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1.
J Phycol ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32180225

RESUMO

Samples of Pithophoraceae, collected in diverse freshwater and damp terrestrial habitats from tropical and subtropical China, were characterized morphologically and ultrastructurally, and their phylogenetic position determined based on nuclear ribosomal DNA sequences. Our phylogenetic analysis resolved a novel lineage of Pithophoraceae, sister to Aegagropilopsis. Based on our phylogenetic results, morphological observations and comparative rDNA ITS2 secondary structure analysis, we propose Chlorocladiella gen. nov., characterized by a well-developed system of prostrate filaments, and describe four new species, C. cochlea sp. nov., C. erecta sp. nov., C. medogensis sp. nov., and C. pisformis sp. nov. Two species were found growing on damp soil, which is an unusual habitat for cladophoralean green algae, indicating that the diversity of Cladophorales in terrestrial habitats may be greater than currently recognized.

2.
Chirality ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32105371

RESUMO

Two novel helical poly(phenylacetylene) derivatives containing chiral phenylethyl carbamate residues in the end of each side chain (PPA-S and PPA-R) were synthesized by polymerization of the corresponding phenylacetylene monomers using Rh(nbd)BPh4 as a catalyst in DMF. The enantioseparation properties of the polymers were evaluated as coated-type chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). Under the same chromatographic conditions, PPA-S and PPA-R showed different enantioseparation properties, indicating that the different interactions between the analytes and the polymers, which result from the different chiral phenylethyl carbamate groups in the end of each side chains. Racemates 1, 7, and 8 could be better resolved on PPA-S, while racemate 6 was separated on PPA-R more efficiently. In addition, the coated-type CSPs showed good solvent tolerability and could work without any damage by introducing the polar solvents, such as CHCl3 and THF, in eluent. Moreover, some racemates could be better resolved on these coated-type CSPs with the addition of THF to the eluent.

3.
Int Urol Nephrol ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32100205

RESUMO

OBJECTIVE: The aim of this study was to summarize in a literature review our treatment experience involving microscopic replantation in a rare case of a completely amputated penis and testes. PATIENT AND METHODS: The penis and testes were completely amputated due to self-mutilation. The 26-year-old patient immediately underwent microscopic replantation of the penis and testes after pre-operative preparation. Potent anti-infectives and anti-depressives, and microcirculation-improving hyperbaric oxygen therapy were utilized after surgery. RESULTS: The time between the amputation and surgery was about 10 h. The patient was followed for 12 months post-surgery. The replanted penis recovered and the patient could urinate normally in the standing position with a maximal urinary flow rate of 20 ml/s. The testes also survived, but their size showed obvious atrophy. The serum testosterone level at 2 months after the operation was 120 ng/dL (normal reference range: 175-781 ng/dL). Erectile function gradually recovered after androgen replacement therapy. CONCLUSION: Complete amputation of the penis and testis is very rare. Efforts should be made to perform the replantation surgery as soon as possible. Microscopic surgical techniques for elaborate vascular and neural anastomosis constitute the basis for a successful replantation. Post-operative comprehensive treatment such as strong anti-infection, analgesia, anti-depression, improvement of microcirculation, and hyperbaric oxygen is crucial for the survival and functional recovery of replanted organs.

4.
Eur J Cancer Prev ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31934913

RESUMO

The association between tea drinking and esophageal cancer is still contradictory. This study is to determine the association between tea drinking and esophageal squamous cell carcinoma focusing on drinking temperature and tea types. A population-based case-control study was conducted in a high esophageal squamous cell carcinoma risk area in China. A total of 942 incident esophageal squamous cell carcinoma cases with historical confirmation and 942 age- and sex- individually matched community controls were recruited from the study area. Trained interviewers using a structured questionnaire collected detailed information on tea drinking, diet, smoking and alcohol drinking habits. Habitual tea drinking temperature was measured with a thermometer during interviews. We analyzed the association between tea consumption, drinking temperature and esophageal squamous cell carcinoma, stratified by tea type, while adjusting for other potentially confounding factors. Drinking very hot tea (>65°C) was significantly associated with the increased risk of esophageal squamous cell carcinoma (odds ratio = 1.67, 95% confidential interval 1.25-2.24) relative to non-drinkers. Consumption of black tea, irrespective of the frequency, intensity and tea leaf amount, was significantly associated with a higher risk (P for trend <0.01). Compared to those who consumed <300 g/month tea leaves at ≤65°C, those who consumed more than 300 g/month tea leave at >65°C had a more than 1.8-fold higher risk of esophageal squamous cell carcinoma for both green tea and black tea. Our results provide more evidence that drinking very hot tea (above 65°C) are significantly associated with an increased risk of esophageal squamous cell carcinoma.

5.
Hypertens Pregnancy ; 39(1): 12-24, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31762345

RESUMO

Objective: The aim of this study was to demonstrate the association between maternal asthma and the risk of hypertensive disorders of pregnancy.Methods: A systematic search of seven databases was conducted. A meta-analysis was performed to calculate risk ratios and 95% CI using random-effects models.Results: Asthma was associated with an increased risk of pregnancy-induced hypertension (RR 1.45, 95%CI 1.29-1.63), transient hypertension of pregnancy (RR 2.00, 95%CI 1.52-2.63), preeclampsia or eclampsia (RR 1.28, 95%CI 1.25-1.32), preeclampsia (RR 1.43, 95%CI 1.31-1.57) and eclampsia (RR 1.56, 95%CI 1.13-2.15).Conclusion: The meta-analysis illustrated that asthma was significantly increased risk of hypertension during pregnancy.

6.
J Photochem Photobiol B ; 202: 111677, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810037

RESUMO

In this examination, chitosan-silk fibroin/polyethylene terephthalate (CTS-SF/PET), chitosan-silk fibroin/polyethylene terephthalate/hydroxyapatite (CTS-SF/PET/HAP) and chitosan-silk fibroin/polyethylene terephthalate/Silver @hydroxyapatite (CTS-SF/PET/Ag@HAP) scaffolds were prepared by utilizing the plasma splashing procedure. Field emission scanning electron microscopy (FESEM) results demonstrated that the outside of the PET covered with HAP nanoparticles. The cell viability results demonstrated that the number of Mesenchymal stem cells (MSCs) primarily spread out on CTS-SF/PET/Ag@HAP. RT-PCR results demonstrated that there was an upregulated mRNA articulation of osseous development-related properties in the CTS-SF/PET/Ag@HAP composite. The in vivo rabbit animal assessment scores of the CTS-SF/PET/Ag@HAP composite were significantly better than those of the CTS-SF/PET at 1 to 3 months. Both in-vivo and in-vitro results exhibited in this investigation recommend that the cytocompatibility and osseointegration of CTS-SF/PET/Ag@HAP tendon were fundamentally improved by expanding the multiplication of cells and up-regulating the outflow of tendon development-related properties. In conclusion, the CTS-SF/PET/Ag@HAP tendon is a promising candidate for Anterior Cruciate Ligament (ACL) replacement in the future.


Assuntos
Ligamento Cruzado Anterior/fisiologia , Materiais Biocompatíveis/química , Durapatita/química , Nanopartículas/química , Osseointegração , Prata/química , Animais , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Artropatias/reabilitação , Artropatias/terapia , Artropatias/veterinária , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Nanopartículas/toxicidade , Osseointegração/efeitos dos fármacos , Coelhos , Tecidos Suporte/química
7.
J Hum Genet ; 65(3): 287-296, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31827253

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneity in presentation, genetic etiology, and clinical outcome. Although numerous ASD susceptibility genes have been described, they only account for a small fraction of the estimated heritability, supporting the need to identify more risk variants. This study reports the whole exome sequencing for 24 simplex families with sporadic cases of ASD. These families were selected following a rigorous family history study designed to exclude families with any history of neurodevelopmental or psychiatric disease. Fifteen rare, de novo variants, including fourteen missense variants and one splicing variant, in thirteen families were identified. We describe a splicing variant in XRCC6 which was predicted to destroy the 5' splice site in intron 9 and introduce a premature stop codon. We observed intron 9 retention in XRCC6 transcripts and reduced XRCC6 expression in the proband. Reduced XRCC6 activity and function may be relevant to ASD etiology due to XRCC6's role in nonhomologous DNA repair and interactions of the C-terminal SAP domain with DEAF1, a nuclear transcriptional regulator that is important during embryonic development.

8.
J Nanosci Nanotechnol ; 20(5): 2713-2721, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31635606

RESUMO

The nanoarchitectonic composites mixed-ZnPc-fMWCNT and linked-ZnPc-fMWCNT were prepared through tetra-[α-(p-amino)benzyloxyl]phthalocyanine Zinc(II) (ZnPc) mixed and covalently linked to multiwalled carbon nanotubes (MWCNTs), respectively. Various spectroscopic methods were used to identify the nanocomposites formed between ZnPc and MWCNTs whether by π-π interaction or by covalent linking. Their photocatalytic properties were fully investigated by carrying out the photodegradation of Rhodamine B (RhB) in aqueous solution under visible light irradiation. The nanocomposites displayed excellent photocatalytic performance, with the photodegradation efficiency as high as 94% for linked-ZnPc-fMWCNT and 83% for mixed-ZnPc-fMWCNT within 3 h irradiation. The repetition test revealed that both nanocomposites have excellent stability and recyclability, and then they are promising candidates as eco-friendly photocatalysts for degradation of organic dyes in aqueous environments.

9.
Environ Sci Pollut Res Int ; 27(5): 4814-4829, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31845243

RESUMO

The phytoplankton (internal driving forces) and environmental variables that affect complex biochemical reactions (external driving forces) play an important role in regulating photosynthetic carbon fixation. Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) exists in various phytoplankton species and is an important enzyme in the photosynthetic process. To investigate the phytoplankton composition (internal driving forces), we selected the functional gene of the Rubisco large subunit (rbcL) as the target gene for this study. Phytoplankton gross primary productivity was measured using light and dark biological oxygen demand bottles to assess the carbon sequestration potential. The fundamental environmental indicators were determined to analyze the mechanisms that drive the carbon fixation process. The correlation results indicated that green algae were only controlled by nitrate, and that diatoms were positively correlated with phosphate. The cluster analysis results demonstrated that nitrite was the major driver controlling phytoplankton primary productivity. During the wet seasons (spring and summer), the contribution of the planktonic community respiration to the carbon sequestration potential was higher than net primary productivity (NPP), followed by dissolved organic carbon and nitrate. During the dry season (autumn), NPP, total nitrogen, and nitrite ranked highest in terms of carbon sequestration potential. The contributions of green algae and diatoms to the carbon sequestration potential were temporally higher than those of cyanobacteria. The maximum carbon sequestration potential occurred during autumn because of diatom production and the function of phosphate, whereas the minimum carbon sequestration potential occurred in summer. Spatially, the upstream carbon sequestration potential was higher compared with downstream because of the effect (contribution) of cyanobacteria (Phormidium), diatoms (Surirella solea and Thalassiosira pseudonana), and environmental variable (nitrite). These findings provide a better understanding of the underlying mechanisms of phytoplankton productivity and the influences of environmental variables on carbon sequestration in urban river ecosystems.

10.
J Autism Dev Disord ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31820342

RESUMO

Although autism spectrum disorder (ASD) is associated with significant mental health concerns, little is known about suicidality, particularly among youth. To address this critical gap in the literature, the current study examined the predictive validity of (1) demographics, (2) core autism symptoms, (3) cognitive abilities and adaptive behavior, (4) comorbid psychopathology, and (5) medical problems, for suicide-related behaviors among autistic youth (N = 481; Mage = 11.56 years). As indices of suicide-related behaviors, parents reported on whether the child had ever (1) talked about killing themselves, and (2) engaged in deliberate self-harm or attempted suicide. These two suicide-related outcomes had distinct clinical correlates, including child age, parental education, restricted and repetitive behaviors, IQ and adaptive behavior, affective and conduct problems, and medical concerns.

11.
Chin Med J (Engl) ; 132(24): 2899-2904, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31855969

RESUMO

BACKGROUND: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development. METHODS: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression. RESULTS: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001). CONCLUSION: As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.

12.
ACS Appl Mater Interfaces ; 11(49): 45805-45817, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31724841

RESUMO

Porous covalent triazine framework (CTF)-based carbon materials have gained increasing attention in energy-storage applications because of their tunable structure, high chemical stability, and rich heteroatom contents. However, CTFs have thus far been exclusively synthesized from small-molecular precursors and generally show unsatisfactory supercapacitive performance. We report herein the construction of a novel range of CTFs of significantly improved supercapacitive performance from polyethynylbenzonitrile (PEBN) as a unique macromolecular precursor for the first time by ionothermal synthesis. CTF-800 synthesized at the optimized condition (800 °C; ZnCl2/PEBN mass ratio of 3:1) shows a nanosheet-like morphology with a high yield (∼90%), high nitrogen content (>5.8%), high specific surface area (1954 m2 g-1), and optimized micropore to meso/macropore surface area ratio (42:58). As the electrode material for supercapacitor application, CTF-800 exhibits a high specific capacitance of 628 F g-1 at 0.5 A g-1, high-rate performance (71% of capacitance retention at 50 A g-1), and excellent cyclic stability (96% of capacitance retention over 20 000 cycles) in a three-electrode system with aqueous 1 M H2SO4 electrolyte. Symmetric supercapacitor devices have been further fabricated with CTF-800 in aqueous 1 M H2SO4, [EMIM][BF4], and LiPF6 electrolytes separately. The device with the aqueous electrolyte shows the highest capacitance of 448 F g-1 (at 0.5 A g-1) and a high energy density of 15.5 W h kg-1. The devices with [EMIM][BF4] and LiPF6 electrolytes exhibit exceptional energy densities of 70 and 78 W h kg-1, respectively, and retain energy densities of 41 and 45 W h kg-1, respectively, even at the high power density of 15 000 W kg-1, confirming their high-rate high-energy performance. Meanwhile, the device with [EMIM][BF4] electrolyte has also been demonstrated to operate well at various temperatures ranging from -20 to 60 °C with remarkable energy-storage performance.

13.
Environ Monit Assess ; 191(11): 688, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664528

RESUMO

Understanding the relative impact sizes of environmental factors and nutrients on the high annual variation of phytoplankton abundance in eutrophic rivers is important for aquatic ecosystem management efforts. In this study, we used phytoplankton dynamic datasets in the eutrophic Fenhe River to show the variations and drivers of phytoplankton abundance under complex, fluctuating environmental conditions during 2012-2017. The temporal and spatial variations of nutrients in the river depicted that the total phosphorus (TP) concentration was higher in the wet season and in downstream. There were increases in total nitrogen (TN) concentration in the normal season and in upstream. The structural equation model (SEM) showed that the phytoplankton abundance increased during the wet season despite the decrease in the TN:TP ratio and was reduced upstream due to the highest TN:TP ratio. Among the environmental variables, water temperature (WT) was an important predictor and positively correlated temporally and spatially to phytoplankton. The interaction of nutrients with the phytoplankton community at different temperature levels indicated that different phytoplankton groups have different nutrient requirements. We can conclude that enhances in temperature and TP concentration will significantly increase phytoplankton abundance and dominance of cyanobacteria and green algae in the future, whereas there was insignificant effect on diatoms. These data indicated that temperature and TP content were the important abiotic factors influencing the phytoplankton growth of the water body, which could provide a reference for the evaluation of environmental alterations in the future.


Assuntos
Monitoramento Ambiental , Fitoplâncton/crescimento & desenvolvimento , Temperatura Ambiente , Poluentes da Água/análise , China , Clorófitas , Cianobactérias/crescimento & desenvolvimento , Diatomáceas/crescimento & desenvolvimento , Ecossistema , Eutrofização , Nitrogênio/análise , Nutrientes , Fósforo/análise , Rios/química , Estações do Ano
14.
Anticancer Drugs ; 30(10): 1031-1037, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31609760

RESUMO

Macroautophagy (hereafter referred to as autophagy) plays essential roles in cellular and organismal homeostasis. Transcription factor EB (TFEB) is a master regulator of autophagy and lysosome biogenesis. It is not fully understood how the function of TFEB in autophagy pathway is regulated. Here, we show that Rac1 GTPase is a negative modulator of autophagy by targeting TFEB. Mechanistically, Rac1 reduces autophagy flux by repressing the expressing of autophagy genes. Further investigation revealed that under nutrient-rich conditions, mammalian target of rapamycin (mTOR) phosphorylates TFEB to facilitate the interaction between Rac1 and TFEB. Biochemical dissection uncovered that guanosine 5'-triphosphate (GTP)-bound form of Rac1 selectively interacts with phosphorylated TFEB. This inhibitory interaction prevents the dephosphorylation and nucleus translocation of TFEB, which hampers the transcriptional activation of autophagy-related genes. Furthermore, Rac1-TFEB axis appeared to be important for tumorigenesis, as overexpression of dephosphorylated mutant of TFEB was able to delay the tumor growth driven by Rac1 overexpression. Together, this study not only elucidates a previously uncharacterized autophagy regulation mechanism involving Rac1 and TFEB under physiological and pathological conditions but also suggests a strategy to treat cancers that are driven by Rac1 overexpression.

15.
Front Psychiatry ; 10: 607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572228

RESUMO

Background: Social-communication difficulties, a hallmark of ASD, autism spectrum disorder (ASD) are often observed in attention - deficit/ hyperactivity disorder (ADHD), although are not part of its diagnostic criteria. Despite sex differences in the prevalence of ASD and ADHD, research examining how sex differences manifest in social and communication functions in these disorders remains limited, and findings are mixed. This study investigated potential sex differences with age in social adaptive function across these disorders, relative to controls. Method: One hundred fifteen youth with ASD, 172 youth with ADHD, and 63 typically developing controls (age range 7-13 years, 75% males) were recruited from the Province of Ontario Neurodevelopmental Disorder (POND) Network. Social adaptive function was assessed using the Adaptive Behavior Assessment System-Second Edition (ABAS-II). The proportions of adaptive behaviors present in each skill area were analyzed as a binomial outcome using logistic regression, controlling for age, and testing for an age-by-sex interaction. In an exploratory analysis, we examined the impact of controlling for core symptom severity on the sex effect. Results: Significant sex-by-age interactions were seen within ASD in the communication (p = 0.005), leisure (p = 0.003), and social skill areas (p < 0.0001). In all three areas, lower scores (indicating poorer function) were found in females compared to males at older ages despite females performing better at younger ages. There were significant differences in the sex-by-age interactions in the social and leisure domains between those with ASD and typically developing controls, with typically developing females showing better scores at older, compared to younger, ages. There were also significant differences in the sex-by-age interactions between ASD and ADHD on the social and leisure domains, as females with ADHD consistently scored higher on social skills than males across all ages, unlike those with ASD. Sex differences across age in the social domains for ADHD were similar to those in the typically developing group. Conclusion: Sex differences in social and communication skill areas were observed between ASD and ADHD, and typically developing controls, with females with ASD performing worse than males at older ages, despite an earlier advantage. These findings reinforce the need to take a developmental approach to understanding sex differences which may have diagnostic, prognostic, and treatment implications.

16.
Child Abuse Negl ; 98: 104229, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31648112

RESUMO

BACKGROUND: Adolescent-to-parent psychological aggression is often a precursor to physical aggression toward their parents. Recently, there have been 4 high-profile matricide cases that happened in China. To date, there is limited research in Confucian filial piety culture on child-to-parent psychological aggression, especially toward the mother who is overwhelming the target of children's aggression. OBJECTIVE: The goal of this study is to explore the prevalence of adolescent-to-mother psychological aggression and examine the role of father violence and maternal parenting style in contributing to these behaviors in Confucian filial piety culture. METHODS: Participants were 1134 students from 7 to 12 grade (M = 14 years, SD = 1.5) in Qingdao located in Shandong Province in east side of China where the Confucian Culture began. The instruments used were a demographics questionnaire, adolescent-to-mother psychological aggression questionnaire, father's violent behavior questionnaire and maternal parenting style questionnaire. RESULTS: Two types of adolescent-to-mother psychological aggression were assessed: contempt and rebellion. The prevalence of adolescent-to-mother contempt and rebellion was 30.7% and 18.7%, respectively. Results from multiple regression analyses indicated that father's conflict with grandparents, maternal control and over-protection were positively associated with adolescent's contempt for mother. Parents divorced, father's conflict with grandparents, father-to-mother physical violence and maternal rejection were positively associated with adolescent's rebellion against mother. Maternal emotional warmth was negatively associated with adolescent's contempt and rebellion against mother. CONCLUSION: Adolescent-to-mother psychological aggression occurs within a broader family context of violence and disharmony. Observational learning of father's conflict with grandparents or violent behaviors toward mother maybe the mechanism of violence passing from generations. However, maternal emotional warmth buffered the negative association between father's conflict with grandparents and adolescent's contempt for mother. But maternal control and over-protection exacerbated the positive relationships between father's conflict with grandparents and adolescent's contempt for mother.

17.
Sci Rep ; 9(1): 14499, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601883

RESUMO

Mapping genetic interactions in mammalian cells is limited due to technical obstacles. Here we describe a method called TCGI (tRNA-CRISPR for genetic interactions) to generate a high-efficient, barcode-free and scalable pairwise CRISPR libraries in mammalian cells for identifying genetic interactions. We have generated a genome- wide library to identify genes genetically interacting with TAZ in cell viability regulation. Validation of candidate synergistic genes reveals the screening accuracy of 85% and TAZ-MCL1 is characterized as combinational drug targets for non-small cell lung cancer treatments. TCGI has dramatically improved the current methods for mapping genetic interactions and screening drug targets for combinational therapies.

18.
NPJ Genom Med ; 4: 26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602316

RESUMO

Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244 and PTCHD1-AS. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.

19.
Biochem Biophys Res Commun ; 519(2): 402-408, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31521245

RESUMO

Endothelial dysfunction (ED) is a crucial and initial stage for the development of cardiovascular diseases. Accumulated evidence has demonstrated causative links between cigarette smoke (CS) and ED. However, the underlying mechanisms remain largely unknown. Pyroptosis is a unique form of inflammatory cell death. In this study, we found that cigarette smoke extract (CSE) increased pyroptosis in endothelial cells (ECs) as evidenced by increasing lactate dehydrogenase release and the number of propidium iodide (PI) positive cells. A specific NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inhibitor (MCC950) pretreatment dramatically reduced CSE-induced pyroptosis. Additionally, we also observed that N-Acetylcysteine (NAC, a ROS scavenger) pretreatment inhibited NLRP3 inflammasome activation as evidenced by suppressing the upregulation of NLRP3, ASC, cleaved-caspase-1, GSDMD-N, IL-1ß and IL-18 protein levels in CSE-treated ECs. Meanwhile, NAC pretreatment also remarkably inhibited CSE-induced EC pyroptosis. Melatonin is a hormone synthesized and secreted by mammalian pineal gland and plays a protective role in various cardiovascular diseases through its powerful anti-inflammatory and antioxidant properties. In this study, melatonin was observed to inhibit ROS production, NLRP3 inflammasome activation and pyroptosis in CSE-treated ECs. Moreover, oxidative stress and NLRP3 inflammasome activation in carotid arteries of smoking rats was also inhibited by melatonin. In conclusion, our study generated two novel findings, (i) CS activates ROS/NLRP3 axis and induces EC pyroptosis; (ii) melatonin attenuates CS-induced EC pyroptosis by inhibiting ROS/NLRP3 axis.

20.
Am J Sports Med ; 47(13): 3247-3255, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31560856

RESUMO

BACKGROUND: Fatty infiltration, inflammation, and apoptosis are common degenerative changes in patients with chronic rotator cuff tears that can lead to muscle atrophy and can even result in massive irreparable rotator cuff tears. Some data have demonstrated the proregenerative, anti-inflammatory, and anti-apoptotic properties of stem cell-derived exosomes in some orthopaedic disorders, but their effect on torn rotator cuff muscles has never been investigated. PURPOSE: To study the effect of exosomes isolated from human adipose-derived stem cells (ASCs-Exos) on muscle degeneration, regeneration, and biomechanical properties in a rat model of a massive rotator cuff tear (MRCT). STUDY DESIGN: Controlled laboratory study. METHODS: A bilateral supraspinatus and infraspinatus tenotomy was performed on rats to create an MRCT model. Forty-two rats were randomly assigned to 3 groups: the sham surgery group, the saline group (lesions treated with a saline injection), and the ASCs-Exos group (lesions treated with an ASCs-Exos injection). Wet muscle weight, fatty infiltration, inflammation, vascularization, regeneration, and biomechanical properties were evaluated at 8 and 16 weeks after surgery. RESULTS: The results revealed that the ASCs-Exos treatment could prevent the atrophy, fatty infiltration, inflammation, and vascularization of muscles in the MRCT model (P < .001). Additionally, the myofiber regeneration and biomechanical properties of ASCs-Exos-treated rotator cuffs were significantly elevated compared with those in the saline-treated group (P < .001). CONCLUSION: This study demonstrates that ASCs-Exos can effectively decrease atrophy and degeneration and improve muscle regeneration and biomechanical properties in torn rotator cuff muscles. CLINICAL RELEVANCE: ASCs-Exos can be used as a new cell-free approach to prevent the muscle degeneration associated with torn rotator cuffs and may be helpful to repair torn rotator cuffs. Nevertheless, further work needs to be done in a large animal model owing to the inherent regenerative potential possessed by rodents.

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