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2.
bioRxiv ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33200127

RESUMO

Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.

3.
Psychogeriatrics ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33207393

RESUMO

AIM: This study aimed to elucidate whether malnutrition is associated with cognitive impairment in an older Chinese population. METHODS: A cross-sectional study was conducted in 2365 participants aged 60 years or older from January 2013 to September 2019. Nutritional status was measured by using the Mini Nutritional Assessment Short Form (MNA-SF). Cognitive function was assessed with the Mini-Mental State Examination (MMSE). The relationship between malnutrition or each Mini Nutritional Assessment Short Form domain and cognitive impairment was examined with univariate and multivariate logistic regression analysis. RESULTS: The prevalence of malnutrition, risk of malnutrition, and cognitive impairment was 5.54%, 33.45%, and 36.74%, respectively. The prevalence was higher in those 80 years and older: 7.88%, 40.75%, and 53.65%, respectively. The Mini-Mental State Examination score was positively correlated with the Mini Nutritional Assessment Short Form score (r = 0.364, P < 0.001). After adjustment for age, gender, education, marital status, and living alone, malnutrition (odds ratio (OR) = 3.927, 95% confidence interval (CI): 2.650-5.819), anorexia (OR = 1.454, 95%CI: 1.192-1.774), weight loss (OR = 1.697, 95%CI: 1.406-2.047), impaired mobility (OR = 4.156, 95%CI: 3.311-5.218), and psychological stress (OR = 1.414, 95%CI: 1.070-1.869) were significantly associated with an increased risk of cognitive impairment. CONCLUSIONS: Our results suggest that the prevalence of malnutrition and cognitive impairment is relatively high and increases with age. Malnutrition, anorexia, weight loss, impaired mobility, and psychological stress are significantly associated with an increased risk of cognitive impairment. Therefore, clinicians should assess the nutritional and cognitive status of the elderly regularly to improve early detection and timely intervention.

4.
Aging (Albany NY) ; 12(20): 20778-20800, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33091878

RESUMO

Long noncoding RNAs (lncRNAs) have been proposed as diagnostic or prognostic biomarkers of head and neck squamous carcinoma (HNSCC). The current study aimed to develop a lncRNA-based prognostic nomogram for HNSCC. LncRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. After the reannotation of lncRNAs, the differential analysis identified 253 significantly differentially expressed lncRNAs in training set TCGA-HNSC (n = 300). The prognostic value of each lncRNA was first estimated in univariate Cox analysis, and 41 lncRNAs with P < 0.05 were selected as seed lncRNAs for Cox LASSO regression, which identified 11 lncRNAs. Multivariate Cox analysis was used to establish an 8-lncRNA signature with prognostic value. Patients in the high-signature score group exhibited a significantly worse overall survival (OS) than those in the low-signature score group, and the area under the receiver operating characteristic (ROC) curve for 3-year survival was 0.74. Multivariable Cox regression analysis among the clinical characteristics and signature scores suggested that the signature is an independent prognostic factor. The internal validation cohort, external validation cohort, and 102 HNSCC specimens quantified by qRT-PCR successfully validate the robustness of our nomogram.

5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(5): 636-642, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32975077

RESUMO

Objective: To study the neuroprotective effect of inhalation of volatile oil of Cang Ai (VOCA) on cerebral ischemia-reperfusion injury model by MRI diffusion tensor imaging. Methods: Twenty-four healthy adult male SD rats were randomly divided into sham operation group, model (middle cerebral artery occlusion (MCAO) ) group and VOCA group. Evaluated the degree of neurological impairment of rats in each group immediately after successful establishment of model or 7 d later according to Zea Longa scoring. Coronal diffusion tensor imaging (DTI) scan was performed at 3 h, 3 d, and 7 d after the model successfully established by using 7.0 T magnetic resonance imaging. Measured the apparent diffusion coefficient (ADC) and anisotropy score (FA) of the DTI in the striatal region and the motion flat zone of the maximum infarct level and then calculate the relative apparent diffusion coefficient (rADC) and relative anisotropy score (rFA). TTC staining was used to evaluate the cerebral infarction volume of rats in each group at 7 d post model establishment, and the correlation analysis of rFA, rADC and neural score was performed. Results: No neurological defect was detected in mice in the sham operation group. The MCAO group and the VOCA group showed neurological defect to different degrees. The neurological function score of the VOCA group was obviously lower than that of MCAO group at 7 th day (P<0.05). The DTI scan results showed that the rADC value of striatum of rats in VOCA group was higher than that in MCAO group at 3 h and 3 d after modeling (P<0.05), while there was no significant difference between the three groups at 7 th day. The rADC value of the motor cortex in the VOCA group was higher than that in the MCAO group at 3 h after modeling (P<0.01), and there was no significant difference at 3 rdday and 7 thday. The rFA value of striatum in VOCA group was higher than that in MCAO group at 3 rd day and 7 th day after modeling (P<0.05). There were no significant differences in rFA value between the MCAO and the VOCA group at three time points. TTC staining results showed that there was no infarcted area in the sham operation group, and the infarct volume in the VOCA group was smaller than that of the MCAO group (P<0.05). Correlation analysis showed that the striatum rFA value was highly correlated with neurological scores (r=-0.847, P<0.01). Conclusion: For the first time, we found that VOCA can effectively protect the neurological function of MCAO rats by reducing the toxic edema of cells in the ischemic area and accelerating the recovery of nerve fiber bundles after cerebral ischemia and reperfusion. rFA and rADC values can be used as effective indicators to evaluate the recovery of nerve function after cerebral ischemia and reperfusion.

6.
Biomed Res Int ; 2020: 9485398, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908926

RESUMO

Objective: Abdominal aortic aneurysm (AAA) development has been characterized by increased expression of vascular endothelial growth factor (VEGF), which contributes to angiogenesis via cyclooxygenase-2 (COX-2). Quercetin, one of the most common and well-researched flavonoids and abundant in vegetables and fruits, has beneficial effects in inhibiting angiogenesis. This study investigated the antiangiogenic effects of quercetin on experimental aneurysms. Methods: We utilized the in vivo AAA mouse model induced by the periaortic application of CaCl2 to examine the effectiveness of quercetin in blocking angiogenesis. Quercetin was administered at 60 mg/kg once daily on the day of the AAA induction and then continued for 6 weeks. Celecoxib, a selective COX-2 inhibitor, was used as the positive control. Results: Our results demonstrated that quercetin significantly attenuated aneurysm growth in AAA mice and medial neovascularization. Accordingly, quercetin decreased the expression of proangiogenic mediators, including VEGF-A, intercellular adhesion molecule-1, vascular cell adhesion molecule 1, and vascular endothelial cadherin. Quercetin treatment also inhibited the expression of COX-2 and hypoxia-inducible factor 1α (HIF-1α). It was also found that quercetin-3-glucuronide, a major quercetin metabolite, downregulated the expression of COX-2, HIF-1α, VEGF-A, and matrix metalloproteinase activities in aortic vascular smooth muscle cells isolated from AAA mice. Conclusion: Quercetin attenuates neovascularization during AAA growth, and this effect is mediated via the inhibition of COX-2, which decreases HIF-1α/VEGF signaling-related angiogenesis.

7.
Exp Cell Res ; 396(1): 112237, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32841643

RESUMO

The proliferation and differentiation of myoblast cells are regulated by the fibroblast growth factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling pathway, negatively modulates the activation of ERK and promotes the differentiation of myoblast cells. LRTM1 is dynamically expressed during myoblast differentiation and skeletal muscle regeneration after injury. In mouse myoblast C2C12 cells, knockout (KO) of Lrtm1 significantly prevents the differentiation of myoblast cells; this effect is associated with the reduction of MyoD transcriptional activity and the overactivation of ERK kinase. Notably, further studies demonstrated that LRTM1 associates with p52Shc and inhibits the recruitment of p52Shc to FGFR1. Taken together, our findings identify a novel negative regulator of FGFR1, which plays an important role in regulating the differentiation of myoblast cells.

8.
PLoS Pathog ; 16(8): e1008697, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776976

RESUMO

The diamondback moth, Plutella xylostella, is a cosmopolitan pest and the first species to develop field resistance to toxins from the gram-positive bacterium Bacillus thuringiensis (Bt). Although previous work has suggested that mutations of ATP-binding cassette transporter subfamily C2 (ABCC2) or C3 (ABCC3) genes can confer Cry1Ac resistance, here we reveal that P. xylostella requires combined mutations in both PxABCC2 and PxABCC3 to achieve high-level Cry1Ac resistance, rather than simply a mutation of either gene. We identified natural mutations of PxABCC2 and PxABCC3 that concurrently occurred in a Cry1Ac-resistant strain (Cry1S1000) of P. xylostella, with a mutation (RA2) causing the mis-splicing of PxABCC2 and another mutation (RA3) leading to the premature termination of PxABCC3. Genetic linkage analysis showed that RA2 and RA3 were tightly linked to Cry1Ac resistance. Introgression of RA2 and RA3 enabled a susceptible strain (G88) of P. xylostella to obtain high resistance to Cry1Ac, confirming that these genes confer resistance. To further support the role of PxABCC2 and PxABCC3 in Cry1Ac resistance, frameshift mutations were introduced into PxABCC2 and PxABCC3 singly and in combination in the G88 strain with CRISPR/Cas9 mediated mutagenesis. Bioassays of CRISPR-based mutant strains, plus genetic complementation tests, demonstrated that the deletion of PxABCC2 or PxABCC3 alone provided < 4-fold tolerance to Cry1Ac, while disruption of both genes together conferred >8,000-fold resistance to Cry1Ac, suggesting the redundant/complementary roles of PxABCC2 and PxABCC3. This work advances our understanding of Bt resistance in P. xylostella by demonstrating mutations within both PxABCC2 and PxABCC3 genes are required for high-level Cry1Ac resistance.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Bactérias/farmacologia , Endotoxinas/farmacologia , Proteínas Hemolisinas/farmacologia , Proteínas de Insetos/metabolismo , Resistência a Inseticidas , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/genética , Sequência de Aminoácidos , Animais , Bacillus thuringiensis , Proteínas de Insetos/química , Proteínas de Insetos/genética , Mariposas/química , Mariposas/genética , Mariposas/metabolismo , Mutação , Alinhamento de Sequência
9.
iScience ; 23(8): 101396, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32777775

RESUMO

Flexible fiber supercapacitors are promising candidate for power supply of wearable electronics. Fabrication of high-performance fibers is in progress yet challenging. The currently available graphene fibers made from wet-spinning or electro-deposition technologies are far away from practical applications due to their unsatisfactory capacitance. Here we report a facile alternately dipping (AD) method to coat graphene on wire-like substrates. The excellent mechanical properties of the substrate with greatly diverse choices can be carried over to the fiber supercapacitors. Under such guideline, the graphene fiber with a titanium core made by our AD method (AD:Ti@RGO) shows an ultra-high specific capacitance of up to 1,722.1 mF cm-2, which is ∼1,000 times that of wet-spinning- and electro-deposition-fabricated neat graphene fibers and presents the highest specific capacitance to date. With excellent mechanical properties and striking electrochemical performances, the AD:Ti@RGO-based supercapacitors light the path to the next-generation technologies for wearable devices.

10.
BMC Complement Med Ther ; 20(1): 248, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778088

RESUMO

BACKGROUND: Chinese Medicine education is part of professional medical training in Hong Kong. An important element of this is herbal medicine, which requires both theoretical and practical knowledge. A field trip programme was adopted to provide students with direct experience of medicinal plants studied in lectures. However, problems with the current programme were identified in learning outcome assessment and long-term knowledge management. To improve the teaching quality, a Moodle e-learning module was designed for augmentation. This study aimed to quantitatively evaluate the effectiveness of the Moodle module in supplementing the current field trip programme. METHODS: Prospective quasi-experiment. Participants were 49 year-2 students in the Bachelor of Chinese Medicine programme. A Moodle module including five online activities regarding two groups of herbal plants was integrated before and after the field trip. Fill-in-the-blank questions were used to assess the learning outcome. Also, a questionnaire was developed to collect student feedback as the secondary outcome. RESULTS: For herbal plants in Group A, the assessment score was higher in Moodle group (29.65 ± 5.0) than for the control group (21.65 ± 6.5) (P <  0.01). For herbal plants in Group B, the assessment score was higher for the Moodle group (28.68 ± 4.7) than for the control group (24.26 ± 7.7) (P <  0.01). The questionnaire results showed that students were satisfied with the Moodle platform. CONCLUSIONS: A specially designed Moodle module may be effective in augmenting the field trip for Chinese herbal medicine education.

11.
Clin Epigenetics ; 12(1): 82, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517789

RESUMO

BACKGROUND: Breast cancer remains in urgent need of reliable diagnostic and prognostic markers. Zinc finger and BTB/POZ domain-containing family proteins (ZBTBs) are important transcription factors functioning as oncogenes or tumor suppressors. The role and regulation of ZBTB16 in breast cancer remain to be established. METHODS: Reverse-transcription PCR and methylation-specific PCR were applied to detect expression and methylation of ZBTB16 in breast cancer cell lines and tissues. The effects of ZBTB16 in breast cancer cells were examined via cell viability, CCK8, Transwell, colony formation, and flow cytometric assays. Xenografts and immunohistochemistry analyses were conducted to determine the effects of ZBTB16 on tumorigenesis in vivo. The specific mechanisms of ZBTB16 were further investigated using Western blot, qRT-PCR, luciferase assay, and co-IP. RESULTS: ZBTB16 was frequently downregulated in breast cancer cell lines in correlation with its promoter CpG methylation status. Restoration of ZBTB16 expression led to induction of G2/M phase arrest and apoptosis, inhibition of migration and invasion, reversal of EMT, and suppression of cell proliferation, both in vitro and in vivo. Furthermore, ectopically expressed ZBTB16 formed heterodimers with ZBTB28 or BCL6/ZBTB27 and exerted tumor suppressor effects through upregulation of ZBTB28 and antagonistic activity on BCL6. CONCLUSIONS: Low expression of ZBTB16 is associated with its promoter hypermethylation and restoration of ZBTB16 inhibits tumorigenesis. ZBTB16 functions as a tumor suppressor through upregulating ZBTB28 and antagonizing BCL6. Our findings also support the possibility of ZBTB16 being a prognostic biomarker for breast cancer.

12.
PLoS Biol ; 18(6): e3000731, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32479501

RESUMO

The nuclear lamina protein lamin A/C is a key component of the nuclear envelope. Mutations in the lamin A/C gene (LMNA) are identified in patients with various types of laminopathy-containing diseases, which have features of accelerated aging and osteoporosis. However, the underlying mechanisms for laminopathy-associated osteoporosis remain largely unclear. Here, we provide evidence that loss of lamin A/C in skeletal muscles, but not osteoblast (OB)-lineage cells, results in not only muscle aging-like deficit but also trabecular bone loss, a feature of osteoporosis. The latter is due in large part to elevated bone resorption. Further cellular studies show an increase of osteoclast (OC) differentiation in cocultures of bone marrow macrophages/monocytes (BMMs) and OBs after treatment with the conditioned medium (CM) from lamin A/C-deficient muscle cells. Antibody array screening analysis of the CM proteins identifies interleukin (IL)-6, whose expression is markedly increased in lamin A/C-deficient muscles. Inhibition of IL-6 by its blocking antibody in BMM-OB cocultures diminishes the increase of osteoclastogenesis. Knockout (KO) of IL-6 in muscle lamin A/C-KO mice diminishes the deficits in trabecular bone mass but not muscle. Further mechanistic studies reveal an elevation of cellular senescence marked by senescence-associated beta-galactosidase (SA-ß-gal), p16Ink4a, and p53 in lamin A/C-deficient muscles and C2C12 muscle cells, and the p16Ink4a may induce senescence-associated secretory phenotype (SASP) and IL-6 expression. Taken together, these results suggest a critical role for skeletal muscle lamin A/C to prevent cellular senescence, IL-6 expression, hyperosteoclastogenesis, and trabecular bone loss, uncovering a pathological mechanism underlying the link between muscle aging/senescence and osteoporosis.


Assuntos
Envelhecimento/patologia , Lamina Tipo A/deficiência , Músculo Esquelético/patologia , Osteoporose/patologia , Animais , Anticorpos Bloqueadores/farmacologia , Fenômenos Biomecânicos , Reabsorção Óssea/complicações , Reabsorção Óssea/patologia , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Diferenciação Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Interleucina-6/metabolismo , Camundongos Knockout , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Osteogênese/efeitos dos fármacos , Osteoporose/sangue , Fenótipo
13.
Zool Res ; 41(4): 437-443, 2020 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-32400976

RESUMO

Sleep is indispensable for human health, with sleep disorders initiating a cascade of negative consequences. As our closest phylogenetic relatives, non-human primates (NHPs) are invaluable for comparative sleep studies and exhibit tremendous potential for improving our understanding of human sleep and related disorders. Previous work on measuring sleep in NHPs has mostly used electroencephalography or videography. In this study, simultaneous videography and actigraphy were applied to observe sleep patterns in 10 cynomolgus monkeys ( Macaca fascicularis) over seven nights (12 h per night). The durations of wake, transitional sleep, and relaxed sleep were scored by analysis of animal behaviors from videography and actigraphy data, using the same behavioral criteria for each state, with findings then compared. Here, results indicated that actigraphy constituted a reliable approach for scoring the state of sleep in monkeys and showed a significant correlation with that scored by videography. Epoch-by-epoch analysis further indicated that actigraphy was more suitable for scoring the state of relaxed sleep, correctly identifying 97.57% of relaxed sleep in comparison with video analysis. Only 34 epochs (0.13%) and 611 epochs (2.30%) were differently interpreted as wake and transitional sleep compared with videography analysis. The present study validated the behavioral criteria and actigraphy methodology for scoring sleep, which can be considered as a useful and a complementary technique to electroencephalography and/or videography analysis for sleep studies in NHPs.

14.
Chem Biol Interact ; 324: 109086, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32275923

RESUMO

Oxidative stress-induced apoptosis of retinal ganglion cells (RGCs) contributes to the development and progression of glaucoma. Sestrin2 (Sesn2), a stress-inducible protein, has a potent antioxidant capacity that can provide cytoprotection against various noxious stimuli. However, whether Sesn2 is involved in protecting RGCs from oxidative stress remains unexplored. The purpose of this study was to evaluate the role of Sesn2 in regulating hydrogen peroxide (H2O2)-induced oxidative stress of RGCs. Here, we showed that Sesn2 expression was induced in RGCs following H2O2 exposure. Sesn2 depletion markedly exacerbated H2O2-induced apoptosis and reactive oxygen species (ROS) generation in RGCs. Notably, upregulation of Sesn2 significantly decreased H2O2-induced apoptosis and ROS generation. Moreover, Sesn2 overexpression increased the nuclear translocation of nuclear factor erythroid-derived 2-like 2 (Nrf2), elevated Nrf2/antioxidant response element (ARE)-mediated transcriptional activity and upregulated the expression of Nrf2 target genes in H2O2-stimulated RGCs. Interestingly, we found that Sesn2 promoted Nrf2/ARE activation through downregulation of kelch-like ECH-associated protein 1 (Keap1). Restoration of Keap1 or inhibition of Nrf2 significantly reversed the Sesn2-mediated protective effect in H2O2-stimulated RGCs. In conclusion, these results elucidated that Sesn2 confers a protective effect in RGCs against H2O2-induced oxidative stress by reinforcing Nrf2/ARE activation via downregulation of Keap1. Our study suggests that the Sesn2/Keap1/Nrf2 axis may play an important role in retinal degeneration in glaucoma.


Assuntos
Apoptose/fisiologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Estresse Oxidativo/fisiologia , Células Ganglionares da Retina/metabolismo , Animais , Elementos de Resposta Antioxidante/fisiologia , Apoptose/efeitos dos fármacos , Regulação para Baixo , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Células Ganglionares da Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
15.
Zhongguo Zhong Yao Za Zhi ; 45(4): 854-860, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237486

RESUMO

L_9(3~4) orthogonal experiment design was used to optimize the preparation of the patches,and investigate its affecting factors and skin irritation. Eugenol was taken as the index component to study the release behavior in vitro and percutaneous penetration of Cangai oil transfersomes patches by HPLC.The results showed that the optimal prescription for preparing Cangai oil transfersomes patches were Eudragit E100 0.6 g, succinic acid 0.08 g,triethyl citrate 0.25 g,glycerol 0.2 g.Patches prepared by the preferred preparation had a flat appearance without obvious bubbles.The initial adhesion was 18.33±2.52, the stickiness was(30.01±2.45) min,and the peel strength was(5.62±0.95) kN·m~(-1).The results of affecting factors experiment showed the order of factors affecting its adhesion was humidity>temperature>lighting,and the skin irritation test results showed no significant skin irritation after 24 h of single administration. The results of drug release behavior in vitro showed that the release and the percutaneous penetration of both Cangai oil patches and Cangai oil transfersomes patches conformed to the Higuchi equation.The release amount of eugenol were 80.66% and 82.25% at 72 h, with no significant difference. The cumulative permeation area of eugenol per unit area reached(0.195 6±0.065 9),(0.131 0±0.045 5) mg·cm~(-2) at 72 h, with significant differences(P<0.05).The experiment results proved that the preparation process of Cangai oil transfersomes patches was stable,and the prepared patches had a good adhesion. At the same time,the preparation of transfersomes patches could alleviate and control the release of the drug to a certain extent, and provide a certain experimental basis for clinical pediatric drug safety.


Assuntos
Óleos Vegetais/farmacologia , Absorção Cutânea , Pele/efeitos dos fármacos , Adesivo Transdérmico , Administração Cutânea , Portadores de Fármacos , Liberação Controlada de Fármacos , Humanos , Ácidos Polimetacrílicos
16.
Oncol Rep ; 43(4): 1089-1102, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32323774

RESUMO

Targeted therapy based on specific genetic alterations has been proven to be an effective treatment for various types of cancer. In the present study, we aimed to explore the efficacy of personalized targeted therapy guided by targeted deep sequencing for patients with advanced biliary tract cancer (BTC) after non­radical resection. Targeted deep sequencing was performed on 49 patients with BTC, to whom biologic agents were recommended. Among 32 patients with stage IV and R2 resection (a non­radical resection), 21 patients underwent conventional chemotherapy (mGEMOX), while the remaining 11 patients received a personalized targeted agent. The genomic landscape of the 49 patients with BTC was determined and the results showed that genetic alterations were enriched in the ERBB family and cell cycle pathway. After a median follow­up of 12 months, the 11 BTC patients with personalized targeted therapy showed a median progression­free survival (PFS) of 4.5 months (2.5­20.5 months), a median overall survival (OS) of 12.9 months (4.7­24.8 months) and a disease control rate (DCR) of 63.6%. In the other 21 BTC patients, who were undergoing conventional chemotherapy, the BTC patients had a median PFS of 1.5 months (0.5­11.6 months), a median OS of 4.1 months (1.3­18.4 months), and a DCR of 33.3%. In addition, 36.4% of the patients in the personalized targeted therapy group experienced grade >2 treatment­related toxicity vs. 19.0% of patients in the conventional chemotherapy group. This real­world study suggests that targeted deep sequencing contributes to the guidance of personalized targeted therapy based on individual actionable mutations, which may benefit advanced BTC patients undergoing non­radical resection.

17.
Front Genet ; 11: 133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194623

RESUMO

Some differentially expressed genes (DEGs) that encode key enzymes involved in steroidogenic biosynthesis (CYP19A1) and key molecules related to gonadal functions (DMRT1, SOX9, AMH, FOXL2, WNT4, RSPO2, and GDF9) have been identified in adult gonadal RNA-seq studies of Reeves' pond turtle (Mauremys reevesii) with temperature-dependent sex determination (TSD). Gonadal functional maintenance and gametogenesis comprises a highly regulated and coordinated biological process, and increasing evidence indicates that microRNAs (miRNAs) may be involved in this dynamic program. However, it is not clear how the regulatory network comprising miRNAs changes the expression levels of these genes. In this study, miRNA sequencing of adult testis and ovary tissues from M. reevesii detected 25 known and 379 novel miRNAs, where 60 miRNAs were differentially expressed in the testis and ovary. A total of 1,477 target genes based on the differentially expressed miRNAs were predicted, where 221 target genes also exhibited differential expression. To verify the accuracy of the sequencing data, 10 differentially expressed miRNAs were validated by quantitative reverse transcription real-time PCR, and were found to be consistent with the transcriptome sequencing results. Moreover, several miRNA/target gene pairs, i.e., mre-let-7a-5p/mre-let-7e-5p and CYP19A1, mre-miR-200a-3p and DMRT1, mre-miR-101-3p and SOX9, and mre-miR-138-5p and AMH were identified. To explore the regulatory role of miRNAs, we conducted target gene enrichment analysis of the miRNAs and 221 target genes in the regulatory network. The signaling pathways related to gonadal functional maintenance and gametogenesis based on the DEGs and target genes were then compared. Our findings provide crucial information to facilitate further research into the regulatory mechanisms involving miRNAs in turtle species with TSD.

18.
Water Environ Res ; 92(11): 1966-1974, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32108974

RESUMO

Heavy metals such as Mn2+ are common contaminants in ammonium-rich wastewater. The information of Mn2+ effect on anammox process needs further investigation. The short- and long-term effects of Mn2+ on anammox were explored by anammox granular sludge. Batch tests showed that the half inhibition value (IC50 ) of Mn2+ was 4.83 mg/L. The anammox activity was severely inhibited in 0.5 hr under 15 mg/L Mn2+ . However, after long-term domestication by increasing the concentration of Mn2+ , both the low-load reactor (R1) and the high-load reactor (R2) performed well, achieving volumetric nitrogen removal rate of 6.36 kg/(m3 ·d) and 13.99 kg/(m3 ·d), respectively. The average ammonium and nitrite removal efficiency of both reactors under 200 mg/L Mn still maintained above 90%. The results from long-term reactors' operation showed that the serious inhibition effect indicated by the batch test was significantly exaggerated. The granules became dispersed after long-term operation in the high-load reactor (R2) which might be correlated to the high osmotic pressure caused by high Mn2+ load, and the mechanism needs to be investigated further. PRACTITIONER POINTS: The half inhibition value of Mn2+ on anammox sludge was 4.83 mg/L in batch experiment. 200 mg/L Mn2+ did not cause any inhibition on anammox process during long-term operation. Granular sludge is finer under high nitrogen loads with 200 mg/L Mn stress.


Assuntos
Compostos de Amônio , Reatores Biológicos , Domesticação , Nitrogênio , Oxirredução , Esgotos
19.
Cancer Biother Radiopharm ; 35(9): 720-730, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31910357

RESUMO

Background: Oral tongue squamous cell carcinoma (OTSCC) is a common type of oral tumor. LncRNAs (long noncoding RNAs) and miRNAs (microRNAs) were identified as regulators in many human cancers. This study aims to explore the molecular basis of HOXA transcript at the distal tip (HOTTIP) in regulating OTSCC progression. Materials and Methods: The expression of HOTTIP, miR-124-3p, and high-mobility group AT-hook 2 (HMGA2) was detected by quantitative real-time polymerase chain reaction. Next, the proliferation was evaluated by 3-(4,5-dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) assay. The migration and invasion were assessed by transwell assay. Furthermore, dual-luciferase reporter assay was performed to confirm the combination between HOTTIP and miR-124-3p, miR-124-3p, and HMGA2. Protein levels of HMGA2, ß-catenin, c-Myc, and E-cadherin were examined by Western blot. The nude mice model was employed to test the tumor growth in vivo. Results: HOTTIP was upregulated in OTSCC tissues and cells, and was highly expressed in positive lymph node metastasis and late-stage OTSCC patients. Silencing HOTTIP impeded proliferation, migration, and invasion of OTSCC cells. Moreover, HOTTIP knockdown inhibited proliferation, migration, and invasion of OTSCC cells by targeting miR-124-3p. Besides, miR-124-3p targeted HMGA2 to block proliferation, migration, and invasion. HMGA2 could rescue the inhibitory effects of HOTTIP interference on proliferation, migration, and invasion. In addition, HMGA2 overexpression reversed the downregulation of ß-catenin and c-Myc protein levels and upregulation of E-cadherin level affected by HOTTIP silencing. Finally, HOTTIP silencing repressed tumor growth and resulted in a great rise on miR-124-3p and E-cadherin expression and a distinct fall on HMGA2, ß-catenin, and c-Myc protein levels. Conclusions: HOTTIP knockdown restrained proliferation, migration, and invasion of OTSCC cells by miR-124-3p/HMGA2 axis through Wnt/ß-catenin pathway.

20.
Int J Dev Neurosci ; 80(2): 73-85, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31910289

RESUMO

Autism spectrum disorder (ASD) comprises a heterogeneous range of neurodevelopmental conditions represented by symptoms including, communication and language deficits, repetitive, and restricted patterns of behavior and inadequate social interactions. Gamma-aminobutyric acid (GABA) is known to mediate I responses in the central nervous system by interacting with GABA signaling receptors. In this context, several recent investigations suggest that imbalances in the GABAergic neurotransmission system may be implicated in the development of ASD as well as several other neurodevelopmental disorders, including Fragile X syndrome (FXS) and Rett syndrome. This review initially expounds the functional role of the GABAergic system in the mature brain and during neurodevelopment. This will be followed by discussions concerning the impact of deficiencies in the system on ASD and the other above-mentioned neurodevelopment disorders. Finally, the connections between these deficiencies and behavioral features observed in the clinic will be considered.

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