Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 683
Filtrar
1.
Mol Med Rep ; 23(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33846788

RESUMO

Zinc­finger E­box­binding homeobox 1 (ZEB1) is involved in epithelial­mesenchymal transition. In the present study, the protective effect of ZEB1 on acute kidney injury (AKI) was explored. The cecal ligation and puncture (CLP) method was performed to establish the AKI model in rats. ZEB1 expression, blood urea nitrogen (BUN) and serum creatinine (SCr) levels, inflammation [interleukin (IL)­1ß, IL­6, and tumour necrosis factor­α], phosphorylated AMP­activated protein kinase (p­AMPK) and phosphorylated mammalian target of rapamycin (p­mTOR) expression, and histopathological changes in CLP­induced AKI rats were assessed. AMPK inhibitor dorsomorphin (DM) was intraperitoneally injected to determine the effect of ZEB1 on AKI and the regulatory mechanism involving the AMPK/mTOR pathway. CLP downregulated ZEB1 expression, increased BUN and SCr levels, promoted inflammation and apoptosis, and increased the acute kidney score in the kidney tissues of CLP­induced AKI rats. Autophagy and the AMPK/mTOR pathway were blocked in CLP­induced AKI rats. ZEB1 overexpression inhibited inflammation and apoptosis, reduced BUN and SCr levels, and activated autophagy and the AMPK/mTOR pathway in CLP­induced AKI rats. The protective effect of ZEB1 overexpression on AKI was reversed by DM. Thus, ZEB1 was revealed to alleviate CLP­induced AKI by activating autophagy and the AMPK/mTOR pathway.

2.
Acta Biomater ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33813092

RESUMO

Dental pulp is a highly vascularized tissue, situated in an inextensible environment surrounded by rigid dentinal walls. The pulp receives its blood supply solely from the small apical foramen of a tooth root. Due to the unique anatomy that controls nutrition supply, regeneration of pulp tissue in a full-length tooth root has long been a challenge in regenerative endodontics. In this study, we designed and synthesized a multifunctional peptide-conjugated, pH-sensitive, non-viral gene vector for fast revascularization and pulp regeneration in a full-length human tooth root. The multifunctional peptide was designed to have distinctive features, including a cell-penetrating peptide to enhance cellular uptake, a nuclear localization signal peptide to assist in the translocation of an angiogenic gene into the nucleus, and a fluorescent tryptophan residue to visualize and quantify the transfection efficiency. Furthermore, a pH-sensitive dimethylmaleic anhydride (DMA) was integrated with the multifunctional peptide to enhance the transfected gene complex to escape from endosomes/lysosomes after internalization. In vitro experiments showed that the multifunctional non-viral gene vector significantly increased internalization and gene transfection efficiency as well as reduced cytotoxicity. After dental pulp stem cells (DPSCs) were transfected with the multifunctional gene vector/pVEGF complexes, the expression of VEGF from the DPSCs was upregulated for more than eight folds, which in turn greatly enhanced endothelial cell migration and vascular-like tube formation. Six weeks after implantation, the VEGF-transfected DPSCs accelerated new blood vessel formation and the regenerated pulp tissue occupied most of the area in the canal of a full-length human tooth root. The multifunctional peptide conjugated non-viral gene delivery is a safe and effective approach for regenerative endodontics. STATEMENT OF SIGNIFICANCE: Pulp regeneration in a full-length tooth root canal has long been a challenge in regenerative endodontics. This is due to the unique root anatomy that allows the blood supply of the tooth root only from a small apical foramen (< 1 mm), leading to a severe barrier for revascularization during pulp regeneration. In this work, we designed a multifunctional peptide-conjugated, pH-sensitive, non-viral gene vector to address this challenge. Our work shows that the peptide-conjugated system was an excellent carrier for fast revascularization and pulp tissue regeneration in a full-length toot root. This study will interest the multidisciplinary readership in gene delivery, biomaterials, and dental/craniofacial tissue engineering community.

3.
Accid Anal Prev ; 154: 106091, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33740459

RESUMO

This study proposed a method for transportation agencies to efficiently and accurately formulate or revise rules for the movement of railway transport while ensuring safety under adverse conditions. Determining such a method in general requires trial-and-error experimentation, which consumes large amounts of time and money. We used the uniform experiment (UE) and generalized linear autoregression (GLAR) to establish our method. Based on it, a series of numerical models were proposed to examine the association between the operational indices of safety (derailment coefficient and rate of wheel unloading) and such factors as the type of wagon, cargo weight, partial loading (covering longitudinal and lateral offset), line condition, and operating speed. The models were used to determine the worst transportation conditions. The results of analysis showed the following: 1) the effect of the speed of operation on the safety indices followed a parabolic law, those of cargo weight and part loading followed a linear law, the type of wagon and line condition exhibited no clear regularity, and some of these factors have an interactive influence. 2) A combination of the UE and GLAR helped deal with the complex multivariate process using the fewest multilevel experiments to accurately determine the most adverse conditions for railway freight transportation. The proposed method provided reference schemes for governmental agencies to study and revise freight management regulations.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33787217

RESUMO

Moth-eye-mimicking nanoprotrusion arrays are typical bioinspired broadband antireflection patterns that improve the transmittance and visibility of optical devices by adjusting different geometrical parameters of nanostructures, such as diameter, height, shape, and periodic arrangement, and widely used in solar cells, electronic displays, and so on. Rapid, net-shape, less complicated, and low-cost fabrication of the glass-based moth-eye nanostructure array is a huge challenge. This work adopted the nanohole array template to transform the moth-eye nanostructures on the optical glass by hot embossing combined with ultrasonic-assisted demolding. To investigate the mode transition and filling behavior of the glass nanostructures when compressed into the nanoholes, we conducted a series of hot embossing tests with various processing parameters and characterized the geometrical morphology of the glass-based nanostructure array, such as height and shape. In these tests, surface defects such as nanocracks will occur when inappropriate processing parameters were applied and we evaluated the transmittance performance of defective and fine glass nanostructures and surface with no nanostructures to reveal the effect of nanostructures with different levels of quality on antireflection. This work provides an effective and environmental-friendly method for the fabrication of moth-eye nanostructure arrays with an improved antireflection performance.

5.
Chemistry ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33749905

RESUMO

A chiral N,N' -dioxide-nickel(II) complex-catalyzed asymmetric amination reaction of 3-bromo-3-substituted oxindoles with anilines was developed. A series of alkyl or aryl 3-amino-indolinones with quaternary stereocenters were obtained in high yields with excellent ee values in one step (up to 99% yield, up to 96% ee). The method provided a readily route to optically active intermediates of 3-amino-2-oxindole-based bioactive compounds. Besides, a possible transition state model was proposed to elucidate the origin of the chirality induction based on the X-ray crystal structure of the catalyst and the adduct.

6.
Zhongguo Gu Shang ; 34(3): 269-74, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33787174

RESUMO

OBJECTIVE: To compare the clinical outcomes of arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) with a tibialis anterior allograft (TAA)versus hamstring tendon autograft (HTA) after 10 years follow-up. METHODS: A clinical data of 107 patients who underwent arthroscopic ACLR with a single bundle tendon between March 2007 and March 2010 was retrospectively analyzed. Among the patients, 48 patients were reconstructed with a tibialis anterior allograft (TAA group), including 26 males and 22 females, ranging in age from 16 to 38 years, with a mean of 27.2±6.2 years;59 patients were reconstructed with a hamstring tendon autograft (HTA group), including 31 males and 28 females, ranging in age from 16 to 40 years, with a mean of 28.0±7.6 years. The preoperative tibial anterior displacement and knee joint function, as well as knee joint stability, tibial anterior displacement and knee joint function at 10 years after operation were observed. Lachman test was used to evaluate the forward joint stability and pivot shift test to evaluate the rotational stability of the knee;KT-2000 side-to-side difference (SSD) was used to measure tibial anterior displacement;International Knee Documentation Committee(IKDC) score and Lysholm score were used to evaluate knee function. RESULTS: The incisions of both groups were healed by first intention, and no early complications occurred after operation. All patients were followed-up 10 to 13 years, the mean time was 11.7 years. There was no graft failure were found during the follow up period. The KT-2000 SSD of the TAA group and the HTA group at ten years after operation were 1.9±0.7 and 1.8±0.6 respectively, which were significantly improved than 8.8±0.9 and 8.6±1.0 preoperatively(P<0.05), but there were no significant difference between the two groups(P>0.05). The total Lysholm score of the TAA group and the HTA group at ten years after operation were 90.4±4.4 and 90.7±3.4 respectively, which were significantly improved than 51.4±13.3 and 51.2±14.6 preoperatively(P<0.05), but there were no significant difference between the two groups(P>0.05). The total IKDC score of the TAA group and the HTA group at ten years after operation were 91.5±4.1 and 90.9±3.2 respectively, which were significantly improved than 45.8±12.2 and 47.0±14.5 preoperatively(P<0.05), but there were no significant difference between the two groups(P>0.05). No significant difference were found between the two groups in Lachman test and pivot shift test at 10 years after operation (P>0.05). CONCLUSION: The TAA and HTA have equal long term effect in ACL reconstruction, doctors and patients can choose the graft according to the actual situation.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Adolescente , Adulto , Aloenxertos , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Artroscopia , Autoenxertos , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
IEEE Trans Cybern ; PP2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33755575

RESUMO

In this article, the event-triggered resilient L∞ control problem is concerned for the Markov jump systems in the presence of denial-of-service (DoS) jamming attacks. First, a fixed lower bound-based event-triggering scheme (ETS) is presented in order to avoid the Zeno problem caused by exogenous disturbance. Second, when DoS jamming attacks are involved, the transmitted data are blocked and the old control input is kept by using the zero-order holder (ZOH). On the basis of this process, the effect of DoS attacks on ETS is further discussed. Next, by utilizing the state-feedback controller and multiple Lyapunov functions method, some criteria incorporating the restriction of DoS jamming attacks are proposed to guarantee the L∞ control performance of the event-triggered Markov closed-loop jump system. In particular, the bounded transition rates rather than the exact ones are taken into account. That is appropriate for the practical environment in which transition rates of the Markov process are difficult to measure accurately. Correspondingly, some criteria are proposed to obtain state-feedback gains and event-triggering parameters simultaneously. Finally, we provide two examples to show the effectiveness of the proposed method.

8.
Zhongguo Gu Shang ; 34(2): 143-7, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33666001

RESUMO

OBJECTIVE: To explore clinical effects of single-tunnel pullout structure fixation and anatomical reconstruction of lateral ligament complex in treating chronic lateral ankle instability. METHODS: From January 2016 to December 2018, clinical data of 23 patients with chronic lateral malleolus instability who underwent anatomical reconstruction of lateral malleolus ligament complex with single-tunnel pullout structure fixation, were retrospectively studied. Among them, including 7 males and 16 females, aged from 17 to 33 years old with an avergae of (26.0±4.3) years old;16 patients classified to grage 0, and 7 patients classified to gradeⅠaccording to Kellgren-Lawrence(K-L) grading;the time of sprain ranged form 2 to 15 with an average of (5.7±2.9) times;the time from injury to operation ranged to 4 to 18 months with an average of (9.0±3.3) months. The range of movement of operative and uninjured ankle joints were measured at 24 months after opertaion, visual analogue scale (VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) were used to evaluate ankle joint function and improvement of pain, K-L grading and MRI scoring of osteoarthritis of ankle (MSOA) were used to evaluate degree of cartilage degeneration of ankle joint. RESULTS: All patients were followed up from 24 to 48 months with an average of (33.4±6.7) months. All the anterior talofibular ligaments and calcaneofibular ligaments were dissected and reconstructed by single-tunnel pullout structure fixation. The range of motion of dorsiflexion, plantarflexion, varus, and valgus on the operative side of ankle joint were smaller than those on the healthy side. There were no statistically differences in dorsiflexion and eversion between operative side and healthy side of ankle joint (P>0.05), while there were statistically differences in plantarflexion and varus (P<0.05). AOFAS score improved from 55.19±6.94 before surgery to 93.77±3.42 at 24 months after operation (P<0.05), and 23 patients were all excellent. VAS score reduced from 5.30±1.12 before opertaion to 1.10±0.81 at 24 months after operation (P<0.05). Forteen patients were grade 0, 8 patients were gradeⅠand 1 patient were gradeⅡaccording to K-L grading, and there were no differences between before and after operation (P>0.05). MSOA score increased from 3.74±2.54 before operation to 7.04±2.51 at 24 months after opertaion (P<0.05). CONCLUSION: Treatment of chronic lateral ankle instability with reconstruction of lateral ligament complex with single-tunnel pullout structure fixation could provide better tendon and bone healing conditions, improve surgical safety and could achieve satisfactory clinical outcomes.


Assuntos
Instabilidade Articular , Ligamentos Laterais do Tornozelo , Idoso , Tornozelo , Articulação do Tornozelo/cirurgia , Feminino , Humanos , Lactente , Instabilidade Articular/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia , Masculino , Estudos Retrospectivos
9.
Aging (Albany NY) ; 13(5): 6866-6877, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33621195

RESUMO

The aim of our study was to examine the association between body mass index (BMI) and the risk of cardiovascular disease (CVD)-specific mortality among Chinese adults with hypertension by sex. This study included 212,394 adult hypertensive patients aged 20-85 years registered in the records of Minhang District during 2007-2018. Cox proportional hazards regression was performed to evaluate the association between BMI and CVD-specific mortality among Chinese adults with hypertension. There were 14,029 deaths over an average of 8.24 years (range, 0.19-11.96 years). The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) across BMI categories (< 18.5 kg/m2, 18.5-24.9 kg/m2 [reference group], 25.0-29.9 kg/m2, and ≥ 30 kg/m2) for CVD-specific mortality were 1.37 (1.22-1.53), 1.00 (reference), 0.95 (0.90-1.01), and 1.21 (1.04-1.40) in males, and 1.44 (1.31-1.59), 1.00 (reference), 0.96 (0.91-1.01), and 1.04 (0.92-1.17) in females. A U-shaped relationship was observed between BMI and CVD-specific mortality (overall association P< 0.001; non-linearity P< 0.001). This association was attenuated in old age. This study revealed a U-shaped relationship between BMI and CVD-specific mortality among hypertensive men and women. In older people, overweight and obesity are potential factors that reduce the risk of CVD death.

10.
Nat Commun ; 12(1): 1253, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33623031

RESUMO

There are no non-hormonal male contraceptives currently on the market despite decades of efforts toward the development of "male pills". Here, we report that triptonide, a natural compound purified from the Chinese herb Tripterygium Wilfordii Hook F displays reversible male contraceptive effects in both mice and monkeys. Single daily oral doses of triptonide induces deformed sperm with minimal or no forward motility (close to 100% penetrance) and consequently male infertility in 3-4 and 5-6 weeks in mice and cynomolgus monkeys, respectively. Male fertility is regained in ~4-6 weeks after cessation of triptonide intake in both species. Either short- or long-term triptonide treatment causes no discernable systematic toxic side effects based on histological examination of vital organs in mice and hematological and serum biochemical analyses in monkeys. Triptonide appears to target junction plakoglobin and disrupts its interactions with SPEM1 during spermiogenesis. Our data further prove that targeting late spermiogenesis represents an effective strategy for developing non-hormonal male contraceptives.


Assuntos
Anticoncepcionais Masculinos/farmacologia , Triterpenos/farmacologia , Administração Oral , Animais , Anticoncepcionais Masculinos/administração & dosagem , Quebras de DNA de Cadeia Dupla , Infertilidade Masculina/patologia , Macaca fascicularis , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Motilidade Espermática/efeitos dos fármacos , Testículo/metabolismo , Triterpenos/administração & dosagem , gama Catenina/metabolismo
11.
Chem Commun (Camb) ; 57(24): 3018-3021, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33624677

RESUMO

Catalytic enantioselective [4+3] cycloaddition reaction between o-quinone methides and oxiranes was achieved by using a chiral N,N'-dioxide/TbIII complex as the catalyst, affording medium-sized hydrodioxepine derivatives in high yields (up to 99%) with good to excellent diastereo-(up to 94 : 6 dr) and enantioselectivities (up to 97% ee). The topographic steric maps and distribution of the buried volume (% VBur) of the catalysts via Cavallo's SambVca 2 tool were collected to effectively represent the chiral pocket of metal complexes of chiral N,N'-dioxides.

12.
Org Lett ; 23(5): 1856-1861, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33621106

RESUMO

The asymmetric catalytic synthesis of 3-cyclotryptamine substituted oxindoles through formal [4 + 2] cycloaddition/cyclization cascade is described. A wide range of cyclotryptamine derivatives were obtained in enantioenriched form under mild reaction conditions and were found to have potential anticancer activity. The strategy enables ready assembly of cyclotryptamine subunits at the C3a-C3a' positions with two quaternary stereogenic centers in cis-selectivity, leading to the concise synthesis of optically active cis-bis(hexahydropyrroloindole) and others of the cyclotryptamine alkaloid family.

13.
Cardiovasc Toxicol ; 21(5): 410-421, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33475962

RESUMO

Ultrafine particles (UFPs) referred to particular matters with aerosol diameter less than 100 nm. Because of the lightweight and small size, UFPs have become an occupational inhalation risk. The UFPs will be accumulated in the deep lung through inhalation, and then reach into all the organs via circulation system; some UFPs even stay in the brain. As previous study reported, UFPs exposure is usually associated with cardiovascular disease, such as atherosclerosis (AS). In our study, we tried to understand how acute UFP exposure caused the biological dysregulation in atherosclerosis. Acute exposure of UFPs were applied to mice for 6 consecutive days, mice were sacrificed after 3, 5, 7, and 10 days post-exposure. Aorta and serum were collected for histological and biomarkers analysis. Mice aortic adventitial fibroblasts (MAFs) were isolated from mice and used to further study to understand the mechanism of UFPs induced atherosclerosis. Compared to the untreated control, the inflammation responses and nitrate stress were observed after acute exposure of UFPs, with increased IL-6, MCP-1, p47phox, and 3-NT levels in the mice serum. Besides, upregulation of microRNAs: miR-301b-3p and Let-7c-1-3p, and their downstream target: Smad2, Smad3, and TGFß1 were also observed in mouse aorta after acute exposure of UFPs. Similar results were identified in vitro as well. Acute exposure of UFPs induced the systematic nitrate stress and inflammation responses, along with the changes of vascular permeability. Dysregulated miRNAs and TGFß/Smads signaling pathway indicated the higher risk of atherosclerosis/vasculature remodeling when exposed to UFPs.

14.
J Am Chem Soc ; 143(5): 2394-2402, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33507075

RESUMO

The homologation of ketones with diazo compounds is a useful strategy to synthesize one-carbon chain-extended acyclic ketones or ring-expanded cyclic ketones. However, the asymmetric homologation of acyclic ketones with α-diazo esters remains a challenge due to the lower reactivity and complicated selectivity. Herein, we report the enantioselective catalytic homologation of acetophenone and related derivatives with α-alkyl α-diazo esters utilizing a chiral scandium(III) N,N'-dioxide as the Lewis acid catalyst. This reaction supplies a highly chemo-, regio-, and enantioselective pathway for the synthesis of optically active ß-keto esters with an all-carbon quaternary center through highly selective alkyl-group migration of the ketones. Moreover, the ring expansion of cyclic ketones was accomplished under slightly modified conditions, affording a series of enantioenriched cyclic ß-keto esters. Density functional theory calculations have been carried out to elucidate the reaction pathway and possible working models that can explain the observed regio- and enantioselectivity.

15.
Med Sci Monit ; 27: e928796, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33497370

RESUMO

BACKGROUND Although radioiodine therapy (RIT) efficacy is thoroughly validated for Graves disease (GD), there is a lack of research on the predictive factors of RIT, especially the optimal thyroid-absorbed dose (TD) with a shorter effective half-life (Teff ≤5 days). The goal of this study was to explore the predictive value of TD in GD patients receiving RIT with a shorter Teff. MATERIAL AND METHODS We studied 208 GD patients receiving RIT with a shorter Teff. Plotting the receiver-operating characteristic (ROC) curve verified the accuracy of TD for predicting RIT efficacy in GD patients. In addition, we conducted univariate and multivariate analyses to investigate the influence of 14 factors, including thyroid weight, TD, 24-h radioiodine uptake rate (RAIU), the highest RAIU, thyrotrophin receptor antibody level, thyroglobulin antibody level, thyroid peroxidase antibody level, and others, on curative effects of RIT. RESULTS Of the 208 study participants, complete remission and the total effectiveness rates were 68.3% and 92.3%, respectively. The threshold value of TD to predict RIT efficacy was 70.2 Gy, based on ROC analysis. Univariate analysis showed that 24-h RAIU, Teff, total iodine dose, iodine dose per gram of thyroid tissue, TD, and thyrotropin receptor antibody level were significantly associated with RIT efficacy. Multivariate analysis indicated that 24-h RAIU, total iodine dose, iodine dose per gram of thyroid tissue, and TD were significant independent predictors of RIT efficacy. CONCLUSIONS Predicting RIT efficacy from TD with a shorter Teff was feasible in GD patients, and TD above 70.2 Gy had an especially high predictive accuracy.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33487116

RESUMO

Bone is composed of dense and solid cortical bone and honeycomb-like trabecular bone. Although cortical bone provides the majority of mechanical strength for a bone, there are few studies focusing on cortical bone repair or regeneration. Osteons (the Haversian system) form structural and functional units of cortical bone. In recent years, emerging evidences have shown that the osteon structure (including osteocytes, lamellae, lacunocanalicular network, and Haversian canals) plays critical roles in bone mechanics and turnover. Therefore, reconstruction of the osteon structure is crucial for cortical bone regeneration. This article provides a systematic summary of recent advances in osteons, including the structure, function, turnover, and regenerative strategies. First, the hierarchical structure of osteons is illustrated and the critical functions of osteons in bone dynamics are introduced. Next, the modeling and remodeling processes of osteons at a cellular level and the turnover of osteons in response to mechanical loading and aging are emphasized. Furthermore, several bioengineering approaches that were recently developed to recapitulate the osteon structure are highlighted. Impact statement This review provides a comprehensive summary of recent advances in osteons, especially the roles in bone formation, remodeling, and regeneration. Besides introducing the hierarchical structure and critical functions of osteons, we elucidate the modeling and remodeling of osteons at a cellular level. Specifically, we highlight the bioengineering approaches that were recently developed to mimic the hierarchical structure of osteons. We expect that this review will provide informative insights and attract increasing attentions in orthopedic community, shedding light on cortical bone regeneration in the future.

18.
J Hazard Mater ; 401: 123349, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32659578

RESUMO

Copper oxide nanoparticles (Nano-CuO) toxicity has been researched widely in recent years. However, the relationship between oxidative stress and ER-stress and the possible mechanisms induced by Nano-CuO have been rarely studied. Here, the mechanism of hepatotoxicity and apoptosis through oxidative stress and ER-stress induced by Nano-CuO was investigated in vivo and in vitro. In in vivo experiments, male Wistar rats were intranasally instilled 10 µg Nano-CuO/g body weight daily for 60 days, which caused liver function impairment, oxidative stress, inflammatory response, histopathological and ultrastructural damage, ER-stress and apoptosis in liver tissue. in vitro experiments on rat hepatocytes BRL-3A cells showed that exposure to Nano-CuO for 24 h resulted in excess production of reactive oxygen species leading to decrease in mitochondria membrane potential causing cell death by inducing apoptosis. However, administration of n-acetyl cysteine decreased the apoptosis in Nano-cuo treated group. The in vivo and in vitro experiments confirmed that oxidative stress triggered ER-stress pathway, leading to the opening of apoptosis pathways of CHOP, JNK, and Caspase-12. In summary, treatment of Nano Cuo triggered oxidative stress by ROS, which in turn resulted in activation of ER stress pathways causing cell death in liver tissue and BRL-3A cells.

19.
Toxicology ; 450: 152668, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33383130

RESUMO

OBJECTIVE: Ozone has become a major air pollutant in recent years, which leading to a variety of lung diseases. This study aimed to explore the mechanisms of pyroptosis and related signaling pathways in ozone-induced lung injury. METHODS: We exposed 120 Wistar rats to ozone, 20 in each group (half male and half female). Ozone exposure concentrations were 0, 0.12, 0.5, 1.0, 2.0 and 4.0 ppm for 6 h. At the same time, we isolated and cultured type I alveolar epithelial cells, then intervened with high mobility group box 1 protein (HMGB1), hyaluronic acid (HA) and Toll-like receptors 2/4 (TLR2/4) inhibitor. In animal experiments, histopathological experiments, TUNEL, ELISA and biochemical indicators were performed. RT-qPCR and western blot experiments assay were used to detect the expression changes of key factors in relevant signal pathways in vivo and in vitro. RESULTS: After acute ozone exposure, the levels of lung cell injury indicators in bronchoalveolar lavage fluid (BALF), as well as the levels of inflammatory factors in BALF, blood, and lung tissue were significantly increased. Male rats were more sensitive to ozone exposure. Low-concentration ozone exposure caused mild interstitial inflammation in rat lung tissue. Severe inflammation and pulmonary edema appeared with increases in concentration. ELISA results in BALF showed that HMGB1 and HA expressions increased gradually with the increase of ozone exposure concentration. RT-qPCR and Western blot showed that when ozone concentrations increased above 0.5 ppm, the expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3), cleaved caspase-1, and N-gasdermin D (N-GSDMD) in the lung tissue increased significantly, suggesting that ozone exposure induces pyroptosis. At the same time, it was found that ozone exposure activated the nuclear factor kappa B (NF-κB) signal pathway, and increased the mRNA expressions of Toll-like receptors TLR2/4. The results of cell experiments showed that after the addition of HMGB1 and HA, the expression of NF-κB and pyroptosis related indexes increased in type I alveolar epithelial cells, while the corresponding expression decreased after the addition of TLR2/4 inhibitors. CONCLUSION: Ozone exposure causes lung injury in a dose- and gender-dependent manner, and is more severe in males. When injured, the levels of HMGB1 and HA in BALF increased, which interact with TLR 2/4 to activate the downstream NF-κB signaling pathway. Further activating the NLRP3 inflammasome complex and regulating the ozone-induced pyroptosis.

20.
J Inorg Biochem ; 214: 111301, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33166867

RESUMO

Two chiral Ru(II) polypyridyl complexes, Δ-[Ru(bpy)2(6-F-dppz)]2+ (Δ-1; bpy = 2,2'-bipyridine, 6-F-dppz = 6-fluorodipyrido[3,2-a:2',3'-c]phenazine) and Λ-[Ru(bpy)2(6-F-dppz)]2+ (Λ-1), have been synthesized and characterized as binders for the RNA poly(U)•poly(A)*poly(U) triplex and poly(A)•poly(U) duplex in this work. Analysis of the UV-Vis absorption spectra and fluorescence emission spectra indicates that the binding of intercalating Δ-1 with the triplex and duplex RNA is greater than that of Λ-1, while the binding affinities of the two enantiomers to triplex structure is stronger than that of duplex structure. Fluorescence titrations show that the two enantiomers can act as molecular "light switches" for triple- and double-helical RNA. Thermal denaturation studies revealed that that the two enantiomers are more stable to Watson-Crick base-paired double strand of the triplex than the Hoogsteen base-paired third strand, but their stability and selectivity are different. For Δ-enantiomer, the increase of the thermal stability of the Watson-Crick base-paired duplex (13 °C) is slightly stronger than of the Hoogsteen base-paired strand (10 °C), displaying no obvious selectivity. However, compared to the Hoogsteen base-paired strand (5 °C), the stability of the Λ-enantiomer to the Watson-Crick base-paired duplex (13 °C) is more significant, which has obvious selectivity. The overall increase in viscosity of the RNA-(Λ-1) system and its curve shape are similar to that of the RNA-(Δ-1) system, suggesting that the binding modes of two enantiomers with RNA are intercalation. The obtained results in this work may be useful for understanding the binding differences in chiral Ru(II) polypyridyl complexes toward RNA triplex and duplex.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...