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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 263: 120183, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34311163

RESUMO

Based on the principle of FRET, we have developed a ratiometric and colorimetric fluorescent probe TFBN, which can specifically recognize SO2 derivatives (SO32-/HSO3-), and exhibit a transition from red to green fluorescence under 405 nm excitation. The probe TFBN owns the advantages of short response time (<3 min), quantitative detection SO2 derivatives in two linear ranges, extremely low detection limit (39 nM), large Stokes shift (239 nm) and wide emission window gap (140 nm). In addition, the NBC structure was used as a fluorescent donor for FRET probes for the first time, which expanded the diversity of donors. Importantly, with low toxicity and good biocompatibility, the probe TFBN successfully detects exogenous and endogenous sulfites in living cells. These characteristics endow the probe TFBN can be successfully used in living cells and mouse imaging.

2.
Nanoscale ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259675

RESUMO

Owing to the economical and practical solution synthesis and coating strategies, silver nanowires (AgNWs) have been considered as one of the most suitable alternative materials to replace commercial indium tin oxide (ITO) transparent electrodes. The primitive AgNW electrode cannot meet the requirements for preparing high performance optoelectronic devices due to its high contact resistance, large surface roughness and poor stability. Thus, various post-treatments for AgNW film optimization are needed before its actual applications, such as welding treatment to decrease contact resistance and passivation to increase film stability. This review investigates recent progress on the preparation and optimization of AgNWs. Moreover, some unique fabrication strategies to produce highly oriented AgNW films with unique anisotropic properties have also been carried out with detailed analysis. The representative devices based on the AgNW electrode have been summarized and discussed at the end of this review.

3.
Sci Rep ; 11(1): 14002, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234193

RESUMO

Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts. Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells. Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells. p-AMPK and p-FOXO3a also translocated from the cytosol to the nucleus by metformin in HDF, but not in AsPC-1 cells. Transfection of si-FOXO3a in HDF increased ROS levels, while wt-FOXO3a-transfected AsPC-1 cells decreased ROS levels. Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect. Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells. Metformin/apigenin combination in AsPC-1 cells increased DNA damage-, apoptosis-, autophagy- and necroptosis-related factors, but not in HDF cells. Oral administration with metformin/apigenin caused dramatic blocks tumor size in AsPC-1-xenografted nude mice. Our results suggest that metformin in cancer cells differentially regulates cellular ROS levels via AMPK-FOXO3a-MnSOD pathway and combination of metformin/apigenin exerts anticancer activity through DNA damage-induced apoptosis, autophagy and necroptosis by cancer cell-specific ROS amplification.

4.
Cells ; 10(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200524

RESUMO

Fluctuating light can cause selective photoinhibition of photosystem I (PSI) in angiosperms. Cyclic electron flow (CEF) around PSI and electron flux from water via the electron transport chain to oxygen (the water-water cycle) play important roles in coping with fluctuating light in angiosperms. However, it is unclear whether plant species in the same genus employ the same strategy to cope with fluctuating light. To answer this question, we measured P700 redox kinetics and chlorophyll fluorescence under fluctuating light in two Paphiopedilum (P.) Pftzer (Orchidaceae) species, P. dianthum and P. micranthum. After transition from dark to high light, P. dianthum displayed a rapid re-oxidation of P700, while P. micranthum displayed an over-reduction of P700. Furthermore, the rapid re-oxidation of P700 in P. dianthum was not observed when measured under anaerobic conditions. These results indicated that photo-reduction of O2 mediated by the water-water cycle was functional in P. dianthum but not in P. micranthum. Within the first few seconds after an abrupt transition from low to high light, PSI was highly oxidized in P. dianthum but was highly reduced in P. micranthum, indicating that the different responses of PSI to fluctuating light between P. micranthum and P. dianthum was attributed to the water-water cycle. In P. micranthum, the lack of the water-water cycle was partially compensated for by an enhancement of CEF. Taken together, P. dianthum and P. micranthum employed different strategies to cope with the abrupt change of light intensity, indicating the diversity of strategies for photosynthetic acclimation to fluctuating light in these two closely related orchid species.

5.
Pathol Oncol Res ; 27: 588532, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257537

RESUMO

Background and Objective: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor of the digestive system worldwide. Chronic hepatitis B virus (HBV) infection and aflatoxin exposure are predominant causes of HCC in China, whereas hepatitis C virus (HCV) infection and alcohol intake are likely the main risk factors in other countries. It is an unmet need to recognize the underlying molecular mechanisms of HCC in China. Methods: In this study, microarray datasets (GSE84005, GSE84402, GSE101685, and GSE115018) derived from Gene Expression Omnibus (GEO) database were analyzed to obtain the common differentially expressed genes (DEGs) by R software. Moreover, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protein-protein interaction (PPI) network was constructed, and hub genes were identified by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, respectively. The hub genes were verified using Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset. Moreover, the Human Protein Atlas (HPA) database was used to verify candidate genes' protein expression levels. Results: A total of 293 common DEGs were screened, including 103 up-regulated genes and 190 down-regulated genes. Moreover, GO analysis implied that common DEGs were mainly involved in the oxidation-reduction process, cytosol, and protein binding. KEGG pathway enrichment analysis presented that common DEGs were mainly enriched in metabolic pathways, complement and coagulation cascades, cell cycle, p53 signaling pathway, and tryptophan metabolism. In the PPI network, three subnetworks with high scores were detected using the Molecular Complex Detection (MCODE) plugin. The top 10 hub genes identified were CDK1, CCNB1, AURKA, CCNA2, KIF11, BUB1B, TOP2A, TPX2, HMMR and CDC45. The other public databases confirmed that high expression of the aforementioned genes related to poor overall survival among patients with HCC. Conclusion: This study primarily identified candidate genes and pathways involved in the underlying mechanisms of Chinese HCC, which is supposed to provide new targets for the diagnosis and treatment of HCC in China.

6.
EMBO Mol Med ; 13(7): e14089, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34102002

RESUMO

The tyrosine phosphatase SHP2 is oncogenic in cancers driven by receptor-tyrosine-kinases, and SHP2 inhibition reduces tumor growth. Here, we report that SHP2 is an essential promoter of endothelial cell survival and growth in the remodeling tumor vasculature. Using genetic and chemical approaches to inhibit SHP2 activity in endothelial cells, we show that SHP2 inhibits pro-apoptotic STAT3 and stimulates proliferative ERK1/2 signaling. Systemic SHP2 inhibition in mice bearing tumor types selected for SHP2-independent tumor cell growth promotes degeneration of the tumor vasculature and blood extravasation; reduces tumor vascularity and blood perfusion; and increases tumor necrosis. Reduction of tumor growth ensues, independent of SHP2 targeting in the tumor cells, blocking immune checkpoints, or recruiting macrophages. We also show that inhibiting the Angiopoietin/TIE2/AKT cascade magnifies the vascular and anti-tumor effects of SHP2 inhibition by blocking tumor endothelial AKT signaling, not a target of SHP2. Since the SHP2 and Ang2/TIE2 pathways are active in vascular endothelial cells of human melanoma and colon carcinoma, SHP2 inhibitors alone or with Ang2/TIE2 inhibitors hold promise to effectively target the tumor endothelium.

7.
Ann Palliat Med ; 10(6): 6577-6587, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34154357

RESUMO

BACKGROUND: This study aimed to explore the efficacy of trypsin inhibitors in the treatment of severe pancreatitis (SP) by meta-analysis. METHODS: The Boolean logic retrieval method was adopted to recruit the relevant literature. Chinese and English databases were respectively searched using a combination of the following search terms: "trypsin inhibitor", "acute pancreatitis", and "severe pancreatitis". The trypsin-treated SP group was set as the experimental group, and the blank control was set as the control group. Meta-analysis was performed using RevMan 5.3 software provided by the Cochrane system. RESULTS: A total of 12 references were included. The meta-analysis suggested that the heterogeneity test results of pancreatic infection incidence were Chi2 =0.51, degrees of freedom (df) =7, I2=0%<50%, and P=1.00>0.01, with risk ratio (RR): 0.80, 95% confidence interval (CI): (0.64, 1.01), Z=1.88, and P=0.06. The heterogeneity test results of extra-pancreatic infection incidence were Chi2 =0.20, df =5, I2=0%<50%, and P=1.00>0.01, with RR: 0.81, 95% CI: (0.62, 1.05), Z=1.60, and P=0.11. The heterogeneity test results of the length of hospital stay were Tau2 =65.69, Chi2 =75.05, df =6, I2=92%>50%, and P<0.0001. The length of hospital stay of the experimental group was shorter than that of the control group, with mean difference (MD): -23.31 and the 95% CI: (-29.60, -17.02), and the difference was statistically significant (Z=7.26, P<0.0001). The heterogeneity test results of the inflammatory factor tumor necrosis factor-α (TNF-α) level were Chi2 =67.28, df =3, I2=96%>50%, and P<0.0001. The level of TNF-α in the experimental group was lower than that in the control group, with MD: -11.69, 95% CI: (-12.51, -10.87), and the difference was statistically significant (Z=27.88, P<0.0001). The heterogeneity test results of the mortality rate were Chi2 =2.52, df =5, I2=0%<50%, and P=0.77>0.01. The mortality rate of the experimental group was lower than that of the control group, with RR: 0.27 and 95% CI: (0.19, 0.40), and the difference was notable (Z=6.75, P<0.0001). DISCUSSION: The meta-analysis performed in this study confirmed that trypsin inhibitors can inhibit the release of inflammatory factors and reduce mortality rate of SP patients.


Assuntos
Pancreatite , Inibidores da Tripsina , Humanos , Tempo de Internação , Inibidores da Tripsina/uso terapêutico
8.
Ann Palliat Med ; 10(6): 6518-6534, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34154362

RESUMO

BACKGROUND: Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) are the four most common drugs for the first-line treatment of tuberculosis (TB). Although chemotherapy drugs are widely used in the treatment of TB, and achieved good results, but the side effects, especially anti-tuberculosis drug-induced liver injury (ATDILI), cannot be overlooked. Many researchers have made efforts to uncover the association of cytochrome P450 (CYP) enzyme genetic polymorphisms with ATDILI. In this study, we systematically reviewed and meta-analyzed the relationship between CYP polymorphism and susceptibility to ATDILI. METHODS: We carried out literature searches of PubMed, Ovid, the Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI). Medical Subject Headings (MeSH) terms including "cytochrome P450 enzyme", "drug-induced liver injury", "polymorphism", "tuberculosis", and "hepatotoxicity" were used as keywords for our searches. RESULTS: The pooled odds ratio (OR) of all studies for CYP2E1 to the risk of ATDILI was 1.18 [95% confidence interval (CI): 0.82-1.71]. The articles in this meta-analysis were observed to be mildly heterogeneous. Further subgroup analysis revealed that the patients who receiving a four-drug protocol (INH + RIF + PZA + EMB) or three-drug protocol (INH + RIF + PZA) regimens showed a higher risk of ATDILI than those who receiving INH alone. However, subgroup analyses according to participants' ethnic origin, study type, and the definition of ATDILI produced no statistically significant results. Associations between other genes in the CYP family and ATDILI were indistinct and equivocal. DISCUSSION: Our meta-analysis has uncovered an association between CYP2E1 RsaI/PstI polymorphisms and ATDILI, especially among patients who receive a four-drug (INH + RIF + PZA + EMB) or three-drug (INH + RIF + PZA) anti-TB treatment regimen.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Tuberculose , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética , Sistema Enzimático do Citocromo P-450/genética , Humanos , Polimorfismo Genético/genética , Tuberculose/tratamento farmacológico
9.
BMC Public Health ; 21(1): 1163, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140014

RESUMO

BACKGROUND: The incidence and risk of tuberculosis (TB) among the elderly population have increased with the ageing population in China. This study aimed to assess the current status and associated factors of TB knowledge, attitudes, and practices among elderly people in Shenzhen City, China, which may provide references for the development of TB prevention and treatment policies targeting elderly people. METHODS: A multistage random sampling method was used to collect data with a self-designed questionnaire from 1078 elderly people (response rate, 90.66%) living in Bao'an District of Shenzhen between September and October 2019. Univariate and multiple linear regression analyses were used to analyse factors associated with TB knowledge, attitudes, and practices among elderly people. RESULTS: Among the respondents, 3.13% had previously been treated for TB, and 3.09% of respondents had family members or friends with a previous TB history. The percentages of elderly people who were aware of TB and had positive attitudes and practices regarding TB were 69.23%, 48.87%, and 42.62%, respectively. Multiple linear stepwise regression analysis showed that elderly people with a junior high school education or higher, a family annual income per capita of less than 100,000 RMB, a better self-perceived health status, and family members or friends with a previous TB history had higher TB knowledge scores (P < 0.05). Elderly people with medical insurance, a junior high school or higher education, a family annual income per capita of less than 100,000 RMB, and family members and friends with a previous TB history had higher TB attitude scores (P < 0.05). In addition, elderly people who were older, had medical insurance, had a junior high school education or higher, and had a family annual income per capita less than 100,000 RMB had higher TB practice scores (P < 0.05). CONCLUSIONS: Elderly people were aware of TB, but their positive attitudes and practices were at a low level. Corresponding prevention and treatment policies should be developed according to these influencing factors to reduce the incidence of TB among elderly people and improve their quality of life.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Tuberculose , Idoso , China/epidemiologia , Estudos Transversais , Humanos , Qualidade de Vida , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
10.
Traffic Inj Prev ; 22(6): 443-448, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124967

RESUMO

OBJECTIVE: Cognitive training for reducing crash rate can be delivered to older drivers via in-person on-road sessions, a driving simulator, or using computer-based cognitive methods. Despite established effectiveness, in-person on-road assessment and rehabilitation are expensive, and limited professional service may not be readily accessible; simulator-based training may not fit every driver due to simulator sickness. In comparison, computerized training is easier to implement and could be delivered with little cost to older drivers with computer access. Based on the Drive Aware Task, a validated measure of attentional processes in hazard detection, we developed a computerized cognitive training method with a focus on hazard detection. In this study, we examined the effectiveness of this newly-developed interactive training program in improving older drivers' detection of road hazards. METHODS: Using a matched-pair design, nine triads of three older drivers (aged 65 or above) with matched pretest performance and gender were formed. For each triad, each participant was randomly allocated to one of the three groups: 1) active training group to receive the two training sessions (1.5-2.5h per session); 2) passive training group to receive two video-watching sessions (i.e., watch the video of training session performance from the corresponding paired participant); 3) no-contact control group. Older drivers' performances on hazard detection and simulated driving were measured before and after training. RESULTS: The active training group showed significant training effects on the computerized hazard detection task and simulated driving performance, while there were only marginal effects in the passive training group and no effects in the no-contact control group. A post-training survey suggested older drivers were receptive to the Drive Aware training program. CONCLUSIONS: The computerized Drive Aware training program has the potential to be used as a prevention and intervention tool to improve older drivers' hazard detection performance. Future studies should examine the effectiveness of this tool in more diverse samples and in long-term outcomes.

11.
Sci Rep ; 11(1): 12614, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34131249

RESUMO

In the adult pancreas, the presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear. Here, we identify that SET domain-containing protein 4 (SETD4), a histone lysine methyltransferase, is expressed in a small cell population in the adult mouse pancreas. Genetic lineage tracing shows that during pancreatic development, descendants of SETD4+ cells make up over 70% of pancreatic cells and then contribute to each pancreatic lineage during pancreatic homeostasis. SETD4+ cells generate newborn acinar cells in response to cerulein-induced pancreatitis in acinar compartments. Ablation of SETD4+ cells compromises regeneration of acinar cells, in contrast to controls. Our findings provide a new cellular narrative for pancreatic development, homeostasis and response to injury via a small SETD4+ cell population. Potential applications may act to preserve pancreatic function in case of pancreatic disease and/or damage.

12.
Food Res Int ; 145: 110419, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34112422

RESUMO

Due to highly nutritious and well-known prebiotic nature, okara (soy by-product) can improve the physiological benefits of probiotic consumption by enhancing the physicochemical stability and bioavailability of bacteria and metabolites, partially in food matrices and then in gastrointestinal tract. Initially, vitamin B2 producing probiotic Lactobacillus plantarum UFG10 was immobilized with 4% okara for soy milk fermentation. SEM micrographs showed firm adherence of UFG10 to okara surface depicting efficient immobilization. Soy milk fermented with okara immobilized UFG10 showed enhanced ß-glucosidase activity, stimulating the biotransformation of isoflavones from glucosides (daidzin, from 27.78 to 9.84 µg/mL; genistin, from 32.58 to 8.33 µg/mL) to aglycones (daidzein, from 0.19 to 30.84 µg/mL; genistein, from 1.42 to 33.10 µg/mL) and higher B2 production (1.53 µg/mL, 12 h) confirmed by HPLC. Okara addition and B2 enrichment could yield relatively higher antioxidant strength than control soy milk. PLSR correlation revealed the effects of okara and B2 on the functional properties of soy milk. After okara immobilization, soy milk showed higher soy protein digestibility after in vitro digestion for 225 min, higher aggregation, and lower protein molecular chains, qualitatively confirmed with Atomic force microscope. Okara immobilized bacterial cells exhibited relatively greater resistance up to 55.1% (p < 0.05) in simulated GIT, indicating okara as an ideal substrate for an efficient immobilization which ultimately improved the fate of soy B2 and protein bioaccessibility and functional products such as isoflavones for micro structural design of soy milk with improved nutrition and digestibility.


Assuntos
Leite de Soja , Digestão , Fermentação , Riboflavina , Vitaminas
13.
Pestic Biochem Physiol ; 176: 104871, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34119216

RESUMO

The cotton bollworm, Helicoverpa armigera, is a polyphagous pest threatening many economically important crops worldwide. Until recently, synthetic pyrethroids remain in wide use for controlling pest insects including the cotton bollworm. Understanding the metabolic mechanism of pyrethroids in a given pest can provide significant implication for a smart choice of insecticides, and such information is useful for the development of novel selective and safe insecticides. In this study, we used complexes of recombinant H. armigera cytochrome P450 CYP9A and NADPH-dependent cytochrome P450 reductase to investigate the capacity of three CYP9A paralogs in the transformation of seven structurally different pyrethroids by metabolism assays. The results showed that the three paralogous CYP9As were able to metabolize multiple pyrethroids. Interestingly, all the three CYP9As transformed pyrethrin-resembling pyrethroids (e.g. bioallethrin) more efficiently than the heavily modified ones (e.g. bifenthrin). These findings suggest that herbivorous insects can cope with synthetic insecticides using their physiological systems that initially evolved to survive exposure to the defensive chemicals in their host plants, adding support to the pre-adaptation hypothesis.


Assuntos
Inseticidas , Mariposas , Piretrinas , Animais , Inativação Metabólica , Resistência a Inseticidas , Inseticidas/farmacologia , Larva , Plantas
14.
Cardiovasc Ther ; 2021: 6628469, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104205

RESUMO

Background: Atrial fibrillation (AF) is the most common serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality in general population. Hypertension is the most prevalent and potentially modifiable risk factor for AF. This study is aimed at evaluating the effect of angiotensin receptor blocker (ARB) or calcium channel blocker (CCB) on AF recurrence among patients with hypertension and AF. Methods: The PubMed, EMBASE, Medline, and Cochrane Collaboration of Controlled Clinical Trials registry databases were searched from their inception to September 2020. Results: A total of 7 randomized controlled trials (RCTs) enrolling 1495 patients were included in our study. This finding showed that ARB had a statistically significant superiority in preventing AF recurrence (OR: 0.43, 95% CI: 0.30-0.72, P = 0.0006) and persistent AF (OR: 0.41, 95% CI: 0.24-0.71, P = 0.001) compared to CCB. Subgroup analysis showed that there was a significant difference in telmisartan subgroup (OR: 0.54, 95% CI: 0.23-1.29, P = 0.17) and nontelmisartan subgroup (OR: 0.42, 95% CI: 0.23-0.77, P = 0.005). Subgroup analysis indicated that nifedipine subgroup did not show a statistically significant difference on AF recurrence between ARB and CCB (OR: 0.88, 95% CI: 0.46-1.68, P = 0.69), but amlodipine subgroup showed that ARB had a significant superiority in prevention of AF recurrence (OR: 0.39, 95% CI: 0.27-0.56, P < 0.0001) compared with CCB. Conclusions: This study suggests that ARB is superior to CCB for preventing the AF recurrence and persistent AF among patients with hypertension and AF.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/epidemiologia , Anlodipino/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Humanos , Hipertensão/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fatores de Risco , Telmisartan/uso terapêutico
15.
Am J Physiol Heart Circ Physiol ; 320(6): H2385-H2400, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33989079

RESUMO

Cell-free hemoglobin (CFH) levels are elevated in septic shock and are higher in nonsurvivors. Whether CFH is only a marker of sepsis severity or is involved in pathogenesis is unknown. This study aimed to investigate whether CFH worsens sepsis-associated injuries and to determine potential mechanisms of harm. Fifty-one, 10-12 kg purpose-bred beagles were randomized to receive Staphylococcus aureus intrapulmonary challenges or saline followed by CFH infusions (oxyhemoglobin >80%) or placebo. Animals received antibiotics and intensive care support for 96 h. CFH significantly increased mean pulmonary arterial pressures and right ventricular afterload in both septic and nonseptic animals, effects that were significantly greater in nonsurvivors. These findings are consistent with CFH-associated nitric oxide (NO) scavenging and were associated with significantly depressed cardiac function, and worsened shock, lactate levels, metabolic acidosis, and multiorgan failure. In septic animals only, CFH administration significantly increased mean alveolar-arterial oxygenation gradients, also to a significantly greater degree in nonsurvivors. CFH-associated iron levels were significantly suppressed in infected animals, suggesting that bacterial iron uptake worsened pneumonia. Notably, cytokine levels were similar in survivors and nonsurvivors and were not predictive of outcome. In the absence and presence of infection, CFH infusions resulted in pulmonary hypertension, cardiogenic shock, and multiorgan failure, likely through NO scavenging. In the presence of infection alone, CFH infusions worsened oxygen exchange and lung injury, presumably by supplying iron that promoted bacterial growth. CFH elevation, a known consequence of clinical septic shock, adversely impacts sepsis outcomes through more than one mechanism, and is a biologically plausible, nonantibiotic, noncytokine target for therapeutic intervention.NEW & NOTEWORTHY Cell-free hemoglobin (CFH) elevations are a known consequence of clinical sepsis. Using a two-by-two factorial design and extensive physiological and biochemical evidence, we found a direct mechanism of injury related to nitric oxide scavenging leading to pulmonary hypertension increasing right heart afterload, depressed cardiac function, worsening circulatory failure, and death, as well as an indirect mechanism related to iron toxicity. These discoveries alter conventional thinking about septic shock pathogenesis and provide novel therapeutic approaches.


Assuntos
Hemoglobinas/metabolismo , Pneumonia/metabolismo , Artéria Pulmonar/fisiopatologia , Choque Séptico/metabolismo , Infecções Estafilocócicas/metabolismo , Acidose/metabolismo , Acidose/fisiopatologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Cães , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Hemoglobinas/farmacologia , Ferro/metabolismo , Ácido Láctico/metabolismo , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/fisiopatologia , Óxido Nítrico/metabolismo , Pneumonia/fisiopatologia , Troca Gasosa Pulmonar , Distribuição Aleatória , Choque Séptico/fisiopatologia , Staphylococcus aureus/crescimento & desenvolvimento
16.
Ecotoxicol Environ Saf ; 218: 112271, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33932654

RESUMO

The regulation of mitochondrial function, which is dominated by oxidative phosphorylation (OXPHOs), is important in fluoride induced cardiovascular disease. Based on the previous study of fluoride-induced mitochondrial structure and membrane potential abnormalities, this study integrated ITRAQ protein quantification and RNA-Seq methods to analyze the sequencing data of rat myocardial tissue under fluoride exposure (0, 30, 60 and 90 mg/L). A total of 22 differentially expressed genes associated with the OXPHOs pathway were screened by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) co-enrichment analysis, and were localizated by Interaction Network and calculated inter-genes and inter-omics correlations by Pearson correlation. In general, fluoride exposure can down-regulate genes related OXPHOs, particularly affecting the assembly of the complex I including Ndufa10, resulting in abnormal mitochondrial ATP synthesis and reduced myocardial energy supply. Most importantly, this study shows that the enriched information from the proteomics can explain the change process of energy production, but the specific molecules involved in energy supply cannot be obtained via transcriptomics information alone. Based on the results of transcriptional and protein analysis, our findings contribute to an innovative understanding of the pathways and molecular changes of myocardial injury induced by fluorosis.

17.
Analyst ; 146(12): 3971-3976, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-33997880

RESUMO

Depression is closely related to overactivation of N-methyl-d-aspartic acid (NMDA) receptors, and Zn2+ is a vital NMDA receptor modulator involved in the pathophysiological and physiological processes of depression. Therefore, quantitative and real-time detection of Zn2+ is very important for understanding the pathogenesis of depression. In this work, a near-infrared (NIR) fluorescent probe ISO-DPA was designed and synthesized for Zn2+ detection with a large Stokes shift (185 nm), high quantum yield (up to 44%), high sensitivity (LOD = 0.106 µM) and good pH stability. The probe showed rapid response within 10 s, accompanied by a distinct fluorescence change from faint to bright pink with the fluorescence intensity increasing 4.5-fold. Moreover, the sensing mechanism of ISO-DPA towards Zn2+ was supported by MALDI-TOF-MS and Job's plot. The probe ISO-DPA could detect instantaneous variation of exogenous and endogenous Zn2+ in PC12 cells. The bioimaging results reveal the increase of the endogenous Zn2+ concentration in PC12 cells under the oxidative stress induced by glutamate and confirm that overactivation of NMDA receptors results in an increase of the Zn2+ level. All the results proved that ISO-DPA is an excellent probe for detecting Zn2+ in solution and living cells and could help us better understand Zn2+ associated pathogenesis of depression.


Assuntos
Depressão , Corantes Fluorescentes , Animais , Diagnóstico por Imagem , Células PC12 , Ratos , Zinco/toxicidade
18.
Ann Palliat Med ; 10(5): 5316-5321, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33977756

RESUMO

BACKGROUND: Intradialytic hypotension (IDH) remains the most frequent severe side effect of hemodialysis (HD) and increases patient morbidity and mortality. Excessive ultrafiltration (UF) is considered the leading cause of IDH. This study developed a suitable prescription of UF to reduce the incidences of IDH episodes. METHODS: A retrospective study was performed to analyze 33,224 HD/hemodiafiltration (HDF) treatments in 312 patients. The prescription of UF were determined following the International Society of Peritoneal Dialysis (ISPD) guideline. The Pearson's method was used to study the correlation between relative variables. The receiver operating characteristic (ROC) curve was used to predict the value of the UF/weight ratio (UF/Wt) for IDH in all patients to establish a diagnostic cut-off point. Univariate and multivariate logistic regression analyses were applied to study the risk factors of IDH. RESULTS: Twelve thousand five hundred and fifty-eight sessions of IDH (38.7%) were identified, among which 1,224 (3.6%) were recorded with intervention against IDH. Both the systolic blood pressure (SBP) and mean arterial pressure (MAP) of the hemodialytic patients were positively correlated with the UF quantity and the UF/Wt, but negatively correlated with blood flow. The ROC curve showed that UF/Wt =0.04 was the cut-off point for IDH. Age [per 10-year increment, odds ratio (OR) =1.005, 95% confidence interval (CI): 1.004 to 1.007, P=0.000], diabetes mellitus (OR =1.209, 95% CI: 1.122 to 1.303, P=0.000), and UF/Wt >0.04 (OR =1.605, 95% CI: 1.532 to 1.682, P=0.000) were all independently associated with higher incidences of IDH. CONCLUSIONS: IDH commonly occurs during HD in Chinese patients. Unchangeable factors such as diabetes and age, and modifiable factors including UF were associated with IDH. A UF/Wt threshold more than 0.04 may be a potential alert for avoiding IDH, especially in the elderly and diabetic patients.


Assuntos
Hipotensão , Ultrafiltração , Idoso , China , Humanos , Hipotensão/etiologia , Prescrições , Diálise Renal/efeitos adversos , Estudos Retrospectivos
19.
Chem Asian J ; 16(12): 1619-1625, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-33932257

RESUMO

Zero-dimensional metal halides have attracted much attention due to their attractive photoelectric properties. Here, we propose a new strategy of synthesizing metal halides crystals by recrystallization in water. The as-synthesized Cs2 InCl5 (H2 O)-orange crystals are dissolved and recrystallized in water (Cs2 InCl5 (H2 O)-blue), with its photoluminescence (PL) changing from orange to blue, both of which are derived from self-trapping excitons (STEs). The time-resolved photoluminescence (TRPL) spectrum of Cs2 InCl5 (H2 O)-blue shows that it has an ultralong lifetime up to milliseconds (τ=52.98 ms), which is expected to be applied in biological sensors. The photoluminescence quantum yield (PLQY) increases from 2.25% to 11.61% in the self-assembly process. By using a post-doping method, the PL of crystals turns into red when we introduce Mn2+ as dopant while there is no obvious change upon using a traditional solvent-thermal method. Recrystallization in water and post-doping provide a new perspective for the synthesis and doping of metal halides.

20.
Expert Rev Vaccines ; : 1-7, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33960275

RESUMO

Objectives: China has implemented universal hepatitis B vaccination since 2002 and provided charge-free hepatitis B immunoglobulin (HBIG) to infants of HBV-infected mothers since July 2011. We aimed to compare mother-to-child transmission (MTCT) in children born before and since July 2011.Methods: In total, 5,149 children of HBV-infected mothers were tested for HBV markers. Group one contained 1,160 children born during August 2002-June 2011 and group two contained 3,989 children born during July 2011-June 2016.Results: In total, 92 (1.8%, 95% confidence interval [95%CI] 1.4-2.2) children were infected with HBV. None (0%, 95%CI 0.0-0.1) of 3,716 children of mothers with negative hepatitis B e antigen (HBeAg) was infected, whereas 92 (6.4%, 95%CI 5.2-7.8) of 1,433 children of HBeAg-positive mothers were infected (p < 0.0001). Among children of HBeAg-positive mothers, MTCT occurred in 10.3% (19/185) (95%CI 6.3-15.6) in group one and 5.8% (73/1,248) (95%CI 4.6-7.3) in group two (p = 0.02).Conclusions: Implementing charge-free active-passive immunoprophylaxis greatly reduces MTCT of HBV in children of HBeAg-positive mothers, highlighting the importance of timely administration of both hepatitis B vaccine and HBIG to prevent MTCT. The still remaining MTCT suggests that reducing maternal virus load before delivery is an additional important measure.

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