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1.
J Clin Invest ; 134(18)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146021

RESUMO

Strategies beyond hormone-related therapy need to be developed to improve prostate cancer mortality. Here, we show that FUBP1 and its methylation were essential for prostate cancer progression, and a competitive peptide interfering with FUBP1 methylation suppressed the development of prostate cancer. FUBP1 accelerated prostate cancer development in various preclinical models. PRMT5-mediated FUBP1 methylation, regulated by BRD4, was crucial for its oncogenic effect and correlated with earlier biochemical recurrence in our patient cohort. Suppressed prostate cancer progression was observed in various genetic mouse models expressing the FUBP1 mutant deficient in PRMT5-mediated methylation. A competitive peptide, which was delivered through nanocomplexes, disrupted the interaction of FUBP1 with PRMT5, blocked FUBP1 methylation, and inhibited prostate cancer development in various preclinical models. Overall, our findings suggest that targeting FUBP1 methylation provides a potential therapeutic strategy for prostate cancer management.


Assuntos
DNA Helicases , Proteínas de Ligação a DNA , Neoplasias da Próstata , Proteína-Arginina N-Metiltransferases , Proteínas de Ligação a RNA , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Humanos , Animais , Camundongos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Metilação , DNA Helicases/genética , DNA Helicases/metabolismo , Progressão da Doença , Linhagem Celular Tumoral , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Mol Biol Cell ; 35(8): ar108, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38959101

RESUMO

Our recent work has uncovered a novel function of HSPA8 as an amyloidase, capable of dismantling the RHIM-containing protein fibrils to suppress necroptosis. However, the impact of HSPA8 inhibitors on cancer regression via necroptosis remains unexplored. In this study, we conducted a comprehensive investigation to assess the potential of HSPA8 inhibitors in enhancing necroptosis both in vitro and in vivo. Our findings indicate that pharmacologic inhibition of HSPA8, achieved either through VER (VER-155008) targeting the nucleotide binding domain or pifithrin-µ targeting the substrate binding domain of HSPA8, significantly potentiates necroptosis induced by diverse treatments in cellular assays. These inhibitors effectively disrupt the binding of HSPA8 to the RHIM protein, impeding its regulatory function on RHIM amyloid formation. Importantly, HSPA8 inhibitors significantly enhanced cancer cell sensitivity to microtubule-targeting agents (MTAs) in vitro, while reversing chemoresistance and facilitating tumor regression by augmenting necroptosis in vivo. Our findings suggest a promising therapeutic approach to cancer through necroptosis modulation via HSPA8 targeting, particularly in combination with MTA drugs for enhanced treatment efficacy.


Assuntos
Proteínas de Choque Térmico HSC70 , Necroptose , Neoplasias , Necroptose/efeitos dos fármacos , Humanos , Animais , Linhagem Celular Tumoral , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Proteínas de Choque Térmico HSC70/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nucleosídeos de Purina
3.
Arch Med Sci ; 20(2): 655-663, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38757011

RESUMO

Introduction: Chronic heart failure (CHF) is a leading cause of deaths induced by cardiovascular disease. This study aimed to investigate the protective effects of emodin in CHF rats and explore the related mechanisms. Material and methods: A total of 56 Wistar rats were used to construct CHF model using the coronary artery ligation. The effects of emodin on cardiac function and inflammation were analyzed in the CHF rats. Expression of miR-26b-5p in the CHF model before and after emodin treatment was estimated by quantitative real-time polymerase chain reaction. The effects of miR-26b-5p on cardiac function and inflammation were also assessed, and its target gene was predicted and confirmed in rat cardiomyocyte H9c2. Results: Emodin treatment could significant improve the cardiac function and inflammation evidenced by the increased increased ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP) and maximum of the first differentiation of left ventricular pressure (+LV dP/dtmax) and decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), left ventricular end diastolic pressure (LVEDP), interleukin (IL)-6, tumor necrosis factor α (TNF-α) levels. Expression of miR-26b-5p was downregulated in the CHF rats (CHF 0.442 ±0.131 vs. Sham 1.044 ±0.160), and this suppressive effect was rescued by emodin (Emodin 0.902 ±0.132 vs. CHF 0.442 ±0.131). The overexpression of miR-26b-5p in CHF rats led to improved cardiac function and inflammatory response. In addition, the emodin-induced increased EF, FS, LVSP and +LV dP/dtmax and decreased ANP, BNP, LVEDP, IL-6 and TNF-α were all abrogated by the knockdown of miR-26b-5p. The target prediction results revealed that PTEN was a target gene of miR-26b-5p in H9c2 cells. Conclusions: All the results indicated that emodin serves a protective role in CHF via regulation of the miR-26b-5p/PTEN pathway. Emodin may be an effective therapeutic agent for CHF treatment.

4.
Nat Commun ; 15(1): 3218, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622151

RESUMO

Flash Joule heating (FJH) is an emerging and profitable technology for converting inexhaustible biomass into flash graphene (FG). However, it is challenging to produce biomass FG continuously due to the lack of an integrated device. Furthermore, the high-carbon footprint induced by both excessive energy allocation for massive pyrolytic volatiles release and carbon black utilization in alternating current-FJH (AC-FJH) reaction exacerbates this challenge. Here, we create an integrated automatic system with energy requirement-oriented allocation to achieve continuous biomass FG production with a much lower carbon footprint. The programmable logic controller flexibly coordinated the FJH modular components to realize the turnover of biomass FG production. Furthermore, we propose pyrolysis-FJH nexus to achieve biomass FG production. Initially, we utilize pyrolysis to release biomass pyrolytic volatiles, and subsequently carry out the FJH reaction to focus on optimizing the FG structure. Importantly, biochar with appropriate resistance is self-sufficient to initiate the FJH reaction. Accordingly, the medium-temperature biochar-based FG production without carbon black utilization exhibited low carbon emission (1.9 g CO2-eq g-1 graphene), equivalent to a reduction of up to ~86.1% compared to biomass-based FG production. Undoubtedly, this integrated automatic system assisted by pyrolysis-FJH nexus can facilitate biomass FG into a broad spectrum of applications.


Assuntos
Carbono , Carvão Vegetal , Grafite , Biomassa , Fuligem
5.
Aesthetic Plast Surg ; 48(3): 333-340, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37697086

RESUMO

BACKGROUND: Poor Bell's phenomenon is often considered a relative contraindication for ptosis surgery, as it increases the risk of corneal exposure and dry eye symptoms after surgery. However, the Bell's phenomenon may vary in different individuals and sleep stages, making it inaccurate to predict the position of the eye during sleep based on awake examination. This study aimed to investigate the role of Bell's phenomenon in ptosis surgery and the management of nocturnal lagophthalmos. METHODS: We conducted a retrospective case series of 23 patients with ptosis and poor Bell's phenomenon who underwent different surgical techniques at Xijing Hospital from April 2020 to June 2021. We assessed Bell's phenomenon at different stages of sleep and collected data on ptosis degree, surgical approach, lagophthalmos, complications, and outcomes. RESULTS: Of the total 23 patients originally considered for study, 9 with frontalis muscle advancement technique, 8 with conjoint fascial sheath suspension, 4 with levator resection technique, and 2 with levator aponeurosis plication technique. All patients achieved satisfactory correction of ptosis. One patient had prolonged lagophthalmos and underwent reoperation to lower the eyelid height. Other complications were minor and resolved with conservative treatment. CONCLUSION: We conclude that poor Bell's phenomenon is not a relative contraindication for ptosis surgery. Nocturnal lagophthalmos should be monitored after ptosis surgery regardless of the Bell's phenomenon results. Tape eyelid closure can be an effective solution to protect the corneal surface during nocturnal lagophthalmos. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Blefaroplastia , Blefaroptose , Lagoftalmia , Humanos , Estudos Retrospectivos , Músculos Oculomotores/cirurgia , Blefaroptose/cirurgia , Blefaroplastia/métodos , Pálpebras/cirurgia
6.
Ann Plast Surg ; 92(1): 12-16, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38117043

RESUMO

BACKGROUND: Lagophthalmos, a common complication after blepharoptosis correction, has plagued oculoplastic surgeons. The goal of this study was to investigate the effect of tape eyelid closure on reducing the occurrence of lagophthalmos after blepharoptosis correction. METHODS: From April 2020 to June 2021, a total of 112 patients with severe congenital ptosis received corrective surgery at the Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University. Of these, 48 underwent frontalis muscle advancement technique and 64 underwent conjoint fascial sheath suspension. Preoperative data collected included demographics, levator function, Bell's phenomenon, and marginal reflex distance 1 (MRD1). Postoperative data included surgery type, MRD1, eyelid closure function, aesthetic outcomes (including eyelid contour, eyelid symmetry, and eyelid crease), keratitis, and other complications. RESULTS: Frontalis muscle advancement technique group: the median of safe eye closure time was 7.3 months (positive Bell's phenomenon; interquartile range [IQR], 3.8-10.8 months) and 13.9 months (poor Bell's phenomenon; IQR, 11.6-16.1 months). There was a significant improvement between the preoperative and postoperative MRD1 (-1.52 ± 0.82 vs 3.85 ± 0.58 mm, P < 0.05). Conjoint fascial sheath suspension group: the median of safe eye closure time was 5.7 months (positive Bell's phenomenon; IQR, 2.9-8.5 months) and 12.4 months (poor Bell's phenomenon; IQR, 8.1-16.7 months). There was a significant improvement between the preoperative and postoperative MRD1 (-1.02 ± 0.91 vs 4.15 ± 1.03 mm, P < 0.05). All patients/guardians were satisfied with the aesthetic outcomes. CONCLUSIONS: Tape tarsorrhaphy is a safe, easy-to-learn method for treating lagophthalmos with a good aesthetic outcome.


Assuntos
Blefaroplastia , Blefaroptose , Lagoftalmia , Humanos , Blefaroptose/cirurgia , Blefaroptose/congênito , Músculos Oculomotores/cirurgia , Pálpebras/cirurgia , Blefaroplastia/métodos , Estudos Retrospectivos , Resultado do Tratamento
7.
Ann Plast Surg ; 92(1): 55-59, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38117045

RESUMO

BACKGROUND: Severe congenital ptosis is a common ocular deformity in pediatric patients that can significantly impact visual development and aesthetic appearance, leading to negative psychosocial outcomes. The frontalis muscle advancement technique is a well-established surgical treatment for severe congenital ptosis. Aesthetic changes of the brow-eye continuum often plays an important role in ptosis surgery. METHODS: We conducted a single-center retrospective case series study of patients with severe congenital ptosis who underwent the frontalis muscle advancement technique at the Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University between April 2020 and June 2021. The study aimed to evaluate the aesthetic changes of the eyebrow-eyelid continuum after surgery. The main outcome measurements included marginal reflex distance 1, palpebral fissure height, eyebrow position, upper eyelid to lower eyebrow distance, lower eyelid to upper eyebrow distance, and nasal base to lower eyelid distance. RESULTS: The study included 48 patients (66 eyelids), with 30 unilateral and 18 bilateral patients. Our analysis found that eyebrow height decreased by an average of 4.8% postoperatively relative to preoperatively in all patients. CONCLUSIONS: The frontalis muscle advancement technique has demonstrated effectiveness in achieving aesthetically pleasing outcomes in children with severe ptosis. It is crucial to pay careful attention to the brow-eye continuum during the correction process, as its harmony can greatly impact the final result.


Assuntos
Blefaroplastia , Blefaroptose , Humanos , Criança , Blefaroplastia/métodos , Estudos Retrospectivos , Blefaroptose/cirurgia , Blefaroptose/congênito , Estética , Músculos/cirurgia , Músculos Oculomotores/cirurgia
8.
Aesthetic Plast Surg ; 47(4): 1430-1438, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37193888

RESUMO

BACKGROUND: For moderate ptosis associated with fair levator function (LF), the levator resection is the most commonly used procedure. However, the levator resection technique still has some disadvantages, such as residual lagophthalmos (RL), undercorrection, conjunctival prolapse, and eyelid contour abnormality. To solve the above problems, our team have made modifications to the levator resection technique in three aspects: releasing the levator muscle sufficiently, preserving the supporting structure of the conjunctiva, and placing multiple suture sites. METHODS: Fifty-seven patients (81 eyes) underwent the modified levator resection technique and were enrolled in the study. Preoperative data collected included age, sex, margin reflex distance 1 (MRD1), and LF. Postoperative data collected included MRD1, RL, patient satisfaction, complications, and length of follow-up. RESULTS: Mean MRD1 significantly increased from 1.45 ± 0.65 mm preoperatively to 3.57 ± 0.51 mm postoperatively. Mean LF significantly increased from 6.49 ± 1.12 mm preoperatively to 9.48 ± 1.39 mm postoperatively. Successful correction was obtained in 77 eyes (95.1%). Mean RL was 1.09 ± 0.57 and 72 eyes (88.9%) showed excellent or good eyelid closure function. Fifty-four patients (94.7%) were completely satisfied with the final result. Complications such as hematoma, infection, conjunctival prolapse, suture exposure, corneal abrasion, and keratitis were not found in any cases during follow-up. CONCLUSION: This modified levator resection technique introduced in this study is effective in correcting moderate congenital blepharoptosis, while minimizing RL, undercorrection, conjunctival prolapse, eyelid contour abnormality by releasing the levator muscle sufficiently, preserving the supporting structure of the conjunctiva, and placing multiple suture sites. LEVEL OF EVIDENCE IV: This journal requires that authors 42 assign a level of evidence to each article. For a full 43 description of these Evidence-Based Medicine ratings, 44 please refer to the Table of Contents or the online 45 Instructions to Authors www.springer.com/00266 .


Assuntos
Blefaroplastia , Blefaroptose , Lagoftalmia , Humanos , Blefaroptose/cirurgia , Blefaroptose/congênito , Pálpebras/anormalidades , Estudos Retrospectivos , Blefaroplastia/métodos , Músculos Oculomotores/cirurgia , Prolapso , Resultado do Tratamento
9.
Front Oncol ; 12: 893132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860588

RESUMO

Purpose: Macrophage polarization plays an essential role in the tumor microenvironment of brain tumors. However, the role of tumor-associated macrophages (TAMs) in medulloblastoma still remains controversial. Thus, we investigated the distribution of macrophages in medulloblastoma tissues and analyzed the association of TAM recruitment and medulloblastoma patients' outcomes. Methods: We obtained a total of 71 paraffin sections from patients with medulloblastoma, and detected the activated phenotype (M1/M2) by monoclonal antibodies for CD68, HLA-DR and CD163 with multiple fluorescence immunohistochemistry method. The number of polarized macrophages was quantified using the InForm software. Outcomes were analyzed according to clinical data and quantified macrophage data. Results: The study revealed that TAMs were significantly higher in sonic hedgehog (SHH) medulloblastoma than in other subgroups, and M1 macrophages in metastatic group were significantly higher than those in non-metastatic group. A Kaplan-Meier survival analysis and multivariate Cox regression model showed the correlation of high percentage of total macrophages (P = 0.038, HR = 0.241) and M1 macrophages (P = 0.034, HR = 0.333) with good 5-year progression-free survival (PFS); however, M2 macrophages had no correlation with survival of medulloblastoma patients (P> 0.05). Conclusion: High percentage of total macrophages and M1 macrophages are correlated with good outcome of medulloblastoma patients. TAMs might be a target of therapy.

11.
J Immunol ; 206(10): 2453-2467, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33941659

RESUMO

The detection of intracellular nucleic acids is a fundamental mechanism of host defense against infections. The dysregulated nucleic acid sensing, however, is a major cause for a number of autoimmune diseases. In this study, we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for both intracellular DNA- and RNA-induced immune responses. We found that in both human and mouse cells, the deletion of G3BP1 led to the dampened cGAS activation by DNA and the insufficient binding of RNA by RIG-I. We further found that resveratrol (RSVL), a natural compound found in grape skin, suppressed both intracellular DNA- and RNA-induced type I IFN production through inhibiting G3BP1. Importantly, using experimental mouse models for Aicardi-Goutières syndrome, an autoimmune disorder found in humans, we demonstrated that RSVL effectively alleviated intracellular nucleic acid-stimulated autoimmune responses. Thus, our study demonstrated a broader role of G3BP1 in sensing different kinds of intracellular nucleic acids and presented RSVL as a potential treatment for autoimmune conditions caused by dysregulated nucleic acid sensing.


Assuntos
Autoimunidade/genética , DNA Helicases/deficiência , DNA Helicases/metabolismo , Espaço Intracelular/metabolismo , Ácidos Nucleicos/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/deficiência , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Helicases/deficiência , RNA Helicases/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/deficiência , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Transdução de Sinais/genética , Células A549 , Animais , Autoimunidade/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA Helicases/antagonistas & inibidores , DNA Helicases/genética , Fibroblastos/metabolismo , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Espaço Intracelular/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas de Ligação a Poli-ADP-Ribose/antagonistas & inibidores , Proteínas de Ligação a Poli-ADP-Ribose/genética , RNA Helicases/antagonistas & inibidores , RNA Helicases/genética , Proteínas com Motivo de Reconhecimento de RNA/antagonistas & inibidores , Proteínas com Motivo de Reconhecimento de RNA/genética , Resveratrol/administração & dosagem , Transdução de Sinais/imunologia , Transfecção
12.
J Craniofac Surg ; 32(6): 2155-2158, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33930010

RESUMO

BACKGROUND AND OBJECTIVE: Defects resulted from the removal of large scars, benign tumors, severe pigmentation abnormalities, and vascular malformations, etc., in the scalp and face need to be repaired to restore the appearance. Here, the authors introduced the application of various expanded superficial temporal artery (STA) flaps in the repair of above defects. METHODS: From Jan. 2015 to Dec. 2018, 19 patients with craniofacial secondary defects received the repair with expanded STA flaps in our clinic. The defects were resulted from the removal of scalp scar (n = 6), neurofibroma (n = 4), sebaceous nevus (n = 3), arteriovenous malformation (n = 2), facial scar (n = 2), and port-wine stain (n = 2). The expanded STA flaps included 14 cases of flaps pedicled by parietal branch of STA, 2 cases of flaps pedicled by parietal branch of STA combined with laser hair removal, 1 case of flaps pedicled by frontal branch of STA, and 2 cases of prefabricated expanded skin flap with the superficial temporal fascia in the neck. RESULTS: The two-stage operation and water-filling expansion were accomplished in all patients. All flaps survived well, except one flap with venous congestion, which resolved after blood-letting and application of drugs promoting venous draining. In the three to six months follow-up, the flaps' color, texture, and thickness were satisfying. CONCLUSIONS: Individual application of different types of expanded STA flaps could achieve ideal results in repairing craniofacial secondary defects.


Assuntos
Procedimentos de Cirurgia Plástica , Couro Cabeludo , Humanos , Estudos Retrospectivos , Couro Cabeludo/cirurgia , Retalhos Cirúrgicos , Artérias Temporais/cirurgia
13.
Nat Commun ; 12(1): 2114, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837182

RESUMO

Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we identify that ~37% (36,941) of the genomes contain a specific trio-nucleotide polymorphism (GGG-to-AAC) in the coding sequence of N, which leads to the amino acid substitutions, R203K/G204R. Interestingly, NR203K/G204R exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. By screening the chemicals known to interfere with N-RNA binding in other viruses, we find that (-)-gallocatechin gallate (GCG), a polyphenol from green tea, disrupts the LLPS of N and inhibits SARS-CoV-2 replication. Thus, our study reveals that targeting N-RNA condensation with GCG could be a potential treatment for COVID-19.


Assuntos
Substituição de Aminoácidos/efeitos dos fármacos , COVID-19/prevenção & controle , Catequina/análogos & derivados , Proteínas do Nucleocapsídeo/genética , SARS-CoV-2/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , COVID-19/virologia , Catequina/farmacologia , Genoma Viral/genética , Humanos , Extração Líquido-Líquido , Proteínas do Nucleocapsídeo/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , SARS-CoV-2/genética , Replicação Viral/genética
14.
Sci Rep ; 11(1): 5638, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707557

RESUMO

Medulloblastoma (MB) is the most common type of brain malignancy in children. Molecular profiling has become an important component to select patients for therapeutic approaches, allowing for personalized therapy. In this study, we successfully identified detectable levels of tumor-derived cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) samples of patients with MB. Furthermore, cfDNA from CSF can interrogate for tumor-associated molecular clues. MB-associated alterations from CSF, tumor, and post-chemotherapy plasma were compared by deep sequencing on next-generation sequencing platform. Shared alterations exist between CSF and matched tumor tissues. More alternations were detected in circulating tumor DNA from CSF than those in genomic DNA from primary tumor. It was feasible to detect MB-associated mutations in plasma of patients treated with chemotherapy. Collectively, CSF supernatant can be used to monitor genomic alterations, as a superior technique as long as tumor-derived cfDNA can be isolated from CSF successfully.


Assuntos
Neoplasias Cerebelares/líquido cefalorraquidiano , Neoplasias Cerebelares/genética , DNA Tumoral Circulante/líquido cefalorraquidiano , DNA Tumoral Circulante/genética , Variação Genética , Meduloblastoma/líquido cefalorraquidiano , Adolescente , Neoplasias Cerebelares/sangue , Criança , DNA Tumoral Circulante/sangue , Feminino , Genoma Humano , Humanos , Masculino , Meduloblastoma/sangue , Fatores de Tempo
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 164-168, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627212

RESUMO

OBJECTIVE: To study the clinical features of children with recurrent medulloblastoma (MB) and treatment regimens. METHODS: A retrospective analysis was performed on 101 children with recurrent MB who were admitted to the hospital from August 1, 2011 to July 31, 2017. The children were followed up to July 31, 2020. The Kaplan-Meier method was used for survival analysis. The Cox regression model was used for multivariate regression analysis. RESULTS: Of the 101 children, 95 underwent remission induction therapy, among whom 51 had response, resulting in a response rate of 54%. The median overall survival (OS) time after recurrence was 13 months, and the 1-, 3-, and 5-year OS rates were 50.5%±5.0%, 19.8%±4.0%, and 10%±3.3% respectively. There was no significant difference in the 5-year OS rate between the children with different ages (< 3 years or 3-18 years), sexes, pathological types, or Change stages, between the children with or without radiotherapy before recurrence or re-irradiation after recurrence, and between the children with different times to recurrence (< 12 months or ≥ 12 months after surgery) (P > 0.05). There were significant differences in the 5-year OS rate between the children with or without reoperation after recurrence and between the children with different recurrence sites (P < 0.05). The children with reoperation after recurrence had a significantly longer survival time than those without reoperation (P=0.007), and the risk of death in children undergoing reoperation after recurrence was 0.389 times (95% confidence interval:0.196-0.774) that in children who did not undergo such reoperation. CONCLUSIONS: As for the recurrence of MB, although remission induction therapy again can achieve remission, such children still have a short survival time. Only reoperation can significantly prolong survival time, and therefore, early reoperation can be considered to improve the outcome of children with recurrent MB.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Neoplasias Cerebelares/terapia , Criança , Humanos , Meduloblastoma/terapia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Taxa de Sobrevida
16.
Cell Res ; 30(12): 1063-1077, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32839552

RESUMO

Necroptosis, a form of programmed cell death, is characterized by the loss of membrane integrity and release of intracellular contents, the execution of which depends on the membrane-disrupting activity of the Mixed Lineage Kinase Domain-Like protein (MLKL) upon its phosphorylation. Here we found myofibers committed MLKL-dependent necroptosis after muscle injury. Either pharmacological inhibition of the necroptosis upstream kinase Receptor Interacting Protein Kinases 1 (RIPK1) or genetic ablation of MLKL expression in myofibers led to significant muscle regeneration defects. By releasing factors into the muscle stem cell (MuSC) microenvironment, necroptotic myofibers facilitated muscle regeneration. Tenascin-C (TNC), released by necroptotic myofibers, was found to be critical for MuSC proliferation. The temporary expression of TNC in myofibers is tightly controlled by necroptosis; the extracellular release of TNC depends on necroptotic membrane rupture. TNC directly activated EGF receptor (EGFR) signaling pathway in MuSCs through its N-terminus assembly domain together with the EGF-like domain. These findings indicate that necroptosis plays a key role in promoting MuSC proliferation to facilitate muscle regeneration.


Assuntos
Fibras Musculares Esqueléticas/patologia , Necroptose , Regeneração , Células-Tronco/patologia , Tenascina/metabolismo , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Humanos , Camundongos , Modelos Biológicos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Necroptose/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Regeneração/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(6): 589-594, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32571457

RESUMO

OBJCTIVE: To study the clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor (cPNET), as well as the risks factors for poor prognosis. METHODS: A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with cPNET from June 2012 to September 2018. RESULTS: The 42 children had a median overall survival (OS) time of 2.0 years and a median event-free survival (EFS) time of 1.3 years; the 1-, 3-, and 5-year OS rates were 76.2%±6.6%, 41.4%±8.7%, 37.3%±8.8% respectively, and the 1-, 3-, and 5-year EFS rates were 64.3%±7.4%, 32.7%±8.0%, 28.0%±8.1% respectively. The univariate analysis showed that there were significant differences in the OS and EFS rates among the children with different patterns of surgical resection, chemotherapy cycles, and risk grades (P<0.05), and there was also a significant difference in the OS rate between the children receiving radiotherapy and those not receiving radiotherapy (P<0.05). The multivariate Cox regression analysis showed that chemotherapy cycles and risk grade were independent influencing factors for EFS and OS rates (P<0.05). The EFS and OS rates increased with the increase in chemotherapy cycles and the reduction in risk grade. CONCLUSIONS: Multimodality therapy with surgery, chemotherapy, and radiotherapy is an effective method for the treatment of cPNET in children. Early diagnosis and treatment and adherence to chemotherapy for as long as possible may improve EFS and OS rates.


Assuntos
Tumores Neuroectodérmicos Primitivos , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Terapia Combinada , Intervalo Livre de Doença , Humanos , Prognóstico , Estudos Retrospectivos
18.
Angew Chem Int Ed Engl ; 59(37): 16013-16022, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32568423

RESUMO

Understanding the thermal aggregation behavior of metal atoms is important for the synthesis of supported metal clusters. Here, derived from a metal-organic framework encapsulating a trinuclear FeIII 2 FeII complex (denoted as Fe3 ) within the channels, a well-defined nitrogen-doped carbon layer is fabricated as an ideal support for stabilizing the generated iron nanoclusters. Atomic replacement of FeII by other metal(II) ions (e.g., ZnII /CoII ) via synthesizing isostructural trinuclear-complex precursors (Fe2 Zn/Fe2 Co), namely the "heteroatom modulator approach", is inhibiting the aggregation of Fe atoms toward nanoclusters with formation of a stable iron dimer in an optimal metal-nitrogen moiety, clearly identified by direct transmission electron microscopy and X-ray absorption fine structure analysis. The supported iron dimer, serving as cooperative metal-metal site, acts as efficient oxygen evolution catalyst. Our findings offer an atomic insight to guide the future design of ultrasmall metal clusters bearing outstanding catalytic capabilities.

19.
Int J Pediatr Otorhinolaryngol ; 136: 110157, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32544638

RESUMO

OBJECTIVE: Infantile hemangiomas (IHs) are the most common benign tumor in infancy. Periorbital IHs may lead to visual dysplasia so prompt and effective treatment should be adopted. In this study, we retrospectively analyzed the diagnosis and treatment of periorbital IHs treated in our clinic and give the strategy for clinical practice. METHODS: From Jan. 2006 to Dec. 2018, 35 patients with periorbital IHs were enrolled into this study, including 13 males. The initial age of treatment ranged from 0.6 to 7 months. The clinical manifestations, imaging examination results, treatment measures and follow-up results were analyzed. Then diagnosis and treatment strategy were summarized. RESULTS: All patients were examined by ultrasound to confirm the depth of tumor, evaluate the effect of treatment and provide the evidence for drug withdrawal. For patients with deep hemangiomas, enhanced CT were added. Intralesional injection of glucocorticoids and oral propranolol were applied. All patients achieved good results. Ocular symptoms were avoided in most of the patients. CONCLUSION: Periorbital IHs have special growth features and can be diagnosed by the appearance, ultrasound, CT scan, and propranolol experimental therapy if necessary. In consideration of potential complications, oral propranolol is the first treatment option for periorbital IHs.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Hemangioma Capilar/diagnóstico , Hemangioma Capilar/tratamento farmacológico , Propranolol/uso terapêutico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Anti-Inflamatórios/uso terapêutico , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Hemangioma Capilar/complicações , Humanos , Lactente , Masculino , Estudos Retrospectivos , Neoplasias Cutâneas/complicações , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia
20.
Angew Chem Int Ed Engl ; 59(19): 7384-7389, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32153103

RESUMO

Single-atom catalysts have drawn great attention, especially in electrocatalysis. However, most of previous works focus on the enhanced catalytic properties via improving metal loading. Engineering morphologies of catalysts to facilitate mass transport through catalyst layers, thus increasing the utilization of each active site, is regarded as an appealing way for enhanced performance. Herein, we design an overhang-eave structure decorated with isolated single-atom iron sites via a silica-mediated MOF-templated approach for oxygen reduction reaction (ORR) catalysis. This catalyst demonstrates superior ORR performance in both alkaline and acidic electrolytes, comparable to the state-of-the-art Pt/C catalyst and superior to most precious-metal-free catalysts reported to date. This activity originates from its edge-rich structure, having more three-phase boundaries with enhanced mass transport of reactants to accessible single-atom iron sites (increasing the utilization of active sites), which verifies the practicability of such a synthetic approach.

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