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1.
Ann Surg Oncol ; 31(2): 1058-1068, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37865941

RESUMO

PURPOSE: We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. METHODS: PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. RESULTS: Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled-61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III-V AEs was 29.5% versus 34.1% (p = 0.621). The pleural progression rates were 13.2 versus 18.9% (p = 0.462) and the median overall survival (OS) was 50.5 versus 52.7 months (p = 0.958). Median time to progression (TTP) in thoracic disease was not reached. There was no significant difference in perioperative AEs, TTP, and OS for total patients and the completeness of cytoreduction (CC) score subgroups (p > 0.05). Age ≥ 60 years (hazard ratio [HR] 4.162, p = 0.026) was an independent risk factor influencing pleural progression, and primary malignant peritoneal mesothelioma (MPM; HR 2.749, p = 0.016) and the presence of two or more serious AEs (SAEs; HR 7.294, p = 0.001) were independent risk factors influencing OS. CONCLUSIONS: HITAC can be performed in carefully selected PC patients who underwent diaphragm resection, with no worsening of the safety profile and a possible benefit for pleural progression. In those patients, age ≥ 60 years is associated with a shorter TTP of thoracic disease, while primary MPM and two or more perioperative SAEs are associated with worse OS.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Diafragma/patologia , Quimioterapia do Câncer por Perfusão Regional , Taxa de Sobrevida
2.
Basic & Clinical Medicine ; (12): 577-581, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1018659

RESUMO

Objective To investigate the needs and feedback from clinical medical students on the diversified teaching mode adopted by the Department of Endocrinology in Peking Union Medical College Hospital.Methods Questionnaires were distributed to the medicine students who were in clinical rotation in Peking Union Medical Col-lege,and the teaching status and teaching effect was investigated.Results A total of 95 valid questionnaires were received.The attending physicians and the teaching resident physicians performed well in the daily teaching activi-ties.The medical students believed that outpatient training was necessary in addition to ward rotations.After the ro-tation in the endocrinology department,the self-evaluated score of mastery of endocrinology knowledge had been significantly improved,especially in those who rotated in outpatient clinic,suggesting that outpatient teaching was of great significance.In addition,the establishment of a self-learning platform including clinical cases and videos in endocrinology could be used as an important supplementary means for clinical teaching.Conclusions Outpatient training improves learning outcomes of medical students,so must be kept and further strengthened in the future.Building a database of typical clinical cases and teaching videos can improve the training quality.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1019487

RESUMO

Objective:To determine the correlation of tumor volume and weight with biochemical parameters in patients with parathyroid adenoma (PA) .Methods:A prospective electronic database collected clinical data on 208 patients with PA treated for the first time by surgery at department of general surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.The relationship between biochemical parameters and tumor volume and weight was analyzed with Spearman’s correlation.Results:Tumor volume and weight were positively correlated with parathyroid hormone (PTH) ( r=0.33, P<0.001; r=0.39, P<0.001), calcium ( r=0.16, P=0.018; r=0.18, P=0.007) and alkaline phosphatase levels ( r=0.24, P<0.001; r=0.27, P<0.001), respectively. Clinical correlates affecting serum PTH were age, serum calcium and tumor weight ( F=30.325, P<0.001) . Conclusions:Tumor burden in patients with PA correlates with some laboratory biochemical parameters. Age and cystic lesions of the tumor may influence the actual serum PTH levels.

4.
Int J Mol Sci ; 24(23)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38069442

RESUMO

The flavonoid glycoside apiin (apigenin 7-O-[ß-D-apiosyl-(1→2)-ß-D-glucoside]) is abundant in apiaceous and asteraceous plants, including celery and parsley. Although several enzymes involved in apiin biosynthesis have been identified in celery, many of the enzymes in parsley (Petroselinum crispum) have not been identified. In this study, we identified parsley genes encoding the glucosyltransferase, PcGlcT, and the apiosyltransferase, PcApiT, that catalyze the glycosylation steps of apiin biosynthesis. Their substrate specificities showed that they were involved in the biosynthesis of some flavonoid 7-O-apiosylglucosides, including apiin. The expression profiles of PcGlcT and PcApiT were closely correlated with the accumulation of flavonoid 7-O-apiosylglucosides in parsley organs and developmental stages. These findings support the idea that PcGlcT and PcApiT are involved in the biosynthesis of flavonoid 7-O-apiosylglucosides in parsley. The identification of these genes will elucidate the physiological significance of apiin and the development of apiin production methods.


Assuntos
Apium , Glicosídeos Cardíacos , Glicosídeos/química , Petroselinum/química , Glicosiltransferases/genética , Flavonoides/química
6.
Plant Physiol ; 193(3): 1758-1771, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37433052

RESUMO

Apiose is a unique branched-chain pentose found in plant glycosides and a key component of the cell wall polysaccharide pectin and other specialized metabolites. More than 1,200 plant-specialized metabolites contain apiose residues, represented by apiin, a distinctive flavone glycoside found in celery (Apium graveolens) and parsley (Petroselinum crispum) in the family Apiaceae. The physiological functions of apiin remain obscure, partly due to our lack of knowledge on apiosyltransferase during apiin biosynthesis. Here, we identified UGT94AX1 as an A. graveolens apiosyltransferase (AgApiT) responsible for catalyzing the last sugar modification step in apiin biosynthesis. AgApiT showed strict substrate specificity for the sugar donor, UDP-apiose, and moderate specificity for acceptor substrates, thereby producing various apiose-containing flavone glycosides in celery. Homology modeling of AgApiT with UDP-apiose, followed by site-directed mutagenesis experiments, identified unique Ile139, Phe140, and Leu356 residues in AgApiT, which are seemingly crucial for the recognition of UDP-apiose in the sugar donor pocket. Sequence comparison and molecular phylogenetic analysis of celery glycosyltransferases suggested that AgApiT is the sole apiosyltransferase-encoding gene in the celery genome. Identification of this plant apiosyltransferase gene will enhance our understanding of the physioecological functions of apiose and apiose-containing compounds.


Assuntos
Apium , Flavonas , Apium/genética , Glicosídeos , Filogenia
7.
Eur Spine J ; 32(7): 2459-2467, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37027035

RESUMO

PURPOSE: Myxopapillary ependymoma (MPE) was classified as grade 2 tumor in the 2021 World Health Organization central nervous system classification because of its high recurrence probability. This study aimed to investigate predictive factors and management of tumor recurrence. METHODS: Seventy-two patients with spinal MPE underwent initial surgical treatment at our hospital between 2011 and 2021. Kaplan-Meier curves and Cox regression were used to analyze the correlation between clinical variables and progression-free survival (PFS). RESULTS: The median age at diagnosis was 33.5 years (range 8-60 years). Twenty-one patients (29.2%) had preoperative spinal drop metastases. Gross total resection (GTR) was performed in 37 patients (51.4%). The median follow-up was 7.2 years, and the follow-up rate was 88.9% (64 of 72 cases). Twelve of the 64 patients (18.9%) relapsed, and preoperative drop metastasis occurred in 7 patients (58.3%). The estimated 5-year and 10-year PFS rates were 82% and 77%, respectively. Univariate analysis showed that GTR was associated with improved PFS (hazard ratio [HR] 0.149, p = 0.014), while preoperative drop metastasis (HR 3.648, p = 0.027) and tumor involvement sacrococcygeal region (HR 7.563, p = 0.003) were associated with tumor recurrence. Adjuvant radiotherapy (RT) was significantly associated with improved PFS in patients with preoperative drop metastasis (p = 0.039). CONCLUSION: Complete surgical resection under the premise of protecting neurological function is an important factor in reducing spinal MPE recurrence. Adjuvant RT is recommended when the tumor invades the capsule with preoperative drop metastasis or adhesion to the nerve and cannot reach GTR.


Assuntos
Ependimoma , Neoplasias da Medula Espinal , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Neoplasias da Medula Espinal/patologia , Radioterapia Adjuvante , Ependimoma/cirurgia , Estudos Retrospectivos
8.
Brain Pathol ; 33(4): e13153, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36751054

RESUMO

H3 K27-altered diffuse midline glioma is a highly lethal pediatric-type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among diffuse midline gliomas with different locations and ages. Compared to tumors located in the brain stem and thalamus, the molecular and clinicopathological features of H3 K27-altered spinal cord glioma are still largely elusive, thus hindering the accurate management of patients. Here we aimed to characterize the clinicopathological and molecular features of H3 K27M-mutant spinal cord glioma in 77 consecutive cases. We found that the H3 K27M-mutant spinal cord glioma, with a median age of 35 years old, had a significantly better prognosis than H3 K27M-mutant brain tumors. We noticed a molecular heterogeneity of H3 K27M-mutant spinal cord astrocytoma via targeted sequencing with 34 cases. TP53 mutation which occurred in 58.8% of cases is mutually exclusive with PPM1D (26%) and NF1 (44%) mutations. The TP53-mutant cases had a significantly higher number of copy number variants (CNV) and a marginally higher proportion of pediatric patients (age at diagnosis <18 years old, p = 0.056). Cox regression and Kaplan-Meier curve analysis showed that the higher number of CNV events (≥3), chromosome (Chr) 9p deletion, Chr 10p deletion, ATRX mutation, CDK6 amplification, and retinoblastoma protein (RB) pathway alteration are associated with worse survival. Cox regression analysis with clinicopathological features showed that glioblastoma histological type and a high Ki-67 index (>10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias da Medula Espinal , Humanos , Criança , Adulto , Adolescente , Histonas/genética , Prognóstico , Fosfatidilinositol 3-Quinases/genética , Glioma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias da Medula Espinal/genética , Mutação , Genômica
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-986004

RESUMO

A 50-year-old man with a 15-year history of elevated blood glucose and an approximately 2-year history of diarrhea was admitted to the Peking Union Medical College Hospital. The initial diagnosis was type 2 diabetes. After repeated pancreatitis and pancreatoduodenectomy, severe pancreatic endocrine and exocrine dysfunction including alternating high and low blood glucose and fat diarrhea occurred. Tests for type 1 diabetes-related antibodies were all negative, C-peptide levels were substantially reduced, fat-soluble vitamin levels were reduced, and there was no obvious insulin resistance. Therefore, a diagnosis of pancreatic diabetes was clear. The patient was given small doses of insulin and supplementary pancreatin and micronutrients. Diarrhea was relieved and blood glucose was controlled. The purpose of this article is to raise clinicians' awareness of the possibility of pancreatic diabetes after pancreatitis or pancreatic surgery. Timely intervention and monitoring may reduce the occurrence of complications.


Assuntos
Masculino , Humanos , Pessoa de Meia-Idade , Glicemia , Diabetes Mellitus Tipo 2/complicações , Pancreaticoduodenectomia/efeitos adversos , Pancreatite Crônica/complicações , Desnutrição/complicações
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-994393

RESUMO

A 36-year-old woman was admitted to the Peking Union Medical College Hospital with a history of fractures for 2 years, limb weakness for 1 year, and ostealgia for 2 months. The patient's examination identified iron deficiency anemia, significantly decreased serum calcium and 25-hydroxyvitamin D3 levels, and increased alkaline phosphatase and parathyroid hormone levels. Imaging showed several typical signs of osteomalacia. Considering the history of Roux-en-Y gastric bypass surgery, the diagnosis was considered to be osteomalacia caused by a postoperative nutritional absorption disorder. The patient was supplemented with calcitriol, calcium, and vitamin D and gradually returned to normal physical activity. The bone metabolism indicators and bone density were significantly improved.

11.
Acta Universitatis Medicinalis Anhui ; (6): 418-422,428, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1038487

RESUMO

Objective @#To investigate the effect of Arginine Vasopressin (AVP) on the median preoptic glutamatergic (MnPOVglut2 ) neurons and its mechanism.@*Methods @#Brain slices were prepared from male Vglut2-tdTomato mice.MnPOVglut2 neurons expressing red fluorescent protein were located by using fluorescence microscope.Wholecell patch clamp technique was used to observe the effect of AVP on the firing frequency of MnPOVglut2 neurons,the effect of synaptic transmission blockers ( STBs) on the AVP-induced change in the firing frequency of MnPOVglut2 neurons,and the effect of AVP V1a receptor antagonist on the AVP-induced change in the firing frequency of MnPOVglut2 neurons. @*Results@#The mean firing frequency of MnPOVglut2 neurons increased during perfusion with artificial cerebrospinal fluid (ACSF) and AVP compared with that during perfusion with ACSF (P<0. 01) ,indicating that AVP excited the MnPOVglut2 neurons.The mean firing frequency of MnPOVglut2 neurons still increased during perfusion with ACSF,STBs,and AVP compared with that during perfusion with ACSF and STBs (P<0. 001) ; moreover,the magnitude of AVP-induced increase in firing frequency didn't change significantly during perfusion with ACSF,STBs,and AVP compared with that during perfusion with ACSF and AVP (P >0. 05 ) ,suggesting that AVP excited the MnPOVglut2 neurons directly in a postsynaptic manner.The magnitude of AVP-induced increase in the firing frequency of MnPOVglut2 neurons declined during perfusion with ACSF,STBs,AVP,and V1areceptor antagonist compared with that during perfusion with ACSF,STBs,and AVP (P<0. 01) ,suggesting that AVP excited MnPOVglut2 neurons directly via V1a receptor.@*Conclusion @#AVP can excite MnPOVglut2 neurons via V1areceptor directly in a postsynaptic manner.This study reveals the molecular marker of MnPO neurons which AVP act on.

12.
Front Public Health ; 10: 812268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35211445

RESUMO

BACKGROUND: Prenatal exposures to polybrominated diphenyl ethers (PBDEs) may affect fetal growth. Small for gestational age (SGA) is a measure based on birth weight and gestational age at birth and represents a good indicator of fetal growth but it has been used only in a small number of studies. The present study aimed to examine the associations between PBDEs exposure and the risk of SGA among participants from a birth cohort in Southwest China. METHODS: The concentrations of eight common PBDE congeners (BDE-28, BDE47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and BDE-209) in 996 human placental samples collected between May to October 2020 were determined. A questionnaire survey was administered regarding maternal characteristics. The outcome data of the newborns were obtained from the medical record. The Mann-Whitney U test and binomial logistic regression analysis were used to assess associations between PBDEs concentrations (as a continuous or categorical variable) and SGA. RESULTS: All PBDE congeners were detected in more than 73% of samples. The median concentrations of ΣPBDEs were 10.08 ng/g lipid weight (lw). BDE-209 was the most abundant PBDE congener, contributed 28% to ΣPBDEs. There were 114 (11.4%) SGA infants. The levels of BDE-99, BDE-100, BDE-209, and the total levels of ΣPBDEs in the SGA group were significantly higher than those in the controls. When classifying the PBDEs concentrations as two categories: low and high, high level of ΣPBDEs was associated with increased risk of SGA [odds ratio (OR): 2.203, 95% confidence interval (CI): 1.453-3.340] after adjusting for potential covariates. The association remained significant when stratifying the data by gender of the newborn (OR: 2.572, 95% CI: 1.337-4.947 for boys; OR: 2.385, 95% CI: 1.315-4.325 for girls). CONCLUSION: The present study adds to the literature by using placenta to measure PBDEs exposure during pregnancy, and provides evidence that prenatal exposure to PBDEs may be associated with the risk of SGA, at least at the levels of exposure in our population.


Assuntos
Éteres Difenil Halogenados , Exposição Materna , China/epidemiologia , Feminino , Idade Gestacional , Éteres Difenil Halogenados/análise , Humanos , Lactente , Recém-Nascido , Masculino , Exposição Materna/efeitos adversos , Placenta/química , Gravidez
13.
Chemosphere ; 293: 133524, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34990723

RESUMO

The study aimed to examine the associations between the level of trihalomethanes and its metabolites in pregnancy and the risks of adverse birth outcomes. We searched the databases of the China National Knowledge Infrastructure, WanFang, Vip, PubMed, and Elsevier Science Direct from database establishment to July 14, 2021 and performed a systematic review and meta-analysis of observational studies reporting associations between trihalomethanes level and abnormally low birth weight and preterm birth. The pooled odds ratio (OR), pooled risk ratio, and pooled risk difference with their 95% confidence interval (CI) were calculated for risk estimates. A total of 24 studies involving 1,118,037 pregnant women were finally enrolled in the present systematic review and meta-analysis. Our research found that abnormally low birth weight was associated with higher levels of total trihalomethanes (OR = 2.45, 95% CI: 1.28, 4.68; P = 0.007). Unexpectedly, the meta-analysis indicated that higher total trihalomethanes level was associated with lower odds of preterm birth (OR = 0.90, 95% CI: 0.81, 0.99; P = 0.03). Our findings indicate that trihalomethanes exposure might be a risk factor for abnormally low birth weight and that it would be prudent to minimize exposure to trihalomethanes during pregnancy because of the risk of abnormally low birth weight. Given some limitations of the systematic review and meta-analysis, our results should be interpreted with caution.


Assuntos
Complicações na Gravidez , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Trialometanos/toxicidade
14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-933428

RESUMO

The majority of primary hyperparathyroidism (PHPT) are sporadic, and less than 10% of cases are hereditary or part of familial syndromes. Glial cell missing 2 (GCM2) was confirmed to be a new pathogenic gene of PHPT in 2016. At present, four GCM2 mutations have been confirmed to have certain correlations with familial or sporadic PHPT. The purpose of this review is to summarize the pathogenesis and clinical features of GCM2 mutation related primary hyperparathyroidism.

15.
Chinese Journal of Neuromedicine ; (12): 516-522, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1035645

RESUMO

Moyamoya disease is a chronic progressive occlusive cerebrovascular disease characterized by progressive occlusion of the terminal internal carotid artery with formation of an abnormal vascular network at the skull base. The pathogenesis of the disease is not fully understood and is mainly thought to be associated with genetic factors, environmental factors and immune inflammatory response. The discovery of relevant biomarkers may provide hope for elucidation of pathogenesis of moyamoya disease and the early diagnosis and treatment of it. From the perspectives of coding gene, non-coding RNA and protein related to moyamoya disease, the possible molecular mechanisms involved in the occurrence and development of moyamoya disease are elaborated to further clarify their value as biomarkers of moyamoya disease.

16.
J Hematol Oncol ; 14(1): 109, 2021 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-34246306

RESUMO

BACKGROUND: The prognosis for diffuse gliomas is very poor and the mechanism underlying their malignant progression remains unclear. Here, we aimed to elucidate the role and mechanism of the RNA N6,2'-O-dimethyladenosine (m6A) reader, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), in regulating the malignant progression of gliomas. METHODS: YTHDF2 mRNA levels and functions were assessed using several independent datasets. Western blotting, quantitative polymerase chain reaction, and immunohistochemistry were used to evaluate the expression levels of YTHDF2 and other molecules in human and mouse tumor tissues and cells. Knockdown and overexpression were used to evaluate the effects of YTHDF2, methyltransferase-like 3 (METTL3), and UBX domain protein 1 (UBXN1) on glioma malignancy in cell and orthotopic xenograft models. RNA immunoprecipitation (RIP), methylated RIP, and RNA stability experiments were performed to study the mechanisms underlying the oncogenic role of YTHDF2. RESULTS: YTHDF2 expression was positively associated with a higher malignant grade and molecular subtype of glioma and poorer prognosis. YTHDF2 promoted the malignant progression of gliomas in both in vitro and in vivo models. Mechanistically, YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-κB activation. We further revealed that UBXN1 overexpression attenuated the oncogenic effect of YTHDF2 overexpression and was associated with better survival in patients with elevated YTHDF2 expression. CONCLUSIONS: Our findings confirmed that YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-κB activation via UBXN1 with a primary focus on m6A modification.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Glioma/genética , Metiltransferases/genética , NF-kappa B/metabolismo , Estabilidade de RNA , Proteínas de Ligação a RNA/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Glioma/patologia , Humanos , Metiltransferases/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo
17.
Cell Death Dis ; 12(7): 631, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145212

RESUMO

Bone marrow-derived mesenchymal stem cells (BM-MSCs), the common progenitor cells of adipocytes and osteoblasts, have been recognized as the key mediator during bone formation. Herein, our study aim to investigate molecular mechanisms underlying circular RNA (circRNA) AFF4 (circ_AFF4)-regulated BM-MSCs osteogenesis. BM-MSCs were characterized by FACS, ARS, and ALP staining. Expression patterns of circ_AFF4, miR-135a-5p, FNDC5/Irisin, SMAD1/5, and osteogenesis markers, including ALP, BMP4, RUNX2, Spp1, and Colla1 were detected by qRT-PCR, western blot, or immunofluorescence staining, respectively. Interactions between circ_AFF4 and miR-135a-5p, FNDC5, and miR-135a-5p were analyzed using web tools including TargetScan, miRanda, and miRDB, and further confirmed by luciferase reporter assay and RNA pull-down. Complex formation between Irisin and Integrin αV was verified by Co-immunoprecipitation. To further verify the functional role of circ_AFF4 in vivo during bone formation, we conducted animal experiments harboring circ_AFF4 knockdown, and born samples were evaluated by immunohistochemistry, hematoxylin and eosin, and Masson staining. Circ_AFF4 was upregulated upon osteogenic differentiation induction in BM-MSCs, and miR-135a-5p expression declined as differentiation proceeds. Circ_AFF4 knockdown significantly inhibited osteogenesis potential in BM-MSCs. Circ_AFF4 stimulated FNDC5/Irisin expression through complementary binding to its downstream target molecule miR-135a-5p. Irisin formed an intermolecular complex with Integrin αV and activated the SMAD1/5 pathway during osteogenic differentiation. Our work revealed that circ_AFF4, acting as a sponge of miR-135a-5p, triggers the promotion of FNDC5/Irisin via activating the SMAD1/5 pathway to induce osteogenic differentiation in BM-MSCs. These findings gained a deeper insight into the circRNA-miRNA regulatory system in the bone marrow microenvironment and may improve our understanding of bone formation-related diseases at physiological and pathological levels.


Assuntos
Células da Medula Óssea/metabolismo , Diferenciação Celular , Fibronectinas/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteogênese , RNA Circular/metabolismo , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Animais , Células Cultivadas , Feminino , Fibronectinas/genética , Humanos , Transplante de Células-Tronco Mesenquimais , Camundongos Endogâmicos BALB C , MicroRNAs/genética , RNA Circular/genética , Transdução de Sinais
18.
Cancer Lett ; 511: 36-46, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-33933553

RESUMO

Understanding the role of N6-methyladenosine (m6A) in tumorigenesis and stem cell maintenance is an emerging field in glioma research. However, it is necessary to study the function of m6A in IDH-mutation and IDH-wildtype gliomas separately. Here, we aimed to elucidate the role and mechanism of the m6A writer METTL3 in regulating the malignant progression of IDH-wildtype gliomas. We demonstrated that METTL3 expression is positively associated with a higher malignant grade and poorer prognosis of IDH-wildtype gliomas but not IDH-mutant gliomas. METTL3 could also promote the malignant progression of gliomas in both in vitro and in vivo models. Mechanistically, METTL3 upregulated MALAT1 expression by enhancing its stability via m6A modification. We further revealed that HuR was essential for METTL3-mediated MALAT1 stabilization, and upregulated MALAT1 subsequently activated NF-κB. Taken together, our findings confirmed that METTL3 promoted the malignant progression of IDH-wildtype gliomas and revealed important insight into the upstream regulatory mechanism of MALAT1 and NF-κB with a primary focus on m6A modification.


Assuntos
Adenosina/análogos & derivados , Neoplasias Encefálicas/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Glioma/metabolismo , Metiltransferases/metabolismo , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo , Adenosina/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Glioma/genética , Glioma/patologia , Xenoenxertos , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais
19.
Gland Surg ; 10(4): 1315-1324, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33968683

RESUMO

BACKGROUND: Breast cancer (BC) has the highest morbidity and the fifth-highest mortality rate among women in China. Peritoneal metastases from BC are rare, and presently, there are no guidelines or international consensus on its treatment. Patients with a prognosis of peritoneal carcinomatosis (PC) have poorer survival rates than patients with other regional metastases from BC. METHODS: Four BC PC patients, who had undergone cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC), participated in this study. Clinicopathologic characteristics and overall survival (OS) data were collected and analyzed. RESULTS: Patients' average age when they underwent CRS + HIPEC was 59.8 years. The average time of CRS + HIPEC was 8.8 h. The median number of resected organ areas was 7. Following CRS + HIPEC, each of the 4 patients survived for 31, 28, 16 and 52 months, respectively. There were no serious adverse events during the perioperative period. CONCLUSIONS: The study examined the detailed process of CRS + HIPEC and found that patients with BC PC may benefit from this treatment. The 4 cases provided evidence that the integrated therapy of CRS + HIPEC is a promising strategy that could improve outcomes for BC PC patients. Further, no serious adverse events (SAEs) occurred during the CRS + HIPEC perioperative period.

20.
Neurosurgery ; 89(2): 300-307, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34015818

RESUMO

BACKGROUND: "Diffuse midline glioma, H3 K27M-mutant" (DMG) mainly arises within the pontine, thalamic, and spinal cord regions. Because of the rarity of spinal cord gliomas, the general knowledge surrounding DMGs is mainly based on pontine and thalamic gliomas, whereas tumor location tends to influence the clinicopathological features and prognosis. OBJECTIVE: To determine the clinicopathological characteristics and molecular profiles of DMGs located in the spinal cord. METHODS: The clinical and molecular pathologic features and prognosis were comprehensively analyzed in a series of 44 patients with spinal cord DMGs. RESULTS: The median age was 36 yr, and 88.7% of patients (39/44) were adults (≥18 yr). Histopathologically, malignant grades included grade II (16 cases), grade III (20 cases), and grade IV (8 cases). Compared with patients with histological grade IV, patients with lower histological grade (grade II/III) were older (37 vs 24 yr, P = .020) and were associated with longer overall survival (24.1 vs 8.6 mo, P = .007). All 30 tested tumors were isocitrate dehydrogenase (IDH) wild type, and 96% of cases (22/23) presented with unmethylated O6-methylguanine-DNA methyltransferase. Univariate and multivariate analyses showed that histological grade and presurgery McCormick Scale scores were independent prognostic factors for overall survival, whereas extensive surgical resection and chemoradiotherapy were not significantly associated with improved survival. The most frequent anatomic locations were the cervical enlargement (C4-T1, n = 16) and conus medullaris (T12-L1, n = 13), which exhibited distinctive clinical characteristics and molecular features. CONCLUSION: The findings provide guidelines for the evidence-based practice of the specialized management of spinal cord DMGs.


Assuntos
Neoplasias Encefálicas , Glioma , Adulto , Glioma/diagnóstico , Glioma/genética , Glioma/terapia , Histonas/genética , Humanos , Mutação/genética , Prognóstico , Medula Espinal
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