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Mitochondrial biogenesis is the process of generating new mitochondria to maintain cellular homeostasis. Here, we report that viruses exploit mitochondrial biogenesis to antagonize innate antiviral immunity. We found that nuclear respiratory factor-1 (NRF1), a vital transcriptional factor involved in nuclear-mitochondrial interactions, is essential for RNA (VSV) or DNA (HSV-1) virus-induced mitochondrial biogenesis. NRF1 deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in mice. Mechanistically, the inhibition of NRF1-mediated mitochondrial biogenesis aggravated virus-induced mitochondrial damage, promoted the release of mitochondrial DNA (mtDNA), increased the production of mitochondrial reactive oxygen species (mtROS), and activated the innate immune response. Notably, virus-activated kinase TBK1 phosphorylated NRF1 at Ser318 and thereby triggered the inactivation of the NRF1-TFAM axis during HSV-1 infection. A knock-in (KI) strategy that mimicked TBK1-NRF1 signaling revealed that interrupting the TBK1-NRF1 connection ablated mtDNA release and thereby attenuated the HSV-1-induced innate antiviral response. Our study reveals a previously unidentified antiviral mechanism that utilizes a NRF1-mediated negative feedback loop to modulate mitochondrial biogenesis and antagonize innate immune response.
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Antivirais , Biogênese de Organelas , Animais , Camundongos , DNA Mitocondrial/genética , Imunidade Inata , Fator 1 Nuclear Respiratório/genéticaRESUMO
Ectopic lipid deposition and mitochondrial dysfunction are common etiologies of obesity and metabolic disorders. Excessive dietary uptake of saturated fatty acids (SFAs) causes mitochondrial dysfunction and metabolic disorders, while unsaturated fatty acids (UFAs) counterbalance these detrimental effects. It remains elusive how SFAs and UFAs differentially signal toward mitochondria for mitochondrial performance. We report here that saturated dietary fatty acids such as palmitic acid (PA), but not unsaturated oleic acid (OA), increase lysophosphatidylinositol (LPI) production to impact on the stability of the mitophagy receptor FUNDC1 and on mitochondrial quality. Mechanistically, PA shifts FUNDC1 from dimer to monomer via enhanced production of LPI. Monomeric FUNDC1 shows increased acetylation at K104 due to dissociation of HDAC3 and increased interaction with Tip60. Acetylated FUNDC1 can be further ubiquitinated by MARCH5 for proteasomal degradation. Conversely, OA antagonizes PA-induced accumulation of LPI, and FUNDC1 monomerization and degradation. A fructose-, palmitate-, and cholesterol-enriched (FPC) diet also affects FUNDC1 dimerization and promotes its degradation in a non-alcoholic steatohepatitis (NASH) mouse model. We thus uncover a signaling pathway that orchestrates lipid metabolism with mitochondrial quality.
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Ácidos Graxos , Mitofagia , Camundongos , Animais , Ácidos Graxos/metabolismo , Dimerização , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Membrana/metabolismoRESUMO
The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Criocirurgia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Criocirurgia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Idoso , Estudos Prospectivos , Adulto , Resultado do Tratamento , Falha de TratamentoRESUMO
Nonradiative recombination losses occurring at the interface pose a significant obstacle to achieve high-efficiency perovskite solar cells (PSCs), particularly in inverted PSCs. Passivating surface defects using molecules with different functional groups represents one of the key strategies for enhancing PSCs efficiency. However, a lack of insight into the passivation orientation of molecules on the surface is a challenge for rational molecular design. In this study, aminothiol hydrochlorides with different alkyl chains but identical electron-donating (-SH) and electron-withdrawing (-NH3 +) groups were employed to investigate the interplay between molecular structure, orientation, and interaction on perovskite surface. The 2-Aminoethane-1-thiol hydrochloride with shorter alkyl chains exhibited a preference of parallel orientations, which facilitating stronger interactions with the surface defects through strong coordination and hydrogen bonding. The resultant perovskite films following defect passivation demonstrate reduced ion migration, inhibition of nonradiative recombination, and more n-type characteristics for efficient electron transfer. Consequently, an impressive power conversion efficiency of 25 % was achieved, maintaining 95 % of its initial efficiency after 500â hours of continuous maximum power point tracking.
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The main obstacles to promoting the commercialization of perovskite solar cells (PSCs) include their record power conversion efficiency (PCE), which still remains below the Shockley-Queisser limit, and poor long-term stability, attributable to crystallographic defects in perovskite films and open-circuit voltage (Voc) loss in devices. In this study, potassium (4-tert-butoxycarbonylpiperazin-1-yl) methyl trifluoroborate (PTFBK) was employed as a multifunctional additive to target and modulate bulk perovskite defects and carrier dynamics of PSCs. Apart from simultaneously passivating anionic and cationic defects, PTFBK could also optimize the energy-level alignment of devices and weaken the interaction between carriers and longitudinal optical phonons, resulting in a carrier lifetime of greater than 3â µs. Furthermore, it inhibited non-radiative recombination and improved the crystallization capacity in the target perovskite film. Hence, the target rigid and flexible p-i-n PSCs yielded champion PCEs of 24.99 % and 23.48 %, respectively. More importantly, due to hydrogen bonding between formamidinium and fluorine, the target devices exhibited remarkable thermal, humidity, and operational tracking at maximum power point stabilities. The reduced Young's modulus and residual stress in the perovskite layer also provided excellent bending stability for flexible target devices.
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The quality of organic thin films critically influences carrier dynamics in organic semiconductors. In neat/doped films, even tiny voids can be penetrated by water or oxygen molecules to create charge-trap states called water/oxygen-induced traps that significantly hinder carrier mobility. While the water/oxygen-induced traps in non-doped films and crystalline states have been investigated comprehensively, there is a lack of thorough examination regarding their properties in the doped state. Therefore, there is a high demand for a molecular design strategy that effectively modulates the molecular stacking behavior in doped films and practical devices and enhances the quality of these films. Herein, we proposed a versatile molecular design principle that enables the formation of "nano-cluster" structures on both the surface and interior of doped films in target molecule 10-(4-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-1'-(4-fluorophenyl)-10H-spiro[acridine-9,9'-xanthene] (DspiroO-F-TRZ), which is modified with a fluorophenyl group. These "nano-cluster" structures exhibit more uniform shapes within doped films and effectively reduce defective state densities while enhancing carrier injection and transport properties, ultimately improving device performance. Notably, TADF-OLED based on DspiroO-F-TRZ demonstrates nearly twice as much efficiency as its control counterpart due to contributions from 'nano-cluster' structure enhancements toward improved electroluminescence performance.
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In single-atom catalysts (SACs), the complexity of the support anchoring sites creates a vast diversity of single-atom species with varied coordination environments. To date, the quantitative distribution of these diverse single-atom species in a given SAC has remained elusive. Recently, CeO2-supported metal SACs have been extensively studied by modulating their local environments via numerous synthetic strategies. However, owing to the absence of a quantitative description, unraveling the site-specific reactivity and regulating their transformation remain challenging. Here, we show that two distinct Pt/CeO2 SACs can be reversibly generated by oxidative and nonoxidative dispersions, which contain varied Pt1On-Ceδ+ single-atom species despite similar Pt charge states and coordination numbers. By means of Raman spectroscopy and computational studies, we semiquantitatively reveal the distribution of diverse Pt1On-Ceδ+ species in each specific SACs. Remarkably, the minority species of Pt1O4-Ce3+-Ov accounting for only 14.2% affords the highest site-specific reactivity for low-temperature CO oxidation among the other abundant counterparts, i.e., Pt1O4-Ce4+ and Pt1O6-Ce4+. The second nearest oxygen vacancy (Ov) not only acts synergistically with the nearby active metal sites to lower the reaction barrier but also facilitates the dynamic transformation from six-coordinated to four-coordinated sites during cyclic nonoxidative and oxidative dispersions. This work elucidates the quantitative distribution and dynamic transformation of varied single-atom species in a given SAC, offering a more intrinsic descriptor and quantitative measure to depict the inhomogeneity of SACs.
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MAIN CONCLUSION: We developed a more realistic modeling framework by integrating stem photosynthesis into the canopy carbon assimilation model to compare the photosynthetic productivity between the stem and leaf of Eucalyptus urophylla plantations. Stems of Eucalyptus species with smooth outer bark have photosynthetic green tissue that can recycle internal stem CO2. However, the potential contribution of stem photosynthesis to forest productivity has not previously been adequately quantified, and we also do not know how it compares to leaf photosynthetic productivity. To assist in addressing this knowledge gap, we conducted field surveys in Eucalyptus urophylla plantations of different ages and developed a more realistic modeling framework by integrating stem photosynthesis into the existing canopy carbon assimilation model. We calculated the proportion of tree stems shaded by neighboring tree trunks based on Poisson spatial point process. Under the stand density of 2000 trees per hectare, the light absorption area of tree trunks of 2-year-old and 7-year-old E. urophylla plantations were 0.11 (± 0.15) and 0.35 (± 0.12) m2 stem m-2 land, the stem photosynthetic productivity (GPPstem) was 0.72 (± 0.45) and 1.81 (± 1.12) mol C m-2 month-1, and the ratios of GPPstem to leaf photosynthetic productivity (GPPleaf) were 5.10 and 8.17% for 2- and 7-year-old plantations, respectively. Overall, this study presents the feasibility of incorporating stem photosynthesis into the productivity prediction of E. urophylla plantations by developing the stem light absorption model.
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Eucalyptus , Fotossíntese , Árvores , Folhas de Planta , CarbonoRESUMO
OBJECTIVES: To explore an optimal model to predict the response of patients with axillary lymph node (ALN) positive breast cancer to neoadjuvant chemotherapy (NAC) with machine learning using clinical and ultrasound-based radiomic features. METHODS: In this study, 1014 patients with ALN-positive breast cancer confirmed by histological examination and received preoperative NAC in the Affiliated Hospital of Qingdao University (QUH) and Qingdao Municipal Hospital (QMH) were included. Finally, 444 participants from QUH were divided into the training cohort (n = 310) and validation cohort (n = 134) based on the date of ultrasound examination. 81 participants from QMH were used to evaluate the external generalizability of our prediction models. A total of 1032 radiomic features of each ALN ultrasound image were extracted and used to establish the prediction models. The clinical model, radiomics model, and radiomics nomogram with clinical factors (RNWCF) were built. The performance of the models was assessed with respect to discrimination and clinical usefulness. RESULTS: Although the radiomics model did not show better predictive efficacy than the clinical model, the RNWCF showed favorable predictive efficacy in the training cohort (AUC, 0.855; 95% CI 0.817-0.893), the validation cohort (AUC, 0.882; 95% CI 0.834-0.928), and the external test cohort (AUC, 0.858; 95% CI 0.782-0.921) compared with the clinical factor model and radiomics model. CONCLUSIONS: The RNWCF, a noninvasive, preoperative prediction tool that incorporates a combination of clinical and radiomics features, showed favorable predictive efficacy for the response of node-positive breast cancer to NAC. Therefore, the RNWCF could serve as a potential noninvasive approach to assist personalized treatment strategies, guide ALN management, avoiding unnecessary ALND.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Terapia Neoadjuvante , Estudos Retrospectivos , Metástase Linfática/patologia , Aprendizado de MáquinaRESUMO
The adsorption of gaseous HCHO by raw lotus shell biochar carbonized at 500, 700, and 900 °C from the perspective of its internal crystal structure and surface functional groups was investigated by an integrated approach of experiments and density functional theory calculations. The results showed that lotus shell biochar carbonized at 700 °C had the best adsorption effect at a HCHO concentration of 10.50 ± 0.30 mg/m3, with an adsorption removal rate of 87.64%. The HCHO removal efficiency by lotus shell biochar carbonized at 500 and 900 °C was determined to be 80.96 and 83.07%, respectively. The HCHO adsorption on lotus shell biochar carbonized at 700 °C conformed to pseudo-second-order kinetics and was predominantly controlled by chemical adsorption. The Langmuir isotherm was the underlying mechanism for the monomolecular layer adsorption with a maximum adsorption capacity of 0.329 mg/g. The density functional theory calculations revealed that the adsorption of HCHO on the surface of CaCO3 and KCl in lotus shell biochar carbonized at 700 °C was a chemical adsorption process, with adsorption energies ranging from -64.375 to -87.554 kJ/mol. The strong interaction between HCHO and the surface was attributed to the electron transfer from HCHO to the surface, facilitated by metal atoms (Ca or K) and the oxygen atoms of HCHO. The carboxyl group on the surface of lotus shell biochar carbonized at 700 °C was identified as the key functional group responsible for HCHO adsorption. This study advanced our understanding of the environmental functions of inorganic crystals and surface functional groups in raw biochar and will enable the further development of biochar materials in environmental applications.
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PURPOSE: Studies have shown that gout can increase the risk of cardiovascular disease. Three-dimensional speckle-tracking echocardiography (3D-STE), a sensitive imaging technology, enables the detection of subtle myocardial dysfunctions. Our aim is to evaluate the left ventricular (LV) functions in patients with gout using 3D-STE. METHODS: 80 subjects: 40 with gout and 40 as normal controls were involved. We obtained and analyzed these parameters from the dynamic images of a 3D full-volume dataset: global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), Twist, 16-segmental time-to-peak longitudinal strain (TTP) and systolic dyssynchrony index (SDI)besides other relevant parameters. RESULTS: Compared with the normal group, gout patients were more likely to have left ventricular remodeling. The patients with gout showed decreased Em, increased E/Em and larger volume index of the left atrium (LAVI) indicating reduced diastolic function. The peak GLS (-17.42 ± 2.02 vs. -22.40 ± 2.57, P < 0.001), GCS (-27.04 ± 3.75 vs. -34.85 ± 4.99, P < 0.001), GRS (38.22 ± 4.28 vs. 46.15 ± 5.17, P < 0.001), and Twist (15.18 ± 5.45 vs. 19.02 ± 5.29, P = 0.015) were significantly lower in patients with gout than in healthy participants. The SDI (5.57 ± 1.46 vs. 4.91 ± 1.19, P = 0.016) was significantly increased in patients with gout compared with normal controls. There was no significant between-group difference in TTP (P = 0.43). The systolic GLS, GRS and GCS peak values increased gradually from the base to the apex, with the lowest values in the basal segment in patients with gout. Receiver-operating characteristic curve analysis revealed among these strains GLS has the largest area under the curve (AUC: 0.93, P < 0.001), the cutoff value of -18.97% with a sensitivity and specificity of 80.0% and 92.0%, respectively, for differentiating two groups. A multivariate linear regression analysis shows that the relationship between gout and strain parameters including GLS, GRS, and GCS is statistically significant (P < 0.001). CONCLUSION: Although patients with gout having a normal ejection fraction, structural remodeling of the left ventricle and subclinical LV deformation may occur. 3D-STE can detect subtle cardiac dysfunctions in patients with gout at an early stage.
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Ecocardiografia Tridimensional , Gota , Disfunção Ventricular Esquerda , Humanos , Ventrículos do Coração/diagnóstico por imagem , Ecocardiografia/métodos , Função Ventricular Esquerda , Gota/complicações , Gota/diagnóstico por imagem , Reprodutibilidade dos Testes , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
The wearable application of flexible organic solar cells (f-OSCs) necessitates high power conversion efficiency (PCE) and mechanical robustness. However, photoactive films based on efficient non-fullerene small molecule acceptors (NF-SMAs) are typically brittle, leading to poor mechanical stability in devices. In this study, we achieved a remarkable PCE of 18.06 % in f-OSCs while maintaining ultrahigh mechanical robustness (with a crack-onset strain (COS) of higher than 11 %) by incorporating a linker dimerized acceptor (DOY-TVT). Compared to binary blends, ternary systems exhibit reduced non-radiative recombination, suppressed crystallization and diffusion of NF-SMAs, and improved load distribution across the chain networks, enabling the dissipation of the load energy. Thus, the ternary f-OSCs developed in this study achieved, high PCE and stability, surpassing binary OSCs. Moreover, the developed f-OSCs retained 97 % of the initial PCE even after 3000 bending cycles, indicating excellent mechanical stability (9.1 % higher than binary systems). Furthermore, the rigid device with inverted structure based on the optimal active layer exhibited a substantial increase in efficiency retention, with 89.6 % after 865â h at 85 °C and 93 % after more than 1300â h of shelf storage at 25 °C. These findings highlight the potential of the linker oligomer acceptor for realizing high-performing f-OSCs with ultrahigh mechanical robustness.
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Despite the great progress of flexible perovskite solar cells (f-PSCs), it still faces several challenges during the homogeneous fabrication of high-quality perovskite thin films, and overcoming the insufficient exciton dissociation. To the ends, we rationally design the ferroelectric two-dimensional (2D) perovskite based on pyridine heterocyclic ring as the organic interlayer. We uncover that incorporation of the ferroelectric 2D material into 3D perovskite induces an increased built-in electric field (BEF), which enhances the exciton dissociation efficiency in the device. Moreover, the 2D seeds could assist the 3D crystallization by forming more homogeneous and highly-oriented perovskite crystals. As a result, an impressive power conversion efficiency (PCE) over 23 % has been achieved by the f-PSCs with outstanding ambient stability. Moreover, the piezo/ferroelectric 2D perovskite intrigues a decreased hole transport barriers at the ITO/perovskite interface under tensile stress, which opens new possibilities for developing highly-efficient f-PSCs.
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In the female reproductive tract, endometrial cancer is the most common malignant tumor. Recently, the specific functions of many miRNAs have been identified in endometrial cancer. However, the contradictory effects of microRNA-373 (miR-373) in different human cancers draw our attention. In the present research, upregulation of miR-373 was identified in endometrial cancer which predicted poor prognosis. Moreover, upregulation of miR-373 promoted the migration, invasion, and proliferation of endometrial cancer cells. To further confirm that results, the EMT and Wnt/ß-Catenin pathways were also investigated, which were promoted by overexpression of miR-373. Then, we further investigate the downstream factor, large tumor suppressor kinase 2 (LATS2) which was inhibited by miR-373. LATS2 was verified as a direct target gene of miR-373 through luciferase reporter assay. Especially, the facilitation of miR-373 for cell proliferation, migration and invasion was impaired by LATS2. Taken together, miR-373 promotes the progression of endometrial cancer through targeting LATS2 and promoting EMT and Wnt/ß-Catenin pathway.
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BACKGROUND The aim of this study was to determine whether poor collaterals contribute to the occurrence of certain types of cognitive disorders in asymptomatic middle cerebral artery stenosis (MCAS). MATERIAL AND METHODS Patients aged ≥45 years with asymptomatic MCAS confirmed by computed tomography angiography were included in a single-center retrospective study. They did not have prior stroke or dementia. Within 7 days of admission, MRI and comprehensive neuropsychological assessment were performed. Cognitive assessment was conducted after 2 years. Two independent neuroradiologists evaluated intracranial collaterals by using the Miteff scale. Demographic date and Fazekas scores were collected. RESULTS A total of 173 patients with asymptomatic MCAS (66% men, mean age 59.4 years) and 42 controls (45% men, mean age 61.4 years) were enrolled. Executive function, attention, and information-processing speed in poor collateral circulation patients were more frequently and more often impaired than those in good collateral circulation patients. Throughout the study period, patients with poor collateral circulation had worse executive function, attention, and information-processing speed than those with moderate collateral circulation. Over time, MCAS patients with good collateral circulation did not show an association with cognitive function. CONCLUSIONS MCAS patients with moderate and poor collateral circulation have impairment of ≥1 cognitive domain over time. The affected domains are consistent with the profile of vascular cognitive impairment. Good collateral circulation is more important in patients with MCAS, and is associated with less risk of cognitive disorders.
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Disfunção Cognitiva/fisiopatologia , Circulação Colateral/fisiologia , Infarto da Artéria Cerebral Média/fisiopatologia , Adulto , Idoso , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/complicações , Angiografia Cerebral/métodos , Circulação Cerebrovascular , Transtornos Cerebrovasculares , Cognição/fisiologia , Disfunção Cognitiva/complicações , Angiografia por Tomografia Computadorizada/métodos , Constrição Patológica/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/fisiopatologiaRESUMO
We studied mycobionts from advanced seedlings and adult mycorrhizal roots of the terrestrial orchid Arundina graminifolia. Fungi were isolated, identified by ITS sequencing, and tested for their impact on seed germination, protocorm formation, and development of advanced seedlings (emergence of first leaf) in vitro. Among the six fungal species isolated, four were not standard orchid mycorrhizal fungi (Fusarium solani, Cylindrocarpon sp., Acremonium sp., and Phlebiopsis flavidoalba) and did not support germination beyond imbibition and greening of the seeds during a span of 35 days. Over the same time, one Tulasnella species isolated from adult mycorrhiza allowed protocorm formation but not further development. However, another Tulasnella species isolated from advanced seedlings facilitated development to the advanced seedling stage. Our results support (i) the inability of occasional orchid root colonizers to support late seed germination, and (ii) the growing literature showing that fungal associates can change over orchid development. Functionally, we show that mycorrhizal taxa isolated from advanced seedlings can be more efficient than those from adults in supporting germination in some species, leading to recommendations for ex situ orchid conservation.
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Fungos/fisiologia , Micorrizas/fisiologia , Orchidaceae/microbiologia , Raízes de Plantas/microbiologia , Especificidade da EspécieRESUMO
CONTEXT: Cassia semen (Cs), a seed of Cassia obtusifolia L. (Leguminosae), is a popular functional beverage. Previous studies reported that Cs displayed antioxidant, antifungal and strong liver protective effects. OBJECTIVE: This study evaluates the hepatoprotective effects of Cs on non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Seventy-two male Wistar rats raised with high-fat diet (HFD) were randomly allotted into model, metformin (0.2 g/kg) and Cs (0.5, 1, and 2 g/kg)-treated groups. Another 12 rats were raised with normal feed as control group; all the rats were orally administrated with drugs and vehicle for 6 weeks. Alanine transferase (ALT), aspartate transaminase (AST), triglycerides (TG), total cholesterol (TC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and low density lipoprotein receptor (LDL-R) mRNA levels were measured at the end of the experiment. RESULTS: Twelve weeks of HFD administration significantly increased the levels of AST, ALT, TG, TC, TNF-α, IL-6, IL-8 and MDA, decreased SOD (199.42 vs. 137.70 U/mg protein) and GSH (9.76 vs. 4.55 mg/g protein) contents, compared to control group. Cs administration group significantly decreased the elevated biomarkers with the ED50 = 1.2 g/kg for NAFLD rats. Cs treatment also prevents the decreased expression of LDL-R mRNA, and improved the histopathological changes compared to model group. CONCLUSIONS: The hepatoprotective effect of Cs on NAFLD may possibly be due to its antioxidant effect. Cs may become a potent hepatoprotective agent in clinical therapy in the future.
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Cassia/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Metformina/farmacologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
Hyperbaric oxygen therapy (HBOT) is an efficient therapeutic option to improve progress of lots of diseases especially hypoxia-related injuries, and has been clinically established as a wide-used therapy for patients with carbon monoxide poisoning, decompression sickness, arterial gas embolism, problematic wound, and so on. In the liver, most studies positively evaluated HBOT as a potential therapeutic option for liver transplantation, acute liver injury, nonalcoholic steatohepatitis, fibrosis and cancer, especially for hepatic artery thrombosis. This might mainly attribute to the anti-oxidation and anti-inflammation of HBOT. However, some controversies are existed, possibly due to hyperbaric oxygen toxicity. This review summarizes the current understandings of the role of HBOT in liver diseases and hepatic regeneration. Future understanding of HBOT in clinical trials and its in-depth mechanisms may contribute to the development of this novel adjuvant strategy for clinical therapy of liver diseases.
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Oxigenoterapia Hiperbárica , Hepatopatias/terapia , Humanos , Regeneração HepáticaRESUMO
The radiation-induced damage to the human body is primarily caused by excessive reactive oxygen species (ROS) production after irradiation. Therefore, the removal of the increase of ROS caused by ionizing radiation (IR) has been the focus of research on radiation damage protective agents. Hypoxia inducible factor (HIF) is a transcription factor in human and plays an important role in regulating the body metabolism. Factor inhibiting HIF (FIH) is an endogenous inhibitor factor of HIF protein under normoxia conditions. It has been shown that the high expression of HIF protein has a certain repair effect on radiation-induced intestinal injury and hematopoietic system damage in mice; however, it is not clear about the effect of HIF on the level of ROS after radiation. In this study, the role of N-oxalyl-d-phenylalanine (NOFD), an FIH inhibitor, for its effect on alleviating ROS level is investigated in the cells. Our results indicate that pretreatment with NOFD can mitigate ROS level and alleviate IR-induced DNA damage and apoptosis in vitro. Therefore, HIF can be used as a target on scavengers. Furthermore, in order to explore the relevant mechanism, we also test the expression of relevant HIF downstream genes in the cells, finding that Notch-2 gene is more sensitive to NOFD treatment. This experiment result is used to support the subsequent mechanism experiments.
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Fenilalanina/farmacologia , Protetores contra Radiação/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Células Cultivadas , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Espaço Intracelular/metabolismo , Fenilalanina/análogos & derivados , Espécies Reativas de Oxigênio/metabolismoRESUMO
This study was intended to analyze effects of lncRNA CRNDE on cervical cancer cell growth and metastasis. Fifty pairs of cervical cancer tissues and corresponding adjacent tissues were collected. Expressions of long non-coding RNAs (lncRNAs) in tissue samples were detected by microarray analysis. Expression levels of CRNDE in cervical cancer cells and normal cells were detected by qRT-PCR. Cell-counting kit-8 (CCK-8) assay and clone formation assay were utilized to evaluate cell growth. Wound healing assay and Transwell assay were conducted to detect the migratory and invasive capability of cervical cancer cells. The expressions of CRNDE in cervical cancer tissues and cells were higher than those in normal tissues and cells. CCK-8 assay and clone formation assay showed that the knockdown of CRNDE could inhibit the cell proliferation of HeLa and C-33A cells. Wound healing assay indicated that the downregulation of CRNDE expression could suppress the cell migration. The result of a Transwell assay demonstrated that the number of invasion cells reduced in the CRNDE-si group in comparison with the Mock group. LncRNA CRNDE could promote the cell growth and stimulate the metastasis of cervical cancer cells.