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1.
Hepatology ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38899975

RESUMO

BACKGROUND AND AIMS: Liver hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. The heterogeneity of this malignancy is driven by a wide range of genetic alterations, leading to a lack of effective therapeutic options. In this study, we conducted a systematic multi-omics characterization of HCC to uncover its metabolic reprogramming signature. APPROACH AND RESULTS: Through a comprehensive analysis incorporating transcriptomic, metabolomic, and lipidomic investigations, we identified significant changes in metabolic pathways related to glucose flux, lipid oxidation and degradation, and de novo lipogenesis in HCC. The lipidomic analysis revealed abnormal alterations in glycerol-lipids, phosphatidylcholine (PC), and sphingolipid (SL) derivatives. Machine-learning techniques identified a panel of genes associated with lipid metabolism as common biomarkers for HCC across different etiologies. Our findings suggest that targeting phosphatidylcholine with saturated fatty acids (SFA-PC) and long-chain sphingolipid biosynthesis pathways, particularly by inhibiting Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) and Ceramide Synthase 5 (CERS5) as potential therapeutic strategies for HCC in vivo and in vitro. Notably, our data revealed an oncogenic role of CERS5 in promoting tumor progression through lipophagy. CONCLUSION: In conclusion, our study elucidates the metabolic reprogramming gnature of lipid metabolism in HCC, identifies prognostic markers, and therapeutic targets, and highlights potential metabolism-related targets for therapeutic intervention in HCC.

2.
Cell Mol Life Sci ; 81(1): 259, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878072

RESUMO

Sex pheromones play crucial role in mating behavior of moths, involving intricate recognition mechanisms. While insect chemical biology has extensively studied type I pheromones, type II pheromones remain largely unexplored. This study focused on Helicoverpa armigera, a representative species of noctuid moth, aiming to reassess its sex pheromone composition. Our research unveiled two previously unidentified candidate type II sex pheromones-3Z,6Z,9Z-21:H and 3Z,6Z,9Z-23:H-in H. armigera. Furthermore, we identified HarmOR11 as an orphan pheromone receptor of 3Z,6Z,9Z-21:H. Through AlphaFold2 structural prediction, molecular docking, and molecular dynamics simulations, we elucidated the structural basis and key residues governing the sensory nuances of both type I and type II pheromone receptors, particularly HarmOR11 and HarmOR13. This study not only reveals the presence and recognition of candidate type II pheromones in a noctuid moth, but also establishes a comprehensive structural framework for PRs, contributing to the understanding of connections between evolutionary adaptations and the emergence of new pheromone types.


Assuntos
Mariposas , Receptores de Feromônios , Atrativos Sexuais , Animais , Atrativos Sexuais/metabolismo , Atrativos Sexuais/química , Mariposas/metabolismo , Mariposas/fisiologia , Receptores de Feromônios/metabolismo , Receptores de Feromônios/genética , Masculino , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , Feminino , Simulação de Acoplamento Molecular , Sequência de Aminoácidos , Filogenia , Simulação de Dinâmica Molecular , Comportamento Sexual Animal/fisiologia
3.
Cell Mol Life Sci ; 80(8): 199, 2023 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-37421463

RESUMO

Male moths utilize their pheromone communication systems to distinguish potential mates from other sympatric species, which contributes to maintaining reproductive isolation and even drives speciation. The molecular mechanisms underlying the evolution of pheromone communication systems are usually studied between closely-related moth species for their similar but divergent traits associated with pheromone production, detection, and/or processing. In this study, we first identified the functional differentiation in two orthologous pheromone receptors, OR14b, and OR16, in four Helicoverpa species, Helicoverpa armigera, H. assulta, H. zea, and H. gelotopoeon. To understand the substrate response specificity of these two PRs, we performed all-atom molecular dynamics simulations of OR14b and OR16 based on AlphaFold2 structural prediction, and molecular docking, allowing us to predict a few key amino acids involved in substrate binding. These candidate residues were further tested and validated by site-directed mutagenesis and functional analysis. These results together identified two hydrophobic amino acids at positions 164 and 232 are the determinants of the response specificity of HarmOR14b and HzeaOR14b to Z9-14:Ald and Z9-16:Ald by directly interacting with the substrates. Interestingly, in OR16 orthologs, we found that position 66 alone determines the specific binding of Z11-16:OH, likely via allosteric interactions. Overall, we have developed an effective integrated method to identify the critical residues for substrate selectivity of ORs and elucidated the molecular mechanism of the diversification of pheromone recognition systems.


Assuntos
Mariposas , Receptores de Feromônios , Animais , Masculino , Receptores de Feromônios/genética , Receptores de Feromônios/metabolismo , Simulação de Acoplamento Molecular , Feromônios/genética , Feromônios/metabolismo , Mariposas/genética , Mariposas/metabolismo
4.
Int J Legal Med ; 137(2): 511-518, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36418581

RESUMO

Forensic DNA analysis of semen-vaginal fluid mixed stains is essential and necessary in sexual assault cases. Here, we used a magnetic bead conjugated acrosin binding protein (ACRBP) antibody to separate and enrich sperm cells from mixed stains. Previously, western blotting indicated that ACRBP was specifically expressed in sperm cells, but not in female blood and epithelial cells, while immunofluorescence data showed ACRBP was localized to the acrosome in sperm cells. In our study, sperm were separated from mixed samples at three sperm cell/female buccal epithelial cell ratios (103:103; 103:104; and 103:105) using a magnetic bead conjugated ACRBP antibody. Subsequently, 23 autosomal short tandem repeat (STR) loci were amplified using the Huaxia™ Platinum PCR Amplification System and genotyped using capillary electrophoresis. The genotyping success rate for STR loci was 90% when the sperm to female buccal epithelial cell ratio was > 1:100 in mixed samples. Our results suggest that the magnetic bead conjugated ACRBP antibody is effective for isolating sperm cells in sexual assault cases.


Assuntos
Corantes , Sêmen , Masculino , Humanos , Feminino , Corantes/metabolismo , Espermatozoides , Coloração e Rotulagem , Fenômenos Magnéticos , Impressões Digitais de DNA/métodos
5.
Diabetes Metab Res Rev ; 38(2): e3487, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34289224

RESUMO

AIMS: To prospectively examine the association between arthritis and type 2 diabetes (T2D) in the Chinese population and confirm this association through a comprehensive meta-analysis of cohort studies. METERIALS AND METHODS: Data were from the China Health and Retirement Longitudinal Study which was started in 2011-2013 and followed up in 2013-2014 and 2015-2016. Arthritis was defined as self-reported physician diagnosis at baseline, and incident T2D was determined by self-reported physician diagnosis, fasting blood glucose ≥7.0 mmol/L or glycosylated haemoglobin ≥6.5% during the follow-ups. Cox proportional hazards regression models were used to assess the association between arthritis and risk for T2D. A meta-analysis was conducted to pool our effect estimate and those from other cohort studies using a random-effects model. RESULTS: Eleven thousand four hundred and eight participants (47.9% men; mean age: 59.3 years) were included in final analyses. During a 4-year follow-up, 981 participants reported incident T2D. Compared with individuals without arthritis, those with arthritis at baseline had an 18% higher risk for incident T2D (multivariable-adjusted hazard ratio: 1.18; 95% confidence interval: 1.04, 1.34). In the meta-analysis of 13 cohort studies including ours, a total of 2,473,514 participants were included with 121,851 incident diabetes. The pooling HR was 1.32 (95% CI: 1.21, 1.44) for the association between arthritis and diabetes. CONCLUSION: Arthritis was associated with an increased risk of incident diabetes in Chinese adults, and the positive association was confirmed in the meta-analysis of cohort studies. Our work can inform clinical trials to assess the effectiveness of arthritis treatments in reducing risk of diabetes.


Assuntos
Artrite , Diabetes Mellitus Tipo 2 , Adulto , Artrite/complicações , Artrite/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco
6.
J Clin Lab Anal ; 36(7): e24502, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35642882

RESUMO

BACKGROUND: Endometrial stromal tumours are uncommon tumours of the uterus. They mainly occur in perimenopausal women. Tumours with typical clinicopathological features do not usually pose diagnostic problems. However, rare clinicopathological features can occur, and clinicians without significant experience may have difficulty diagnosing these tumours and managing these patients. METHODS: Herein, we report a case of endometrial stromal sarcoma that occurred in a 25-year-old woman. The pathological features, immunophenotype, treatment and prognosis were discussed. RESULTS: The tumour revealed morphological heterogeneity, and there were similar proliferative-type endometrial stromal cells, an extensive amount of mature adipose tissue, and prominent rhabdomyoblastic and smooth muscle cells. Histopathological and immunohistochemical studies confirmed low-grade endometrial stromal sarcoma with smooth muscle, adipocytic and rhabdomyoblastic differentiation (approximately 60% were differentiated tissues). The final treatment of the tumour was total abdominal hysterectomy with bilateral salpingo-oophorectomy. There was no evidence of recurrence for 109 months postoperatively. CONCLUSIONS: We found that low-grade endometrial stromal tumours with extensive adipocytic and prominent rhabdomyoblastic differentiation are misdiagnosed because they are infrequent. They must be differentiated from rhabdomyosarcoma with accurate identification of adipocytes, and long-term follow-up is needed.


Assuntos
Neoplasias do Endométrio , Tumores do Estroma Endometrial , Sarcoma do Estroma Endometrial , Adulto , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/cirurgia , Tumores do Estroma Endometrial/diagnóstico , Tumores do Estroma Endometrial/patologia , Tumores do Estroma Endometrial/cirurgia , Feminino , Humanos , Prognóstico , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/patologia , Sarcoma do Estroma Endometrial/cirurgia
7.
Int J Mol Sci ; 23(11)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35682919

RESUMO

Sugarcane (Saccharum officinarum L.) is one of the world's highly significant commercial crops. The amounts of synthetic nitrogen (N2) fertilizer required to grow the sugarcane plant at its initial growth stages are higher, which increases the production costs and adverse environmental consequences globally. To combat this issue, sustainable environmental and economic concerns among researchers are necessary. The endophytic diazotrophs can offer significant amounts of nitrogen to crops through the biological nitrogen fixation mediated nif gene. The nifH gene is the most extensively utilized molecular marker in nature for studying N2 fixing microbiomes. The present research intended to determine the existence of novel endophytic diazotrophs through culturable and unculturable bacterial communities (EDBCs). The EDBCs of different tissues (root, stem, and leaf) of five sugarcane cultivars (Saccharum officinarum L. cv. Badila, S. barberi Jesw.cv Pansahi, S. robustum, S. spontaneum, and S. sinense Roxb.cv Uba) were isolated and molecularly characterized to evaluate N2 fixation ability. The diversity of EDBCs was observed based on nifH gene Illumina MiSeq sequencing and a culturable approach. In this study, 319766 operational taxonomic units (OTUs) were identified from 15 samples. The minimum number of OTUs was recorded in leaf tissues of S. robustum and maximum reads in root tissues of S. spontaneum. These data were assessed to ascertain the structure, diversity, abundance, and relationship between the microbial community. A total of 40 bacterial families with 58 genera were detected in different sugarcane species. Bacterial communities exhibited substantially different alpha and beta diversity. In total, 16 out of 20 genera showed potent N2-fixation in sugarcane and other crops. According to principal component analysis (PCA) and hierarchical clustering (Bray-Curtis dis) evaluation of OTUs, bacterial microbiomes associated with root tissues differed significantly from stem and leaf tissues of sugarcane. Significant differences often were observed in EDBCs among the sugarcane tissues. We tracked and validated the plethora of individual phylum strains and assessed their nitrogenase activity with a culture-dependent technique. The current work illustrated the significant and novel results of many uncharted endophytic microbial communities in different tissues of sugarcane species, which provides an experimental system to evaluate the biological nitrogen fixation (BNF) mechanism in sugarcane. The novel endophytic microbial communities with N2-fixation ability play a remarkable and promising role in sustainable agriculture production.


Assuntos
Microbiota , Saccharum , Bactérias/genética , Humanos , Nitrogênio , Fixação de Nitrogênio , Saccharum/genética
8.
Int J Mol Sci ; 23(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36430736

RESUMO

Sugarcane, a cash crop, is easily affected by low temperature, which results in a decrease in yield and sugar production. Breeding a new variety with cold tolerance is an essential strategy to reduce loss from cold stress. The identification of germplasms and genes/proteins with cold tolerance is a vital step in breeding sugarcane varieties with cold tolerance via a conventional program and molecular technology. In this study, the physiological and biochemical indices of 22 genotypes of S. spontaneum were measured, and the membership function analysis method was used to comprehensively evaluate the cold tolerance ability of these genotypes. The physiological and biochemical indices of these S. spontaneum genotypes showed a sophisticated response to low temperature. On the basis of the physiological and chemical indices, the genotypes were classified into different cold tolerance groups. Then, the high-tolerance genotype 1027 and the low-tolerance genotype 3217 were selected for DIA-based proteomic analysis by subjecting them to low temperature. From the four comparison groups, 1123, 1341, 751, and 1693 differentially abundant proteins (DAPs) were identified, respectively. The DAPs based on genotypes or treatments participated in distinct metabolic pathways. Through detailed analysis of the DAPs, some proteins related to protein homeostasis, carbohydrate and energy metabolism, amino acid transport and metabolism, signal transduction, and the cytoskeleton may be involved in sugarcane tolerance to cold stress. Furthermore, five important proteins related to cold tolerance were discovered for the first time in this study. This work not only provides the germplasms and candidate target proteins for breeding sugarcane varieties with cold tolerance via a conventional program and molecular breeding, but also helps to accelerate the determination of the molecular mechanism underlying cold tolerance in sugarcane.


Assuntos
Saccharum , Melhoramento Vegetal , Proteômica , Saccharum/metabolismo , Temperatura
9.
Langmuir ; 37(13): 4042-4048, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33754728

RESUMO

Understanding the influence of fine atmospheric particles (PM2.5) on cellular biophysical properties is an integral part for comprehending the mechanisms underlying PM2.5-induced diseases because they are closely related to the behaviors and functions of cells. However, hitherto little work has been done in this area. In the present work, we aimed to interrogate the influence of the PM2.5 water-soluble compound (PM2.5-WSC) on the biophysical performance of a human lung carcinoma epithelial cell line (A549) by exploring the cellular morphological and mechanical changes using atomic force microscopy (AFM)-based imaging and nanomechanics. AFM imaging showed that PM2.5-WSC treated cells exhibited evidently reduced lamellipodia and an increased height when compared to the control group. AFM nanomechanical measurements indicated that the treated cells had higher elastic energy and lower adhesion work than the control group. Our western blot assay and transmission electron microscopy (TEM) results revealed that after PM2.5-WSC treatment, the contents of cytoskeletal components (ß-actin and ß-tubulin) increased, but the abundance of cell surface microvilli decreased. The biophysical changes of PM2.5-WSC-treated cells measured by AFM can be well correlated to the alterations of the cytoskeleton and surface microvilli identified by the western blot assay and TEM imaging. The above findings confirm that the adverse risks of PM2.5 on cells can be reliably assessed biophysically by characterizing the cellular morphology and nanomechanics. The demonstrated technique can be used to diminish the gap of our understanding between PM2.5 and its harmful effects on cellular functions.


Assuntos
Citoesqueleto , Água , Células A549 , Humanos , Microscopia de Força Atômica , Material Particulado/toxicidade
10.
Biol Res ; 54(1): 19, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238380

RESUMO

In the era of climate change, due to increased incidences of a wide range of various environmental stresses, especially biotic and abiotic stresses around the globe, the performance of plants can be affected by these stresses. After oxygen, silicon (Si) is the second most abundant element in the earth's crust. It is not considered as an important element, but can be thought of as a multi-beneficial quasi-essential element for plants. This review on silicon presents an overview of the versatile role of this element in a variety of plants. Plants absorb silicon through roots from the rhizospheric soil in the form of silicic or monosilicic acid. Silicon plays a key metabolic function in living organisms due to its relative abundance in the atmosphere. Plants with higher content of silicon in shoot or root are very few prone to attack by pests, and exhibit increased stress resistance. However, the more remarkable impact of silicon is the decrease in the number of seed intensities/soil-borne and foliar diseases of major plant varieties that are infected by biotrophic, hemi-biotrophic and necrotrophic pathogens. The amelioration in disease symptoms are due to the effect of silicon on a some factors involved in providing host resistance namely, duration of incubation, size, shape and number of lesions. The formation of a mechanical barrier beneath the cuticle and in the cell walls by the polymerization of silicon was first proposed as to how this element decreases plant disease severity. The current understanding of how this element enhances resistance in plants subjected to biotic stress, the exact functions and mechanisms by which it modulates plant biology by potentiating the host defence mechanism needs to be studied using genomics, metabolomics and proteomics. The role of silicon in helping the plants in adaption to biotic stress has been discussed which will help to plan in a systematic way the development of more sustainable agriculture for food security and safety in the future.


Assuntos
Silício , Estresse Fisiológico , Agricultura , Plantas , Solo
11.
Biol Res ; 54(1): 15, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933166

RESUMO

BACKGROUND: Water stress is one of the serious abiotic stresses that negatively influences the growth, development and production of sugarcane in arid and semi-arid regions. However, silicon (Si) has been applied as an alleviation strategy subjected to environmental stresses. METHODS: In this experiment, Si was applied as soil irrigation in sugarcane plants to understand the mitigation effect of Si against harmful impact of water stress on photosynthetic leaf gas exchange. RESULTS: In the present study we primarily revealed the consequences of low soil moisture content, which affect overall plant performance of sugarcane significantly. Silicon application reduced the adverse effects of water stress by improving the net photosynthetic assimilation rate (Anet) 1.35-18.75%, stomatal conductance to water vapour (gs) 3.26-21.57% and rate of transpiration (E) 1.16-17.83%. The mathematical models developed from the proposed hypothesis explained the functional relationships between photosynthetic responses of Si application and water stress mitigation. CONCLUSIONS: Silicon application showed high ameliorative effects on photosynthetic responses of sugarcane to water stress and could be used for mitigating environmental stresses in other crops, too, in future.


Assuntos
Saccharum , Silício , Desidratação , Fotossíntese , Folhas de Planta , Água
12.
BMC Musculoskelet Disord ; 22(1): 185, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588805

RESUMO

BACKGROUND: The purpose of the study was to investigate whether pelvic incidence (PI) will affect the occurrence of PJK in Lenke 5 AIS patients after correction surgery and try to explore a better surgical scheme based on PI. METHODS: Lenke 5C AIS patients that underwent correction surgery with a minimum of a 2-year follow-up were identified. Demographic and radiographic data were collected preoperatively, postoperatively, and at the final follow-up. The comparison between the PJK and the Non-PJK group was conducted and the subgroup analysis was performed based on the preoperative value of PI to investigate the potential mechanism of PJK. Clinical assessments were performed using the Scoliosis Research Society (SRS)-22 questionnaire. RESULTS: The mean preoperative Cobb angle of the TL/L curve was 53.4°±8.6. At the final follow-up, the mean TL/L Cobb angle was drastically decreased to 7.3°±6.8 (P < 0.001). The incidence of PJK in Lenke 5 AIS was 18.6 %, 21.9 % (7/32) in the low PI group (PI < 45°) and 15.8 % (6/38) in the high PI group (PI ≥ 45°), and there was no statistical difference between the two groups (χ2 = 0.425, P = 0.514). For low PI patients, there is no significant difference where the UIV is located with regards to the TK apex between the PJK and Non-PJK subgroups (χ2 = 1.103, P = 0.401). For high PI patients, PJK was more likely to occur when UIV was cephalad to than caudal to the TK apex (31.25 % vs. 4.7 %, P = 0.038). There was no significant difference in the selection of LIV between the two groups. CONCLUSIONS: There is no difference in the incidence of PJK between the Lenke 5 AIS patients with low PI (< 45°) and high PI (≥45°), but the main risk factor of PJK should be different. For patients with low PI, overcorrection of LL should be strictly avoided during surgery. For patients with high PI, the selection of UIV should not be at or cephalad to the apex of thoracic kyphosis to retain more mobile thoracic segments.


Assuntos
Cifose , Escoliose , Fusão Vertebral , Humanos , Cifose/diagnóstico por imagem , Cifose/epidemiologia , Cifose/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Escoliose/diagnóstico por imagem , Escoliose/epidemiologia , Escoliose/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia
13.
BMC Plant Biol ; 20(1): 220, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32423383

RESUMO

BACKGROUND: Nitrogen is an essential element for sugarcane growth and development and is generally applied in the form of urea often much more than at recommended rates, causing serious soil degradation, particularly soil acidification, as well as groundwater and air pollution. In spite of the importance of nitrogen for plant growth, fewer reports are available to understand the application and biological role of N2 fixing bacteria to improve N2 nutrition in the sugarcane plant. RESULTS: In this study, a total of 350 different bacterial strains were isolated from rhizospheric soil samples of the sugarcane plants. Out of these, 22 isolates were selected based on plant growth promotion traits, biocontrol, and nitrogenase activity. The presence and activity of the nifH gene and the ability of nitrogen-fixation proved that all 22 selected strains have the ability to fix nitrogen. These strains were used to perform 16S rRNA and rpoB genes for their identification. The resulted amplicons were sequenced and phylogenetic analysis was constructed. Among the screened strains for nitrogen fixation, CY5 (Bacillus megaterium) and CA1 (Bacillus mycoides) were the most prominent. These two strains were examined for functional diversity using Biolog phenotyping, which confirmed the consumption of diverse carbon and nitrogen sources and tolerance to low pH and osmotic stress. The inoculated bacterial strains colonized the sugarcane rhizosphere successfully and were mostly located in root and leaf. The expression of the nifH gene in both sugarcane varieties (GT11 and GXB9) inoculated with CY5 and CA1 was confirmed. The gene expression studies showed enhanced expression of genes of various enzymes such as catalase, phenylalanine-ammonia-lyase, superoxide dismutase, chitinase and glucanase in bacterial-inoculated sugarcane plants. CONCLUSION: The results showed that a substantial number of Bacillus isolates have N-fixation and biocontrol property against two sugarcane pathogens Sporisorium scitamineum and Ceratocystis paradoxa. The increased activity of genes controlling free radical metabolism may at least in part accounts for the increased tolerance to pathogens. Nitrogen-fixation was confirmed in sugarcane inoculated with B. megaterium and B. mycoides strains using N-balance and 15N2 isotope dilution in different plant parts of sugarcane. This is the first report of Bacillus mycoides as a nitrogen-fixing rhizobacterium in sugarcane.


Assuntos
Interações entre Hospedeiro e Microrganismos , Microbiota , Fixação de Nitrogênio , Bactérias Fixadoras de Nitrogênio/metabolismo , Saccharum/crescimento & desenvolvimento , Interações Hospedeiro-Patógeno , Bactérias Fixadoras de Nitrogênio/classificação , Bactérias Fixadoras de Nitrogênio/isolamento & purificação , Rizoma/crescimento & desenvolvimento , Rizoma/microbiologia , Saccharum/microbiologia
14.
Phys Biol ; 18(1): 016002, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32906104

RESUMO

Toxic abnormal aggregation of α-synuclein (α-Syn) is a feature of Parkinson's disease. Several biochemical and biophysical studies have demonstrated that many post-translational modifications (PTM) of α-Syn could distinctly alleviate its oligomerization-mediated toxicity. Recently, a compelling link is emerging between the PTM O-GlcNAcylation (O-GlcNAc) and protein aggregation, yet the underlying molecular mechanism remains unclear. Based on the all-atom molecular dynamics simulations, we found that O-GlcNAc modifications can suppress the process of oligomerization of α-Syn aggregates via a steric effect-the additional O-linked glycosyl group disrupts the formation of hydrogen bonds (H-bonds) between α-Syn monomers. Besides, we proposed a theoretical model to further capture the physical mechanism of α-Syn aggregation/disaggregation in the absence/presence of O-GlcNAc-modified α-Syn. Our findings unveil the molecular mechanism of the O-GlcNAc-induced inhibition of α-Syn oligomerization, which may help to understand how O-GlcNAc prevents the oligomerization of other proteins and provides the guideline for the development of O-GlcNAc-based therapeutic strategies in neurodegenerative diseases.


Assuntos
Doenças Neurodegenerativas/tratamento farmacológico , Processamento de Proteína Pós-Traducional , alfa-Sinucleína/metabolismo , Acilação , Modelos Biológicos , Polimerização , Agregação Patológica de Proteínas/metabolismo , alfa-Sinucleína/química
15.
J Chem Phys ; 152(11): 114115, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32199430

RESUMO

All-atom molecular dynamics (MD) simulations of bio-macromolecules can yield relatively accurate results while suffering from the limitation of insufficient conformational sampling. On the other hand, the coarse-grained (CG) MD simulations efficiently accelerate conformational changes in biomolecules but lose atomistic details and accuracy. Here, we propose a novel multiscale simulation method called the adaptively driving multiscale simulation (ADMS)-it efficiently accelerates biomolecular dynamics by adaptively driving virtual CG atoms on the fly while maintaining the atomistic details and focusing on important conformations of the original system with irrelevant conformations rarely sampled. Herein, the "adaptive driving" is based on the short-time-averaging response of the system (i.e., an approximate free energy surface of the original system), without requiring the construction of the CG force field. We apply the ADMS to two peptides (deca-alanine and Ace-GGPGGG-Nme) and one small protein (HP35) as illustrations. The simulations show that the ADMS not only efficiently captures important conformational states of biomolecules and drives fast interstate transitions but also yields, although it might be in part, reliable protein folding pathways. Remarkably, a ∼100-ns explicit-solvent ADMS trajectory of HP35 with three CG atoms realizes folding and unfolding repeatedly and captures the important states comparable to those from a 398-µs standard all-atom MD simulation.


Assuntos
Substâncias Macromoleculares/química , Modelos Químicos , Peptídeos/química , Conformação Molecular , Simulação de Dinâmica Molecular , Conformação Proteica
16.
J Nutr ; 149(6): 989-995, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31070764

RESUMO

BACKGROUND: Litter size affects fetal development but its relation to diet-induced fatty liver later in life is unknown. OBJECTIVES: This aim of this study was to test the hypothesis that litter size influences postweaning fatty liver development in response to soybean oil-supplemented diet. METHODS: Weanling twin (TW) or triplet (TP) male lambs (n = 16) were fed a control diet or 2% soybean oil-supplemented diet (SO) for 90 d. Liver tissue morphology, biochemical parameters, and lipid metabolic enzymes were determined. Hepatic gene expression was analyzed by RNA sequencing (n = 3), followed by enrichment analysis according to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes involved in lipid metabolism were further verified by quantitative reverse transcriptase-polymerase chain reaction (n = 4). All data were analyzed by a 2-factor ANOVA, apart from differentially expressed genes, which were identified by the Benjamini-Hochberg approach (q value ≤0.05). RESULTS: SO increased liver triglyceride (by 55%) and nonesterified fatty acid (by 54%) concentrations in TPs (P ≤ 0.05) but not in TWs (P > 0.05). SO also induced a 2.3- and 2.1-fold increase in the liver steatosis score of TPs and TWs, respectively (P ≤ 0.05). Moreover, SO reduced the activity of lipolytic enzymes including hepatic lipase and total lipase in TPs by 47% and 25%, respectively (P ≤ 0.05). In contrast, activities of lipogenic enzymes, including malic enzyme and acetyl coenzyme A carboxylase, were significantly higher in TPs (P ≤ 0.05). Moreover, TPs had higher expression of lipogenic genes, such as FASN (by 45%) and APOB (by 72%), and lower expression of lipolytic genes, such as PRKAA2 (by 28%) and CPT1A (by 43%), compared with TWs (P ≤ 0.05). CONCLUSIONS: TPs have a gene expression profile that is more susceptible to SO-induced fatty liver than that of TWs, which indicates that insufficient maternal nutrient supply at fetal and neonatal stages may increase the risk of nonalcoholic fatty liver disease.


Assuntos
Suplementos Nutricionais/efeitos adversos , Tamanho da Ninhada de Vivíparos/fisiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Óleo de Soja/administração & dosagem , Óleo de Soja/efeitos adversos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Modelos Animais de Doenças , Feminino , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Masculino , Troca Materno-Fetal/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Carneiro Doméstico
18.
Sensors (Basel) ; 19(13)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252562

RESUMO

The geometric error motions of rotary stages greatly affect the accuracy of constructed machines such as machine tools, measuring instruments, and robots. In this paper, an embedded sensor system for real-time measurement of two radial and three angular error motions of a rotary stage is proposed, which makes use of a rotary encoder with multiple scanning heads to measure the rotational angle and two radial error motions and a miniature autocollimator to measure two tilt angular errors of the axis of rotation. The assembly errors of the grid disc of the encoder and the mirror for autocollimator are also evaluated and compensated. The developed measuring device can be fixed inside the rotary stage. In the experiments, radial error motions of two points on the axis (h = 5 mm and 60 mm) were measured and calibrated with LVDTs, and the data showed that the radial error motions of the axis were less than 20 µm, and the calibration residual errors were less than 2 µm. When intermittent external forces were applied to the stage, the change of the stage's error motion could also be monitored accurately.

19.
J Orthop Sci ; 24(1): 68-74, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30245090

RESUMO

BACKGROUND: Spinal tuberculosis accounts for more than 50% of bone tuberculosis cases. This study compared clinical, radiological and functional outcomes between anterior and posterior approaches for treatment of middle or lower thoracic spinal tuberculosis in elderly patients. METHODS: We retrospectively examined middle or lower thoracic spinal tuberculosis (T5-T12) in patients over 65 years. All procedures included debridement, decompression, autologous bone graft and fixation. Surgical procedure, surgical duration, estimated blood loss during surgery and laboratory results were recorded. Pleural effusion volume, thoracic cavity volume, Oswestry Disability Index score, neurological status, radiological parameters and complication rate were evaluated. RESULTS: No significant difference was found in surgical duration, blood loss, kyphosis angle correction, loss of correction, thoracic cavity volume, or complication rate between the two groups (P > 0.05). Average postoperative pleural effusion volumes were 605.9 ± 209.5 mL (377-1074 mL) and 262.9 ± 228.1 mL (0-702.4 mL) in the anterior and posterior groups, respectively (P = 0.004). Average hospitalization durations were 26.4 ± 10.5 days (17-53 days) and 19.2 ± 5.0 days (14-30 days) (P = 0.04). Average postoperative serum albumin levels were 24.19 ± 3.84 g/L (19-29.5 g/L) and 28.24 ± 2.52 g/L (24.4-31.6 g/L) (P = 0.01). No relapse or reinfection was observed in either group at the final follow-up. Surgical revision was not required in either group. CONCLUSIONS: Both anterior and posterior surgeries can be used to treat middle or lower thoracic spinal (T5-T12) tuberculosis in elderly patients. In general, the posterior approach might be superior, especially for patients with poor general health.


Assuntos
Desbridamento/métodos , Descompressão Cirúrgica/métodos , Fusão Vertebral/métodos , Vértebras Torácicas , Tuberculose da Coluna Vertebral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Parafusos Ósseos , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Tuberculose da Coluna Vertebral/diagnóstico
20.
Cancer Sci ; 109(6): 1799-1810, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29660200

RESUMO

The odd-skipped related 1 (OSR1) gene encodes a zinc-finger transcription factor. The expression and significance of OSR1 in human tumors remains unclear. We found that OSR1 was downregulated in lung cancers, and its expression was correlated with poor differentiation. Overexpression of OSR1 by OSR1 gene transfection into H1299 cells (H1299-OSR1) inhibited the proliferation and invasion of lung cancer cells. Knockdown of OSR1 with small interfering (si)RNA against OSR1 in A549 cells (A549-siOSR1) enhanced the proliferation and invasion of lung cancer cells. Western blot analysis showed that the expression level of GSK3ß increased, while that of p-GSK3ß, nuclear ß-catenin, cyclin D1, c-Myc and matrix metallopeptidase 7 significantly decreased in the H1299-OSR1 cells, and this pattern was reversed in the A549-siOSR1 cells compared to that in the control cells. Furthermore, upregulation of sex-determining region Y-box 9 (SOX9) by SOX9 gene transfection increased the expression of ß-catenin, which was inhibited by OSR1. The mRNA and protein expression levels of SOX9 and ß-catenin were reduced in H1299-OSR1 cells and increased in A549-siOSR1 cells. In conclusion, the expression of OSR1 was more reduced in lung cancer tissues than in normal lung tissues, and was correlated with poor differentiation. OSR1 downregulated the activity of the Wnt signaling pathway by suppressing the expression of SOX9 and ß-catenin.


Assuntos
Proliferação de Células/genética , Neoplasias Pulmonares/genética , Proteínas Serina-Treonina Quinases/genética , Fatores de Transcrição SOX9/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Células A549 , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA , Fatores de Transcrição SOX9/metabolismo , beta Catenina/metabolismo
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