Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 91
Filtrar
1.
RSC Adv ; 14(29): 20595-20603, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38946764

RESUMO

The operation of the Cansolv tail gas treatment device in natural gas plants generates acidic and alkaline wastewater from the venturi unit and amine purification unit (APU), respectively. The APU wastewater is complex in composition and contains hard-to-degrade organic matter, which can adversely impact the normal functioning of the water treatment system. This study assesses the efficacy of three ozone-based advanced oxidation processes (ozone (O3), ozone/hydrogen peroxide (O3/H2O2), and ozone/Fenton (O3/Fenton)) for treating Cansolv wastewater, with chemical oxygen demand (COD) and total organic carbon (TOC) serving as indicators of organic degradation. The findings demonstrate that all three processes effectively eliminate coloration and reducible sulfur, with O3/Fenton exhibiting superior performance in removing organic substances. The treated wastewater has a clarified light-yellow appearance with residual COD levels at 43 mg L-1. Under the optimum Fenton oxidation conditions (initial pH 5, H2O2 dosage 97.8 mmol L-1, FeSO4·7H2O dosage 550 mg L-1), average TOC and COD removal rates reached 50% and 97%, respectively. After a treatment duration of 60 minutes, the wastewater demonstrated an enhanced membrane-specific flux, confirming the effectiveness of the O3/Fenton oxidation process in mitigating membrane fouling while ensuring the stable operation of the wastewater treatment system.

2.
Cell ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38908367

RESUMO

Insufficient telomerase activity, stemming from low telomerase reverse transcriptase (TERT) gene transcription, contributes to telomere dysfunction and aging pathologies. Besides its traditional function in telomere synthesis, TERT acts as a transcriptional co-regulator of genes pivotal in aging and age-associated diseases. Here, we report the identification of a TERT activator compound (TAC) that upregulates TERT transcription via the MEK/ERK/AP-1 cascade. In primary human cells and naturally aged mice, TAC-induced elevation of TERT levels promotes telomere synthesis, blunts tissue aging hallmarks with reduced cellular senescence and inflammatory cytokines, and silences p16INK4a expression via upregulation of DNMT3B-mediated promoter hypermethylation. In the brain, TAC alleviates neuroinflammation, increases neurotrophic factors, stimulates adult neurogenesis, and preserves cognitive function without evident toxicity, including cancer risk. Together, these findings underscore TERT's critical role in aging processes and provide preclinical proof of concept for physiological TERT activation as a strategy to mitigate multiple aging hallmarks and associated pathologies.

3.
Sci Rep ; 14(1): 13940, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886463

RESUMO

Perilla frutescens (L.) Britton, a member of the Lamiaceae family, stands out as a versatile plant highly valued for its unique aroma and medicinal properties. Additionally, P. frutescens seeds are rich in Îs-linolenic acid, holding substantial economic importance. While the nuclear and chloroplast genomes of P. frutescens have already been documented, the complete mitochondrial genome sequence remains unreported. To this end, the sequencing, annotation, and assembly of the entire Mitochondrial genome of P. frutescens were hereby conducted using a combination of Illumina and PacBio data. The assembled P. frutescens mitochondrial genome spanned 299,551 bp and exhibited a typical circular structure, involving a GC content of 45.23%. Within the genome, a total of 59 unique genes were identified, encompassing 37 protein-coding genes, 20 tRNA genes, and 2 rRNA genes. Additionally, 18 introns were observed in 8 protein-coding genes. Notably, the codons of the P. frutescens mitochondrial genome displayed a notable A/T bias. The analysis also revealed 293 dispersed repeat sequences, 77 simple sequence repeats (SSRs), and 6 tandem repeat sequences. Moreover, RNA editing sites preferentially produced leucine at amino acid editing sites. Furthermore, 70 sequence fragments (12,680 bp) having been transferred from the chloroplast to the mitochondrial genome were identified, accounting for 4.23% of the entire mitochondrial genome. Phylogenetic analysis indicated that among Lamiaceae plants, P. frutescens is most closely related to Salvia miltiorrhiza and Platostoma chinense. Meanwhile, inter-species Ka/Ks results suggested that Ka/Ks < 1 for 28 PCGs, indicating that these genes were evolving under purifying selection. Overall, this study enriches the mitochondrial genome data for P. frutescens and forges a theoretical foundation for future molecular breeding research.


Assuntos
Uso do Códon , Genoma Mitocondrial , Perilla frutescens , Edição de RNA , Edição de RNA/genética , Perilla frutescens/genética , Filogenia , Repetições de Microssatélites/genética , RNA de Transferência/genética , Composição de Bases , Anotação de Sequência Molecular
4.
Sci Rep ; 14(1): 8523, 2024 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609472

RESUMO

Herb genomics, at the forefront of traditional Chinese medicine research, combines genomics with traditional practices, facilitating the scientific validation of ancient remedies. This integration enhances public understanding of traditional Chinese medicine's efficacy and broadens its scope in modern healthcare. Stachys species encompass annual or perennial herbs or small shrubs, exhibiting simple petiolate or sessile leaves. Despite their wide-ranging applications across various fields, molecular data have been lacking, hindering the precise identification and taxonomic elucidation of Stachys species. To address this gap, we assembled the complete chloroplast (CP) genome of Stachys geobombycis and conducted reannotation and comparative analysis of seven additional species within the Stachys genus. The findings demonstrate that the CP genomes of these species exhibit quadripartite structures, with lengths ranging from 14,523 to 150,599 bp. Overall, the genome structure remains relatively conserved, hosting 131 annotated genes, including 87 protein coding genes, 36 tRNA genes, and 8 rRNA genes. Additionally, 78 to 98 SSRs and long repeat sequences were detected , and notably, 6 highly variable regions were identified as potential molecular markers in the CP genome through sequence alignment. Phylogenetic analysis based on Bayesian inference and maximum likelihood methods strongly supported the phylogenetic position of the genus Stachys as a member of Stachydeae tribe. Overall, this comprehensive bioinformatics study of Stachys CP genomes lays the groundwork for phylogenetic classification, plant identification, genetic engineering, evolutionary studies, and breeding research concerning medicinal plants within the Stachys genus.


Assuntos
Genoma de Cloroplastos , Stachys , Teorema de Bayes , Filogenia , Melhoramento Vegetal
5.
Journal of Experimental Hematology ; (6): 1108-1112, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1009968

RESUMO

OBJECTIVE@#To study the expression level of serum B-cell maturation antigen (sBCMA) in the peripheral blood of newly diagnosed multiple myeloma (MM) patients, and explore its relationship with the prognosis of MM patients.@*METHODS@#The peripheral blood of 31 newly diagnosed MM patients and 30 healthy volunteers were collected. The level of sBCMA in the peripheral blood was detected by enzyme-linked immunosorbent assay (ELISA). The correlation between the level of sBCMA and the prognosis of MM patients was analyzed.@*RESULTS@#The level of sBCMA in newly diagnosed MM patients was significantly higher than that in healthy controls (P <0.05). The level of sBCMA was closely related to the plasma cells ratio in bone marrow, the M protein level and the treatment (P <0.05). The level of sBCMA was negatively correlated with the overall survival (OS) of MM patients (r =-0.47). MM patients with low expression of sBCMA had significantly longer OS than patients with high expression of sBCMA (P <0.05).@*CONCLUSION@#The level of sBCMA is significantly increased in MM patients, which is expected to be a new indicator for evaluating the curative efficacy and prognosis of MM patients. Targeting sBCMA may provide new ideas for the treatment of MM.


Assuntos
Humanos , Mieloma Múltiplo , Antígeno de Maturação de Linfócitos B/metabolismo , Prognóstico
6.
Virus Res ; 312: 198716, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35240224

RESUMO

Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage. We performed reverse transcriptase droplet digital PCR (RT-ddPCR) and luminex assays to investigate virus proliferation and immune reactions in BV2 MGs infected with influenza A(H1N1)pdm09 virus. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to investigate the dynamic change in the protein expression profile in BV2 MGs to gain insight into the CNS response to influenza A (H1N1) pdm09 infection. Our results showed that the influenza A(H1N1)pdm09 virus was replicative and productive in BV2 MG cells, which produced cytokines such as interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. The expression of osteopontin (OPN) in the influenza A (H1N1) pdm09-infected BV2 MGs was upregulated at 16 and 32 h post-infection (hpi) compared to that in the control group, resulting in aggravated brain damage and inflammation. Our study indicates that OPN signalling might provide new insights into the treatment of CNS injury and neurodegenerative diseases in IAE.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Citocinas/genética , Expressão Gênica , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Microglia
7.
Front Microbiol ; 13: 791563, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308357

RESUMO

Mukawa virus (MKWV), a novel tick-borne virus (TBV) of the genus Phlebovirus of family Phenuiviridae, has been firstly reported in Ixodes persulcatus in Japan. In this study, we made an epidemiological investigation in China to obtain the geographic distribution and genetic features of this virus outside Japan. We screened 1,815 adult ticks (665 I. persulcatus, 336 Dermacentor silvarum, 599 Haemaphysalis longicornis, 170 Rhipicephalus microplus, 45 Haemaphysalis concinna) and 805 wild small mammals collected from eight provinces. The positive rate of 6.77% (45/665, including 18 female and 27 male I. persulcatus) and 2.22% (1/45, 1 male H. concinna) were obtained from I. persulcatus and H. concinna in Heilongjiang province, respectively. No evidence of MKWV infection was found in other three tick species or any of the mammalian species. The virus can infect the Vero cells successfully, indicating the ability of MKWV to replicate in mammalian cells. A phylogenetic tree based on the nucleotide sequences of L, M, and S segments demonstrated that the Japanese MKWV variant, our two MKWV variants, and KURV were clustered with the members of the mosquito/sandfly-borne phleboviruses and distant from other tick-borne phenuiviruses. A phylogenetic analysis based on 895 bp partial L gene sequences (n = 46) showed that all MKWV sequences were separated into three lineages. Our results showed the presence of MKWV in I. persulcatus and H. concinna in northeast of China, highlighting the necessity of epidemiological study in wider regions. Due to the ability of MKWV to replicate in mammalian cells, the potential for zoonosis, and wide distribution of I. persulcatus and H. concinna in China, the important vectors of MKWV, further screening to more tick species, wild animals, domestic animals, and humans raises up practical significance.

8.
Epidemics ; 39: 100553, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35287110

RESUMO

BACKGROUND: Understanding the relative transmissibility of SARS-CoV-2 virus across different contact settings and the possibility of superspreading events is important for prioritizing disease control. Such assessment requires proper consideration of individual level exposure history, which is made possible by contact tracing. METHODS: The case-ascertained study in Shandong, China including 97 laboratory-confirmed index cases and 3158 close contacts. All close contacts were quarantined after their last exposure of index cases. Contacts were tested for COVID-19 regularly by PCR to identify both symptomatic and asymptomatic infections. We developed a Bayesian transmission model to the contact tracing data to account for different duration of exposure among individuals to transmission risk in different settings, and the heterogeneity of infectivity of cases. RESULTS: We estimate secondary attack rates (SAR) to be 39% (95% credible interval (CrI): 20-64%) in households, 30% (95% CrI: 11-67%) in healthcare facilities, 23% (95% CrI: 7-51%) at workplaces, and 4% (95% CrI: 1-17%) during air travel. Models allowing heterogeneity of infectivity of cases provided a better goodness-of-fit. We estimated that 64% (95% CrI: 55-72%) of cases did not generate secondary transmissions, and 20% (95% CrI: 15-26%) cases explained 80% of secondary transmissions. CONCLUSIONS: Household, healthcare facilities and workplaces are efficient setting for transmission. Timely identification of potential superspreaders in most transmissible settings remains crucial for containing the pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Teorema de Bayes , COVID-19/epidemiologia , China/epidemiologia , Busca de Comunicante , Humanos
9.
Int Immunopharmacol ; 105: 108547, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35066448

RESUMO

BACKGROUND: Tissue kallikrein offers a wide spectrum of biological activity in the protection against various types of injury. However, information on its role in tacrolimus (TAC)-induced renal injury is limited. OBJECTIVES: This study aimed to assess the beneficial effects of pancreatic kininogenase (PK) in a rat model of chronic TAC nephrotoxicity and in vitro. METHODS: Sprague Dawley rats were treated daily with either TAC or PK or a combination of the two for four weeks. The influence of PK on renal injury was examined in terms of renal function, histopathology, cytokine expression, oxidative stress, intracellular organelles, programmed cell death, and PI3K/AKT signaling. Human kidney proximal tubular (HK-2) cells and mouse mesangial (SV40 MES13) cells treated with TAC and PK were also studied. RESULTS: PK treatment improved renal function and histopathology. This effect was paralleled by downregulation of proinflammatory and profibrotic cytokine expression. TAC-induced oxidative stress was closely associated with endoplasmic reticulum stress and mitochondrial dysfunction, resulting in excessive programmed cell death (apoptosis and autophagy) that was significantly abrogated by concurrent PK interference with PI3K/AKT signaling. PK also stimulated bradykinin receptor 1 (B1R) and B2R mRNA synthesis and increased bioactive nitric oxide (NO) and cAMP concentrations in TAC-treated kidneys. Blockade of either B1R or B2R eliminated the renoprotective effects of PK. In HK-2 and SV40 MES13 cells, PK decreased TAC-induced overproduction of intracellular reactive oxygen species and inhibited apoptotic cells, whereas cell viability was improved. Moreover, activated PI3K/AKT signaling in HK-2 cells was inhibited by PK and the PI3K inhibitor, LY294002. CONCLUSIONS: These findings indicate that PK treatment protects against chronic TAC nephrotoxicity via inhibition of PI3K/AKT signaling.


Assuntos
Fosfatidilinositol 3-Quinases , Tacrolimo , Animais , Apoptose , Rim , Camundongos , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores da Bradicinina/metabolismo , Tacrolimo/farmacologia , Calicreínas Teciduais/metabolismo , Calicreínas Teciduais/farmacologia
10.
Ecotoxicol Environ Saf ; 229: 113063, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34890985

RESUMO

Antibiotic residues and antibiotic resistance have been widely reported in aquatic environments. Hydrolysis of antibiotics is one of the important environmental processes. Here we investigated the hydrolytic transformation of four tetracycline antibiotics i.e. tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC) and doxycycline (DC) under different environmental conditions, and determined their parents and transformation products in the wastewater treatment plants (WWTPs). The results showed that the hydrolysis of the four tetracyclines followed first-order reaction kinetics, and the acid-catalyzed hydrolysis rates were significantly lower than the base-catalyzed and neutral pH hydrolysis rates. The effect of temperature on tetracycline hydrolysis was quantified by Arrhenius equation, with Ea values ranged from 42.0 kJ mol-1 to 77.0 kJ mol-1 at pH 7.0. In total, nine, six, eight and nine transformation products at three different pH conditions were identified for TC, CTC, OTC and DC, respectively. The main hydrolysis pathways involved the epimerization/isomerization, and dehydration. According to the mass balance analysis, 4-epi-tetracycline and iso-chlortetracycline were the main hydrolytic products for TC and CTC, respectively. The 2 tetracyclines and 4 hydrolysis products were found in the sludge samples in two WWTPs, with concentrations from 15.8 ng/g to 1418 ng/g. Preliminary toxicity evaluation for the tetracyclines and their hydrolysis products showed that some hydrolysis products had higher predicted toxicity than their parent compounds. These results suggest that the hydrolysis products of tetracycline antibiotics should also be included in environmental monitoring and risk assessment.


Assuntos
Tetraciclina , Purificação da Água , Antibacterianos , Hidrólise , Cinética , Tetraciclina/toxicidade , Tetraciclinas
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-956149

RESUMO

Objective:To investigate the relationship between substance addiction, T lymphocytes and depression in methamphetamine (MA) withdrawal patients.Methods:A total of 105 men who met the inclusion criteria were selected from compulsory isolation drug rehabilitation center of Baini lake, Hunan Province.All participants were suveyed by desires for drug questionnaire(DDQ) and self-rating depression scale (SDS), and the function of T lymphocyte subsets were detected by flow cytometry.All data were managed and analyzed using the SPSS 21.0 and AMOS 21.0 statistical software packages.Results:(1) The respondents were mainly junior high school or below (81.9%), unmarried and divorced (67.6%), unemployed (55.2%), hot suction (47.6%), and careless friends (32.4%), and 67.7% of MA abstinence had depressive symptoms. (2) SDS was positively correlated with desire and intention(DI), negative reinforcement (NR) and CD8+ %( r=0.408-0.897, all P<0.01), while negatively correlated with medication control, CD3+ %, CD4+ %, and CD4+ /CD8+ ( r=-0.792--0.263, all P<0.01). DI had significant positive correlation with CD8 + %( r=0.216, P<0.05), and negative correlation with CD4+ /CD8+ ( r=-0.217, P<0.05). NR had significant positive correlation with CD8 + %( r=0.259, P<0.05), and had significant negative correlations with CD3+ %, CD4+ %, and CD4+ /CD8+ ( r=-0.275-0.200, all P<0.05). Medication cotrol had a significant negative correlation with CD8+ %( r=-0.363, P<0.05), and significant positive correlations with CD4+ % and CD4+ /CD8+ ( r=0.288, 0.261, both P<0.05). (3)The model fitting index showed that DI, NR and medication control had significant direct effects on T lymphocyte subsets (all P<0.05). DI, medication control and T lymphocyte subsets had significant direct effects on self-evaluation of depressive symptoms (all P<0.05). NR, DI and medication control indirectly affected depressive symptoms through T lymphocyte subsets (all P<0.05). There were three path relationships: ① DI indirectly affected SDS via T lymphocyte subsets; ② Medication control indirectly affected SDS via T lymphocyte subsets; ③ NR indirectly affected SDS via T lymphocyte subsets. Conclusion:The structural equation model suggests that the degree of addiction in MA abstinence affecting depressive mood may be related to hypofunctional T lymphocyte subsets and provide methods for the prevention and treatment of drug addiction.

12.
Front Microbiol ; 12: 738808, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721338

RESUMO

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease with high mortality. However, detailed analysis is lacking to explore the complex effect of sex with age or comorbidities. Methods: A retrospective cohort study was performed among 2,938 SFTS patients entered during 2011-2020 in Xinyang, China. The case fatality rate (CFR) was estimated for their association with sex, age, and comorbidities by an interactive way. The difference of immune response between sex was explored in an age dependent way. Results: An overall CFR of 15.3% (450/2,938) was obtained, which appeared to be higher in males than in females [17.7% vs. 13.6%, adjusted odds ratio (aOR) = 1.24; 95% CI, 1.00-1.53; P = 0.048] and increased dramatically with age (P < 0.001). The associations between sex and SFTS fatal outcome were age-dependent and varied according to the status of comorbidities. The mortality-related risk conferred by older age was more pronounced in males, with aOR (95% CI) to be 5.76 (3.75-8.84) vs. 5.30 (3.54-7.95) in female. Sex-stratified analysis disclosed significant associations between death and comorbidities among female patients (aOR = 1.87, 95% CI: 1.40-2.49; P < 0.001), while none among males. Among females, the significant associations between presence of comorbidity and fatal outcome differed among age groups, with aOR (95% CI) decreased from 2.28 (1.16-4.46) in ≤60 years, to 2.06 (1.34-3.18) in 60-70 years and further to 1.55 (0.97-2.47) in >70 years. Altogether 194 SFTS patients were randomly selected for the test of B cells, natural killer (NK) cells, CD4 cells percentages, and anti-SFTSV IgM antibody level, the results revealed that males >60 years had significantly decreased percentages of B cells, CD4 cells, lower anti-SFTSV IgM antibody titer, and increased level of NK cells than male aged ≤60 years, while none of these age specific differences was observed in the females. This finding underlies the more pronounced age specific difference in CFR among male than female. Conclusions: Males had a significantly higher mortality of SFTS than did females, and more likely to be affected by aging for SFTS mortality. This difference can be explained by the effect from comorbidities and the host immunity. It is essential to take a sex- and age-based approach to SFTS treatment and management.

13.
J Food Biochem ; 45(10): e13889, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34426988

RESUMO

In the present study, the anti-inflammatory effect of Lycium barbarum polysaccharide (LBP) and the possible molecular mechanism thereof were examined, so as to perceive the pharmacological action of LBP. With acute peritonitis in mice as the inflammatory model, the protective effect of LBP on peritonitis mice was evaluated by recording the effect of behavioral scores, studying the pathological damage of intestine and liver, and detecting the levels of inflammatory cytokines. Additionally, by establishing an lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, the effect of LBP on RAW264.7 cell phenotype and culture supernatant inflammatory markers was observed. Finally, the activation of inflammation-related target genes, such as iNOS, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) p65, and IκBα, were further detected. The results reveal that pretreatment with LBP could decrease the behavioral score of inflammatory mice, inhibit the secretion of pro-inflammatory factors, and reduce liver and intestine injury. LBP can regulate the effect of lipopolysaccharide on the polarization of RAW264.7 cells, and reduce the production of NO and cytokines (TNF-α, IL-1ß, IL-6). Further, LBP pretreatment was found to be able to significantly reduce the expression of iNOS, TLR4, NF-κB p65, and IκBα in macrophages. The present research provides evidence that LBP exerts potential anti-inflammatory activity in LPS-induced RAW264.7 macrophages via inhibiting TLR4 and NF-κB inflammatory sites and improving the behavior score of peritonitis mice. PRACTICAL APPLICATIONS: In recent years, the number of deaths worldwide has continued to rise as a result of inflammation. Despite said rise in deaths, many synthetic drugs with anti-inflammatory properties are significantly expensive and also have a host of side effects. Thus, the development of new anti-inflammatory drugs derived from medicinal plants has broad application potential. As such, in the present study, lipopolysaccharide (LPS)-induced macrophages were used to establish inflammatory cell models to verify the anti-inflammatory effect of Lycium barbarum polysaccharides (LBP). Findings were made that LBP could reduce the expression levels of inflammatory cytokines and NO by regulating macrophage polarization and NF-κB translocation, and thus, could exert anti-inflammatory activity. In addition, by intraperitoneal injection of LPS to establish peritonitis mice models, LBP pretreatment was found to have significantly modified the behavioral score of mice, while decreasing the secretion of inflammatory factors and the damage to several organs. The present study provides a basis for further understanding the effects of LBP in acute inflammation.


Assuntos
Lycium , Peritonite , Animais , Medicamentos de Ervas Chinesas , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Camundongos , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico
14.
Nat Aging ; 1(12): 1162-1174, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-35036927

RESUMO

Amyloid-induced neurodegeneration plays a central role in Alzheimer's disease (AD) pathogenesis. Here, we show that telomerase reverse transcriptase (TERT) haploinsufficiency decreases BDNF and increases amyloid-ß (Aß) precursor in murine brain. Moreover, prior to disease onset, the TERT locus sustains accumulation of repressive epigenetic marks in murine and human AD neurons, implicating TERT repression in amyloid-induced neurodegeneration. To test the impact of sustained TERT expression on AD pathobiology, AD mouse models were engineered to maintain physiological levels of TERT in adult neurons, resulting in reduced Aß accumulation, improved spine morphology, and preserved cognitive function. Mechanistically, integrated profiling revealed that TERT interacts with ß-catenin and RNA polymerase II at gene promoters and upregulates gene networks governing synaptic signaling and learning processes. These TERT-directed transcriptional activities do not require its catalytic activity nor telomerase RNA. These findings provide genetic proof-of-concept for somatic TERT gene activation therapy in attenuating AD progression including cognitive decline.


Assuntos
Doença de Alzheimer , Telomerase , Camundongos , Humanos , Animais , Doença de Alzheimer/genética , Telomerase/genética , Peptídeos beta-Amiloides/metabolismo , Cognição , Neurônios/metabolismo
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1004026

RESUMO

【Objective】 To analyze the quality level of the laboratory pre-analytical phase, so as to take effective quality improvement interventions to further standardize the operation and provide basis for ensuring the quality of blood testing. 【Methods】 Pre-analytical phase quality indicators of blood screening laboratory in Shanghai Blood Center were established, and those had serious impact on blood safety were defined as the sentinel indicators. The pre-analytical quality level of our laboratory from 2018 to 2020 was statistically analyzed in terms of four parts including sample collection, preservation and submission, centrifugation and quality inspection, which contained 17 indicators. 【Results】 Eleven sentinel indicators were established, and the order of peak value from high to low in three years was as follows: " label omission" rated at 0.000 62% (2020), " label error" 0.000 57% (2018), " inappropriate storage of samples before detection" 0.007 39 (2018), " unqualified application form for sample detection" 0.007 39 (2018). The causes were analyzed and relevant measures were taken. Six monitoring indicators were established, and the order of peak value from high to low in three years was as follows: " insufficient sample" rated at 0.002 59% (year 2018), " hemolysis" 0.002 80% (year 2020), " pale color of blood supernatant (diluted)" 0.000 86 (2018), " automatic sampling interfered by blood clot" 0.027 02% (2018). 【Conclusion】 The quality indexes of pre-analytical phase in our laboratory have reached the level of domestic and international clinical laboratories. The establishment of pre-analytical quality indicators and sentinel indicators, with effective analysis and application, can fully record and monitor the quality of each link before laboratory testing, which is helpful to timely identify risks, detect deviations, and quickly implement corrective and preventive measures, thus further ensure the safety of clinical blood use.

16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-906395

RESUMO

Objective:To investigate the effects of curdione on the proliferation, apoptosis and cell cycle of triple negative breast cancer cell line MDA-MB-231. Method:MDA-MB-231 cells were cultured<italic> in vitro</italic> with capecitabine (positive control) and curdione at different concentrations (125, 250, 500, 1 000, and 2 000 μmol·L<sup>-1</sup>), respectively, for detecting their viability using the cell counting kit-8 (CCK-8) at 24 and 48 h. Three effective inhibitory concentrations (250, 500, and 1 000 μmol·L<sup>-1</sup>) against cell proliferation were selected for subsequent experiments. The effect of curdione on cell cycle was determined by flow cytometry combined with propidium iodide (PI) staining. After the set-up of high-concentration (2 000 μmol·L<sup>-1</sup>) group, the effect of curdione on cell mitochondrial membrane potential was measured by JC-1(5,5,6,6-tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide) staining, followed by the detection of cell apoptosis by flow cytometry combined with Annexin V-FITC/PI double staining. The changes in cell cycle status and apoptosis-related protein expression following curdione intervention were assayed by Western blot. Result:Compared with the blank control, curdione at 250, 500, 1 000, and 2 000 μmol·L<sup>-1 </sup>significantly inhibited the proliferation of MDA-MB-231 cells (<italic>P</italic><0.01), exhibiting a concentration- and time-response relationship. The half maximal inhibitory concentration (IC<sub>50</sub>) values at 24 and 48 h were 1 607 and 1 401 μmol·L<sup>-1</sup>, respectively. Curdione at 250, 500, and 1 000 μmol·L<sup>-1</sup> arrested cells in G<sub>1</sub> phase. Curdione at 250 μmol·L<sup>-1 </sup>had no effect on cell mitochondrial membrane potential, which, however, declined significantly in the 500, 1 000, and 2 000 μmol·L<sup>-1 </sup>groups (<italic>P</italic><0.05, <italic>P</italic><0.01). Curdione at 250, 500, and 1 000 μmol·L<sup>-1 </sup>obviously increased the proportion of apoptotic cells (<italic>P</italic><0.05, <italic>P</italic><0.01). Curdione at each concentration elevated the Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio (<italic>P</italic><0.05, <italic>P</italic><0.01), but did not change the cysteinyl aspartate-specific protease-3 (Caspase-3) expression. The protein expression levels of Caspase-9, cleaved Caspase-9, cleaved Caspase-3, p53, and p21 were up-regulated (<italic>P</italic><0.05). Conclusion:A certain concentration of curdione inhibits the proliferation of MDA-MB-231 cells, which may be related to its efficacy in arresting cell cycle and inducing apoptosis.

17.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-875497

RESUMO

Background/Aims@#Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. @*Methods@#Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. @*Results@#LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. @*Conclusions@#LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-883992

RESUMO

Objective:To observe the changes of plasma oxytocin (OT), arginine vasopressin (AVP) and anxiety after exercise intervention in male opioids-dependent patients.Methods:Forty-five male opioids addicts who met the inclusion criteria and voluntarily participated in exercise rehabilitation were enrolled.According to stratified random sampling, all subjects were divided into exercise group ( n=22) and control group( n=23). Exercise group attended aerobic exercise combined with resistance training intervention, 5 times per week for 8 weeks.Aerobic exercise was mainly treadmill and elliptical, while resistance training was based on strength and endurance training.Subjects completed self-rating anxiety scale (SAS) and Chinese perceived stress perception scale (CPSS) before and after intervention, as well as physical fitness tests. Besides, plasma OT and AVP levels were detected.Independent sample t-test, paired sample t-test, and Chi-square test were conducted by using SPSS 20.0 software. Results:Before the intervention, there were no significant differences between the two groups in demography, drug history, SAS, CPSS, plasma OT and AVP(all P>0.05). The overall anxiety detection rate was 66.67%, the scores of SAS and CPSS were both higher than the Chinese norm, and the difference was significant(both P<0.01) . After the intervention, the levels of plasma AVP, the scores of SAS and CPSS in the exercise group (AVP(19.57±2.23)pg/ml, SAS(50.17±10.09), CPSS(36.59±6.36)) were significantly lower than those in the control group (AVP(22.53±2.56)pg/ml, SAS(57.12±12.00), CPSS(43.09±5.57), all P<0.05), and plasma OT((61.98±5.27) pg/ml) was significantly higher than that in the control group ((54.64±7.62) pg/ml)( P<0.01). Compared with baseline, maximal oxygen uptake(VO 2max), 1 min push-ups and sitting body flexion increased significantly in the exercise group (all P<0.05). Conclusion:Opioids drug addicts were prone to excessive stress and anxiety and other negative emotions in the process of drug withdrawal. Eight-week aerobic combined with resistance exercise changed the plasma OT and AVP levels of opioids addicts, effectively alleviated the perceived stress, improved the anxiety state and their health related fitness level.

19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-919163

RESUMO

Background/Aims@#Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. @*Methods@#Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). @*Results@#Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. @*Conclusions@#Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-798354

RESUMO

Objective: To investigate effect of curdione on the migration and invasion of human breast cancer HCC1937 cells and its mechanism.Method: HCC1937 cells were cultured in vitro and treated with curdione at various doses (0, 12.5, 25, 50, 100, 200, 400 μmol·L-1) for 24, 48 h, the cell viability was detected by cell counting kit-8 method. curdione groups (12.5, 25, 50 μmol·L-1) and blank group were established. The effect of curdione on the adhesion of HCC1937 cells was detected by the cell adhesion assay. The effect of curdione on migration of HCC1937 cells was detected by wound healing assay. The effect of curdione on the migration and invasion of HCC1937 cells were detected by transwell chamber assay. The effect of curdione on regulation of mitogen-activated protein kinase(MAPK)and protein kinase B(Akt)signaling pathways and the protein expressions of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) of HCC1937 cells were detected by the Western blot analysis. Effect of curdione on mRNA expressions of MMP-2 and MMP-9 of HCC1937 cells were detected by Real-time PCR.Result: Compared with the blank group, curdione (12.5, 25, 50 μmol·L-1) groups had no significant effect on cell viability, but a remarkable effect on cell viability HCC1937 cells, and cell viability was gradually decreased with the increase of the concentration of curdione (PP-1) had a significant effect on cell adhesion rate, migration rate and invasion rate of HCC1937 cells (PP-1) could down-regulate phosphorylation levels of key proteins extracellular regulated protein kinases(ERK), c-Jun N-terminal kinase(JNK), Akt on MAPK and Akt signaling pathways (PConclusion: curdione can inhibit the migration and invasion of human breast cancer HCC1937 cells, and the mechanism may be related to down-regulation of phosphorylation levels of key proteins ERK, JNK, Akt on MAPK and Akt signaling pathways, so as to reduce the expressions of MMP2 and MMP-9.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...