCC tissues, including PD-L (B7-H1), B7-H3, B7-H4, and P65, was evaluated by quantitative real-time PCR (qPCR) and western blot. In addition, immunofluorescence was used to determine the subcellular localization of the P65 protein, a key factor in the NF-κB pathway. An online HCC patients' dataset was also used to detect the connection between AFP and P65. Results: Overexpression of AFP could enhance proliferation, invasion, and migration of HCC cells. Both qPCR and western blot results demonstrated that the expressions of PD-L1, B7-H4, and P65 were significantly higher in the AFP group compared to the controls (P < 0.05). Immunofluorescence results indicated that the majority of the P65 protein was located in the cytoplasm in the control group but was translocated to the nucleus in the AFPup group. The Spearman correlation coefficient confirms that AFP has a positive correlation with P65 in HCC patients (R = 0.33, P=0.05). Conclusion: AFP could enhance proliferation, invasion, and migration in HCC cells. The upregulation of AFP would increase the PD-L1 and B7-H4 mRNA and protein expression in HCC tissues through the upregulation and activation of the P65 protein.

13.
Stem Cell Res ; 48: 101930, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32777767

RESUMO

Mutations in Junctophilin-2(JPH2) gene is the cause of hypertrophic cardiomyopathy (HCM) and leading inherited cause of left ventricular hypertrophy and myofilaments disarray. JPH2 protein, a member of the Junctophilin family, is mainly expressed in heart and plays an important role in E-C coupling. We have generated a homozygous JPH2 knockout (JPH2-KO) human embryonic stem cell (hESC) line using an episomal vector-based CRISPR/Cas9 system. This JPH2-KO hESC line maintained stem cell like morphology, pluripotency, normal karyotype and could differentiate into all three germ layers in vivo.

14.
Org Lett ; 22(17): 6903-6906, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32822200

RESUMO

Two novel polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperfols A (1) and B (2), and two known biosynthetically related precursors (3 and 4) were isolated from Hypericum perforatum. Compound 1 possesses an unprecedented 2,3-seco-PPAP with a fused 5/5/9/5 tetracyclic skeleton, and 2 features a 30-norPPAP. Their structures were established by spectroscopic analysis, computer-assisted structure elucidation software, and electronic circular dichroism calculations. Moreover, compounds 1 and 4 exhibit significant cytotoxicity against human erythroleukemia cells by inducing cell apoptosis.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32748757

RESUMO

BACKGROUND: Deoxypodophyllotoxin, isolated from theTraditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant antitumor activity with strong toxicity in vitro and in vivo. OBJECTIVE: In this article, we synthesized a series of deoxypodophyllotoxin derivatives, and evaluated their antitumor effectiveness. METHODS: The anti tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. RESULTS: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29 andMG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. CONCLUSION: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

16.
Cell Biosci ; 10: 88, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32699606

RESUMO

Background: Mesenchymal stem/stromal cells (MSCs) and macrophages are critical components in many tissue microenvironments, including that in adipose tissue. The close interaction between MSCs and macrophages modulates various adipose-related disease development. However, the effects of macrophages on the fate of MSCs remain largely elusive. We here studied the effect of macrophages on the adipogenic differentiation of MSCs. Methods: Macrophages were obtained from THP-1 cells treated with phorbol-12-myristate-13-acetate (PMA). The induced matured macrophages were then induced to undergo classically activated macrophage (M1) or alternatively activated macrophage (M2) polarization with Iipopolysaccharide (LPS)/interferon (IFN)-γ and interleukin (IL)-4/IL-13, respectively. The supernatants derived from macrophages under different conditions were applied to cultured human adipose tissue-derived mesenchymal stem/stromal cells (hADSCs) undergoing adipogenic differentiation. Adipogenic differentiation was evaluated by examining Oil Red O staining of lipid droplets and the expression of adipogenesis-related genes with real-time quantitative polymerase chain reaction (Q-PCR) and western blot analysis. Results: The adipogenic differentiation of hADSCs was impaired when treated with macrophage-derived supernatants, especially that from the M1-polarized macrophage (M1-sup). The inhibitory effect was found to be mediated by the inflammatory cytokines, mainly tumor necrosis factor-α (TNF-α) and IL-1ß. Blocking TNF-α and IL-1ß with neutralizing antibodies partially alleviated the inhibitory effect of M1-sup. Conclusion: Macrophage-derived supernatants inhibited the adipogenic differentiation of hADSCs in vitro, irrespective of the polarization status (M0, M1 or M2 macrophages). M1-sup was more potent because of the higher expression of pro-inflammatory cytokines. Our findings shed new light on the interaction between hADSCs and macrophages and have implications in our understanding of disrupted adipose tissue homeostasis under inflammation.

17.
Aging (Albany NY) ; 12(14): 14736-14753, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32701062

RESUMO

PURPOSE: The purpose of this study was to investigate the impact of clinicopathological factors and treatments on the overall survival (OS) and esophageal cancer-specific survival (ECSS) of stages I-III esophageal cancer (EC) patients and to establish a prognostic visual nomogram. METHODS: We collected clinical data of patients diagnosed with stages I-III EC without receiving chemotherapy from 2004 to 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. Prognoses were analyzed using the R language software, and nomograms were obtained according to the visual processing logistic regression model, which was verified using the Harrell C-index, receiver operating characteristic (ROC) curve, and calibration curve. RESULTS: A total of 4,305 patients were selected, mostly white males. Most patients were over 60 years old and old age predicted poor prognosis. EC, primarily adenocarcinoma, occurred mostly in the lower third of the esophagus. About half of the patients had T1 (58.00%) and grade II (50.41%) cancer. Of all the patients, 2,448 was treated with surgery and the majority (n = 1,476; 64.85%) of these patients had stage I EC. Stages I-III patients underwent surgery had significantly better OS and ECSS, and endoscopic therapy was associated with the best outcome amongst all the surgical methods. 3.67% of the patients received radiotherapy, predominantly postoperative radiotherapy (2.69%). Older age, squamous cell carcinoma, overlapping lesion of the esophagus, and grades II and III were high-risk factors for poor OS and ECSS for stage I patients, whereas endoscopic therapy, esophagectomy, and esophagectomy with gastrectomy were low-risk factors. Stage II patients with older age, male sex, T3, N1, and grades II and III had shorter OS and ECSS, but patients with any surgical treatment had significantly longer OS and ECSS. T4, N1, and grade III correlated negatively with OS and ECSS in stage III patients, and any surgical treatment correlated positively with longer OS and ECSS. The OS and ECSS rates of stages I-III EC patients with a total score of more than 150 points in the nomogram were both only 40% after 3 years and 30% after 5 years. The C-index, ROC curve, and calibration curve indicated that the nomograms established in this study were suitable to assess patient prognosis. CONCLUSION: The nomogram established in this study is an effective clinical tool to predict the prognosis of stages I-III EC patients without chemotherapy.

18.
Huan Jing Ke Xue ; 41(4): 1987-1996, 2020 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608708

RESUMO

Based on the panel data of 255 cities in China, this study built a spatial Durbin model to study the impact of China's industrialization on the PM2.5 pollution level. Meanwhile, an environmental governance tool characterized by forest and grass coverage was introduced to explore the internal mechanism and exogenous driving force of EKC. The results show that ① the relationship between industrialization and PM2.5 concentration is obviously an inverted u-shaped, and the EKC hypothesis was verified. ② The formation of the EKC curve was caused by the external factors and not the endogenous mechanism of economic growth. Forest-grass coverage plays a regulating role in the relationship between industrialization and PM2.5 pollution level, namely the inverted u-shaped structure of environmental EKC results from environmental governance tool with forest and grass cover rather than the automatic adjustment of economic growth. ③ The influence of industrialization on PM2.5 concentration has a spatial spillover effect. Urban industrialization not only affects the PM2.5 concentration in local regions but also its neighboring region.

19.
Stem Cell Res Ther ; 11(1): 280, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660551

RESUMO

BACKGROUND: Human umbilical cord mesenchymal stem cell (hUC-MSC) therapy is considered as a promising approach in the treatment of intrauterine adhesions (IUAs). Considerable researches have already detected hUC-MSCs by diverse methods. This paper aims at exploring the quantitative distribution of CM-Dil-labeled hUC-MSCs in different regions of the uterus tissue of the dual injury-induced IUAs in rats and the underlying mechanism of restoration of fertility after implantation of hUC-MSCs in the IUA model. METHODS: In this study, we investigated the quantification of the CM-Dil-labeled hUC-MSCs migrated to the dual injured uterus in Sprague Dawley rats. Additionally, we investigated the differentiation of CM-Dil-labeled hUC-MSCs. The differentiation potential of epithelial cells, vascular endothelial cells, and estrogen receptor (ER) cells were assessed by an immunofluorescence method using CK7, CD31, and ERα. The therapeutic impact of hUC-MSCs in the IUA model was assessed by hematoxylin and eosin, Masson, immunohistochemistry staining, and reproductive function test. Finally, the expression of TGF-ß1/Smad3 pathway in uterine tissues was determined by qRT-PCR and Western blotting. RESULTS: The CM-Dil-labeled cells in the stroma region were significantly higher than those in the superficial myometrium (SM) (71.67 ± 7.98 vs. 60.92 ± 3.96, p = 0.005), in the seroma (71.67 ± 7.98 vs. 23.67 ± 8.08, p = 0.000) and in the epithelium (71.67 ± 7.98 vs. 4.17 ± 1.19, p = 0.000). From the 2nd week of treatment, hUC-MSCs began to differentiate into epithelial cells, vascular endothelial cells, and ER cells. The therapeutic group treated with hUC-MSCs exhibited a significant decrease in fibrosis (TGF-ß1/Smad3) as well as a significant increase in vascularization (CD31) compared with the untreated rats. CONCLUSION: Our findings suggested that the distribution of the migrated hUC-MSCs in different regions of the uterine tissue was unequal. Most cells were in the stroma and less were in the epithelium of endometrium and gland. Injected hUC-MSCs had a capacity to differentiate into epithelial cells, vascular endothelial cells, and ER cells; increase blood supply; inhibit fibration; and then restore the fertility of the IUA model.

20.
Front Aging Neurosci ; 12: 93, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477092

RESUMO

Amyloid plaques and neurofibrillary tangles (NFTs) are hallmark lesions of Alzheimer's disease (AD) related to ß-amyloid (Aß) deposition and intraneuronal phosphorylated tau (pTau) accumulation. Sortilin C-terminal fragments (shortened as "sorfra") can deposit as senile plaque-like lesions within AD brains. The course and pattern of sorfra plaque formation relative to Aß and pTau pathogenesis remain unknown. In the present study, cerebral and subcortical sections in postmortem human brains (n = 46) from aged and AD subjects were stained using multiple markers (6E10, ß-secretase 1, pTau, and sortilin antibodies, as well as Bielschowsky silver stain). The course and pattern of sorfra plaque formation relative to Thal Aß and Braak NFT pathogenic stages were determined. Sorfra plaques occurred in the temporal, inferior frontal and occipital neocortices in cases with Thal 1 and Braak III stages. They were also found additionally in the hippocampal formation, amygdala, and associative neocortex in cases with Thal 2-4 and Braak IV-V. Lastly, they were also found in the primary motor, somatosensory, and visual cortices in cases with Thal 4-5 and Braak VI. Unlike Aß and pTau pathologies, sorfra plaques did not occur in subcortical structures in cases with Aß/pTau lesions in Thal 3-5/Braak IV-VI stages. We establish here that sorfra plaques are essentially a cerebral proteopathy. We believe that the development of sorfra plaques in both cortical and hippocampal regions proceeds in a typical spatiotemporal pattern, and the stages of cerebral sorfra plaque formation partially overlap with that of Aß and pTau pathologies.

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