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1.
Am J Ophthalmol ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32413410

RESUMO

PURPOSE: To determine whether an association exists between dry eye disease (DED) and statin use and/or dyslipidemia. DESIGN: Retrospective, case-control study. METHODS: -SETTING: University of North Carolina (UNC) affiliated healthcare facilities. -STUDY POPULATION: 72,931 patients seen at UNC ophthalmology clinics over a 10 year period. -MAIN OUTCOME MEASURES: Odds ratios (ORs) calculated between DED and a history of low, moderate, or high-intensity statin use; and ORs calculated between DED and abnormal lipid panel values. RESULTS: 39,336 individuals (53.9% female) were analyzed after exclusion of individuals with confounding risk factors for DED. Of these, 3,399 patients (8.6%) carried a diagnosis of DED. Low, moderate, and high intensity statin regimens were used by 751 (1.9%), 2,655 (6.8%), and 1,036 (2.6%), respectively. Lipid abnormalities were identified as follows: total cholesterol >200, 4,558 (11.6%); HDL <40, 2,078 (5.3%); LDL >130, 2,756 (7.0%); and TGs >150, 2,881 (7.3%). The odds of carrying a diagnosis of DED given the presence of low, moderate, and high-intensity statin use were 1.39 (1.13,1.72), 1.47 (1.30,1.65), and 1.46 (1.21,1.75), respectively. The odds of carrying a diagnosis of DED given the presence of total cholesterol >200, HDL <40, LDL >130, and TGs >150 were 1.66 (1.52,1.82), 1.45 (1.26,1.67), 1.55 (1.39,1.74), and 1.43 (1.27,1.61), respectively. CONCLUSIONS: A history of statin use or dyslipidemia is associated with an increased odds of having a DED diagnosis. Further studies are needed to determine whether statin use and/or dyslipidemia increase the risk of DED.

2.
J Med Entomol ; 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32277701

RESUMO

Tick-borne diseases are a growing threat to public health in the United States, especially among outdoor workers who experience high occupational exposure to ticks. Long-lasting permethrin-impregnated clothing has demonstrated high initial protection against bites from blacklegged ticks, Ixodes scapularis Say (Acari: Ixodidae), in laboratory settings, and sustained protection against bites from the lone star tick, Amblyomma americanum (L.) (Acari: Ixodidae), in field tests. However, long-lasting permethrin impregnation of clothing has not been field tested among outdoor workers who are frequently exposed to blacklegged ticks. We conducted a 2-yr randomized, placebo-controlled, double-blinded trial among 82 outdoor workers in Rhode Island and southern Massachusetts. Participants in the treatment arm wore factory-impregnated permethrin clothing, and the control group wore sham-treated clothing. Outdoor working hours, tick encounters, and bites were recorded weekly to assess protective effectiveness of long-lasting permethrin-impregnated garments. Factory-impregnated clothing significantly reduced tick bites by 65% in the first study year and by 50% in the second year for a 2-yr protective effect of 58%. No significant difference in other tick bite prevention method utilization occurred between treatment and control groups, and no treatment-related adverse outcomes were reported. Factory permethrin impregnation of clothing is safe and effective for the prevention of tick bites among outdoor workers whose primary exposure is to blacklegged ticks in the northeastern United States.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32336604

RESUMO

BACKGROUND: The incidence of various open shoulder procedures has changed over time. In addition, various fellowships provide overlapping training in open shoulder surgery. There is a lack of information regarding the relationship between surgeon training and open shoulder procedure type and incidence in early career orthopedic surgeons. METHODS: The American Board of Orthopaedic Surgery Part-II database was queried from 2002 to 2016 for reported open shoulder procedures. The procedures were categorized as follows: arthroplasty, revision arthroplasty, open instability, trauma, and open rotator cuff. We evaluated procedure trends as well as their relationship to surgeon fellowship categorized by Sports, Shoulder/Elbow, Hand, Trauma, and "Other" fellowship as well as no fellowship training. We additionally evaluated complication data as it related to procedure, fellowship category, and volume. RESULTS: Over the 2002-2016 study period, there were increasing cases of arthroplasty, revision arthroplasty, and trauma (P < .001). There were decreasing cases in open instability and open rotator cuff (P < .001). Those with Sports training reported the largest overall share of open shoulder cases. Those with Shoulder/Elbow training reported an increasing overall share of arthroplasty cases and higher per candidate case numbers. The percentage of early career orthopedic surgeons reporting 5 or more arthroplasty cases was highest among Shoulder/Elbow candidates (P < .001). Across all procedures, those without fellowship training were least likely to report a complication (odds ratio [OR], 0.76; 95% confidence interval, 0.67-0.86; P < .001). Shoulder/Elbow candidates were least likely to report an arthroplasty complication (OR, 0.84, P = .03) as was any surgeon reporting 5 or more arthroplasty cases (OR, 0.81; 95% confidence interval, 0.70-0.94; P = .006). CONCLUSION: The type and incidence of open shoulder surgery procedures continues to change. Among early career surgeons, those with more specific shoulder training are now performing the majority of arthroplasty-related procedures, and early career volume inversely correlates with complications.

4.
Sex Med Rev ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32147498

RESUMO

INTRODUCTION: Conflicting evidence exists on the relationship between bicycle riding and erectile dysfunction (ED). A major limitation to several prior studies is the lack of a validated measure of ED. OBJECTIVE: To assess the relationship between cycling and clinically validated ED based on existing literature. METHODS: We searched several major databases from database inception through 2018 using a variety of search terms relating to "cycling" and "erectile dysfunction." Studies were included if they were written in English, reported original data, compared ED between cyclists and non-cycling controls, and used a validated measure of ED, such as the International Index of Erectile Function or the subset Sexual Health Inventory for Men (SHIM). Age, SHIM score, and comorbidities were extracted for all groups. Primary outcomes for each group were mean SHIM score and presence of ED (SHIM ≤ 21). A generalized linear mixed-effects model was used to fit the collected data for meta-analysis. Main outcome measures were unadjusted odds ratios of ED for cyclists and non-cyclists, mean SHIM score difference between cyclists and noncyclists, and both of these measures adjusted for age and comorbidities. RESULTS: After a systematic evaluation of 843 studies, 6 studies met our inclusion criteria, encompassing 3,330 cyclists and 1,524 non-cycling controls. When comparing cyclists to non-cyclists in an unadjusted analysis, there were no significant differences in the odds of having ED or mean SHIM score. However, when controlling for age and comorbidities, cyclists had significantly higher odds of having ED (odds ratio: 2.00; 95% confidence interval: 1.57, 2.55). CONCLUSIONS: Limited evidence supports a positive correlation between cycling and ED when adjusting for age and several comorbidities. Heterogeneity among studies suggests that further investigation into certain populations of cyclists that may be more vulnerable to ED may be beneficial. Gan ZS, Ehlers ME, Lin FC, et al. Systematic Review and Meta-Analysis of Cycling and Erectile Dysfunction. Sex Med 2020;XX:XXX-XXX.

5.
Invest New Drugs ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170576

RESUMO

Dezocine is an opioid analgesic with both µ-receptor agonist and antagonist activities. Administration of opioids influences the immune system through immune cells. Dendritic cells (DC) play crucial functions in inducing T cell response and mediating immune functions. DC surface displays several different opioid receptors whose expression is induced during DC maturation. We aimed to explore the effects of dezocine on DCs and T cells, as well as on tumor treatment. Mice were intraperitoneally administrated with increasing doses of dezocine (0.75, 1.25 and 2.0 mg/kg). Mouse bone marrow-derived dendritic cells (BMDCs) were then isolated from the bone marrow. The BMDC surface markers were evaluated by flow cytometry. T cell proliferation was assessed by the carboxyfluorescein succinimidyl ester assay. The number of mature DCs were increased by dezocine treatment in both human umbilical cord blood and mouse peripheral blood, suggesting that dezocine enhanced BMDC maturation. Dezocine-treated BMDCs promoted CD8+ T cell proliferation and cytotoxicity, while dezocine treatment inhibited tumor metastasis in mice. We therefore conclude that the administration of dezocine promotes BMDC maturation and inhibits tumor metastasis through elevating CD8+ T cell proliferation and cytotoxicity.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32205739

RESUMO

PURPOSE: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is a recently discovered protein that is considered important in causing mutations in tumor cell genome bases. Whether APOBEC3B is expressed in nasopharyngeal carcinoma (NPC) still remains unknown. Studies have shown that programmed-cell-death receptor-1 ligand (PD-L1) is highly expressed in NPC, but its clinical significance has not been fully elucidated. We aimed to evaluate APOBEC3B and PD-L1 protein expression in NPC and also investigate their prognostic significance. MATERIALS AND METHODS: One hundred and three patients with NPC were retrospectively collected in this study, and were followed-up for 5 years. The expression of APOBEC3B and PD-L1/PD-1 in NPC was detected by immunohistochemical staining. RESULTS: High expression of APOBEC3B was observed in 42.7% of NPC patients. The high expression rate of APOBEC3B was 31.5% in patients without recurrence or metastasis within 5 years, and 55.1% in those patients with recurrence or metastasis, and the difference was statistically significant (P=0.016). There was no significant difference in APOBEC3B expression among patients with different sex, age group, and clinical stage (P>0.05). The positive expression rate of PD-L1 was 55.3% in all patients with NPC. There was no significant difference in PD-L1 expression among patients with different sex, age group, clinical stage, and tumor recurrence or metastasis condition (P> 0.05). There was no significant correlation between the expression of APOBEC3B and PD-L1 in NPC patients. The positive expression rate of PD-1 was 1.9% (2/103) in patients with NPC. CONCLUSIONS: APOBEC3B showed association with aggressive behavior and poor outcome in NPC, and is also considered as a potential marker for predicting NPC recurrence or metastasis. PD-L1 is not associated with the aggressive behavior and poor outcome in NPC.

7.
Int Immunopharmacol ; 83: 106421, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32217462

RESUMO

Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells derived from bone marrow. These cells are developed from immature myeloid cells and have strong negative immunomodulatory effects. In the context of pathology (such as tumor, autoimmune disease, trauma, and burns), MDSCs accumulate around tumor and inflammatory tissues, where their main role is to inhibit the function of effector T cells and promote the recruitment of regulatory T cells. MDSCs can be used in organ transplantation to regulate the immune responses that participate in rejection of the transplanted organ. This effect is achieved by increasing the production of MDSCs in vivo or transfusion of MDSCs induced in vitro to establish immune tolerance and prolong the survival of the graft. In this review, we discuss the efficacy of MDSCs in a variety of transplantation studies as well as the induction of immune tolerance to prevent transplant rejection through the use of common clinical immunosuppressants combined with MDSCs.

8.
Biometrics ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022247

RESUMO

In patients with Plasmodium vivax malaria treated with effective blood-stage therapy, the recurrent illness may occur due to relapse from latent liver-stage infection or reinfection from a new mosquito bite. Classification of the recurrent infection as either relapse or reinfection is critical when evaluating the efficacy of an anti-relapse treatment. Although one can use whether a shared genetic variant exists between baseline and recurrence genotypes to classify the outcome, little has been suggested to use both sharing and nonsharing variants to improve the classification accuracy. In this paper, we develop a novel classification criterion that utilizes transition likelihoods to distinguish relapse from reinfection. When tested in extensive simulation experiments with known outcomes, our classifier has superior operating characteristics. A real data set from 78 Cambodian P. vivax malaria patients was analyzed to demonstrate the practical use of our proposed method.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 231: 118109, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062512

RESUMO

Puerariae Radix (PR) is a natural herb whose active ingredient is mainly flavonoids. To explore the interaction between PR flavonoids and DNA not only has important biological implications for understanding the mechanism of action, but also helps develop PR products for the design of appropriate dietary interventions to aid cancer treatment. In this work, we comprehensively studied the interaction between six kinds of PR flavonoids and DNA from four different and progressive levels, including molecular docking, multi-spectral analysis, and functional analysis in vitro and in cell. Results show that the DNA binding affinity of six flavonoids is in an order of quercetin > formononetin > daidzein > puerarin > 4'-methoxy puerarin > puerarin 6″-O-xyloside (POS), in which quercetin can significantly inhibit DNA amplification owing to its strongest binding affinity. The binding between quercetin and DNA is further revealed to be intercalated binding, which can cause conformational changes in DNA, thereby exhibiting an activity of cell cycle arrest and anti-proliferative. This property of quercetin can be utilized for the further development of flavonoids with anticancer activity. In addition to the potential application, this work also provides a platform for the comprehensive study of the interaction between micromolecules and DNA.

10.
J Hazard Mater ; 388: 122081, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31958610

RESUMO

The heavy metals, namely lead (Pb), cadmium (Cd), and mercury (Hg), have been studied extensively in various independent studies. It has been seen that these metals are usually detected simultaneously in the human blood at low levels. However, it is unknown whether exposure to these heavy metal mixtures (MM) can induce neurological damages at these low levels. Therefore, we investigated the influence of the Pb, Cd, and Hg mixture on the nervous system in rats at exposure doses equivalent to those normally found in the human blood. After pregnant rats being exposed to MM via drinking water throughout the gestation and lactation, their offspring were followed-up till adulthood. MM caused cognitive deficits and impairments in a dose-dependent manner. Furthermore, MM disrupted dendritic spines, the structural basis of learning and memory, and induced changes in spine-related pathways. Meanwhile, we explored an early and safe way to remedy these impairments through a postnatal enriched environment. The enriched environment ameliorated MM-impaired cognitive function, synaptic plasticity, and spine-related pathways. This study demonstrated that low-dose co-exposure to Pb, Cd, and Hg can cause cognitive and synaptic plasticity deficits and timely intervention through the enriched environment has a certain corrective effect.

11.
Angle Orthod ; 90(1): 77-84, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31403836

RESUMO

OBJECTIVES: To (1) introduce a novel machine learning method and (2) assess maxillary structure variation in unilateral canine impaction for advancing clinically viable information. MATERIALS AND METHODS: A machine learning algorithm utilizing Learning-based multi-source IntegratioN frameworK for Segmentation (LINKS) was used with cone-beam computed tomography (CBCT) images to quantify volumetric skeletal maxilla discrepancies of 30 study group (SG) patients with unilaterally impacted maxillary canines and 30 healthy control group (CG) subjects. Fully automatic segmentation was implemented for maxilla isolation, and maxillary volumetric and linear measurements were performed. Analysis of variance was used for statistical evaluation. RESULTS: Maxillary structure was successfully auto-segmented, with an average dice ratio of 0.80 for three-dimensional image segmentations and a minimal mean difference of two voxels on the midsagittal plane for digitized landmarks between the manually identified and the machine learning-based (LINKS) methods. No significant difference in bone volume was found between impaction ([2.37 ± 0.34] [Formula: see text] 104 mm3) and nonimpaction ([2.36 ± 0.35] [Formula: see text] 104 mm3) sides of SG. The SG maxillae had significantly smaller volumes, widths, heights, and depths (P < .05) than CG. CONCLUSIONS: The data suggest that palatal expansion could be beneficial for those with unilateral canine impaction, as underdevelopment of the maxilla often accompanies that condition in the early teen years. Fast and efficient CBCT image segmentation will allow large clinical data sets to be analyzed effectively.

12.
J Infect Dis ; 221(3): 428-437, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31549156

RESUMO

BACKGROUND: In Southeast Asia, people are often coinfected with different species of malaria (Plasmodium falciparum [Pf] and Plasmodium vivax [Pv]) as well as with multiple clones of the same species. Whether particular species or clones within mixed infections are more readily transmitted to mosquitoes remains unknown. METHODS: Laboratory-reared Anopheles dirus were fed on blood from 119 Pf-infected Cambodian adults, with 5950 dissected to evaluate for transmitted infection. Among 12 persons who infected mosquitoes, polymerase chain reaction and amplicon deep sequencing were used to track species and clone-specific transmission to mosquitoes. RESULTS: Seven of 12 persons that infected mosquitoes harbored mixed Pf/Pv infection. Among these 7 persons, all transmitted Pv with 2 transmitting both Pf and Pv, leading to Pf/Pv coinfection in 21% of infected mosquitoes. Up to 4 clones of each species were detected within persons. Shifts in clone frequency were detected during transmission. However, in general, all parasite clones in humans were transmitted to mosquitoes, with individual mosquitoes frequently carrying multiple transmitted clones. CONCLUSIONS: Malaria diversity in human hosts was maintained in the parasite populations recovered from mosquitoes fed on their blood. However, in persons with mixed Pf/Pv malaria, Pv appears to be transmitted more readily, in association with more prevalent patent gametocytemia.

13.
Sci Total Environ ; 701: 134901, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31710906

RESUMO

Heavy metal lead (Pb) is widely distributed in the environment and can induce neurodegeneration. Accumulating evidence has shown that ryanodine receptors (RyRs) play vital roles in neurodegenerative brain. However, whether aberrant RyRs levels contribute to Pb-induced neurodegeneration has largely remained unknown. In the present study, we report the important role of elevated levels of RyRs in Pb-induced neurodegeneration. Pb was found to upregulate the levels of RyRs in the rat hippocampal tissues and rat pheochromocytoma (PC12) cells. Furthermore, exposure to Pb induced neurodegenerative cognitive impairment in rats, depressed the long-term potentiation (LTP) in the rat brain slices, increased the neuronal intracellular free calcium concentration ([Ca2+]i), inhibited the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine 3',5'-monophosphate (cAMP) response element binding protein (CREB) as well as the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl2), and activated the phosphorylation of extracellular regulated protein kinases (Erk) protein both in vitro and in vivo. In addition, the knockdown of RyR3 in PC12 cells significantly decreased the [Ca2+]i levels, increased the CaMKIIα and CREB phosphorylation, decrease the phosphorylation of Erk, and elongated the cognitive function-related neurite outgrowth after exposure to Pb. Moreover, treatment with a RyRs agonist showed the involvement of RyRs in Pb-induced depression in LTP in the rat brain slices. In summary, we determined that Pb-mediated upregulation of RyRs led to neurodegeneration via high levels of free calcium, depression of the calcium-dependent CaMKIIα/CREB mnemonic signaling pathway, and activation of the calcium-dependent Erk/Bcl2 apoptotic signaling pathway. These findings on the impact of Pb on the levels of RyRs could further improve our understanding of Pb-induced neurotoxicity and provide a promising molecular target to antagonize Pb-induced neurodegenerative diseases.


Assuntos
Chumbo/toxicidade , Doenças Neurodegenerativas/induzido quimicamente , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Animais , Sinalização do Cálcio/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Ratos
14.
BMC Public Health ; 19(1): 1596, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783747

RESUMO

BACKGROUND: Regular physical activity is an important component of healthy living and wellbeing. Current guidelines recommend that adults participate in at least 150 min of moderate or vigorous-intensity physical activity weekly. In spite of the benefits, just over half of U.S. adults meet these recommendations. Calorie-only food labels at points of food purchase have had limited success in motivating people to change eating behaviors and increase physical activity. One new point of purchase approach to promote healthy behaviors is the addition of food labels that display the physical activity requirement needed to burn the calories in a food item (e.g. walk 15 min). METHODS: The Physical Activity Calorie Expenditure (PACE) Study compared activity-based calorie-expenditure food labels with calorie-only labels at three Blue Cross and Blue Shield of North Carolina worksite cafeterias. After 1 year of baseline data collection, one cafeteria had food items labeled with PACE labels, two others had calorie-only food labels. Cohort participants were asked to wear an accelerometer and complete a self-report activity questionnaire on two occasions during the baseline year and twice during the intervention year. RESULTS: A total of 366 study participants were included in the analysis. In the PACE-label group, self-reported physical activity increased by 13-26% compared to the calorie-only label group. Moderate-to-vigorous physical activity (MVPA) increased by 24 min per week in the PACE-label group compared to the calorie-label group (p = 0.06). Changes in accelerometer measured steps, sedentary time, and MVPA had modest increases. Change ranged from 1 to 12% with effect size values from 0.08 to 0.15. Baseline physical activity level significantly moderated the intervention effects for all physical activity outcomes. Participants in both label groups starting in the lowest tertile of activity saw the largest increase in their physical activity. CONCLUSION: Results suggest small positive effects for the PACE labels on self-reported and objective physical activity measures. Minutes of weekly MVPA, strength training, and exercise activities showed modest increases. These results suggest that calorie-expenditure food labels may result in some limited increases in physical activity.

15.
Huan Jing Ke Xue ; 40(7): 3135-3145, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854711

RESUMO

Titanate nanotubes (TNTs) were synthesized via a hydrothermal method using P25 and NaOH as the raw materials. The composition and morphology of the nanotubes were characterized by X-ray diffraction and transmission electron microscopy. The adsorption characteristics and the rules of ammonium in aqueous solutions were tested in the static system. The results showed that when the alkali concentration was 10 mol·L-1, titanate nanotubes with a length of approximately 120 nm and a diameter of approximately 8 nm were obtained. The equilibrium adsorption capacity of ammonium was 10.67 mg·g-1. When the pH ranged between 3 and 8, TNTs effectively adsorbed ammonium. The equilibrium adsorption time was 1 h, and this followed the pseudo second-order model. The results from the intra-particle model also showed that the adsorption process of ammonium by TNTs was controlled by surface adsorption and inter-particle diffusion. The Temkin model gave the best fit for the adsorption of ammonium onto TNTs. The thermodynamic experiments showed that the adsorption of titanate nanotubes on ammonium was a spontaneous endothermic process. Coexisting anions and cations had an inhibitory effect on the adsorption of ammonium. The order of influence was SO42- > Cl- > H2PO4- and K+ > Na+ > Ca2+, respectively. The adsorption effect of ammonium by regenerated TNTs remained more than 88.64% after five repeat usages. The results of Fourier transform infrared spectroscopy showed that the ammonium adsorption mechanism of titanate nanotubes was ion-exchange between NH4+ and Na+ in the TNTs. Titanate nanotubes can effectively remove ammonium from water because of their good recycling capacity and large adsorption capacity.

16.
Int J Mol Sci ; 21(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881804

RESUMO

Both OGT1 (O-linked ß-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex. We previously described how global histone H4 acetylation levels were modulated by OGT1/O-GlcNAcylation-mediated NSL3 stability. However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown. Here, we present evidence from biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex. Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1. Importantly, O-GlcNAcylation of this site is involved in the regulation of the ubiquitin-degradation of NSL3, because this site mutation (T755A) promotes the ubiquitin-mediated degradation of NSL3. Further in-depth research found that ubiquitin conjugating enzyme E2 S (UBE2S) accelerated the degradation of NSL3 via direct binding to it. Interestingly, OGT1 and UBE2S competitively bind to NSL3, suggesting the coordination of OGT1-UBE2S in regulating NSL3 stability. Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex. In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells. Taken together, our results provide new insight into the elucidation of the molecular mechanism of the MOF/NSL complex.


Assuntos
Histona Acetiltransferases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Acetilação , Células HEK293 , Histona Acetiltransferases/química , Holoenzimas/química , Holoenzimas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , N-Acetilglucosaminiltransferases/antagonistas & inibidores , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismo , Ligação Proteica , Estabilidade Proteica , Proteólise , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Treonina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo
17.
Cell Commun Signal ; 17(1): 147, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727175

RESUMO

Neutrophils have long been considered as cells playing a crucial role in the immune defence against invading pathogens. Accumulating evidence strongly supported the direct and indirect regulatory effects of neutrophils on adaptive immunity. Exogenous cytokines or cytokines produced in an autocrine manner as well as a cell-to-cell contact between neutrophils and T cells could induce the expression of MHC-II and costimulatory molecules on neutrophils, supporting that neutrophils may function as antigen-presenting cells (APCs) in respects of presenting antigens and activating T cells. In addition to the inflammatory roles, neutrophils also have the propensity and ability to suppress the immune response through different mechanisms. In this review, we will mainly highlight the heterogeneity and functional plasticity of neutrophils and the antigen-presenting capacity of different neutrophil subsets. We also discuss mechanisms relevant to the regulatory effects of neutrophils on adaptive immunity. Understanding how neutrophils modulate adaptive immunity may provide novel strategies and new therapeutic approaches for diseases associated with neutrophils.

18.
Opt Express ; 27(21): 30552-30562, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684300

RESUMO

Balanced homodyne detection relies on a beam splitter to superpose the weak signal input and strong local oscillator. However, recent investigation shows that a high gain phase sensitive amplifier (PSA) can be viewed as homodyne detector, in which the strong pump of PSA serves as the local oscillator [1]. Here, we analyze a new method of measuring the continuous variable entanglement by assisting a balanced homodyne detector with the PSA and implement it experimentally. Before measuring quadrature amplitude with the balanced homodyne detectors, two entangled fields generated from a pulse pumped fiber optical parametric amplifier are simultaneously coupled into the PSA. We find that the normalized noise for both the difference and sum of the quadrature amplitudes of the two entangled fields fall below the shot noise limit by about 4.6 dB, which is the record degree of entanglement measured in optical fiber systems. The experimental results illustrate that the advantages of the new measurement method include but not limit to tolerance to detection loss and characterizing entanglement with only one homodyne detector. The influence of mode-mismatching due to multi-mode property of entanglement on the measured noise reduction can also be greatly mitigated, indicating the new method is advantageous over the traditional measurement in multi-mode case.

19.
Crit Rev Anal Chem ; : 1-12, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613139

RESUMO

Cancer is a global disease which has been disturbing researchers in medicine and seriously threatens patients' health and lifetime around the world in the past several decades. Due to the characteristics of cancer cells, such as uncontrollable cell proliferation, cell invasion and metastasis to surrounding tissues, lower grade of differentiation, higher telomerase activity and others, it has been one of the most usual lethal factors, next to heart disease in incidence. Cancer mortality can be decreased by early diagnosis, and the people who with treatment at an early stage have an obvious improved survival rate. Consequently, early detection is significant for better understanding the pathogenesis of cancer and improving the prognosis of patients. In situ detection technique is a vital tool for imaging and cellular pathology research, which can provide effective information about tumor markers in the early cancer detection. In view of low expression of most tumor markers in the early stage of cancers, detection techniques based on DNA signal amplification and DNA nanodevices can provide a strong support for the diagnosis and detection of cancers. In this review, we summarize the research progress of different analytical techniques for detecting various tumor markers that have been reported in recent years. We compare different DNA amplification and nanodevices, then provide guidance and suggestions for better understanding in situ analysis of cancer cells.

20.
Environ Int ; 133(Pt B): 105192, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31639605

RESUMO

The heavy metals lead (Pb), cadmium (Cd) and mercury (Hg) are common environmental pollutants that can be detected simultaneously in blood, serum, and urine samples from the general human population. However, there is limited information regarding toxicity of low-level exposure to Pb, Cd, and Hg mixtures. Our previous research showed the interaction of these three elements at low concentrations in vitro. In this study, we further evaluate early effects of low dose exposure to Pb, Cd, and Hg mixtures on the brain, heart, liver, kidney, and testicle in rats. Pregnant rats were exposed to various concentrations of heavy metal mixtures (MM) in drinking water, during gestation and lactation, and the impacts on offspring were measured at postnatal day 23. Our results showed that the concentrations of Pb, Cd, and Hg in the blood of rat pups were similar to those in the blood of the general human population. Additionally, the MM concentrations in their blood and brain significantly increased in a dose-dependent manner. MM exposure caused histopathological changes in the brain, liver, kidney and testicle. Statistically significant increases in liver CYP450 and PON1, kidney KIM1, and decrease in testicle SDH were observed. In the brain, significant increases were detected in oxidative stress, intracellular free calcium, and cell apoptosis. Further neurobehavioral testing revealed that MM exposure caused dose-dependent impairments in learning and memory as well as sensory perception. MM exposure also disrupted synapse remodeling, which may be associated with pathways involved in dendritic spine growth, maintenance, and elimination. These results suggested that exposure to Pb, Cd, and Hg mixtures, at human environmental exposure related levels, caused damage to multiple organs as well as impairments in neurobehavioral functions of rats. Our findings emphasize the need to control and regulate potential sources of heavy metal contamination.


Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Lactação , Chumbo/toxicidade , Mercúrio/toxicidade , Animais , Exposição Ambiental , Feminino , Gravidez , Ratos , Ratos Sprague-Dawley
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