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1.
Nanomaterials (Basel) ; 12(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35407346

RESUMO

Hydrogen evolution reaction (HER) has a dominant function in energy conversion and storage because it supplies a most effective way for converting electricity into sustainable high-purity hydrogen. Layered double hydroxides (LDHs) have shown promising performance in the process of electrochemical water oxidation (a half-reaction for water splitting). Nevertheless, HER properties have not been well released due to the structural characteristics of related materials. Herein, a simple and scalable tactics is developed to synthesize chromium-doped CoFe LDH (CoFeCr LDH). Thanks to oxygen vacancy, optimized electronic structure and interconnected array hierarchical structure, our developed ternary CoFeCr-based layered double hydroxide catalysts can provide 10 mA cm-2 current density at -0.201 V vs. RHE with superior long-term stability in alkaline electrolyte. We anticipate that the simple but feasible polymetallic electronic modulation strategy can strengthen the electrocatalytic property of the layered double hydroxides established in the present study, based on a carbon neutral and hydrogen economy.

2.
Sci Rep ; 12(1): 5980, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395871

RESUMO

The burdens and trends of gastric cancer are poorly understood, especially in high-prevalence countries. Based on the Global Burden of Disease Study 2019, we analyzed the incidence, death, and possible risk factors of gastric cancer in five Asian countries, in relation to year, age, sex, and sociodemographic index. The annual percentage change was calculated to estimate the trends in age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). The highest ASIR per 100,000 person-years in 2019 was in Mongolia [44 (95% uncertainty interval (UI), 34 to 55)], while the lowest was in the Democratic People's Republic of Korea (DPRK) [23 (95% UI, 19 to 29)]. The highest ASDR per 100,000 person-years was in Mongolia [46 (95% UI, 37 to 57)], while the lowest was in Japan [14 (95% UI, 12 to 15)]. Despite the increase in the absolute number of cases and deaths from 1990 to 2019, the ASIRs and ASDRs in all five countries decreased with time and improved sociodemographic index but increased with age. Smoking and a high-sodium diet were two possible risk factors for gastric cancer. In 2019, the proportion of age-standardized disability-adjusted life-years attributable to smoking was highest in Japan [23% (95% UI, 19 to 28%)], and the proportions attributable to a high-sodium diet were highest in China [8.8% (95% UI, 0.21 to 33%)], DPRK, and the Republic of Korea. There are substantial variations in the incidence and death of gastric cancer in the five studied Asian countries. This study may be crucial in helping policymakers to make better decisions and allocate appropriate resources.


Assuntos
Neoplasias Gástricas , Carga Global da Doença , Saúde Global , Humanos , Incidência , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco , Sódio , Neoplasias Gástricas/epidemiologia
3.
Adv Sci (Weinh) ; : e2200010, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35332693

RESUMO

For heterogeneous catalysts, the active sites exposed on the surface have been investigated intensively, yet the effect of the subsurface-underlying atoms is much less scrutinized. Here, a surface-engineering strategy to dope Ru into the subsurface/surface of Co matrix is reported, which alters the electronic structure and lattice strain of the catalyst surface. Using hydrogen evolution (HER) as a model reaction, it is found that the subsurface doping Ru can optimize the hydrogen adsorption energy and improve the catalytic performance, with overpotentials of 28 and 45 mV at 10 mA cm-2 in alkaline and acidic media, respectively, and in particular, 28 mV in neutral electrolyte. The experimental results and theoretical calculations indicate that the subsurface/surface doping Ru improves the HER efficiency in terms of both thermodynamics and kinetics. The approach here stands as an effective strategy for catalyst design via subsurface engineering at the atomic level.

4.
Neurol Sci ; 43(2): 899-905, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34973075

RESUMO

BACKGROUND: Nocebo effect is prevalent among neurological diseases, resulting in low adherence and treatment outcome. We sought to examine the nocebo effect in randomized controlled trials (RCTs) in multiple system atrophy (MSA). METHODS: We searched RCTs in MSA from Medline since September, 2021. RCTs for drug treatment conducted in adult MSA patients with more than 5 cases in each treatment arm were included. We assessed the number of dropout due to placebo intolerance. We also did a symptomatic/disease-modifying subgroup analysis based on two different treatment purposes. The STATA software was used for statistical analysis. Overall heterogeneity was assessed using the Cochran Q and I2. RESULTS: Data were extracted from 11 RCTs fulfilling our search criteria. Of 540 placebo-treated patients, 64.2% reported at least one adverse event (AE) and 7.5% reported dropout because of AEs. The chance of dropping out because of an AE and experiencing at least one AE did not differ between placebo and active drug treatment arms. Besides, the pooled nocebo dropout rate in the symptomatic subgroup was similar to that of the disease-modifying subgroup. CONCLUSION: In MSA RCTs, nocebo dropout rate was not at a low level among neurological disorders. Nocebo effect was an important reason of dropout because of AE in placebo and active drug treatment arms. Different treatment purposes may not influence nocebo effect.


Assuntos
Atrofia de Múltiplos Sistemas , Efeito Nocebo , Humanos , MEDLINE , Atrofia de Múltiplos Sistemas/tratamento farmacológico , Resultado do Tratamento
5.
Carbohydr Polym ; 278: 118960, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973775

RESUMO

In our continuous exploration for bioactive polysaccharides, a novel polysaccharide FMP-2 was isolated and purified from the fruiting bodies of Morchella esculenta by alkali-assisted extraction. FMP-2 had an average molecular weight of 1.09 × 106 Da and contained mannose, glucuronic acid, glucose, galactose, and arabinose in a molar ratio of 4.10:0.22:1.00:5.75:0.44. The backbone of FMP-2 mainly consisted of 1,2-α-D-Galp, 1,6-α-D-Galp, and 1,4-α-D-Manp, with branches of 1,4,6-α-D-Manp and 1,2,6-α-D-Galp. FMP-2 can stimulate phagocytosis and promote the secretion of NO, ROS, and cytokines like IL-6, IL-1ß, and TNF-α in RAW264.7 cells ranging from 25 to 400 µg/mL. FMP-2 had great repairing effect on the immune injury of zebrafish induced by chloramphenicol. The phagocytosis ability of zebrafish macrophages and the proliferation of neutrophils can be greatly enhanced by polysaccharide FMP-2 with concentrations from 50 to 200 µg/mL. These findings suggest that FMP-2 might be used as a potential immunomodulator in the food and pharmaceutical industries.


Assuntos
Álcalis/química , Ascomicetos/química , Carpóforos/química , Polissacarídeos Fúngicos/farmacologia , Galactose/análogos & derivados , Fatores Imunológicos/farmacologia , Mananas/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/isolamento & purificação , Galactose/química , Galactose/isolamento & purificação , Galactose/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Mananas/química , Mananas/isolamento & purificação , Camundongos , Neutrófilos/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Peixe-Zebra
6.
Saudi J Gastroenterol ; 28(1): 46-53, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34856726

RESUMO

BACKGROUND: Endoscopy-related infections have caused multiple outbreaks. The importance of surveillance culture is gradually recognized, but sampling techniques are not consistent in many guidelines. It is unclear whether the Flush-Brush-Flush sampling method (FBFSM) is more sensitive than the conventional flush sampling method (CFSM) and whether different sampling brushes have different effects. METHODS: The propensity score matching method was done with two matching ways, 1:1 nearest neighbor propensity score matching and full matching was used to analyze the surveillance culture data collected by FBFSM and CFSM. We fit a confounder-adjusted multiple generalized linear logistic regression model to estimate the marginal odds ratio (OR). A paired study was applied to compare the sampling effect of polyurethane foam (PU) head brush and polyamide (PA) head brush. RESULT: From 2016 to 2020, 316 reprocessed endoscope samples were collected from all 59 endoscopy centers in Tianjin. About 279 (88.3%) reprocessed endoscopes met the threshold of Chinese national standards (<20 CFU/Channel). The qualified rate of reprocessed endoscopes sampling by CFSM (91.8%) and FBFSM (81.6%) was statistically different (p < 0.05). The adjusted OR by full matching for FBFSM was 7.98 (95% confidence interval: 3.35-21.78). Forty one pairs of colonoscopes, after reprocessing from 27 centers, were tested by PA and PU brushes, and no difference was found in microbial recovery. CONCLUSION: FBFSM was confirmed to be a more sensitive sampling technique. PU and PA brushes had no significant difference in sampling effect.


Assuntos
Desinfecção , Contaminação de Equipamentos , Desinfecção/métodos , Endoscópios , Humanos , Controle de Infecções/métodos , Pontuação de Propensão
7.
ACS Nano ; 15(12): 19394-19408, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34806870

RESUMO

The dense extracellular matrix (ECM) in tumor tissues resists drug diffusion into tumors and leads to a poor prognosis. To address this problem, glucose oxidase (GOx)-modified ferritin loaded with luminol-curcumin was fabricated. Once delivered to the tumor, this luminol-based self-illuminating nanocage could actively convert glucose to reactive oxygen species (ROS) to achieve starvation therapy. Then, excessive ROS were transmitted to luminol, thereby emitting 425 nm blue-violet light. Momentarily, light was further absorbed by curcumin and ROS production was amplified. Abundant ROS helps break down the ECM network to penetrate deep into tumors. In addition, ROS produced after cell internalization can induce apoptosis of tumor cells by decreasing the mitochondrial membrane potential and can promote ferroptosis by consuming reduced glutathione. Effective penetration and multiple pathways inducing tumor cell death contributed to the efficient antitumor effect (tumor inhibition rate of GOx-modified ferritin loaded with luminol-curcumin: 71.73%). This study developed a glucose-driven self-illuminating nanocage for active tumor penetration via ROS-mediated destruction of the ECM and provided the synergetic mechanism of apoptosis and ferroptosis.


Assuntos
Ferroptose , Neoplasias , Glucose Oxidase , Humanos , Luminol , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio
8.
Ann Transl Med ; 9(20): 1513, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790719

RESUMO

BACKGROUND: Lymph node ratio (LNR) has advantages in predicting prognosis compared with American Joint Committee on Cancer (AJCC) pathological N stage. However, the prognostic value of a novel T stage-lymph node ratio (TLNR) classification for colon cancer combining LNR and pathological primary tumor stage (T stage) is currently unknown. METHODS: We included 62,294 patients with stage I-III colon cancer from the Surveillance, Epidemiology, and End Results Program as a training cohort. External validation was performed in 3,327 additional patients. A novel LNR stage was established and combined with T stage in a novel TLNR classification. Patients with similar survival were grouped according to T and LNR stages, with T1LNR1 as a reference. RESULTS: We developed a novel TLNR classification as follows: stages I (T1LNR1-2, T1LNR4), IIA (T1LNR3, T2LNR1-2, T3LNR1), IIB (T1LNR5, T2LNR3-4, T3LNR2, T4aLNR1), IIC (T2LNR5, T3LNR3-4, T4aLNR2, T4bLNR1), IIIA (T3LNR5, T4aLNR3-4, T4bLNR2), IIIB (T4aLNR5, T4bLNR3-4), and IIIC (T4bLNR5). In the training cohort, the novel TLNR classification had better prognostic discrimination (area under receiver operating characteristic curve, 0.621 vs. 0.608, two-sided P<0.001), superior model-fitting ability for predicting overall survival (Akaike information criteria, 561,129 vs. 562,052), and better net benefits compared with the AJCC 8th tumor/node/metastasis classification. Similar results were found in the validation cohort for predicting both overall and disease-free survival. CONCLUSIONS: This novel TLNR classification may provide better prognostic discrimination, model-fitting ability, and net benefits than the AJCC 8th TNM classification, for potentially better stratification of patients with operable stage I-III colon cancer; however, further studies are required to validate the novel TLNR classification.

9.
Huan Jing Ke Xue ; 42(11): 5210-5219, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708960

RESUMO

Real-time BTEX(including benzene, toluene, ethylbenzene, m-, p-, and o-xylenes) were measured continuously in Tianjin urban site in July 2019 and January 2020 using a Syntech Spectras GC955 analyzer. The BTEX concentration levels, composition, and evolutionary mechanisms during typical pollution episodes were investigated. The potential sources of BTEX were analyzed qualitatively using the diagnostic ratios method. Finally, the BTEX health risk was evaluated by using the human exposure analysis and evaluation method according to US EPA. The averaged total mixing ratio of BTEX were 1.32×10-9 and 4.83×10-9 during ozone pollution and haze episodes, respectively. Benzene was the most abundant species, followed by toluene. The mixing ratio of BTEX was largely affected by short southwestern distance transportation in January, while local emissions in July. In addition, the BTEX mixing ratio depended on the influence of temperature and relative humidity(RH) in July, while the concentration was more sensitive to changes in RH when the temperature was low in January. Diagnostic ratios and source implications suggested that the BTEX was affected mainly by biomass/biofuel/coal burning during haze episodes. The traffic related emissions also had an impact except for the influence of biomass/biofuel/coal burning in July. The averaged hazard quotient(HQ) values were 0.072 and 0.29 during ozone pollution and haze episodes, respectively, which were in the upper safety range limit recommended by the US EPA. The carcinogenic risk posed by benzene in both cleaning and pollution processes was higher than the safety threshold set by the US EPA, which should be monitored carefully.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Benzeno/análise , Benzeno/toxicidade , Derivados de Benzeno/análise , Derivados de Benzeno/toxicidade , Monitoramento Ambiental , Humanos , Medição de Risco , Tolueno/análise , Tolueno/toxicidade , Xilenos
10.
World J Gastrointest Oncol ; 13(9): 1184-1195, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34616522

RESUMO

BACKGROUND: It remains controversial as to which pathological classification is most valuable in predicting the overall survival (OS) of patients with gastric cancer (GC). AIM: To assess the prognostic performances of three pathological classifications in GC and develop a novel prognostic nomogram for individually predicting OS. METHODS: Patients were identified from the Surveillance, Epidemiology, and End Results program. Univariate and multivariate analyses were performed to identify the independent prognostic factors. Model discrimination and model fitting were evaluated by receiver operating characteristic curves and Akaike information criteria. Decision curve analysis was performed to assess clinical usefulness. The independent prognostic factors identified by multivariate analysis were further applied to develop a novel prognostic nomogram. RESULTS: A total of 2718 eligible GC patients were identified. The modified Lauren classification was identified as one of the independent prognostic factors for OS. It showed superior model discriminative ability and model-fitting performance over the other pathological classifications, and similar results were obtained in various patient settings. In addition, it showed superior net benefits over the Lauren classification and tumor differentiation grade in predicting 3- and 5-year OS. A novel prognostic nomogram incorporating the modified Lauren classification showed superior model discriminative ability, model-fitting performance, and net benefits over the American Joint Committee on Cancer 8th edition tumor-node-metastasis classification. CONCLUSION: The modified Lauren classification shows superior net benefits over the Lauren classification and tumor differentiation grade in predicting OS. A novel prognostic nomogram incorporating the modified Lauren classification shows good model discriminative ability, model-fitting performance, and net benefits.

11.
Chem Commun (Camb) ; 57(48): 5985, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34095918

RESUMO

Retraction of 'Chemical synthesis and antigenic activity of a phosphatidylinositol mannoside epitope from Mycobacterium tuberculosis' by Shi-Yuan Zhao et al., Chem. Commun., 2020, 56, 14067-14070, DOI: 10.1039/D0CC05573E.

12.
Aging (Albany NY) ; 13(11): 15032-15043, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031267

RESUMO

BACKGROUND: Human amniotic epithelial cells (hAECs) are seed cells used to treat acute myocardial infarction (AMI), but their mechanism remains unclear. METHODS: We cultured hAECs and extracted exosomes from culture supernatants. Next, we established a stable AMI model in rats and treated them with hAECs, exosomes, or PBS. We assess cardiac function after treatment by echocardiography. Additionally, heart tissues were collected and analyzed by Masson's trichrome staining. We conducted the tube formation and apoptosis assays to explore the potential mechanisms. RESULTS: Cardiac function was improved, and tissue fibrosis was decreased following implantation of hAECs and their exosomes. Echocardiography showed that the EF and FS were lower in the control group than in the hAEC and exosome groups, and that the LVEDD and LVESD were higher in the control group (P<0.05). Masson's trichrome staining showed that the fibrotic area was larger in the control group. Tube formation was more efficient in the hAEC and exosome groups (P<0.0001). Additionally, the apoptosis rates of myocardial cells in the hAEC and exosome groups were significantly decreased (P<0.0001). CONCLUSIONS: hAECs and their exosomes improved the cardiac function of rats after AMI by promoting angiogenesis and reducing the apoptosis of cardiac myocytes.


Assuntos
Âmnio/citologia , Células Epiteliais/metabolismo , Células Epiteliais/transplante , Exossomos/transplante , Coração/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Animais , Apoptose , Células Cultivadas , Modelos Animais de Doenças , Eletrocardiografia , Exossomos/metabolismo , Exossomos/ultraestrutura , Fibrose , Humanos , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Miócitos Cardíacos , Ratos Sprague-Dawley
13.
J Nanobiotechnology ; 19(1): 132, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971910

RESUMO

Molecular imaging technology enables us to observe the physiological or pathological processes in living tissue at the molecular level to accurately diagnose diseases at an early stage. Optical imaging can be employed to achieve the dynamic monitoring of tissue and pathological processes and has promising applications in biomedicine. The traditional first near-infrared (NIR-I) window (NIR-I, range from 700 to 900 nm) imaging technique has been available for more than two decades and has been extensively utilized in clinical diagnosis, treatment and scientific research. Compared with NIR-I, the second NIR window optical imaging (NIR-II, range from 1000 to 1700 nm) technology has low autofluorescence, a high signal-to-noise ratio, a high tissue penetration depth and a large Stokes shift. Recently, this technology has attracted significant attention and has also become a heavily researched topic in biomedicine. In this study, the optical characteristics of different fluorescence nanoprobes and the latest reports regarding the application of NIR-II nanoprobes in different biological tissues will be described. Furthermore, the existing problems and future application perspectives of NIR-II optical imaging probes will also be discussed.


Assuntos
Raios Infravermelhos , Imagem Molecular/métodos , Imagem Óptica/métodos , Animais , Tecnologia Biomédica , Liberação Controlada de Fármacos , Fluorescência , Humanos , Neoplasias/diagnóstico por imagem , Razão Sinal-Ruído , Células-Tronco , Cirurgia Assistida por Computador/métodos
14.
Chem Commun (Camb) ; 57(29): 3563-3566, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33704281

RESUMO

The water oxidation reaction plays a major role in many alternative-energy systems because it provides the electrons and protons required for the use of renewable electricity. We report the tuning of the iron molybdate (FeMoO4) electron structure via a coupled interface between the catalytic centers and the substrate. Our developed FeMoO4 catalysts can provide a 50 mA cm-2 current density at 1.506 V vs. RHE with excellent stability in 1.0 M KOH. The improved performance can be ascribed to the synergy of the optimized electronic structures and hierarchical nanostructure.

16.
J Ethnopharmacol ; 270: 113776, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33421597

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: After cerebral ischemia/reperfusion injury, pro-inflammatory M1 and anti-inflammatory M2 phenotypes of microglia are involved in neuroinflammation, in which activation of NLRP3 inflammasome and subsequent pyroptosis play essential roles. Salvianolic Acids for Injection (SAFI) is Chinese medicine injection which composed of multiple phenolic acids extracted from Radix Salviae Miltiorrhizae, and has been reported to generate neuroprotective effects after cerebral ischemic insult in clinical and animal studies. AIM OF THE STUDY: The present study was designed to investigate whether SAFI exerts neuroprotective effects by switching microglial phenotype and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia. MATERIALS AND METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) model in co-cultured primary neurons and primary microglia were utilized. The neuroprotective effect of SAFI was evaluated through measuring neurological deficit scores, neuropathological changes, inflammatory factors, cell phenotype markers, and related proteins of NLRP3 inflammasome/pyroptosis axis. RESULTS: The results showed that SAFI treatment was able to: (1) produce a significant increase in neurological deficit scores and decrease in infarct volumes, and alleviate histological injury and neuronal apoptosis in cerebral cortex in MCAO/R model; (2) increase neuronal viability and reduce neuronal apoptosis in the OGD model; (3) reshape microglial polarization patterns from M1-like phenotype to M2-like phenotype; (4) inhibit the activation of the NLRP3 inflammasome and the expression of proteins related to NLRP3 inflammasome/pyroptosis axis in vivo and in vitro. CONCLUSION: These findings indicate that SAFI exert neuroprotective effect, probably via reducing neuronal apoptosis, switching microglial phenotype from M1 towards M2, and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia.


Assuntos
Alcenos/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Polifenóis/farmacologia , Piroptose/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Sistema ASC de Transporte de Aminoácidos/genética , Sistema ASC de Transporte de Aminoácidos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Caspase 1/genética , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Injeções Intraperitoneais , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas de Ligação a Fosfato/antagonistas & inibidores , Proteínas de Ligação a Fosfato/genética , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
17.
Brain Res Bull ; 169: 156-166, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33508403

RESUMO

OBJECTIVE: To explore the potential analgesic effect of melatonin and its underlying molecular mechanisms in a neuropathic pain model induced by spinal nerve ligation (SNL). METHODS: The experimental animals were divided into different groups including sham, vehicle, melatonin (MT) treatment, caspase-1 inhibitor (VX-765) treatment and MT2 antagonist (4P-PDOT) treatment. On the first three successive postoperative days, rats were intraperitoneally administered with MT, VX-765 or combination of MT and 4P-PDOT. Hyperalgesic behavior after SNL was evaluated using the paw withdrawal threshold (PWT). We then assessed expression of tumor necrosis factor-α (TNF-α), IL-18, interleukin-1ß (IL-1ß), NLRP3 inflammasome components, and nuclear factor-κB (NF-κB) activation using enzyme-linked immunosorbent assay kits (ELISA), real-time PCR, immunohistochemistry, and western blot, respectively, in spinal cord horn tissues extracted on postoperative day 7. RESULTS: The results showed that melatonin treatment alleviated SNL-induced allodynia. We observed an SNL-induced upregulation of TNF-α, IL-18, IL-1ß, NLRP3, ASC, cleaved caspase-1, and NF-κB in the lumbar spinal cord horn of rats, which was significantly attenuated by intraperitoneal injection of melatonin or VX-765. Additionally, co-treatment of melatonin and 4P-PDOT abrogated the analgesic and anti-inflammatory effect of melatonin. CONCLUSION: Melatonin had potent analgesic and anti-inflammatory effects in SNL-induced neuropathic pain via NF-κB/NLRP3 inflammasome signaling pathway. Our results therefore suggested that this pathway could represent a novel therapeutic target for the management of neuropathic pain.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Melatonina/farmacologia , Neuralgia/tratamento farmacológico , Nervos Espinhais/lesões , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Dipeptídeos/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Masculino , Melatonina/uso terapêutico , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuralgia/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Nervos Espinhais/metabolismo , para-Aminobenzoatos/farmacologia
18.
Biochem Biophys Res Commun ; 540: 90-94, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33450485

RESUMO

MapA is a histidine acid phosphatase (HAP) from Legionella pneumophila that catalyzes the hydroxylation of a phosphoryl group from phosphomonoesters by an active-site histidine. Several structures of HAPs, including MapA, in complex with the inhibitor tartrate have been solved and the substrate binding tunnel identified; however, the substrate recognition mechanism remains unknown. To gain insight into the mechanism of substrate recognition, the crystal structures of apo-MapA and the MapAD281A mutant in complex with 5'-AMP were solved at 2.2 and 2.6 Å resolution, respectively. The structure of the MapAD281A/5'-AMP complex reveals that the 5'-AMP fits fully into the substrate binding tunnel, with the 2'-hydroxyl group of the ribose moiety stabilized by Glu201 and the adenine moiety sandwiched between His205 and Phe237. This is the second structure of a HAP/AMP complex solved with 5'-AMP binding in a unique manner in the active site. The structure presents a new substrate recognition mechanism of HAPs.


Assuntos
Fosfatase Ácida/química , Fosfatase Ácida/metabolismo , Histidina/metabolismo , Legionella pneumophila/enzimologia , Fosfatase Ácida/genética , Adenina/metabolismo , Sequência de Aminoácidos , Apoenzimas/metabolismo , Domínio Catalítico , Legionella pneumophila/genética , Modelos Moleculares , Mutação , Fenilalanina/metabolismo , Ligação Proteica , Ribose/metabolismo , Alinhamento de Sequência , Especificidade por Substrato , Tartaratos/metabolismo
19.
Reprod Biol ; 20(4): 573-579, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33203587

RESUMO

Testicular sperm aspiration- (TESA) or micro-dissection testicular sperm extraction- (MD-TESE) combined intracytoplasmic sperm injection (ICSI) was the only option for non-obstructive azoospermia (NOA) patients to have a biological offspring and they had different success rates in sperm retrieval. Our study aimed to find predictor(s) for predicting the sperm retrieval rate (SRR) in NOAs and guide clinicians in choosing different surgical approaches, TESA or MD-TESE for NOAs. 294 NOAs who had undergone TESA or MD-TESE were divided into TESA group and MD-TESE group. Depending on sperm retrieval, each group was divided into two subgroups: successful subgroups and failure subgroups. They respectively were 24 cases and 131 cases, 53 cases and 86 cases. Clinical data, including body mass index (BMI), testicular volume, and serum hormone levels, were analyzed in a retrospective manner. The results showed that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and SRR were lower in TESA group as compared to these in MD-TESE group, while testicular volume was higher (P < 0.05). The surgical approach of sperm retrieval significantly affected the SRR (P < 0.05). In TESA subgroups, testicular volume, FSH and LH differed significantly (P < 0.05). In MD-TESE subgroups, the level of FSH and LH differed significantly between both groups (P < 0.05). Using logistics regression, we found a negative correlation (ß=-0.083) between FSH and the SRR in TESA group but a positive correlation (ß = 0.064) in MD-TESE group (P < 0.05). In conclusion, serum FSH level can predict the SRR of NOAs and guide the clinicians while selecting the suitable surgery approach for NOAs.


Assuntos
Azoospermia/sangue , Azoospermia/cirurgia , Hormônio Foliculoestimulante/sangue , Recuperação Espermática/estatística & dados numéricos , Humanos , Hormônio Luteinizante/sangue , Masculino , Curva ROC , Injeções de Esperma Intracitoplásmicas , Testículo/patologia , Testículo/cirurgia , Resultado do Tratamento
20.
Chem Commun (Camb) ; 56(93): 14713-14716, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33174544

RESUMO

We report FeOOH supported on Ni foam which enables highly efficient UOR electrocatalysis and can be readily produced through a hydrolysis reaction. Our developed UOR catalyst as the anode can provide a current density of 200 mA cm-2 at 1.427 V vs. RHE, as well as remarkable operational stability, representing the best yet reported noble metal-free urea electrolyser.

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