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Sugarcane, a vital cash crop, contributes significantly to the world's sugar supply and raw materials for biofuel production, playing a significant role in the global sugar industry. However, sustainable productivity is severely hampered by biotic and abiotic stressors. Genetic engineering has been used to transfer useful genes into sugarcane plants to improve desirable traits and has emerged as a basic and applied research method to maintain growth and productivity under different adverse environmental conditions. However, the use of transgenic approaches remains contentious and requires rigorous experimental methods to address biosafety challenges. Clustered regularly interspaced short palindromic repeat (CRISPR) mediated genome editing technology is growing rapidly and may revolutionize sugarcane production. This review aims to explore innovative genetic engineering techniques and their successful application in developing sugarcane cultivars with enhanced resistance to biotic and abiotic stresses to produce superior sugarcane cultivars.
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BACKGROUND: Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk. METHODS: A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique. RESULTS: Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37-0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16-0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35-0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42-0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05-1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P < 0.05). CONCLUSION: The rs9625066 polymorphism of MIAT might be associated with IS susceptibility in Chinese population, in which AA/CA plays a protective role in IS, whereas the CC genotype increases the risk of developing IS, suggesting it might be a marker predictive of IS risk.
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AVC Isquêmico , Infarto do Miocárdio , RNA Longo não Codificante , Acidente Vascular Cerebral , Humanos , Biomarcadores , Predisposição Genética para Doença , AVC Isquêmico/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Acidente Vascular Cerebral/genéticaRESUMO
Background: Ischemic stroke (IS) represents a major cause of morbidity and mortality across the globe. The aberrant expression of miR-365 has been found to be implicated in a wide array of human diseases, including atherosclerosis and cancer. Studies on single-nucleotide polymorphisms (SNPs) in miRNA genes can help gain insight into the susceptibility to the condition. This study aimed to examine the relationship between miR-365 SNPs and the risk of IS. Methods: The study recruited 215 IS patients and 220 controls. The SNPscans genotyping was employed to genotype three polymorphic loci (rs121224, rs30230, and rs178553) of miR-365. The relative expression of miR-365 in peripheral blood mononuclear cells of the patients and controls was determined by using real-time quantitative PCR. Results: The miR-365 rs30230 polymorphism exhibited a significant association with the risk of developing IS (TC vs. CC: adjusted OR = 0.55, 95% CI: 0.33-0.92, P = 0.022; TT vs. CC: adjusted OR = 0.34, 95% CI: 0.14-0.85, P = 0.021; TC +TT vs. CC: adjusted OR = 0.51, 95% CI: 0.31-0.83, P = 0.007; T vs. C: adjusted OR = 0.57, 95% CI: 0.39-0.83, P = 0.004). Haplotype analysis revealed that the C-T-G haplotype was associated with a decreased risk of IS (OR = 0.68, 95% CI: 0.46-1.00, P = 0.047). Furthermore, miR-365 expression was significantly higher in IS patients than in controls (P < 0.001). Interestingly, patients with rs30230 TC or TT genotypes had lower miR-365 levels compared to their counterparts with CC genotypes (P < 0.001). Conclusions: The miR-365 rs30230 polymorphism might bear an association with IS susceptibility in the Chinese population, and the rs30230 TC/TT genotype might be a protective factor against IS.
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BACKGROUND: Situs inversus totalis (SIT) is a rare condition in which the positions of abdominal and thoracic organs present a "mirror image" of the normal ones in the median sagittal plane. Although minimally invasive surgery has evolved to achieve laparoscopic gastrectomy for gastric cancer (GC) patients with SIT, it is difficult to perform lymphadenectomy (LND) in such a transposed anatomical condition. Herein, we report the cases of two patients with SIT who successfully underwent laparoscopy-assisted gastrectomy (LAG) with D2 LND. CASE SUMMARY: Case 1: A 65-year-old man was admitted for intermittent abdominal pain and distension, occasional belching, and acid reflux for 4 mo. He was diagnosed with GC (cT3N1-2M0) with SIT. Before surgery, he had undergone four cycles of neoadjuvant chemotherapy and immunotherapy. Then, the patient was evaluated as having a partial response, and laparoscopy-assisted distal gastrectomy with D2 LND and Billroth II reconstruction were performed. The operation was performed successfully within 240 min with an estimated blood loss of 50 mL and no severe complications. The patient was discharged on postoperative day (POD) 9. Case 2: A 55-year-old man was admitted for upper abdominal distension with pain and discomfort after eating for 3 mo. He was diagnosed with GC (cT3N1M0) with SIT. He had a history of hypertension for more than 10 years; however, his blood pressure was well-controlled via regular medication. We performed laparoscopy-assisted total gastrectomy with D2 LND and Roux-en-Y reconstruction. The operation was performed successfully within 168 min with an estimated blood loss of 50 mL and no severe complications. The patient was discharged on POD 10. CONCLUSION: LAG with D2 LND could be considered an accessible, safe, and curative procedure for advanced GC patients with SIT.
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BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging. CASE SUMMARY: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen. The patient had no history of hepatitis, did not drink alcohol, and had no family history of cancer. Abdominal contrast-enhanced computed tomography (CT) revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm, with blood supplied by the left inferior phrenic artery. The patient underwent laparoscopic surgery, and HCC was identified by postoperative pathology. Additionally, specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC. The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery. Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis. CONCLUSION: This asymptomatic ectopic HCC case described achieved an excellent result due to early detection, radical resection, and systematic surveillance.
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Highly efficient sulfate reduction coupled to autotrophic denitrification plus nitrification is demonstrated by integrating an anaerobic membrane bioreactor (AnMBR) with a membrane aerated biofilm reactor (MABR). Concurrent chemical oxygen demand (COD) removal and sulfate reduction were accomplished in the AnMBR, while simultaneous nitrification and autotrophic denitrification were carried out in the MABR. Separate operation of the MABR achieved >90% total nitrogen (TN) removal when the N/S ratio was controlled at 0.4 gN/gS. The integrated AnMBR-MABR system efficiently resisted influent variability, realizing >95% COD removal in the AnMBR and >75% TN removal in the MABR when the influent COD/N ratio was above 4 gCOD/gN. Membrane fouling did not happen during â¼170 days of operation. Due to sulfide oxidation, a large amount of elemental sulfur (S0) accumulated in the MABR biofilm, where it served as an electron donor for denitrification. Microbial community analysis indicated that Nitrospira and Thiobacillus played key roles in nitrification and sulfide-driven denitrification, respectively, and that they occurred in different layers of the biofilm. This novel process offers advantages of a small land-area footprint, modular operation, and high efficiency electron-donor and oxygen utilizations, particularly for wastewater with a low COD/N ratio.
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Nitrificação , Águas Residuárias , Desnitrificação , Nitrogênio , Biofilmes , Reatores Biológicos , SulfatosRESUMO
BACKGROUND: The miR-208 gene is one of the microRNAs now under active studies, and has been found to play significant roles in an array of cardiovascular diseases. Nevertheless, until now, no studies have examined the relationship between the susceptibility to ischemic stroke (IS) and genetic variations in miR-208. This study explored the association between the miR-208 polymorphisms (rs178642, rs8022522, and rs12894524) and the risk of IS. METHODS: A total of 205 cases of IS and 211 control subjects were included. The SNPscans genotyping test was employed to determine the genotypes of the three polymorphisms. RESULTS: Significant correlation was observed between rs8022522 polymorphism and risk of IS on the basis of analyses of genotypes, models and alleles (GA vs. GG: adjusted OR = 2.159, 95% CI: 1.052-4.430, P = 0. 036; AA vs. GG: adjusted OR = 5.154, 95% CI: 1.123-23.660, P = 0.035; dominant model: adjusted OR = 1.746, 95% CI, 1.075-2.838, P = 0.025; G vs. A: adjusted OR = 2.451, 95% CI: 1.374-4.370, P = 0.002). CONCLUSIONS: The rs8022522 polymorphism of the miR-208 gene is significantly associated with an elevated risk of ischemic stroke in Chinese.
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AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , MicroRNAs/genéticaRESUMO
In this work, the bioelectrochemical system (BES) is a feasible alternative for successfully degrading typical refractory emerging contaminant triclosan (TCS). A single-chamber BES reactor with an initial TCS concentration of 1 mg/L, an applied voltage of 0.8 V, and a solution buffered with 50 mM PBS degraded 81.4 ± 0.2% of TCS, exhibiting TCS degradation efficiency improvement to 90.6 ± 0.2% with a biocathode formed from a reversed bioanode. Both bioanode and biocathode were able to degrade TCS with comparable efficiencies of 80.8 ± 4.9% and 87.3 ± 0.4%, respectively. Dechlorination and hydrolysis were proposed as the TCS degradation pathway in the cathode chamber, and another hydroxylation pathway was exclusive in the anode chamber. Microbial community structure analysis indicated Propionibacteriaceae was the predominant member in all electrode biofilms, and the exoelectrogen Geobacter was enriched in anode biofilms. This study comprehensively revealed the feasibility of operating BES technology for TCS degradation.
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Triclosan , EletrodosRESUMO
BACKGROUND: The impact of host skin microbiome on horizontal transmission of tick-borne pathogens , and of pathogen associated transstadial and transovarial changes in tick microbiome are largely unknown, but are important to control increasingly emerging tick-borne diseases worldwide. METHODS: Focusing on a rickettsiosis pathogen, Rickettsia raoultii, we used R. raoultii-positive and R. raoultii-negative Dermacentor spp. tick colonies to study the involvement of skin microbiota in cutaneous infection with rickettsiae in laboratory mice, and the function of the tick microbiome on maintenance of rickettsiae through all tick developmental stages (eggs, larvae, nymphs, adults) over two generations. RESULTS: We observed changes in the skin bacteria community, such as Chlamydia, not only associated with rickettsial colonization but also with tick feeding on skin. The diversity of skin microbiome differed between paired tick-bitten and un-bitten sites. For vertical transmission, significant differences in the tick microbiota between pathogenic rickettsia-positive and -negative tick chorts was observed across all developmental stages at least over two generations, which appeared to be a common pattern not only for R. raoultii but also for another pathogenic species, Candidatus Rickettsia tarasevichiae. More importantly, bacterial differences were complemented by functional shifts primed for genetic information processing during blood feeding. Specifically, the differences in tick microbiome gene repertoire between pathogenic Rickettsia-positive and -negative progenies were enriched in pathways associated with metabolism and hormone signals during vertical transmission. CONCLUSIONS: We demonstrate that host skin microbiome might be a new factor determining the transmission of rickettsial pathogens through ticks. While pathogenic rickettsiae infect vertebrate hosts during blood-feeding by the tick, they may also manipulate the maturation of the tick through changing the functional potential of its microbiota over the tick's life stages. The findings here might spur the development of new-generation control methods for ticks and tick-borne pathogens. Video Abstract.
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Ixodidae , Infecções por Rickettsia , Doenças Transmitidas por Carrapatos , Carrapatos , Animais , Camundongos , Ixodidae/microbiologia , Infecções por Rickettsia/microbiologia , Doenças Transmitidas por Carrapatos/microbiologia , Larva/microbiologiaRESUMO
Introduction: Ticks are the most important obligate blood-feeding vectors of human pathogens. With the advance of high-throughput sequencing, more and more bacterial community and virome in tick has been reported, which seems to pose a great threat to people. Methods: A total of 14 skin specimens collected from tick-bite patients with mild to severe symptoms were analyzed through meta-transcriptomic sequencings. Results: Four bacteria genera were both detected in the skins and ticks, including Pseudomonas, Acinetobacter, Corynebacterium and Propionibacterium, and three tick-associated viruses, Jingmen tick virus (JMTV), Bole tick virus 4 (BLTV4) and Deer tick mononegavirales-like virus (DTMV) were identified in the skin samples. Except of known pathogens such as pathogenic rickettsia, Coxiella burnetii and JMTV, we suggest Roseomonas cervicalis and BLTV4 as potential new agents amplified in the skins and then disseminated into the blood. As early as 1 day after a tick-bite, these pathogens can transmit to skins and at most four ones can co-infect in skins. Discussion: Advances in sequencing technologies have revealed that the diversity of tick microbiome and virome goes far beyond our previous understanding. This report not only identifies three new potential pathogens in humans but also shows that the skin barrier is vital in preventing horizontal transmissions of tick-associated bacteria or virus communities to the host. It is the first research on patients' skin infectome after a tick bite and demonstrates that more attention should be paid to the cutaneous response to prevent tick-borne illness.
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Coxiella burnetii , Rickettsia , Picadas de Carrapatos , Doenças Transmitidas por Carrapatos , Carrapatos , Vírus , Animais , Humanos , Carrapatos/microbiologia , Pele , Vírus/genéticaRESUMO
PURPOSE: To investigate the differences between dominant and nondominant eyes in femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) with 50% angle kappa compensation on diopter and visual quality. SETTING: University hospital. DESIGN: Retrospective clinical study. METHODS: 109 patients (218 eyes, 100%) with myopia who underwent FS-LASIK were randomly selected. The preoperative pupil size, center position, and offset between the coaxially sighted corneal light reflex ( P-Dist ) of the patients was recorded. In preoperative and postoperative 6 months, an iTrace wavefront aberrometer was used to measure the corneal, internal optics, and total aberrations. RESULTS: The 6 months postoperatively for corneal coma of the dominant eyes were 0.141 ± 0.055 µm and the nondominant eyes were 0.157 ± 0.033 µm, which was significantly greater than the dominant eyes ( P = .028). The postoperative corneal coma aberration changes were positively correlated with preoperative P-Dist , the dominant eyes ( r = 0.221, P = .023), and the nondominant eyes ( r = 0.251, P = .009). CONCLUSIONS: Adjusting the angle kappa percentage in the nondominant eyes to be higher than that of the dominant eyes in individualized corneal refractive surgery may help find the ablation center closest to the visual axis.
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Aberrações de Frente de Onda da Córnea , Ceratomileuse Assistida por Excimer Laser In Situ , Humanos , Acuidade Visual , Estudos Retrospectivos , Coma , Refração Ocular , Lasers de Excimer/uso terapêuticoRESUMO
Typically, airway remodeling caused by migration and proliferation of airway smooth muscle cells (ASMCs) plays a crucial role in the pathophysiological characteristics of asthma development. Cystatin 1 (CST1), a protein-coding gene referred to as Cystatin SN, is highly expressed in asthma patients. However, the role of CST1 and related molecular mechanisms in the development of asthma remains to be explored. This study aims to investigate the role of CST1 in asthma progression and present related molecular mechanisms. To explore these aspects, human ASMCs with platelet-derived growth factor BB (PDGF-BB) are initially stimulated and applied as a cellular model of asthma. Further, CST1 is knocked down with small interfering ribose nucleic acid (siRNA) overexpressed with plasmids. Then, 5-ethynyl-2'-deoxyuridine (EdU) and Cell Count Kit (CCK)-8 assays are applied to assess the cell proliferation rates. Further, Transwell and Western blot analyses for migration of cells and expression of MMP1 and MMP9 proteins are assessed, respectively. Under PDGF-BB stimulation, human ASMCs showed an increased CST1 expression, enhanced proliferation, and migration abilities, as well as up-regulated PI3K/AKT signaling pathway. Further, knockdown or overexpression of CST1 presented the declined or enhanced proliferation, migration, and up-regulation of the PI3K/AKT signaling pathway of human ASMCs. Inhibiting PI3K/AKT signaling pathway displayed the reduced migration and proliferation of human ASMCs. In summary, these findings indicated that CST1 played an essential role in the progression of asthma by activating the PI3K/AKT signaling pathway and promoting the migration and proliferation abilities of human ASMCs treated with PDGF-BB.
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Asma , Proteínas Proto-Oncogênicas c-akt , Humanos , Becaplermina/farmacologia , Becaplermina/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Cistatinas Salivares/metabolismo , Proliferação de Células , Células Cultivadas , Transdução de Sinais , Asma/genética , Asma/metabolismo , Miócitos de Músculo Liso/metabolismo , Movimento CelularRESUMO
RATIONALE: Central retinal artery occlusion (CRAO) sparing the cilioretinal artery (CLRA) with severe subretinal fluid and non-characteristic cherry-red spot is uncommon. In the present case, the patient received an intravitreal injection of anti- vascular endothelial growth factor, which is very rare. PATIENT CONCERNS: A 59-year-old man underwent vitrectomy of the left eye for diabetic retinopathy and vitreous hemorrhage. Six months after the operation, the patient presented with sudden painless visual-acuity decline in his left eye and was diagnosed with CRAO; his best corrected visual acuity was weak light perception. Whole retinal edema was seen on the fundus, and macular gray retinal opacification was present without a characteristic cherry-red spot. Optical coherence tomography revealed subretinal fluid (SRF) in the papillomacular bundle and inner retinal thickening. Fundus fluorescein angiography confirmed that the central retinal artery was not filled at 40 seconds and that the CLRA supplied a part of the macular area. Eight months after the second intravitreal injection of ranibizumab, Optical coherence tomography showed a significant reduction in inner retinal hyperreflectivity and the thickness of the nasal macular retina. The SRF was clearly absorbed, and the visual acuity improved to 1.1 logMAR units. DIAGNOSIS: Atypical CRAO. INTERVENTIONS: The patient was treated with intravitreal injection of anti-VEGF in his left eye. The thickness of the nasal macular retina decreased. OUTCOMES: The SRF was clearly absorbed, and the patient's visual acuity significantly improved. LESSONS: When CRAO occurs in patients with diabetic retinopathy sparing the CLRA, the non-characteristic cherry-red spot may be due to macular inner retinal edema, SRF and other factors. According to the patient's condition, anti-vascular endothelial growth factor can be administered as appropriate to inhibit choroidal neovascularization, reduce SRF in the macular retina, and save some vision.
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Retinopatia Diabética , Edema Macular , Papiledema , Oclusão da Artéria Retiniana , Masculino , Humanos , Pessoa de Meia-Idade , Líquido Sub-Retiniano , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Papiledema/complicações , Oclusão da Artéria Retiniana/etiologia , Artérias Ciliares , Inibidores da Angiogênese/uso terapêutico , Edema Macular/etiologia , Edema Macular/complicações , Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Anticorpos Monoclonais/uso terapêuticoRESUMO
Background: Estimating the growth of pulmonary sub-solid nodules (SSNs) is crucial to the successful management of them during follow-up periods. The purpose of this study is to (1) investigate the measurement sensitivity of diameter, volume, and mass of SSNs for identifying growth and (2) seek to establish a deep learning-based model to predict the growth of SSNs. Methods: A total of 2,523 patients underwent at least 2-year examination records retrospectively collected with sub-solid nodules. A total of 2,358 patients with 3,120 SSNs from the NLST dataset were randomly divided into training and validation sets. Patients from the Yibicom Health Management Center and Guangdong Provincial People's Hospital were collected as an external test set (165 patients with 213 SSN). Trained models based on LUNA16 and Lndb19 datasets were employed to automatically obtain the diameter, volume, and mass of SSNs. Then, the increase rate in measurements between cancer and non-cancer groups was studied to evaluate the most appropriate way to identify growth-associated lung cancer. Further, according to the selected measurement, all SSNs were classified into two groups: growth and non-growth. Based on the data, the deep learning-based model (SiamModel) and radiomics model were developed and verified. Results: The double time of diameter, volume, and mass were 711 vs. 963 days (P = 0.20), 552 vs. 621 days (P = 0.04) and 488 vs. 623 days (P< 0.001) in the cancer and non-cancer groups, respectively. Our proposed SiamModel performed better than the radiomics model in both the NLST validation set and external test set, with an AUC of 0.858 (95% CI 0.786-0.921) and 0.760 (95% CI 0.646-0.857) in the validation set and 0.862 (95% CI 0.789-0.927) and 0.681 (95% CI 0.506-0.841) in the external test set, respectively. Furthermore, our SiamModel could use the data from first-time CT to predict the growth of SSNs, with an AUC of 0.855 (95% CI 0.793-0.908) in the NLST validation set and 0.821 (95% CI 0.725-0.904) in the external test set. Conclusion: Mass increase rate can reflect more sensitively the growth of SSNs associated with lung cancer than diameter and volume increase rates. A deep learning-based model has a great potential to predict the growth of SSNs.
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Background: Jingmen tick virus (JMTV) has attracted great attention due to its potential pathogenicity in humans and its transmission by ticks. Dermacentor silvarum (D. silvarum) is one of the dominant tick species in northeastern China, and can transmit many pathogens to humans and animals. However, there have been no report of transmission of JMTV by D. silvarum. Materials and Methods: Ticks were collected from vegetation at the Aershan Port in Inner Mongolia in April 2019. And we do attempt to infect D. silvarum with JMTV by the immersion technique in laboratory conditions. The transmission of JMTV was examined by reverse transcriptase PCR, fluorescence in situ hybridization, and indirect immunofluorescence assay. Statistical analysis was performed using SPSS 24.0. Results: We found that JMTV may only be maintained in the tick without replication, and could not be transmitted to a host following transstadial transmission. Moreover, no virus colonization was found in the midgut or salivary glands of unfed D. silvarum; therefore, D. silvarum may not be susceptible to JMTV infection and therefore unlikely to carry and transmit JMTV. Conclusion: Our study has to some extent filled the knowledge gap regarding the possibility of JMTV transmission by a medically important tick vector, D. silvarum.
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Dermacentor , Animais , China/epidemiologia , Dermacentor/genética , Vetores de Doenças , Humanos , Hibridização in Situ Fluorescente/veterináriaRESUMO
A novel near-infrared fluorescent probe SWJT-5 based on dicyanoisophorone was synthesized. It achieved the rapid (within 40 s) and discriminative detection of Cys over Hcy and GSH with a large Stokes shift (205 nm). It showed high selectivity and sensitivity for Cys, and had an obvious enhancement of fluorescence emission. The detection limit was 0.43 µM. This probe also had low background interference and little damage to biological samples. Therefore, SWJT-5 had been applied to bioimaging in living cells successfully.
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Cicloexanonas , Cisteína , Corantes Fluorescentes , Animais , Glutationa , Homocisteína , Camundongos , Imagem Óptica/métodosRESUMO
BACKGROUND: Mitophagy protects against cerebral ischemia/reperfusion (CI/R)-induced neuronal apoptosis via mitochondrial clearance. Although taurine-upregulated gene 1 (lncRNA TUG1) has been proposed to be involved in the neuronal apoptosis evoked by CI/R, its specific role in mitophagy during the progression of CI/R injury remains unknown. METHODS: The CI/R rat model was established using middle cerebral artery occlusion/reperfusion (MCAO/R). Human neuroblastoma cell line SH-SY5Y was subjected to oxygen-glucose deprivation and reoxygenation (OGD/R). Ubiquitination assay, co-immunoprecipitation assay, RNA pull-down, and RNA immunoprecipitation were used to determine the interplay among TUG1, sirtuin 1 (SIRT1), and F-box and WD repeat domain-containing 7 (FBXW7). RESULTS: The upregulation of the TUG1 level and downregulation of the mitophagy were observed in both MCAO/R-treated rats and OGD/R-treated cells. The administration of si-TUG1 (a siRNA directed against TUG1) potentiated mitophagy and suppressed neuronal apoptosis in OGD/R-treated cells. However, the neuroprotective effect of si-TUG1 was reversed by mitophagy inhibitor or SIRT1 knockdown in vitro. Functionally, TUG1 enhanced FBXW7-mediated SIRT1 ubiquitination by upregulating FBXW7 expression. The overexpression of FBXW7 abrogated the si-TUG1-reinforced mitophagy by decreasing SIRT1 expression, thus aggravating neuronal apoptosis in the OGD/R+si-TUG1-treated cells. In rats with MCAO/R, the interference of TUG1 clearly decreased neuronal apoptosis, lessened the infarct volume, and relieved the neurological deficits. CONCLUSION: TUG1 knockdown promotes SIRT1-induced mitophagy by suppressing FBXW7-mediated SIRT1 degradation, thus relieving the neuronal apoptosis induced by CI/R injury. LncRNA TUG1 promotes neuronal apoptosis through inhibition of mitophagy. TUG1 decreased SIRT1 expression by promoting FBXW7-mediated SIRT1 ubiquitination. FBXW7/SIRT1 axis mediated the effect of TUG1 on OGD/R-induced neuronal apoptosis by regulating mitophagy.
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Isquemia Encefálica , MicroRNAs , Neuroblastoma , RNA Longo não Codificante , Traumatismo por Reperfusão , Humanos , Ratos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Mitofagia , Proteína 7 com Repetições F-Box-WD/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Isquemia Encefálica/genética , Apoptose/genética , Glucose/metabolismo , MicroRNAs/genéticaRESUMO
Ticks and tick-borne rickettsial diseases have been gaining greater attention in China over the past decade. However, most published studies to date have occurred in Northern China, with limited investigations occurring in China's southern provinces. As part of larger surveillance efforts, a cross-sectional survey was conducted in six sites at Guangdong, Guangxi and Yunnan investigating rickettsial infection in ticks. A total of 581 ticks were collected from hosts and screened via PCR, targeting rrs, gltA, ompB, sca4, and ompA gene fragments. Two of 12 Haemaphysalis formosensis ticks were infected with novel Rickettsia strain GD01, which was closest phylogenetically (97.3-98.9 % identity) to Rickettsia tamurae strain AT-1, but not within the same clade. Another detected strain (GD02) shared similar identity, 99-100 % across four gene targets, to recently detected Candidatus Rickettsia longicornii isolate ROK-HL727, with an overall prevalence of 12.5 % (71/569). The presence of such pathogens calls for increased public health attention and active surveillance in patients reporting recent tick bites.
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Genes Bacterianos , Rickettsia/isolamento & purificação , Carrapatos/microbiologia , Animais , China , Estudos Transversais , Filogenia , Rickettsia/classificação , Rickettsia/genéticaRESUMO
A dicyanoisophorone/acrylate-combined probe (DDP) was synthesized and designed as a near-infrared (NIR) fluorescent sensor for the rapid identification of Cys over Hcy and GSH in aqueous solution with a large Stokes shift (143 nm). The detection limit of Cys was 1.23 µM, which was lower than that of the intracellular Cys concentration. DDP was cell membrane-permeable and had been successfully applied to the detection of intracellular Cys in HeLa cells. The detection mechanism was determined by 1H NMR titration, MS and DFT calculations.