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1.
J Exp Bot ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32147696

RESUMO

Heavy metal contamination is a major environmental and human health hazard in many areas of the world. Organic acids sequester heavy metals and protect plant roots from the effects of toxicity; however, it is largely unknown how these acids are regulated in response to heavy metal stress. Here, protein kinase MdSOS2L1 from apple was functionally characterized. MdSOS2L1 was found to involve in the regulation of malate excretion, and inhibit cadmium uptake into roots. Using the DUAL membrane system in a screen of an apple cDNA library with MdSOS2L1 as a bait, a malate transporter, MdALMT14, was identified as an interactor. Bimolecular fluorescence complementation, pull-down and co-immunoprecipitation assays further indicated the interaction of the two proteins. Transgenic analyses showed that MdSOS2L1 is required for cadmium-induced phosphorylation at the Ser358 site of MdALMT14; a modification that enhanced the stability of the MdALMT14 protein. MdSOS2L1 was also shown to enhance cadmium tolerance in an MdALMT14-dependent manner. This study sheds light on the roles of the MdSOS2L1-MdALMT14 complex in physiological responses to cadmium toxicity.

2.
Cell Death Dis ; 11(3): 181, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32165613

RESUMO

Fatty acids are the most major substrate source for adult cardiac energy generation. Prohibitin 2 (PHB2), a highly conserved protein located in mitochondrial inner membrane, plays key roles in cellular energy metabolic homeostasis. However, its functions in regulating cardiac fatty acid metabolism have remained largely unknown. Our study demonstrates that cardiac-specific knockout of Phb2 leads to accumulation of lipid droplets and causes heart failure. Mechanistically, ablation of PHB2 impairs cardiac fatty acid oxidation (FAO) through downregulating carnitine palmitoyltransferase1b (CPT1b), a rate-limiting enzyme of cardiac mitochondrial FAO. Moreover, overexpression of CPT1b alleviates impaired FAO in PHB2-deficient cardiomyocytes. Thus, our study provides direct evidence for the link between PHB2 and cardiac fatty acid metabolism. Our study points out that PHB2 is a potential FAO regulator in cardiac mitochondrial inner membrane, as well as the connection between PHB2 and CPT1b and their relationships to cardiac pathology especially to cardiac fatty acid metabolic disorder.

3.
Food Funct ; 11(2): 1754-1763, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32043502

RESUMO

Carvacryl acetate (CA) is a semisynthetic monoterpenic ester obtained from essential oils, and it exerts an antioxidation effect. The purpose of our study was to investigate whether CA could provide neuroprotection against oxidative stress caused by cerebral ischemia-reperfusion injury (CIRI) and elucidate the underlying mechanism. Middle cerebral artery occlusion (MCAO)-induced damage was established in Sprague Dawley (SD) rats and PC12 cells were exposed to hydrogen peroxide (H2O2) to imitate oxidative stress damage. TTC, HE and Nissl staining were used to observe the pathological morphology of lesions. The contents of ROS and MDA, and the activity of SOD were measured to reflect the level of oxidative stress. In addition, the TUNEL method was used to assess injuries in vitro, and the expression of Nrf2 was determined by immunohistochemical staining and western blot analysis. Importantly, we constructed and validated Nrf2 knockdown PC12 cells to confirm the key role of Nrf2 in the neuroprotective effect of CA against oxidative stress injuries. CA alleviated CIRI in rats with MCAO, as shown by brain tissue pathophysiology. The contents of ROS and MDA were reduced, and the SOD activity was augmented by the simultaneous promotion of Nrf2 expression. In addition, the H2O2-induced injury in Nrf2-knockdown PC12 cells was more serious than it was in control cells, and CA-mediated neuroprotection was exclusively inhibited by the knock down of Nrf2 in PC12 cells. In conclusion, it is shown here that CA has the effect of relieving cerebral ischemia reperfusion-induced oxidative stress injury via the Nrf2 signalling pathway.

4.
World J Surg Oncol ; 18(1): 4, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901243

RESUMO

BACKGROUND: The purpose of this meta-analysis is to compare the safety and efficacy of en bloc transurethral resection of bladder tumor (EBRT) versus conventional transurethral resection of bladder tumor (CTURBT). METHODS: We performed a meta-analysis of relevant articles through November 2019 using PubMed, Embase, and Cochrane Central Register to compare the safety and efficacy of EBRT versus CTURBT. The main endpoint included the operation time (OT), hospitalization time (HT), catheterization time (AT), perioperative period complications, bladder detrusor muscle found in the specimen, the residual tumor on the base, the ratio of the same site recurrence, and 12/24/36-month recurrence rate. Cochrane Collaboration's Revman software, version 5.3, was used for statistical analysis. RESULTS: A total of 19 studies with 2651 patients were included, 1369 underwent EBRT and 1282 underwent CTURBT. Patients treated with EBRT had a significantly lower AT, HT, obturator nerve reflex, bladder perforation, bladder irritation, postoperative complications, and 24-month recurrence rate than those who underwent CTURBT. While no significant difference was found in terms of OT, the ratio of bladder detrusor muscle found in the specimen, the residual tumor on the base, 12-month recurrence rate, 36-month recurrence rate, and the ratio of the same site recurrence. In mitomycin subgroup, EBRT was superior to CTURBT in terms of 12/24-month recurrence rate. Similarly, in the prospective subgroup and retrospective subgroup, EBRT had a lower 24-month recurrence rate than CTURBT. However, no significant difference was found in the low, intermediate, and high-risk group in the light of 12-36-month recurrence rate. CONCLUSIONS: Based on the included 19 articles, EBRT had a significantly lower AT, HT, intraoperative and postoperative complications, and 24-month recurrence rate than those treated with CTURBT. Well-designed randomized controlled trials were needed to reevaluate these outcomes. TRIAL REGISTRATION: This meta-analysis was reported in agreement with the PRISMA statement and was registered on PROSPERO 2019 CRD42019121673.

5.
Chemosphere ; 243: 125331, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995863

RESUMO

The effects of reaction temperature, residence time, sulfuric acid and potassium hydroxide on the total concentration and speciation of N and P, potentially toxic elements (salts and metal elements) of pig manure during its hydrothermal carbonization (HTC) were investigated. Concentrations of Cl, K, Na and Mg in the hydrochars were much lower but total N, P and nitrate-nitrogen (NO3--N) contents were significantly higher than in untreated pig manure. The acid-extractable fractions of Cu and Zn in hydrochars were 0.03-0.63 and 0.17-0.66 times lower than those in pig manure and decreased significantly with increasing reaction temperature. The addition of sulfuric acid (H2SO4) or potassium hydroxide (KOH) in HTC reduced the contents of P, Ca, Mg, Cl and heavy metal elements (HMEs) in hydrochars, and the removal rates of Cu and Zn were up to 55% and 59%, respectively. Overall, the rapid treatment of pig manure by HTC reduced the harm of salts and HMEs, and effectively recovered the nutrients in pig manure. The HTC under alkaline conditions was desirable for optimizing the main elemental composition of the hydrochars.

6.
Acta Pharmacol Sin ; 41(1): 93-100, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31285534

RESUMO

PARK2, which encodes Parkin, is a disease-causing gene for both neurodegenerative disorders and cancer. Parkin can function as a neuroprotector that plays a crucial role in the regulation of mitophagy, and germline mutations in PARK2 are associated with Parkinson's disease (PD). Intriguingly, recent studies suggest that Parkin can also function as a tumor suppressor and that somatic and germline mutations in PARK2 are associated with various human cancers, including lung cancer. However, it is presently unknown how the tumor suppressor activity of Parkin is affected by these mutations and whether it is associated with mitophagy. Herein, we show that wild-type (WT) Parkin can rapidly translocate onto mitochondria following mitochondrial damage and that Parkin promotes mitophagic clearance of mitochondria in lung cancer cells. However, lung cancer-linked mutations inhibit the mitochondrial translocation and ubiquitin-associated activity of Parkin. Among all lung cancer-linked mutants that we tested, A46T Parkin failed to translocate onto mitochondria and could not recruit downstream mitophagic regulators, including optineurin (OPTN) and TFEB, whereas N254S and R275W Parkin displayed slower mitochondrial translocation than WT Parkin. Moreover, we found that deferiprone (DFP), an iron chelator that can induce mitophagy, greatly increased the death of A46T Parkin-expressing lung cancer cells. Taken together, our results reveal a novel mitophagic mechanism in lung cancer, suggesting that lung cancer-linked mutations in PARK2 are associated with impaired mitophagy and identifying DFP as a novel therapeutic agent for PARK2-linked lung cancer and possibly other types of cancers driven by mitophagic dysregulation.

7.
Clin Chim Acta ; 501: 66-71, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31756311

RESUMO

OBJECTIVE: To screen long non-coding RNA (lncRNA) related to glucokinase regulatory protein gene (GCKR), its differential expression was analyzed in patients with Type 2 diabetes mellitus (T2DM) and control samples. The correlation of lncRNA with GCKR was verified and its potential value as a molecular marker of T2DM was assessed. METHODS: Lymphocyte RNA was extracted from five patients with T2DM and five patients with non-T2DM. The expression profiles of circulating lncRNAs and mRNAs were obtained by microarray. Bioinformatics analysis was used to screen lncRNAs associated with the GCKR gene in 127 patients with T2DM and 130 patients with non-T2DM were selected. The expression levels of the GCKR gene and lncRNA (ENST00000588707.1 and TCONS_00004187) in the T2DM group and control group were verified by real-time PCR. Additionally, a correlation analysis was conducted. The value of circulating ENST00000588707.1 and TCONS_00004187 as biomarkers for the diagnosis of T2DM was performed by receiver operating characteristic curve analysis. RESULTS: We identified 68 lncRNAs and 74 mRNAs differentially expressed from the expression profile. Compared with the control group, the expression levels of the GCKR gene and lncRNA ENST00000588707.1 and TCONS_00004187 in the T2DM group were significantly lower (P < 0.05). The correlation analysis revealed that ENST00000588707.1 and TCONS_00004187 were correlated with GCKR gene expression and glycolipid metabolism (P < 0.05). ROC analysis showed that the area under the curve value of ENST00000588707.1 between T2DM patients and non-T2DM patients was 0.816 (95% CI: 0.764-0.869, sensitivity 72.0%, specificity 80.3%) and the AUC value of TCONS_00004187 was 0.826 (95% CI: 0.774-0.879, sensitivity 81.6%, specificity 61.3%). CONCLUSION: lncRNA ENST0000588707.1 and TCONS_00004187 could serve as potential biomarkers for T2DM, which could involve in glycolipid metabolism by regulating the GCKR gene.

8.
Brain Res ; 1727: 146569, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31783001

RESUMO

Ubiquitination and its reverse process, deubiquitination, play essential roles in neural development, function, and plasticity. A20, a ubiquitin editing enzyme that can remove K63-polyubiquitin chains from substrates and attach K48-polyubiquitin chains to them, is a critical component in the NF-κB signaling pathway in the immune system. This dual ubiquitin enzyme is also present in mammalian brains, but its potential role in neurons and synapses is unknown. We show that A20 in pyramidal neurons potently regulates dendritic arborization, spine morphogenesis, and synaptic transmission through an NF-κB-dependent mechanism. In cultured hippocampal neurons, overexpression of A20 reduced dendritic complexity and spine size and density, whereas A20 knockdown increased spine size and density, as well as clustering of the postsynaptic scaffold PSD-95 and glutamate receptor subunit GluA1. A20 effects in vitro were recapitulated in vivo where increasing or decreasing A20 expression in mouse brains reduced and enhanced spine density, respectively. Functionally, A20 knockdown significantly increased the amplitude, but not frequency of miniature excitatory postsynaptic currents, suggesting a role in postsynaptic efficacy. A20 negatively regulated NF-κB activation in neurons and A20 mutants deficient in either the deubiquitinase or the ubiquitin ligase activity failed to suppress NF-κB activation or reduce spine morphogenesis. Finally, selective inhibition of NF-κB abolished A20 knockdown-elicited spine formation, suggesting that A20 exerts its modulation on synapses through NF-κB signaling. Together, our study reveals a previously unknown role for A20, the only known ubiquitin editing enzyme with both deubiquitinase and ubiquitin ligase activity, in dendritic arborization, spine remodeling, and synaptic plasticity.

9.
Drug Des Devel Ther ; 13: 4021-4033, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819373

RESUMO

Aim: The aim of this study was to characterize curcumin (CUR)-loaded CD133 aptamer A15 liposomes for their antitumor activity in vitro and in vivo. Methods: The modified CUR liposomes were prepared by the thin-film hydration technique. Results: The particles showed spherical shape under electron microscopy with sizes <100 nm. Initial drug burst release was observed within 2 hrs and then the drug was continuously released over 48 hrs. No aggregation or precipitation of liposomes was observed during storage for 3 months. In vitro results showed that blank LPs had lower cellular cytotoxicity. Both liposomes of CUR (with or without A15 modified) exhibited a similar trend of cellular cytotoxicity at the same concentration. With the extension of incubation time, A15-CUR LPs showed a greater inhibitory effect on cells. Cell internalization in DU145 cells was higher for A15-CUR LPs than others. An in vivo study using DU145 prostate carcinoma bearing mice showed that A15-CUR LPs reduced tumor growth more than other forms of CUR. Conclusion: These results indicate that A15 modified CUR liposomes are a promising candidate for antitumor drug delivery.

10.
Nat Genet ; 51(12): 1691-1701, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31740836

RESUMO

In the mammalian genome, the clustered protocadherin (cPCDH) locus provides a paradigm for stochastic gene expression with the potential to generate a unique cPCDH combination in every neuron. Here we report a chromatin-based mechanism that emerges during the transition from the naive to the primed states of cell pluripotency and reduces, by orders of magnitude, the combinatorial potential in the human cPCDH locus. This mechanism selectively increases the frequency of stochastic selection of a small subset of cPCDH genes after neuronal differentiation in monolayers, 10-month-old cortical organoids and engrafted cells in the spinal cords of rats. Signs of these frequent selections can be observed in the brain throughout fetal development and disappear after birth, except in conditions of delayed maturation such as Down's syndrome. We therefore propose that a pattern of limited cPCDH-gene expression diversity is maintained while human neurons still retain fetal-like levels of maturation.


Assuntos
Caderinas/genética , Cromatina/genética , Síndrome de Down/patologia , Células-Tronco Pluripotentes Induzidas/citologia , Neurônios/fisiologia , Adulto , Animais , Astrócitos/citologia , Astrócitos/fisiologia , Encéfalo/citologia , Encéfalo/embriologia , Diferenciação Celular , Linhagem Celular , Síndrome de Down/genética , Regulação da Expressão Gênica , Histonas/genética , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Células-Tronco Pluripotentes Induzidas/transplante , Camundongos , Pessoa de Meia-Idade , Neurônios/citologia , Regiões Promotoras Genéticas , Ratos , Análise de Célula Única , Medula Espinal/citologia , Medula Espinal/transplante , Transplante Heterólogo
11.
J Med Chem ; 62(24): 11324-11334, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31765154

RESUMO

Diverse platinum drug candidates have been designed to improve inhibitory potency and overcome resistance for orthotopic tumors. However, the antimetastatic properties have rarely been reported. We herein report that homospermidineplatin (4a), a polyamine-Pt(IV) prodrug, can potently inhibit tumor growth in situ and reverse cisplatin resistance as expected, and more importantly, 4a displays remarkably elevated antimetastatic activity in vivo (65.7%), compared to those of cisplatin (27.0%) and oxaliplatin (19.6%). The underlying molecular mechanism indicates that in addition to targeting nuclear DNA, 4a can modulate polyamine metabolism and function in a manner different from that of cisplatin. By upregulating SSAT and PAO, 4a downregulates the concentrations of Put, Spd, and Spm, which favors the suppression of fast-growing tumor cells. Moreover, the p53/SSAT/ß-catenin and PAO/ROS/GSH/GSH-Px pathways are involved in the inhibition of 4a-induced tumor metastasis. Our study implies a promising strategy for the design of platinum drugs for the treatment of terminal cancer.

13.
Chin Med J (Engl) ; 132(19): 2362-2372, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31567373

RESUMO

OBJECTIVE: Premature ejaculation (PE) is regarded as one of the most common male sexual dysfunctions. This review introduced several pharmaceutical and surgical methods for the management of PE. The definition, etiology, behavioral, and psychological therapy of PE were also discussed. DATA SOURCES: "Premature," "ejaculation," or "sexual dysfuction" were used as the medical subject headings (MeSH) to obtain relevant articles before June 2019 on Pubmed, Google Scholar and CNKI. Most articles used were written in English and several Chinese articles were also cited. STUDY SELECTION: Full-text articles of retrospective/prospective/randomized controlled trials were analyzed. Animal experiments and letters were excluded. RESULTS: There are four PE sub-types: lifelong PE, acquired PE, natural variable PE, and subjective PE. Behavioral therapy, psychotherapy, medication, topical anesthetics, and surgery are currently used for the treatment of PE. However, all the above treatments have limitations. Therefore, novel ways should be investigated to more efficiently control PE. CONCLUSIONS: The pharmaceutical therapy that is currently being used in clinical practice for the management of PE is still the main choice globally due to its good efficacy. Surgery may be a choice for patients who are resistant to medication. However, it should be performed cautiously.

14.
Front Microbiol ; 10: 2135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572340

RESUMO

Tuberculosis is still a major threat to global public health. Here, a novel diagnosis assay, termed as multiple cross displacement amplification combined with nanoparticle-based lateral flow biosensor (MCDA-LFB), was developed to simultaneously detect IS6110 and IS1081 of Mycobacterium tuberculosis (MTB) in DNA extracted from reference strain H37Rv and clinical samples. The amplification can be finished within 30 min at a fixed temperature (67°C), thus the whole procedure, including rapid template preparation (15 min), isothermal reaction (30 min) and result reporting (2 min), can be completed within 50 min. The limit of detection of multiplex MCDA assay was 10 fg per reaction. By using the multiplex MCDA protocol, cross-reaction with non-mycobacteria and non-tuberculous mycobacteria (NTM) strains was not observed. Among clinically diagnosed TB patients, the sensitivity of liquid culture, Xpert MTB/RIF and multiplex MCDA assay was 42.0% (50/119), 49.6% (59/119), and 88.2% (105/119), respectively. Among culture positive samples, the sensitivity of Xpert MTB/RIF and multiplex MCDA assay was 86.0% (43/50) and 98.0% (49/50), respectively. Among culture negative samples, the sensitivity of Xpert MTB/RIF and multiplex MCDA assay was 23.2% (16/69) and 81.2% (56/69), respectively. The specificity was 100% (60/60) for Xpert MTB/RIF and 98.3% (59/60) for multiplex MCDA. Therefore, the multiplex MCDA assay for MTB detection is rapid, sensitive and easy to use and may be a promising test for early diagnosis of TB.

15.
J Cancer ; 10(21): 5114-5123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602264

RESUMO

Sinularin, a soft corals-derived natural product, exerts anti-tumorigenic activity in various types of human cancer cells. However, the action of Sinularin and its mechanism in renal carcinoma is not well understood. In the current study, we demonstrated that Sinularin inhibited the viability of human renal cancer cells 786-O and ACHN in a dose- and time-dependent manner, but did not show significant toxicity against non-malignant HRCEpic cells. Cell cycle analysis revealed that Sinularin induced G2/M arrest significantly. In addition, Sinularin could induce apoptosis in cells along with caspase-3/-9 activation, release of mitochondrial proteins, up-regulation of pro-apoptotic Bcl-2 family proteins and inhibition of anti-apoptotic Bcl-2 family proteins. Sinularin could also repress the activation of PI3K/Akt/mTOR signaling pathway. Moreover, Sinularin triggered the activation of MAPKs and p38 activation was essential for the anti-tumor effect of Sinularin. The generation of ROS (reactive oxygen species) was critical for Sinularin-induced apoptosis since ROS scavenger NAC (N-acetyl cysteine) could block the Sinularin-triggered apoptosis. In conclusion, all the results indicated that Sinularin may be applied as a therapeutic natural agent for human renal cancer.

16.
Blood Adv ; 3(15): 2342-2354, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31391167

RESUMO

Platelet activation requires fully functional mitochondria, which provide a vital energy source and control the life span of platelets. Previous reports have shown that both general autophagy and selective mitophagy are critical for platelet function. However, the underlying mechanisms remain incompletely understood. Here, we show that Nix, a previously characterized mitophagy receptor that plays a role in red blood cell maturation, also mediates mitophagy in platelets. Genetic ablation of Nix impairs mitochondrial quality, platelet activation, and FeCl3-induced carotid arterial thrombosis without affecting the expression of platelet glycoproteins (GPs) such as GPIb, GPVI, and αIIbß3 Metabolic analysis revealed decreased mitochondrial membrane potential, enhanced mitochondrial reactive oxygen species level, diminished oxygen consumption rate, and compromised adenosine triphosphate production in Nix -/- platelets. Transplantation of wild-type (WT) bone marrow cells or transfusion of WT platelets into Nix-deficient mice rescued defects in platelet function and thrombosis, suggesting a platelet-autonomous role (acting on platelets, but not other cells) of Nix in platelet activation. Interestingly, loss of Nix increases the life span of platelets in vivo, likely through preventing autophagic degradation of the mitochondrial protein Bcl-xL. Collectively, our findings reveal a novel mechanistic link between Nix-mediated mitophagy, platelet life span, and platelet physiopathology. Our work suggests that targeting platelet mitophagy Nix might provide new antithrombotic strategies.

17.
Front Genet ; 10: 615, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396257

RESUMO

Background: Leukoaraiosis (LA) is shown as white matter hyperintensities on T2-weighted magnetic resonance imaging brain scans. Together with candidate gene association studies (CGAS), multiple genome-wide association studies (GWAS) have reported large numbers of single nucleotide polymorphisms (SNPs) to be associated with LA in European populations. To date, no replication studies have been reported in independent Chinese samples. Methods: Here, we performed a candidate gene association study comprising 220 Chinese subjects with LA and 50 controls. Thirty-nine polymorphisms on 32 risk genes were selected from previous studies, and they were genotyped through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Genetic association analysis was firstly performed in all subjects with LA. Then, the same analysis was conducted in the six random sampling cohorts of 50 LA patients, respectively. Data analyses on the associations of SNPs with LA risk were evaluated through Pearson's χ2 and multivariate logistic regression tests. Results: We found that eight polymorphisms in six genes (PMF1, ICAM1, TRIM65, AGT, FBF1, and ACOX1) were significantly associated with LA in the genetic association tests. Except for those eight gene variants, 24 other polymorphisms were not found to be significantly associated with LA in general genetic model, dominant model, recessive model, or multiplicative model. Among those eight polymorphisms, rs2984613 in PMF1 showed significant association with LA in the cohort of 220 LA subjects, and such significant association remained in both general genetic model (OR: 0.262, 95% CI: 0.091-0.752, p adj = 0.030) and recessive model (OR: 0.323, 95% CI: 0.119-0.881, p adj = 0.038) when controlling for clinical variables. Seven other significant variants (rs5498 in ICAM1, rs699 in AGT, rs2305913 in FBF1, rs1135640 in ACOX1, and rs3760128, rs7214628, and rs7222757 in TRIM65) were identified in those six random sampling tests that were conducted in the adjusted cohorts of 50 LA patients. In addition, except for rs699 which showed detrimental effect and represented a risk variant for LA, seven other polymorphisms seemed to exert protective effects on LA and to reduce the risk of LA. It is necessary to confirm these associations in an independent cohort. Conclusions: This first replication study on multiple genes in an independent Chinese population did not replicate any risk polymorphisms for LA other than rs 699 in AGT but revealed the significantly negative associations of PMF1, ICAM1, TRIM65, FBF1, and ACOX1 polymorphisms with LA. It not only supported the strong ethnic differences in the genetics of LA but also indicated that those six identified genes may be involved in Chinese white matter lesions. Larger scales of CGAS and GWAS are necessary to confirm and decipher those ethnic-Han specific risk genes for LA in China.

18.
Cell Res ; 29(9): 754-766, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31366990

RESUMO

The impairment of mitochondrial bioenergetics, often coupled with exaggerated reactive oxygen species (ROS) production, is a fundamental disease mechanism in organs with a high demand for energy, including the heart. Building a more robust and safer cellular powerhouse holds the promise for protecting these organs in stressful conditions. Here, we demonstrate that NADH:ubiquinone oxidoreductase subunit AB1 (NDUFAB1), also known as mitochondrial acyl carrier protein, acts as a powerful cardio-protector by conferring greater capacity and efficiency of mitochondrial energy metabolism. In particular, NDUFAB1 not only serves as a complex I subunit, but also coordinates the assembly of respiratory complexes I, II, and III, and supercomplexes, through regulating iron-sulfur biosynthesis and complex I subunit stability. Cardiac-specific deletion of Ndufab1 in mice caused defective bioenergetics and elevated ROS levels, leading to progressive dilated cardiomyopathy and eventual heart failure and sudden death. Overexpression of Ndufab1 effectively enhanced mitochondrial bioenergetics while limiting ROS production and protected the heart against ischemia-reperfusion injury. Together, our findings identify that NDUFAB1 is a crucial regulator of mitochondrial energy and ROS metabolism through coordinating the assembly of respiratory complexes and supercomplexes, and thus provide a potential therapeutic target for the prevention and treatment of heart failure.

19.
Front Plant Sci ; 10: 964, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428110

RESUMO

Upland cotton (Gossypium hirsutum L.) is the most important source of natural fiber in the world. Early-maturity upland cotton varieties are commonly planted in China. Nevertheless, lint yield of early-maturity upland cotton varieties is strikingly lower than that of middle- and late-maturity ones. How to effectively improve lint yield of early maturing cotton, becomes a focus of cotton research. Here, based on 72,792 high-quality single nucleotide polymorphisms of 160 early-maturing upland cotton accessions, we performed genome-wide association studies (GWASs) for lint percentage (LP), one of the most lint-yield component traits, applying one single-locus method and six multi-locus methods. A total of 4 and 45 significant quantitative trait nucleotides (QTNs) were respectively identified to be associated with LP. Interestingly, in two of four planting environments, two of these QTNs (A02_74713290 and A02_75551547) were simultaneously detected via both one single-locus and three or more multi-locus GWAS methods. Among the 42 genes within a genomic region (A02: 74.31-75.95 Mbp) containing the above two peak QTNs, Gh_A02G1269, Gh_A02G1280, and Gh_A02G1295 had the highest expression levels in ovules during seed development from 20 to 25 days post anthesis, whereas Gh_A02G1278 was preferentially expressed in the fibers rather than other organs. These results imply that the four potential candidate genes might be closely related to cotton LP by regulating the proportion of seed weight and fiber yield. The QTNs and potential candidate genes for LP, identified in this study, provide valuable resource for cultivating novel cotton varieties with earliness and high lint yield in the future.

20.
Orthop Surg ; 11(4): 664-670, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31456324

RESUMO

OBJECTIVES: To review the experience at our center with elastic stable titanium flexible intramedullary nails (ESIN) for pediatric femoral shaft unstable fractures. METHODS: From January 2015 to January 2017, 56 consecutive patients with femur shaft fractures were treated in our hospital. History and radiologic parameters were retrospectively reviewed. The inclusion criteria were: femur shaft fractures treated by ESIN or locking compressing plates (LCP); more than 2 years' follow-up care; and complete clinical information. A total of 51 patients were included according to the criteria: 16 girls and 35 boys. Ages at operation averaged 5.9 ± 2.8 years. OUTCOME: anteroposterior (AP) and lateral X-ray radiographs were performed every 2 weeks before the fracture healing, every 3 months until 1 year, then once a year after the surgery. Clinical examinations were recorded for any clinical deformity, hardware prominence, pain, and infection. ESIN were applied in either a retrograde or an antegrade fashion for 29 patients. For 22 patients, LCP were implanted. For the remaining 5 cases, instruments other than ESIN and LCP were applied. RESULTS: The average follow-up time was 29 months (range, 24-37 months). The average operation time was 78.2 min (range, 25-155 mins). The average blood loss in surgery was 69.6 mL (range, 3-700 mL). The average healing of fracture time was 2.2 month (range, 1-6 months). The average removal of implants time was 7.8 months (range, 3-20 months). The average expense for index operation was CNY 31 100 (CNY 17 500-142 200). Comminution grades were strongly correlated with time to fracture union (P < 0.001, r = 0.53) and time to implant removal (P = 0.006, r = 0.38). For comminuted pattern, the operation time and blood loss during operation in LCP were significantly higher than those in ESIN (P = 0.037 and P = 0.006, respectively). Other clinical parameters were similar between the two groups. No clinically detectable LLD, rotational or angular deformity was found. All patients recovered full knee range of motion. In this series, 30 patients (59%) had complications; 26 minor complications (51%) did not require unplanned surgery, most of which were prominence of hardware; 4 patients (8%) had a major complication and underwent an unplanned surgery. Of these, 2 were refractures distal to primary fracture and 2 were intolerable prominence of ESIN. CONCLUSIONS: Elastic stable intramedullary nails provide equivalent outcomes but decreased operative time and blood loss during surgery, and lower hospitalization cost in treating low-grade comminuted femur shaft fracture compared with plating techniques. The results of this study support the use of ESIN over plates in low-grade comminuted femur shaft fractures despite the fact that both options are indicated.


Assuntos
Pinos Ortopédicos , Placas Ósseas , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas/instrumentação , Fraturas Cominutivas/cirurgia , Titânio , Perda Sanguínea Cirúrgica , Criança , Pré-Escolar , Feminino , Consolidação da Fratura , Humanos , Masculino , Duração da Cirurgia , Medição da Dor , Estudos Retrospectivos
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