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1.
Acta Odontol Scand ; : 1-10, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32421379

RESUMO

Objective: This systematic review aimed to assess the efficacy of occlusal splints in the treatment of temporomandibular disorders (TMDs).Material and Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Four databases (Medline via Pubmed, Web of Science, Embase and Scopus) were searched, the last search was conducted on April 2020. Randomised controlled trials (RCTs) employing the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) or Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) as diagnostic criteria and including occlusal splint as one of the experimental groups were included in the present study. The data from the included studies were extracted and assessed for risk of bias.Results: Eleven studies were included. The sample size ranged from 12 to 96 subjects. The male to female ratio was 0 to 25%. The mean length of follow-up was 4 months. Occlusal splint had a positive effect on mandibular movements in all included studies. Seven studies showed a positive effect of occlusal splint on chronic pain reduction and pain intensity, while two others showed improvement of temporomandibular joint clicking sounds and locking of the jaws. Moreover, improvements in mouth opening, depression, and anxiety symptoms, were reported in four studies.Conclusions: An occlusal splint can be considered as a non-invasive treatment approach for patients with TMD, especially those with signs and symptoms of restriction of mandibular movement and pain. Moreover, the present findings highlighted an urgent need of a standardised consensus regarding the prognostic evaluation of TMD.

2.
Phys Rev E ; 101(4-1): 042402, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32422851

RESUMO

Collective behaviors by self-organization are ubiquitous in nature and human society and extensive efforts have been made to explore the mechanisms behind them. Artificial intelligence (AI) as a rapidly developing field is of great potential for these tasks. By combining reinforcement learning with evolutionary game (RLEG), we numerically discover a rich spectrum of collective behaviors-explosive events, oscillation, and stable states, etc., that are also often observed in the human society. In this work, we aim to provide a theoretical framework to investigate the RLEGs systematically. Specifically, we formalize AI-agents' learning processes in terms of belief switches and behavior modes defined as a series of actions following beliefs. Based on the preliminary results in the time-independent environment, we investigate the stability at the mixed equilibrium points in RLEGs generally, in which agents reside in one of the optimal behavior modes. Moreover, we adopt the maximum entropy principle to infer the composition of agents residing in each mode at a strictly stable point. When the theoretical analysis is applied to the 2×2 game setting, we can explain the uncovered collective behaviors and are able to construct equivalent systems intuitively. Also, the inferred composition of different modes is consistent with simulations. Our work may be helpful to understand the related collective emergence in human society as well as behavioral patterns at the individual level and potentially facilitate human-computer interactions in the future.

3.
Oncogene ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32372060

RESUMO

Hepatocellular carcinoma (HCC) metastasis is largely responsible for HCC-associated recurrence and mortality. We aimed to identify metastasis-related long non-coding RNAs (lncRNAs) to understand the molecular mechanism of HCC metastasis. We first identified that miR-1258 was downregulated in HCC tissues both in The Cancer Genome Atlas (TCGA) and Sun Yat-sen University Cancer Center (SYSUCC) dataset. MiR-1258 expression negatively correlated with recurrence-free survival and overall survival of HCC patients. MiR-1258 overexpression inhibited migration and invasion of HCC cells both in vitro and in vivo, whereas miR-1258 downregulation promoted cell metastasis. Luciferase assays verified direct binding of miR-1258 to Smad2 and Smad3, thereby attenuating TGF-ß/Smad signaling. We further established that lncRNA LINC01278 was a negative regulator of miR-1258. In vivo and in vitro assays demonstrated that LINC01278-mediated HCC metastasis was dependent on miR-1258 expression. Furthermore, miR-1258 downregulation in turn increased LINC01278 expression. We also observed that TCF-4 could bind to the LINC01278 promoter site. In addition, LINC01278 downregulation decreased migration and invasion of HCC cells induced by ß-catenin and TGF-ß1 both in vitro and in vivo. We uncovered a novel mechanism for ß-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 feedback loop activation in HCC metastasis, and the study indicated that LINC01278 could serve as a therapeutic target for HCC metastasis.

4.
Biosens Bioelectron ; 162: 112234, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32392153

RESUMO

A new organic-inorganic heterostructure was prepared by the hydrothermal deposition of poly (3,4-dioxoethylthiophene) (PEDOT) on TiO2 nanowire arrays (TiONWs) to construct a biosensor that can simultaneously function as photoelectrochemical (PEC) and electrochemical (EC) sensor to detect lactate. In both cases, the PEDOT-TiONWs heterostructure not only acted as an immobilization platform for lactate dehydrogenase (LDH) and coenzyme NAD+, but also generated current signals, which were further amplified by the cyclic catalytic mechanism. Specifically, LDH catalytically converted lactate to pyruvate, meanwhile NAD+ was transformed to NADH. For PEC sensing, the photo-generated holes from PEDOT-TiONWs could oxidize NADH back to NAD+, fulfilling a catalytic cycle. Herein, PEDOT significantly promoted the separation of electron-hole pairs and enhanced PEC signals due to its well-matched energy levels with TiONWs, high conductivity and strong visible light absorption. A dynamic range of 0.5-300 µM was observed between the PEC signals and lactate concentration, based on which a sensitivity of 0.1386 ± 0.0053 µA µM-1 and a detection limit of 0.08 ± 0.0032 µM were estimated. For EC sensing, PEDOT-TiONWs could directly oxidize NADH to NAD+ at ~0.54 V to realize the cyclic amplification due to the high conductivity and strong electrocatalytic capability of the heterostructure. The EC biosensor displayed a similar performance upon PEC mode of operation, except the relatively poor selectivity due to the possible oxidation of the interferences at the potentials > 0.54 V.

5.
Proc Natl Acad Sci U S A ; 117(19): 10414-10421, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32350143

RESUMO

The rise of oxygen on the early Earth about 2.4 billion years ago reorganized the redox cycle of harmful metal(loids), including that of arsenic, which doubtlessly imposed substantial barriers to the physiology and diversification of life. Evaluating the adaptive biological responses to these environmental challenges is inherently difficult because of the paucity of fossil records. Here we applied molecular clock analyses to 13 gene families participating in principal pathways of arsenic resistance and cycling, to explore the nature of early arsenic biogeocycles and decipher feedbacks associated with planetary oxygenation. Our results reveal the advent of nascent arsenic resistance systems under the anoxic environment predating the Great Oxidation Event (GOE), with the primary function of detoxifying reduced arsenic compounds that were abundant in Archean environments. To cope with the increased toxicity of oxidized arsenic species that occurred as oxygen built up in Earth's atmosphere, we found that parts of preexisting detoxification systems for trivalent arsenicals were merged with newly emerged pathways that originated via convergent evolution. Further expansion of arsenic resistance systems was made feasible by incorporation of oxygen-dependent enzymatic pathways into the detoxification network. These genetic innovations, together with adaptive responses to other redox-sensitive metals, provided organisms with novel mechanisms for adaption to changes in global biogeocycles that emerged as a consequence of the GOE.

6.
Life Sci ; 252: 117612, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32247004

RESUMO

AIMS: Intestinal mucositis is the most common side effect of 5-fluorouracil (5-Fu) treatment in cancer patients. Previous research suggested that andrographolide (Andro) attenuated the intestinal injury in colitis or diarrhea in mice. The present study was aimed at investigating the protective effect of Andro against 5-Fu induced intestinal mucositis and the underlying mechanism. MAIN METHODS: BALB/C mice were injected 5-Fu at a dose of 100 mg/kg for 5 days to induce intestinal mucositis. Andro at different doses (25, 50, 100 mg/kg/day) was administered. Weight loss, diarrhea score, cellular apoptosis and proliferation were evaluated. Apoptosis related proteins were detected by Western blotting. Then, NCM460 cells were used to explore the possible mechanism in vitro. The effect of Andro on the anti-tumor efficacy of 5-Fu was investigated in H22 tumor-bearing mice. KEY FINDINGS: Andro significantly ameliorated the 5-Fu induced weight loss and diarrhea. The apoptosis of intestinal cells was also attenuated by Andro treatment both in vivo and in vitro. Besides, Andro markedly down-regulated the 5-Fu-induced protein expression of caspase8/3, Bax and the phosphorylation of p38. Moreover, 5-Fu significantly reduced the viability of NCM460 cells, which was restored by the Andro pretreatment. Furthermore, asiatic acid, an agonist of p38 MAPK, reversed the anti-apoptotic effect of Andro in NCM460 cells. Andro did not weaken the anti-H22 tumor effect of 5-Fu in vivo. SIGNIFICANCE: We have demonstrated that p38 MAPK inhibition mediates anti-apoptotic effects of Andro against 5-Fu induced intestinal mucositis, suggesting that Andro may benefit the patients undergoing 5-Fu based chemotherapy.

7.
Virol Sin ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32236817

RESUMO

Porcine adenoviruses (PAdVs) are classified into three species, PAdV-A, PAdV-B, and PAdV-C. The genomes of PAdV-A and PAdV-C have been well characterized. However, the genome of PAdV-B has never been completely sequenced, and the epidemiology of PAdV-B remains unclear. In our study, we have identified a novel strain of PAdV-B, named PAdV-B-HNU1, in porcine samples collected in China by viral metagenomic assay and general PCR. The genome of PAdV-B-HNU1 is 31,743 bp in length and highly similar to that of California sea lion adenovirus 1 (C. sea lion AdV-1), which contains typical mastadenoviral structures and some unique regions at the carboxy-terminal end. Especially, PAdV-B-HNU1 harbors a dUTPase coding region not clustering with other mastadenoviruses except for C. sea lion AdV-1 and a fiber coding region homologous with galectin 4 and 9 of animals. However, the variance of GC contents between PAdV-B-HNU1 (55%) and C. sea lion AdV-1 (36%) indicates their differential evolutionary paths. Further epidemiologic study revealed a high positive rate (51.7%) of PAdV-B-HNU1 in porcine lymph samples, but low positive rates of 10.2% and 16.1% in oral swabs and rectal swabs, respectively. In conclusion, this study characterized a novel representative genome of a lymphotropic PAdV-B with unique evolutionary origin, which contributes to the taxonomical and pathogenic studies of PAdVs.

8.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(4): 290-293, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32312363

RESUMO

OBJECTIVE: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A retrospective analysis was performed for the clinical data of 115 children who were diagnosed with SARS-CoV-2 infection in the Wuhan Children's Hospital, including general information, history of close contact with individuals of SARS-CoV-2 infection, early clinical symptoms, laboratory examination results, and lung CT results. RESULTS: Among the 115 children, there were 73 boys (63.5%) and 42 girls (36.5%), with a male/female ratio of 1:0.58. Of the 115 children, 105 (91.3%) had a definite history of close contact with individuals of SARS-CoV-2-infection. An increase in alanine aminotransferase was observed in 11 children (9.6%) and an increase in CK-MB was found in 34 children (29.6%). As for clinical symptoms, 29 children (25.2%) had fever, 47 (40.9%) had respiratory symptoms (including cough, rhinorrhea, and nasal congestion), and 61 (53.0%) were asymptomatic. Lung CT findings showed ground glass opacity, fiber opacities, patchy changes, and pulmonary consolidation in 49 children (42.6%), among whom 2 children had "white lung"; 39 children (33.9%) only had lung texture enhancement and 27 children (23.5%) had no pulmonary imaging changes. Among the 115 children, 3 were critically ill, among whom 1 had been cured and the other 2 were under continuous treatment. CONCLUSIONS: Most of the children with SARS-CoV-2 infection have a close contact history. Critical cases are rare and there is a high proportion of asymptomatic infection.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Alanina Transaminase/sangue , Doenças Assintomáticas , Betacoronavirus , Criança , Técnicas de Laboratório Clínico , Busca de Comunicante , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/diagnóstico por imagem , Tosse/etiologia , Estado Terminal , Feminino , Febre/etiologia , Humanos , Masculino , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
J Environ Manage ; 262: 110310, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32250793

RESUMO

Identifying the spatio-temporal variations of evapotranspiration (ET) from its components (soil evaporation and plant transpiration) can greatly improve our understanding of water-cycle and biogeochemical processes. However, partitioning evapotranspiration into evaporation (E) and transpiration (T) at regional scale with high accuracy still remains a challenge. This study has aimed to reveal the spatio-temporal variations of evapotranspiration and its components by using an improved Shuttleworth-Wallace (SWH) model to partition ET in the Yellow River Basin during 1981-2010. The environmental factors affecting the spatial and temporal variations of evapotranspiration and its components were also assessed. Results showed that the mean annual ET, T and E in the Yellow River Basin were 372.18 mm, 179.64 mm, and 192.54 mm, respectively, over the last 30 years. The spatial pattern of mean annual ET and T displayed a decreasing trend from southeast to northwest in the Yellow River Basin, and the temporal variation showed a significant increasing trend with rates of 1.72 mm yr-1 and 1.54 mm yr-1, respectively. It meant that T accounted for the variations of ET, while E showed no significant changes in recent decades. Moreover, the normalized differential vegetation index (NDVI) and temperature were identified as the main factors controlling the variations of ET and T in the Yellow River Basin. Among them, the area with NDVI as the dominant factor for ET and T could reach 63.82% and 78.47% of the whole basin respectively. However, the variations of E were affected by complex factors, and evaporation in the western alpine region was mainly controlled by temperature. Our findings are expected to not only have implications for developing sustainable policies of water management and ecological restoration in this region, but also provide valuable insight in methodology of ET partitioning in regional or global scale.


Assuntos
Transpiração Vegetal , Rios , China , Solo , Temperatura , Água
10.
Protein Pept Lett ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264804

RESUMO

The unfolded protein response (UPR) is a protective mechanism against endoplasmic reticulum (ER) stress that induces a series of signal transduction pathways to eliminate misfolded proteins. The UPR mechanism is highly conserved in fungi, higher organisms, plants and mammals. The UPR pathway is activated to stabilize ER functions when there are too many unfolded proteins or misfolded proteins in the ER. However, stress continues when ER proteins are stimulated by toxic substances that affect the balance of the UPR pathway, which causes changes in the structure and function of the ER and other organelles. These ultimately disrupt homeostasis in the body and cause pathological reactions that can be fatal. The UPR mechanism has clear effects on stabilizing the protein-folding environment. Dysfunction or disruption of the UPR mechanism is associated with numerous disorders, including neurodegenerative diseases, loss of control of protein secretion, cerebral ischemia and epilepsy, neuropsychiatric diseases, eye diseases, skin diseases, metabolic and inflammatory diseases, atherosclerosis, and heart disease. Thus, characterization of UPR function and its dysfunction has significant importance and has broad application prospects, which make research into the UPR a research hotspot.

11.
Neurol India ; 68(2): 383-388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189704

RESUMO

Context: A well-established cell line of hemangioblastomas (HBs) is still lacking. Aim: This study aims to explore a stable way to establish primary cell lines of HB stromal cells and investigate the morphological and molecular features of these cells. Patients and Methods: Specimens of HBs from 13 patients were collected for establishment of primary cell lines of stromal cells. The details on cell culture were described, and the characterizations of cultured cells were conducted by morphological observation, immunocytochemical staining of inhibin-α, brachyury, CD133, CD34, GFAP, CD31, NeuN, CD45, Oligo2, and transmission electron microscopy. Results: Eleven cases were successfully cultured with a success rate of 84.6%. The cultured cells survived for 10 generations with an estimated doubling time of 77.2 ± 5.89 h. Light microscopy revealed that these cells showed vigorous growth status and presented as polygons or trigons with significant heterogeneity. The immunocytochemical staining showed that inhibin-α, brachyury, CD133, and CD34 were expressed in all the cultured cells, whereas the expression of GFAP, CD31, NeuN, CD45, and Oligo2 was all negative. Transmission electron microscopy confirmed that the cultured cells were stromal cells with typical lipid droplets. The phenomenon of lysosomal autophagy was commonly observed without apoptotic cells in late stage. Conclusion: Appropriate selection of tumor specimens, short duration of devascularization, ideal digestion time, and nutritious medium are critical points for establishment of primary cell line of HB stromal cells. Stromal cells from both von Hippel-Lindau disease-related HBs and sporadic HBs might originate from embryologically arrested hemangioblasts.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32131442

RESUMO

The present study investigated the adsorption of Cd2+ by nonmagnetic and magnetic biochars (CMB and M-CMB) derived from chicken manure, respectively. The adsorption characteristics were investigated as a function of initial pH, contact time, initial Cd2+ concentration and magnetic separation. Adsorption process of both biochars were better described by Pseudo-second-order kinetic equation and Freundlich isotherm model, which were spontaneous and endothermic in nature. It was found that maximum capacities were 60.69 and 41.07 mg/g obtained at the initial Cd2+ concentration of 180 mg/L for CMB and M-CMB, and the turbidity of adsorption-treated solution was reduced from 244.3 to 11.3 NTU after magnetic separation of 0.5 min. These indicated that M-CMB had lower adsorption capacity of Cd2+ than CMB, though it was successfully separated from the treated solutions. Furthermore, both biochars before and after adsorption were analyzed by SEM-EDS, XRD and FTIR. Adsorption mechanisms mainly included precipitation, ion-exchange, complexation and Cπ-coordination, in which precipitation and ion-exchange dominated the adsorption process by CMB, while in M-CMB, precipitation was always predominant mechanism, followed by ion-exchange. The two other mechanisms of complexation and Cπ-coordination were trivial in both biochars, jointly contributing 7.21% for CMB and 5.05% for M-CMB to total adsorption. The findings deepen our understanding of the mechanisms governing the adsorption process, which are also important for future practical applications in the removal of heavy metals from wastewater by the biochars.

14.
BMC Genomics ; 21(1): 190, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122294

RESUMO

BACKGROUND: The AIG (avrRpt2-induced gene) family of GTPases, characterized by the presence of a distinctive AIG1 domain, is mysterious in having a peculiar phylogenetic distribution, a predilection for undergoing expansion and loss, and an uncertain functional role, especially in invertebrates. AIGs are frequently represented as GIMAPs (GTPase of the immunity associated protein family), characterized by presence of the AIG1 domain along with coiled-coil domains. Here we provide an overview of the remarkably expanded AIG repertoire of the freshwater gastropod Biomphalaria glabrata, compare it with AIGs in other organisms, and detail patterns of expression in B. glabrata susceptible or resistant to infection with Schistosoma mansoni, responsible for the neglected tropical disease of intestinal schistosomiasis. RESULTS: We define the 7 conserved motifs that comprise the AIG1 domain in B. glabrata and detail its association with at least 7 other domains, indicative of functional versatility of B. glabrata AIGs. AIG genes were usually found in tandem arrays in the B. glabrata genome, suggestive of an origin by segmental gene duplication. We found 91 genes with complete AIG1 domains, including 64 GIMAPs and 27 AIG genes without coiled-coils, more than known for any other organism except Danio (with > 100). We defined expression patterns of AIG genes in 12 different B. glabrata organs and characterized whole-body AIG responses to microbial PAMPs, and of schistosome-resistant or -susceptible strains of B. glabrata to S. mansoni exposure. Biomphalaria glabrata AIG genes clustered with expansions of AIG genes from other heterobranch gastropods yet showed unique lineage-specific subclusters. Other gastropods and bivalves had separate but also diverse expansions of AIG genes, whereas cephalopods seem to lack AIG genes. CONCLUSIONS: The AIG genes of B. glabrata exhibit expansion in both numbers and potential functions, differ markedly in expression between strains varying in susceptibility to schistosomes, and are responsive to immune challenge. These features provide strong impetus to further explore the functional role of AIG genes in the defense responses of B. glabrata, including to suppress or support the development of medically relevant S. mansoni parasites.

15.
Nano Lett ; 20(4): 2791-2798, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32155076

RESUMO

As the two most representative operation modes in an optical imaging system, bright-field imaging and phase contrast imaging can extract different morphological information on an object. Developing a miniature and low-cost system capable of switching between these two imaging modes is thus very attractive for a number of applications, such as biomedical imaging. Here, we propose and demonstrate that a Fourier transform setup incorporating an all-dielectric metasurface can perform a two-dimensional spatial differentiation operation and thus achieve isotropic edge detection. In addition, the metasurface can provide two spin-dependent, uncorrelated phase profiles across the entire visible spectrum. Therefore, based on the spin-state of incident light, the system can be used for either diffraction-limited bright-field imaging or isotropic edge-enhanced phase contrast imaging. Combined with the advantages of planar architecture and ultrathin thickness of the metasurface, we envision this approach may open new vistas in the very interdisciplinary field of imaging and microscopy.

16.
Dalton Trans ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32057042

RESUMO

Efficient and low-cost catalysts for catalytic wet air oxidation (CWAO) under ambient conditions are of great significance for the degradation of hydrophobic organic contaminants. In this study, four LDH catalysts were prepared and their catalytic performance was studied by the degradation of nitrobenzene. The CuCoFe-LDH shows the best catalytic activity with an NB removal efficiency of 41.2%. The CuCoFe-LDH exhibited a typical layer structure, with a specific surface area of 167.32 m2 g-1, and Cu2+, Co2+ and Fe3+ were evenly dispersed on the crystal. The NB removal efficiency was increased by 12.5% through adding formic acid. After five recycling processes, the NB removal efficiency was 18.9% because 3.8 mg g-1 of Co was leached out of the LDH. In the CWAO process, H2O2, ˙OH, ˙O2- and 1O2 were successfully formed through activated oxygen by the CuCoFe-LDH catalyst under ambient conditions. This work further broadens the application scope of layered double hydroxides (LDHs) in the degradation of organic pollutants by CWAO under ambient conditions.

17.
Cell Commun Signal ; 18(1): 27, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066462

RESUMO

BACKGROUND: Excessive light exposure is a detrimental environmental factor that plays a critical role in the pathogenesis of retinal degeneration. However, the mechanism of light-induced death of retina/photoreceptor cells remains unclear. The mammalian/mechanistic target of rapamycin (mTOR) and Poly (ADP-ribose) polymerase-1 (PARP-1) have become the primary targets for treating many neurodegenerative disorders. The aim of this study was to elucidate the mechanisms underlying light-induced photoreceptor cell death and whether the neuroprotective effects of mTOR and PARP-1 inhibition against death are mediated through apoptosis-inducing factor (AIF). METHODS: Propidium iodide (PI)/Hoechst staining, lentiviral-mediated short hairpin RNA (shRNA), Western blot analysis, cellular fraction separation, plasmid transient transfection, laser confocal microscopy, a mice model, electroretinography (ERG), and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which rapamycin/3-Aminobenzamide (3AB) exert neuroprotective effects of mTOR/PARP-1 inhibition in light-injured retinas. RESULTS: A parthanatos-like death mechanism was evaluated in light-injured 661 W cells that are an immortalized photoreceptor-like cell line that exhibit cellular and biochemical feature characteristics of cone photoreceptor cells. The death process featured over-activation of PARP-1 and AIF nuclear translocation. Either PARP-1 or AIF knockdown played a significantly protective role for light-damaged photoreceptors. More importantly, crosstalk was observed between mTOR and PARP-1 signaling and mTOR could have regulated parthanatos via the intermediate factor sirtuin 1 (SIRT1). The parthanatos-like injury was also verified in vivo, wherein either PARP-1 or mTOR inhibition provided significant neuroprotection against light-induced injury, which is evinced by both structural and functional retinal analysis. Overall, these results elucidate the mTOR-regulated parthanatos death mechanism in light-injured photoreceptors/retinas and may facilitate the development of novel neuroprotective therapies for retinal degeneration diseases. CONCLUSIONS: Our results demonstrate that inhibition of the mTOR/PARP-1 axis exerts protective effects on photoreceptors against visible-light-induced parthanatos. These protective effects are conducted by regulating the downstream factors of AIF, while mTOR possibly interacts with PARP-1 via SIRT1 to regulate parthanatos. Video Abstract Schematic diagram of mTOR interacting with PARP-1 to regulate visible light-induced parthanatos. Increased ROS caused by light exposure penetrates the nuclear membrane and causes nuclear DNA strand breaks. PARP-1 detects DNA breaks and synthesizes PAR polymers to initiate the DNA repair system that consumes a large amount of cellular NAD+. Over-production of PAR polymers prompts the release of AIF from the mitochondria and translocation to the nucleus, which leads to parthanatos. Activated mTOR may interact with PARP-1 via SIRT1 to regulate visible light-induced parthanatos.

19.
Aging (Albany NY) ; 12(3): 2530-2544, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32023551

RESUMO

Circular RNA (circRNA) is a novel class of noncoding RNAs, and the roles of circRNAs in the development of cardiac hypertrophy remain to be explored. Here, we investigate the potential roles of circRNAs in cardiac hypertrophy. By circRNA sequencing in left ventricular specimens collected from 8-week-old mice with isoproterenol hydrochloride-induced cardiac hypertrophy, we found 401 out of 3323 total circRNAs were dysregulated in the hypertrophic hearts compared with the controls. Of these, 303 circRNAs were upregulated and 98 were downregulated. Moreover, the GO and KEGG analyses revealed that the majority of parental gene of differentially expressed circRNAs were not only related to biological process such as metabolic process and response to stimulus, but also related to pathway such as circulatory system and cardiovascular diseases. On the other hand, total 1974 miRNAs were predicted to binding to these differentially expressed circRNAs, and the possible target mRNAs of those miRNAs were also predicted and analyzed in terms of functional annotation. Finally, we identified that ANF and miR-23a are downstream targets of circRNA wwp1, suggesting that circRNA wwp1 exerts inhibitory roles of cardiac hypertrophy via down-regulation of ANF and miR-23a, which underlying the potential mechanisms whereby circRNA regulates cardiac hypertrophy.

20.
CNS Neurosci Ther ; 26(3): 288-296, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32064759

RESUMO

A large number of families worldwide suffer from the physical and mental burden posed by stroke. An increasing number of studies aimed at the prevention and treatment of stroke have been conducted. Specifically, manipulating the immune response to stroke is under intense investigation. Microglia are the principal immune cells in the brain and are the first line of defense against the pathophysiology induced by stroke. Increasing evidence has suggested that microglia play diverse roles that depend on dynamic interactions with neurons, astrocytes, and other neighboring cells both in the normal brain and under pathological conditions, including stroke. Moreover, there are dynamic alterations in microglial functions with respect to aging and sex differences in the human brain, which offer a deep understanding of the conditions of stroke patients of different ages and sex. Hence, we review the dynamic microglial reactions caused by aging, sex, and crosstalk with neighboring cells both in normal conditions and after stroke and relevant potential interventions.

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