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1.
Front Chem ; 9: 750404, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733821

RESUMO

Fluorescence imaging technique, characterized by high sensitivity, non-invasiveness and no radiation hazard, has been widely applicated in the biomedical field. However, the depth of tissue penetration is limited in the traditional (400-700 nm) and NIR-I (the first near-infrared region, 700-900 nm) imaging, which urges researchers to explore novel bioimaging modalities with high imaging performance. Prominent progress in the second near-infrared region (NIR-II, 1000-1700 nm) has greatly promoted the development of biomedical imaging. The NIR-II fluorescence imaging significantly overcomes the strong tissue absorption, auto-fluorescence as well as photon scattering, and has deep tissue penetration, micron-level spatial resolution, and high signal-to-background ratio. NIR-II bioimaging has been regarded as the most promising in vivo fluorescence imaging technology. High brightness and biocompatible fluorescent probes are crucial important for NIR-II in vivo imaging. Herein, we focus on the recently developed NIR-II fluorescent cores and their applications in the field of biomedicine, especially in tumor delineation and image-guided surgery, vascular imaging, NIR-II-based photothermal therapy and photodynamic therapy, drug delivery. Besides, the challenges and potential future developments of NIR-II fluorescence imaging are further discussed. It is expected that our review will lay a foundation for clinical translation of NIR-II biological imaging, and inspire new ideas and more researches in this field.

2.
Cancer Commun (Lond) ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738326

RESUMO

BACKGROUND: To date, there is no approved blood-based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker. METHODS: We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre-treatment serum SEMA4C levels, measured using optimized in-house enzyme-linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities. RESULTS: We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls (P < 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900-0.941) and 0.932 (95%CI: 0.911-0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early-stage breast cancer (n = 366) and ductal carcinoma in situ (n = 85) were 0.931 (95%CI: 0.916-0.946) and 0.879 (95%CI: 0.832-0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (P < 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors. CONCLUSIONS: Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.

3.
Cells ; 10(9)2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34571841

RESUMO

Numb family proteins (NFPs), including Numb and Numblike (Numbl), are commonly known for their role as cell fate determinants for multiple types of progenitor cells, mainly due to their function as Notch inhibitors. Previous studies have shown that myocardial NFP double knockout (MDKO) hearts display an up-regulated Notch activation and various defects in cardiac progenitor cell differentiation and cardiac morphogenesis. Whether enhanced Notch activation causes these defects in MDKO is not fully clear. To answer the question, we examined the spatiotemporal patterns of Notch1 expression, Notch activation, and Numb expression in the murine embryonic hearts using multiple approaches including RNAScope, and Numb and Notch reporter mouse lines. To further interrogate the interaction between NFPs and Notch signaling activation, we deleted both Notch1 or RBPJk alleles in the MDKO. We examined and compared the phenotypes of Notch1 knockout, NFPs double knockout, Notch1; Numb; Numbl and RBPJk; Numb; Numbl triple knockouts. Our study showed that Notch1 is expressed and activated in the myocardium at several stages, and Numb is enriched in the epicardium and did not show the asymmetric distribution in the myocardium. Cardiac-specific Notch1 deletion causes multiple structural defects and embryonic lethality. Notch1 or RBPJk deletion in MDKO did not rescue the structural defects in the MDKO but partially rescued the defects of cardiac progenitor cell differentiation, cardiomyocyte proliferation, and trabecular morphogenesis. Our study concludes that NFPs regulate progenitor cell differentiation, cardiomyocyte proliferation, and trabecular morphogenesis partially through Notch1 and play more roles than inhibiting Notch1 signaling during cardiac morphogenesis.


Assuntos
Coração/fisiologia , Proteínas de Membrana/metabolismo , Morfogênese/fisiologia , Miocárdio/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptor Notch1/metabolismo , Animais , Diferenciação Celular/fisiologia , Feminino , Masculino , Camundongos , Organogênese/fisiologia , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo
4.
Proc Natl Acad Sci U S A ; 118(35)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34446551

RESUMO

Many G protein-coupled receptors and other signaling proteins localize to the ciliary membrane for regulating diverse cellular processes. The BBSome composed of multiple Bardet-Biedl syndrome (BBS) proteins is an intraflagellar transport (IFT) cargo adaptor essential for sorting signaling proteins in and/or out of cilia via IFT. Leucine zipper transcription factor-like 1 (LZTFL1) protein mediates ciliary signaling by controlling BBSome ciliary content, reflecting how LZTFL1 mutations could cause BBS. However, the mechanistic mechanism underlying this process remains elusive thus far. Here, we show that LZTFL1 maintains BBSome ciliary dynamics by finely controlling BBSome recruitment to the basal body and its reassembly at the ciliary tip simultaneously in Chlamydomonas reinhardtii LZTFL1 directs BBSome recruitment to the basal body via promoting basal body targeting of Arf-like 6 GTPase BBS3, thus deciding the BBSome amount available for loading onto anterograde IFT trains for entering cilia. Meanwhile, LZTFL1 stabilizes the IFT25/27 component of the IFT-B1 subcomplex in the cell body so as to control its presence and amount at the basal body for entering cilia. Since IFT25/27 promotes BBSome reassembly at the ciliary tip for loading onto retrograde IFT trains, LZTFL1 thus also directs BBSome removal out of cilia. Therefore, LZTFL1 dysfunction deprives the BBSome of ciliary presence and generates Chlamydomonas cells defective in phototaxis. In summary, our data propose that LZTFL1 maintains BBSome dynamics in cilia by such a dual-mode system, providing insights into how LZTFL1 mediates ciliary signaling through maintaining BBSome ciliary dynamics and the pathogenetic mechanism of the BBS disorder as well.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(6): 593-598, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34130781

RESUMO

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (n=1 184), tracheal intubation (n=166), and extensive cardiopulmonary resuscitation (ECPR; n=116). The three groups were compared in terms of general information and clinical outcomes. RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (P < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased (P < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased (P < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications (P < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group (P < 0.05). CONCLUSIONS: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.


Assuntos
Cesárea , Recém-Nascido Prematuro , Peso ao Nascer , China , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos Retrospectivos
6.
Curr Med Sci ; 41(2): 342-347, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33877552

RESUMO

Yolk sac tumors (YSTs) are rare malignant germ cell tumors that usually affect young females. To date, there have been few studies on YSTs. We evaluated the relationship between clinicopathologic characteristics of patients with ovarian YSTs and disease outcome based on Surveillance, Epidemiology, and End Results data. The Kaplan-Meier method and log-rank test were used to evaluate differences in survival rates. Data for 269 patients were analyzed. The incidence of YSTs among ovarian germ cell tumors (OGCTs) cases was 0.4%; median patient age was 22.0 years, and most tumors were unilateral. Patients presented with distant metastasis (37.5%), localized disease (49.1%), and regional spread (8.9%). American Joint Committee on Cancer stage was available for 13 patients (stage IA, n=2; stage IC, n=1; stage IIIA, n=1; stage IIIB, n=3; stage IIIC, n=2; and stage IV, n=4). Survival rates at 1, 3, and 5 years were 91.0%, 84.0%, and 83.2%, respectively, for overall survival (OS) and 92.0%, 85.4%, and 84.5%, respectively, for disease-specific survival (DSS). The 5-year OS and DSS of patients with ovary tumors were 91.5% and 92.9%, respectively, compared to 74.8% and 77.2%, respectively, for those with extra-ovarian spread (P<.001 for both OS and DSS). Age >50 years was associated with shorter OS and DSS (both P<0.001), whereas no associatios of OS and DSS were observed with pathologic grade (P=0.49 for OS and 0.52 for DSS). In summary, YSTs are typically unilateral, of a high grade, and localized to the ovary; extra-ovarian spread has a poor outcome, and postmenopausal women have worse prognosis than premenopausal women.


Assuntos
Tumor do Seio Endodérmico/epidemiologia , Tumor do Seio Endodérmico/patologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Fatores Etários , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Análise de Sobrevida
7.
Reprod Sci ; 28(6): 1718-1732, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33751459

RESUMO

Human umbilical cord mesenchymal stem cell (UC-MSC) application is a promising arising therapy for the treatment of premature ovarian failure (POF). However, little is known about the inflammation regulatory effects of human umbilical cord MSCs (UC-MSCs) on chemotherapy-induced ovarian damage, regardless of in vivo or in vitro. This study was designed to investigate the therapeutic effects of UC-MSC transplantation and underlying mechanisms regarding both apoptosis and inflammation in POF mice. The chemotherapy-induced POF models were induced by intraperitoneal injection of cyclophosphamide. Ovarian function parameters, granulosa cell (GC) apoptosis, and inflammation were examined. Morphological staining showed that UC-MSC treatment increased the ovary size, and the numbers of primary and secondary follicles, but decreased the number of atretic follicles. Estradiol levels in the UC-MSC-treated group were increased while follicle-stimulating hormone levels were reduced compared to those in the POF group. UC-MSCs inhibited cyclophosphamide-induced GC apoptosis and inflammation. Meanwhile, phosphorylation of AKT and P38 was elevated after UC-MSC treatment. Tracking of UC-MSCs in vivo indicated that transplanted UC-MSCs were only located in the interstitium of ovaries rather than in follicles. Importantly, UC-MSC-derived extracellular vesicles protected GCs from alkylating agent-induced apoptosis and inflammation in vitro. Our results suggest that UC-MSC transplantation can reduce ovary injury and improve ovarian function in chemotherapy-induced POF mice through anti-apoptotic and anti-inflammatory effects via a paracrine mechanism.

9.
Elife ; 102021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33587040

RESUMO

Certain ciliary signaling proteins couple with the BBSome, a conserved complex of Bardet-Biedl syndrome (BBS) proteins, to load onto retrograde intraflagellar transport (IFT) trains for their removal out of cilia in Chlamydomonas reinhardtii. Here, we show that loss of the Arf-like 6 (ARL6) GTPase BBS3 causes the signaling protein phospholipase D (PLD) to accumulate in cilia. Upon targeting to the basal body, BBSomes enter and cycle through cilia via IFT, while BBS3 in a GTP-bound state separates from BBSomes, associates with the membrane, and translocates from the basal body to cilia by diffusion. Upon arriving at the ciliary tip, GTP-bound BBS3 binds and recruits BBSomes to the ciliary membrane for interacting with PLD, thus making the PLD-laden BBSomes available to load onto retrograde IFT trains for ciliary exit. Therefore, BBS3 promotes PLD exit from cilia via the BBSome, providing a regulatory mechanism for ciliary signaling protein removal out of cilia.

10.
Hereditas ; 158(1): 3, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33388093

RESUMO

BACKGROUND: Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection. METHODS: Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein-protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out. RESULTS: Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified, and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p = 0.041), more requirements of mechanical ventilation (p = 0.034), more frequent hospitalization (p < 0.001) and longer cumulative hospital stay (p = 0.012). CONCLUSION: IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.


Assuntos
Recém-Nascido Prematuro , Proteínas de Membrana/genética , Infecções por Vírus Respiratório Sincicial/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Recém-Nascido , Tempo de Internação , Mapas de Interação de Proteínas , Respiração Artificial
11.
World J Clin Cases ; 8(21): 5116-5127, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33269248

RESUMO

BACKGROUND: Normal size ovarian cancer syndrome (NOCS) is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features. It is extremely rare with only a few cases reported in the literature. More data are needed to clarify its biological behavior and compare the differences with abnormal size ovarian cancer. AIM: To assess the clinical and pathological features of NOCS patients treated in our institution in the last 10 years and to explore risk factors for relapse and survival. METHODS: Patients who were pathologically diagnosed with NOCS between 2008 and 2018 were included. Papillary serous ovarian carcinoma (PSOC) patients were initially randomly recruited as the control group. Demographics, tumor characteristics, treatment procedures, and clinical follow-up were retrospectively collected. Risk factors for progression-free survival and overall survival were assessed. RESULTS: A total of 110 NOCS patients were included; 80 (72.7%) had primary adnexal carcinoma, two (1.8%) had mesotheliomas, 18 (16.4%) had extraovarian peritoneal serous papillary carcinoma, and eight (7.3%) had metastatic tumors. Carbohydrate antigen (CA)125 and ascites quantity were lower in the NOCS cohort than in the PSOC group. The only statistically significant risk factors for worse overall survival (P < 0.05) were the levels of CA199 and having fewer than six chemotherapy cycles. The 1-year, 3-year, and 5-year survival rates were 75.5%, 27.7%, and 13.8%, respectively. CONCLUSION: The clinical symptoms of the NOCS group are atypical, and the misdiagnosis rate is high. Ascites cytology and laparoscopic exploration are valuable in the early diagnosis to avoid a misdiagnosis. The level of CA199 is the most important predictor of overall survival, and more than six cycles of chemotherapy contributes to the increased survival rates of NOCS patients.

12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(10): 897-902, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33148384

RESUMO

Objective To compare the efficiency of four methods for extracting extracellular vesicles (EVs) from human umbilical cord mesenchymal stem cells(hUCMSCs). Methods EVs were isolated from the conditioned medium of hUCMSCs by ultracentrifugation (group A), or ultrafiltration combined with ultracentrifugation (group B), or ultrafiltration combined with polyethylene glycol precipitation (group C), or ultrafiltration combined with aqueous two phase system (group D). The total protein concentration of EVs in each group was determined by BCA method. The expression of Alix, CD9, and calnexin were detected by Western blotting. The morphology of EVs was analyzed by transmission electron microscopy. The particle size distribution and particle concentration of EVs were measured by nanoparticle tracking analysis. Results The total protein concentrations of EVs extracted by the above four methods were (1.92±1.77) µg/µL, (18.1±1.07) µg/µL, (6.33±1.02) µg/µL, (36.48±23.13) µg/µL from group A to D respectively. We observed the expression of CD9 and Alix, but not calnexin, in EVs from group A, B and C. However, the expression levels of CD9 and Alix were lowest in group C. In addition, the expression of CD9, Alix and calnexin were undetectable in EVs from group D. The particle concentrations of EVs in group A, B and C were 0.85×1011 particles/mL, 0.63×1011 particles/mL, 1.83×1011 particles/mL, respectively. Meanwhile, the particle distributions were all within the size range of EVs. We also observed the typical saucer-like membrane structure in EVs from group A, B and C. Conclusion The method of ultrafiltration combined with ultracentrifugation could be applied to the experiments demanding large amounts of EVs. The method of ultracentrifugation is recommended for the extraction of little amounts of EVs due to the lower risk of EV fragmentation.


Assuntos
Meios de Cultivo Condicionados , Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Microscopia Eletrônica de Transmissão , Ultracentrifugação , Ultrafiltração , Cordão Umbilical/citologia
13.
BMC Pediatr ; 20(1): 522, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33190629

RESUMO

BACKGROUND AND AIM: Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants. METHODS: This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables. RESULTS: Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979). CONCLUSIONS: A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.


Assuntos
Displasia Broncopulmonar , Peso ao Nascer , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/prevenção & controle , China/epidemiologia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Leite Humano , Estudos Retrospectivos
14.
Medicine (Baltimore) ; 99(48): e23477, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33235138

RESUMO

Bronchopulmonary dysplasia (BPD) remains a major complication and accounts for high morbidity and mortality of preterm infants. The present study aimed to identify the key genes in the development of BPD and to provide some new insights into the pathogenesis of BPD. The GSE108754 dataset was downloaded from Gene Expression Omnibus database containing 5 samples of BPD patients and 6 of non-BPD infants. The differentially expressed genes (DEGs) between BPD and non-BPD patients were identified by R software. The pathway and function enrichment analyses were performed through Database for Annotation Visualization and Integrated Discovery website. The protein-protein interaction network for DEGs was established by Cytoscape software and the most highly connected module was selected through MCODE plugin. Furthermore, the clinical sample verification among 25 BPD patients and 10 non-BPD infants was carried out in our center. Finally, based on the results above, the gene set enrichment analysis focusing on CD74 upregulated status was employed. Totally, 189 DEGs including 147 upregulated genes and 42 downregulated genes between BPD and non-BPD patients were screened out. The pathway and function enrichments revealed these DEGs were mainly enriched in asthma, intestinal immune network for IgA production, antigen processing and presentation and immune response. Thirteen DEGs (CD74, HLA-DMA, HLA-DRA, HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DRB5, HLA-DPA1, HLA-DOA, HLA-DPB1, HLA-DQB2, HLA-DQA2, and HLA-DQB1) were determined as hub genes. The mRNA expression levels of the 13 hub genes were tested by quantitative real-time polymerase chain reaction among our clinical samples. Eventually, CD74 was confirmed to be the most significant highly expressed in BPD samples (P < .001) and its expression level was negatively correlated with gestational age (r = -0.653) and birth weight (r = -0.675). The gene set enrichment analysis results showed the gene sets associated with lupus erythematosus, viral myocarditis, immune network for IgA production, graft versus host disease, cell adhesion molecules and so no were differentially enriched with the phenotype of high-expression CD74. In conclusion, CD74 may serve to predict the BPD development and provide a new therapeutic target for BPD.


Assuntos
Antígenos de Diferenciação de Linfócitos B/genética , Displasia Broncopulmonar/genética , Antígenos de Histocompatibilidade Classe II/genética , Recém-Nascido Prematuro , Estudos de Casos e Controles , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Marcadores Genéticos , Humanos , Recém-Nascido , Masculino , Mapas de Interação de Proteínas , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
15.
Eur J Clin Microbiol Infect Dis ; 39(12): 2211-2223, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32761481

RESUMO

Since the outbreak of novel coronavirus infection pneumonia in Wuhan City, China, in late 2019, such cases have been gradually reported in other parts of China and abroad. Children have become susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their immature immune function. As the outbreak has progressed, more cases of novel coronavirus infection/pneumonia in children have been reported. Compared with adults, the impact of SARS-CoV-2 infection in children is less severe, with a lower incidence and susceptibility in children, which results in fewer children being tested, thereby underestimating the actual number of infections. Therefore, strengthening the diagnosis of the disease is particularly important for children, and early and clear diagnosis can determine treatment strategies and reduce the harm caused by the disease to children. According to the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (trial version 7) issued by National Health Committee and the latest diagnosis and treatment strategies for novel coronavirus infection pneumonia in children, this review summarizes current strategies on diagnosis and treatment of SARS-CoV-2 infection in children.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/genética , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , RNA Viral/sangue , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Doenças Assintomáticas , Betacoronavirus/patogenicidade , Biomarcadores/sangue , COVID-19 , Teste para COVID-19 , Criança , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Tosse/diagnóstico , Combinação de Medicamentos , Diagnóstico Precoce , Febre/diagnóstico , Humanos , Hidroxicloroquina/uso terapêutico , Interferon-alfa/uso terapêutico , Lopinavir/uso terapêutico , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Guias de Prática Clínica como Assunto , RNA Viral/genética , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
16.
Eur J Clin Microbiol Infect Dis ; 39(12): 2309-2315, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32683596

RESUMO

During the COVID-19 outbreak, the mobile cabin hospital has effectively isolated and treated patients diagnosed as mild-moderate disease. However, a detailed clinical course has not been well described. We included 483 patients who were isolated and treated from Feb 6, 2020, to Feb 15, 2020, including definite outcome (discharge or deterioration). Sixty-two patients were transferred to severe cases, of whom were trasfered to designated hospital for intensive care. By March 9, 2020, all patients were discharged without dead. The mobile cabin hospital provides feasible strategy of isolation of mild-moderate cases and timely intervention during the virus outbreak.


Assuntos
Doença das Coronárias/diagnóstico , Infecções por Coronavirus/diagnóstico , Pneumopatias/diagnóstico , Pandemias , Alta do Paciente/estatística & dados numéricos , Isolamento de Pacientes/métodos , Pneumonia Viral/diagnóstico , Idoso , Betacoronavirus/patogenicidade , Índice de Massa Corporal , COVID-19 , Teste para COVID-19 , China/epidemiologia , Técnicas de Laboratório Clínico , Comorbidade , Doença das Coronárias/epidemiologia , Doença das Coronárias/fisiopatologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Pneumopatias/epidemiologia , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Unidades Móveis de Saúde , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(7): 690-695, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32669162

RESUMO

OBJECTIVE: To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China. METHODS: The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data. RESULTS: In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates. CONCLUSIONS: Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.


Assuntos
Hiperbilirrubinemia Neonatal , Bilirrubina , China , Potenciais Evocados Auditivos do Tronco Encefálico , Humanos , Recém-Nascido , Estudos Retrospectivos
18.
Int J Mol Med ; 46(2): 653-662, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32626923

RESUMO

Hypoxic/ischemic (HI) brain damage (HIBD) is a major cause of acute neonatal brain injury, leading to high mortality and serious neurological deficits. The antisense RNA of brain­derived neurotrophic factor (BDNF­AS) is transcribed from the opposite strand of the BDNF gene. The aim of the present study was to investigate the role of BDNF­AS in HI­induced neuronal cell injury in vivo and in vitro. Reverse transcription­quantitative PCR (RT­qPCR) assays indicated that BDNF­AS expression was significantly upregulated in HI­injured neonatal brains and hippocampal neurons. However, BDNF expression was downregulated in HI­injured neonatal brains and hippocampal neurons. Cell Counting Kit­8 assays, Hoechst staining, calcein­AM/PI staining, immunostaining, water maze tests and rotarod tests demonstrated that BDNF­AS silencing protected against hypoxia­induced primary hippocampal neuron injury in vitro and HI­induced brain injury in vivo. Mechanistically, RT­qPCR assays and western blotting indicated that BDNF­AS silencing led to increased expression of BDNF and activated the BDNF­mediated signaling pathway, as demonstrated by increased expression levels of BDNF, phosphorylated­Akt and phosphorylated­tropomyosin receptor kinase B. Collectively, the present study provides important insights into the pathogenesis of HIBD, and it was indicated that BDNF­AS silencing may be a promising approach for the treatment of neonatal HIBD.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Western Blotting , Infarto Encefálico/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Feminino , Imunofluorescência , Hipocampo/citologia , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Neurônios/metabolismo , Gravidez , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Mol Med Rep ; 22(2): 1440-1448, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32627010

RESUMO

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the main causes of death and nervous system damage in neonates. The aim of the present study was to investigate the effect of the Toll­like receptor 4 (TLR4) antagonist TAK­242 on HIE. The Rice­Vannucci method was used for ligation of the left common carotid artery, followed by hypoxic treatment for 2.5 h to establish a neonatal HIE rat model. Rats were intraperitoneally injected with 7.5 ml/kg TAK­242 after hypoxia­ischemia. It was demonstrated that TAK­242 significantly reduced the infarct volume and cerebral edema content of neonatal rats after HIE, alleviating neuronal damage and neurobehavioral function deficits. Furthermore, TAK­242 decreased the protein expression levels of TLR4, MyD88, TIR­domain­containing adapter­inducing interferon­ß (TRIF), NF­κB, tumor necrosis factor α (TNF­α) and interleukin­1ß in the hippocampus. The present results suggested that TAK­242 may exert a neuroprotective effect after HIE by inhibiting the TLR4/MyD88/TRIF/NF­κB signaling pathway, and reducing the release of downstream inflammatory cytokines.


Assuntos
Hipóxia-Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Sulfonamidas/uso terapêutico , Receptor 4 Toll-Like , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Animais Recém-Nascidos , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/metabolismo
20.
Dev Cell ; 54(5): 593-607.e5, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32668208

RESUMO

Genetic lineage tracing unravels cell fate and plasticity in development, tissue homeostasis, and diseases. However, it remains technically challenging to trace temporary or transient cell fate, such as epithelial-to-mesenchymal transition (EMT) in tumor metastasis. Here, we generated a genetic fate-mapping system for temporally seamless tracing of transient cell fate. Highlighting its immediate application, we used it to study EMT gene activity from the local primary tumor to a distant metastatic site in vivo. In a spontaneous breast-to-lung metastasis model, we found that primary tumor cells activated vimentin and N-cadherin in situ, but only N-cadherin was activated and functionally required during metastasis. Tumor cells that have ever expressed N-cadherin constituted the majority of metastases in lungs, and functional deletion of N-cad significantly reduced metastasis. The seamless genetic recording system described here provides an alternative way for understanding transient cell fate and plasticity in biological processes.


Assuntos
Antígenos CD/genética , Caderinas/genética , Diferenciação Celular/genética , Transição Epitelial-Mesenquimal/genética , Metástase Neoplásica/genética , Antígenos CD/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Caderinas/metabolismo , Diferenciação Celular/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metástase Neoplásica/patologia , Vimentina/metabolismo
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