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Ambient fine particulate matter (PM2.5) is a threat to public health. The P2 X 7purinergic receptor (P2X7R) is a modulator that responds to inflammation. Yet the role of P2X7R in the mediation of PM2.5-induced pulmonary cytotoxicity is rarely investigated. In this study, the expression of P2X7R and its effect on cell viability, oxidative damage, apoptosis, mitochondrial dysfunction and underlying mechanism following PM2.5 treatment in rat alveolar macrophages (NR8383) were analyzed. The outcome indicated that PM2.5 exposure significantly increased the expression of P2X7R, while P2X7R antagonist oATP markedly alleviate the production of reactive oxygen species (ROS), Nitrite Oxidation (NO), mitochondrial membrane potential, apoptosis rate, and release of inflammatory cytokines. In contrast, P2X7 agonist BzATP showed opposite effect in PM2.5-treated NR8383 cells. Therefore, these results demonstrated that P2X7R participated in PM2.5-induced pulmonary toxicity, while the blockade of P2X7R is a promising therapeutic approach of treating PM2.5-induced lung diseases.
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Material Particulado , Receptores Purinérgicos P2X7 , Ratos , Animais , Receptores Purinérgicos P2X7/metabolismo , Material Particulado/toxicidade , Pulmão , Espécies Reativas de Oxigênio/metabolismo , Estresse OxidativoRESUMO
BACKGROUND: The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) has not been elucidated, but urinary microorganisms and metabolites have been shown to be closely associated with the inflammatory response of IC/BPS. Nevertheless, the exact mechanisms related to this response have not been clarified. METHODS: 16S rRNA sequencing and untargeted metabolomics techniques were used to analyse the urinary microbial and metabolite profiles of 30 IC/BPS patients and 30 healthy controls, and correlation analyses were performed to explore the mechanisms by which they might be involved in the inflammatory response of IC/BPS. RESULTS: Twenty-eight differential genera, such as Lactobacillus and Sphingomonas, were identified. A total of 44 differential metabolites such as 1,3,7-trimethyluric acid and theophylline were screened. The abundance of Lactobacillus and Escherichia-Shigella was significantly higher in the urine of female IC/BPS patients and healthy controls compared to males, while Bacteroides and Acinetobacter were lower than in males. The results of the Pearson correlation analysis suggested that differential microorganisms may influence the composition of metabolites. The Lactobacillus genus may be a protective bacterium against IC/BPS, whereas Sphingomonas may be a pathogenic factor. The differential metabolite theophylline, as an anti-inflammatory substance, may downregulate the inflammatory response of IC/BPS. CONCLUSIONS: This study revealed microbial and metabolite profiles in the urine of IC/BPS patients versus healthy controls in both males and females. We also found some microorganisms and metabolites closely related to the inflammatory response of IC/BPS, which provided directions for future aetiological and therapeutic research.
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Cistite Intersticial , Masculino , Humanos , Feminino , Cistite Intersticial/urina , RNA Ribossômico 16S/genética , Teofilina , Metabolômica , MetabolomaRESUMO
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI), which is widely used for anti-HIV-1. Evidences revealed that several central nervous system side effects could be observed in mice and patients with administration of EFV. However, the detailed mechanisms are still unknown. In this study, we investigated the effects of long-term EFV treatment on cognitive functions and the potential underlying mechanisms in mice. We maintained C57BL/6 mice aged 2 months with treatment containing 40 or 80 mg/kg/day EFV for 5 months, while control group treated with saline. The cognitive functions were evaluated by novel object recognition test, Barnes maze test and Morris water maze. The results showed significant short-term memory impairment in 40 and 80 mg/kg groups, and notable spatial learning and memory impairments in 80 mg/kg group, without any spontaneous activity alteration. Moreover, EFV induced impairments in dendritic integrity and synaptic plasticity in hippocampus. Furthermore, Significant increases were observed in the expression levels of pro-IL-1ß, a similar tendency of TNF-α and phosphorylation of p65 of the 80 mg/kg group compared with control group. These results imply that long-term EFV treatment causes synaptic dysfunction resulting in cognitive deficits, which might be induced by the enhanced pro-inflammatory cytokines IL-1ß and TNF-α via activating NF-κB pathway.
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Alcinos/toxicidade , Benzoxazinas/toxicidade , Cognição/efeitos dos fármacos , Disfunção Cognitiva/fisiopatologia , Ciclopropanos/toxicidade , Transtornos da Memória/fisiopatologia , Doenças Neuroinflamatórias/fisiopatologia , Animais , Cognição/fisiologia , Disfunção Cognitiva/induzido quimicamente , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/induzido quimicamente , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/induzido quimicamente , Inibidores da Transcriptase Reversa/toxicidade , Aprendizagem Espacial/efeitos dos fármacos , Aprendizagem Espacial/fisiologia , Sinapsinas/metabolismo , Sinaptofisina/metabolismo , Sinaptotagmina I/metabolismo , Fatores de TempoRESUMO
Drosophila, Arabidopsis, Synechocystis, Homo (DASH) cryptochromes belong to the cryptochrome/photolyase family and can act as DNA repair enzymes. In bacteria and fungi, they also can play regulatory roles, but in plants their biological functions remain elusive. Here, we characterize CRY-DASH1 from the green alga Chlamydomonas reinhardtii. We perform biochemical and in vitro photochemical analysis. For functional characterization, a knock-out mutant of cry-dash1 is used. CRY-DASH1 protein is localized in the chloroplast and accumulates at midday. Although the photoautotrophic growth of the mutant is significantly reduced compared to the wild-type (WT), the mutant has increased levels of photosynthetic pigments and a higher maximum photochemical efficiency of photosystem II (PS II). Hyper-stacking of thylakoid membranes occurs together with an increase in proteins of the PS II reaction center, D1 and its antenna CP43, but not of their transcripts. CRY-DASH1 binds fully reduced flavin adenine dinucleotide and the antenna 5,10-methenyltetrahydrofolate, leading to an absorption peak in the UV-A range. Supplementation of white light with UV-A increases photoautotrophic growth of the WT but not of the cry-dash1 mutant. These results suggest a balancing function of CRY-DASH1 in the photosynthetic machinery and point to its role as a photoreceptor for the UV-A range separated from the absorption of photosynthetic pigments.
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Arabidopsis , Chlamydomonas reinhardtii , Synechocystis , Animais , Arabidopsis/genética , Chlamydomonas reinhardtii/genética , Criptocromos/genética , Drosophila , LuzRESUMO
Random multiple light scattering in disordered photonics leads to interesting and unexpected physical phenomena. Here, we demonstrate two types of partially disordered nano-porous metallic oxide materials: disordered grating nano-pores and two-dimensional disordered nano-tubes, which are produced just with one-step anodic oxidation. The relations among the processing parameters, morphology properties and multiple scattering characteristics are investigated. The surface morphology controllability can be achieved by simply changing the processing direct voltages, leading to different scattering properties. The probabilistic model of partially disordered nano-porous metallic oxide is constructed according to the nano-structure characteristics of oxide, and the rigorous coupled wave analysis is utilized for optical field simulation to exhibit the theoretical multiple scattering properties. Futhermore, the experimental scattering fields are measured and are analysed by statistical method. The research focuses on the disorder caused by one-step oxidation, which is distinct from previous studies that introducing disorder into periodic materials, and would open up new prospects for sensing, bionics and structural color.
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Introducing disorder into a periodic nanostructure can lead to specific optical behaviors. We present a method of anodic oxidation by adjusting the applied voltage and process time to introduce disorder to TiO2 nanotubes. The surface morphology of TiO2 was numerically investigated according to the morphologies measured with a scanning electron microscope by imaging processing and a statistical method. TiO2 nanotubes obtained under different fabrication conditions have various tube radii ranging from 20-40 nm and wall thicknesses ranging from 20-70 nm. We also evaluated the degree of disorder of the tube radius of the TiO2 nanotubes. The reflected scattering light distributions of laser sources were optically measured at different observing distances, which indicate that the presence of nanotubes enhances the scattering effect, reducing the scattered light intensity by more than 75%, and provide the relationship between the scattering effect and surface morphology of nanotubes. This discovery offers TiO2 nanotubes important application prospects in optical limiting and light confinement, such as stealth coating.
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Microalgae contribute significantly to carbon fixation on Earth. Global warming influences their physiology and growth rates. To understand algal short-term acclimation and adaptation to changes in ambient temperature, it is essential to identify and characterize the molecular components that sense small temperature changes as well as the downstream signaling networks and physiological responses. Here, we used the green biflagellate alga Chlamydomonas reinhardtii as a model system in which to study responses to temperature. We report that an RNA recognition motif (RRM)-containing RNA-binding protein, Musashi, occurs in 25 putative splice variants. These variants bear one, two, and three RRM domains or even lack RRM domains. The most abundant Musashi variant, 12, with a molecular mass of 60 kD, interacts with two clock-relevant members of RNA metabolism, the subunit C3 of the RNA-binding protein CHLAMY1 and the 5'-3' exoribonuclease XRN1. These proteins are able to integrate temperature information by up- or down-regulation of their protein levels in cells grown at low (18°C) or high (28°C) temperature. We further show that the 60-kD Musashi variants with three RRM domains can bind to (UG)7 repeat-containing RNAs and are up-regulated in cells grown at a higher temperature during early night. Intriguingly, the 60-kD Musashi variant 12, as well as C3 and XRN1, confer thermal acclimation to C. reinhardtii, as shown with mutant lines. Our data suggest that these three proteins of the RNA metabolism machinery are key members of the thermal signaling network in C. reinhardtii.
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Aclimatação/fisiologia , Proteínas de Algas/metabolismo , Chlamydomonas reinhardtii/fisiologia , Isoformas de Proteínas/genética , Proteínas de Ligação a RNA/genética , Proteínas de Algas/genética , Chlamydomonas reinhardtii/genética , Exorribonucleases/genética , Exorribonucleases/metabolismo , Mutação , Plantas Geneticamente Modificadas , Domínios Proteicos , Mapeamento de Interação de Proteínas , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , TemperaturaRESUMO
The main purpose of this study was to examine if naringin contributed to the regulation of cholesterol homeostasis and inflammatory cytokine expressions in cholesterol and 25-OH-cholesterol-treated HepG2 cells and TNF-α-treated HUVECs. The gene and protein expressions related to cholesterol homeostasis and inflammation were determined by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting. We obtained the following results: (1) A concentration-dependent increase of LDLR and CYP7A1 expressions was observed, through activating expressions of SREBP2 and PPARy in HepG2 cells after exposure to naringin; (2) EL gene and protein expressions in HUVECs were inhibited by naringin; (3) the expressions of inflammatory factors such as CRP, TNF-α, ICAM-1 and VCAM-1 in HepG2 cells, ICAM-1 and VCAM-1 in HUVECs restrained by naringin were confirmed; (4) NF-κB and ERK1/2 activities were quenched by naringin. In summary, naringin might not only effectively reduce cholesterol levels by stimulating cholesterol metabolism but also inhibit inflammatory response through reducing inflammatory cytokine expressions. The effects of naringin were achieved via modulating NF-κB and ERK signaling pathways.
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Anti-Inflamatórios não Esteroides/farmacologia , Anticolesterolemiantes/farmacologia , Colesterol/metabolismo , Flavanonas/farmacologia , Homeostase/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Subunidade p50 de NF-kappa B/efeitos dos fármacos , Células Cultivadas , Hepatócitos/efeitos dos fármacos , Humanos , Receptores de LDL/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 2/biossínteseRESUMO
Algae encode up to five different types of cryptochrome photoreceptors. So far, relatively little is known about the biological functions of the DASH (Drosophila, Arabidopsis, Synechocystis and Homo)-type cryptochromes. The green alga Chlamydomonas reinhardtii encodes two of them. CRY-DASH1 also called DCRY1 has its maximal absorption peak in the UV-A range. It is localized in the chloroplast and plays an important role in balancing the photosynthetic machinery. Here, we performed a comparative analysis of chloroplast proteins from wild type and a knockout mutant of CRY-DASH1 named cry-dash1mut, using label-free quantitative proteomics as well as immunoblotting. Our results show upregulation of enzymes involved in specific pathways in the mutant including key enzymes of chlorophyll and carotenoid biosynthesis consistent with increased levels of photosynthetic pigments in cry-dash1mut. There is also an increase in certain redox as well as photosystem I and II proteins, including D1. Strikingly, CRY-DASH1 is coregulated in a D1 deletion mutant, where its amount is increased. In contrast, key proteins of the central carbon metabolism, including glycolysis/gluconeogenesis, dark fermentation and the oxidative pentose phosphate pathway are downregulated in cry-dash1mut. Similarly, enzymes of histidine biosynthesis are downregulated in cry-dash1mut leading to a reduction in the amount of free histidine. Yet, transcripts encoding for several of these proteins are at a similar level in the wild type and cry-dash1mut or even opposite. We show that CRY-DASH1 can bind to RNA, taking the psbA RNA encoding D1 as target. These data suggest that CRY-DASH1 regulates plastidial metabolic pathways at the posttranscriptional level.
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Chlamydomonas reinhardtii , Proteínas de Cloroplastos , Criptocromos , Fotossíntese , Plastídeos , Vias Biossintéticas , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/metabolismo , Proteínas de Cloroplastos/genética , Proteínas de Cloroplastos/metabolismo , Criptocromos/genética , Criptocromos/metabolismo , Regulação para Baixo , Histidina/biossíntese , Histidina/genética , Plastídeos/genética , Plastídeos/metabolismo , Raios Ultravioleta , Deleção de Genes , Transcrição GênicaRESUMO
OBJECTIVE: To explore the relationship between serum estrogen levels and urinary incontinence in a nationally representative female population. MATERIALS AND METHODS: We included women who had serum estradiol measurements and self-reported urinary incontinence problems in the 2013-2016 National Health and Nutrition Examination Survey cycles. A weighted multivariable logistic regression model was used to determine the association between urinary incontinence and serum estrogen levels after adjusting for age, race, Body Mass Index, diabetes, venipuncture, hypertension, poverty-to-income ratio, smoking, marital status, alcohol use, education, and menopause. RESULT: A total of 4114 individuals were ultimately included in our study. Of these women, 1200 (29.17%) complained of urge urinary incontinence (UUI), 1674 (40.69%) complained of stress urinary incontinence (SUI), 730 (17.74%) complained of mixed urinary incontinence (MUI). Women in the lowest quartile of serum estrogen were more likely to complain of UUI compared to those in the highest quartile (OR=1.885; 95% CI=1.042-3.412, P = .039). No association was noted between serum estrogen levels and SUI or MUI. CONCLUSION: Our study shows a significant association between low serum estrogen level and the increased likelihood of UUI in women. Further research is required to validate our findings, elucidate the physiological mechanisms that underlie them, and assess potential therapeutic implications.
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Estrogênios , Inquéritos Nutricionais , Incontinência Urinária , Humanos , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Incontinência Urinária/sangue , Incontinência Urinária/epidemiologia , Estrogênios/sangue , Adulto , Estados Unidos/epidemiologia , Idoso , Incontinência Urinária de Urgência/epidemiologia , Incontinência Urinária de Urgência/sangueRESUMO
PURPOSE: Androgen receptors are expressed in the pelvic floor and lower urinary tract. However, the association between serum testosterone and overactive bladder (OAB) in women remains unclear. This study aimed to investigate their association in a nationally representative population. METHODS: In this cross-sectional study, we collected data on female participants older than 20 years with serum total testosterone measurements and OAB questionnaires from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression models were used to analyze the relationship between testosterone and OAB in women. RESULTS: Data on 4991 women was analyzed in this study, of whom 25.9% had OAB symptoms. Women with lower serum testosterone had an increased frequency of urge urinary incontinence and nocturia compared to participants with enough testosterone. The multivariate logistic models showed that those women with a testosterone level less than 18.5 ng/dL had significantly higher odds of OAB compared to those with a testosterone level greater than 18.5 ng/dL [OR 95% CI = 1.271 (1.073-1.505), P = 0.0076]. Separate interaction analyses revealed no significant effect of age, BMI, diabetes, education, alcohol use and menopause on the association between serum testosterone and OAB. Sensitivity analyses demonstrated that additional variables (depression, stroke and stress urinary incontinence) had no significant effect on this relationship. CONCLUSIONS: Low serum testosterone is associated with an increased likelihood of OAB in women. This supports the potential therapeutic role of testosterone supplementation in women with OAB. Given the direct and indirect effects of testosterone on the pelvic floor and lower urinary tract, a potential mechanism for this relationship can be further explored in translational studies.
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Inquéritos Nutricionais , Testosterona , Bexiga Urinária Hiperativa , Humanos , Feminino , Bexiga Urinária Hiperativa/sangue , Bexiga Urinária Hiperativa/epidemiologia , Estudos Transversais , Testosterona/sangue , Pessoa de Meia-Idade , Adulto , Idoso , Adulto JovemRESUMO
In this study, we proposed two, symptom-dependent, HIV/AIDS models to investigate the dynamical properties of HIV/AIDS in the Fujian Province. The basic reproduction number was obtained, and the local and global stabilities of the disease-free and endemic equilibrium points were verified to the deterministic HIV/AIDS model. Moreover, the indicators $ R_0/ $ and $ R_0^e $ were derived for the stochastic HIV/AIDS model, and the conditions for stationary distribution and stochastic extinction were investigated. By using the surveillance data from the Fujian Provincial Center for Disease Control and Prevention, some numerical simulations and future predictions on the scale of HIV/AIDS infections in the Fujian Province were conducted.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Síndrome da Imunodeficiência Adquirida/epidemiologia , Infecções por HIV/epidemiologia , Número Básico de Reprodução , Entropia , Modelos BiológicosRESUMO
Radionuclide uranium is a great threat to human health, due to its high chemical toxicity and radioactivity. Finding suitable uranium decorporation to reduce damage caused by uranium internal contamination is an important aspect of nuclear emergency response. However, the poor selectivity and/or high toxicity of the only excretory promoter approved by Food and Drug Administration (FDA) is an obvious disadvantage. Herein, we choose an edible natural product, the traditional Chinese medicine called Perilla frutescens (PF), which has wide sources and can be used as an excellent and effective uranyl decorporation. In vivo uranium decorporation assays illustrate the removal efficiency of uranium in kidney were 68.87% and 43.26%, in femur were 56.66% and 54.53%, by the test of prophylactic and immediate administration, respectively. Cell level experiments confirmed that it had better biocompatibility than CaNa3-DTPA (CaNa3-diethylenetriamine pentaacetate, a commercial actinide excretion agent). In vitro static adsorption experiments exhibited that its excellent selectivity sorption for uranyl. All those results findings would provide new research insights about natural product for uranyl decorporation.
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Produtos Biológicos , Perilla frutescens , Urânio , Humanos , Urânio/toxicidade , Quelantes/farmacologia , Rim , Produtos Biológicos/farmacologiaRESUMO
Introduction: Understanding the impact of deep groundwater depth on vegetation communities and soil in sand dunes with different underground water tables is essential for ecological restoration and the conservation of groundwater. Furthermore, this understanding is critical for determining the threshold value of groundwater depth that ensures the survival of vegetation. Method: This paper was conducted in a semi-arid region in eastern China, and the effects of deep groundwater depth (6.25 m, 10.61 m, and 15.26 m) on vegetation communities and soil properties (0-200 cm) across three dune types (mobile, semi-fixed, and fixed dunes) were evaluated in a sand ecosystem in the Horqin Sandy Land. Results: For vegetation community, variations in the same species are more significant at different groundwater depths. For soil properties, groundwater depth negatively influences soil moisture, total carbon, total nitrogen, available nitrogen, available phosphorus concentrations, and soil pH. Besides, groundwater depth also significantly affected organic carbon and available potassium concentrations. In addition, herb species were mainly distributed in areas with lower groundwater depth, yet arbor and shrub species were sparsely distributed in places with deeper groundwater depth. Discussion: As arbor and shrub species are key drivers of ecosystem sustainability, the adaptation of these dominant species to increasing groundwater depth may alleviate the negative effects of increasing groundwater depth; however, restrictions on this adaptation were exceeded at deeper groundwater depth.
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Understanding the effects of groundwater depth on soil microbiota and multiple soil functions is essential for ecological restoration and the implementation of groundwater conservation. The current impact of increased groundwater levels induced by drought on soil microbiota and multifunctionality remains ambiguous, which impedes our understanding of the sustainability of water-scarce ecosystems that heavily rely on groundwater resources. This study investigated the impacts of altered groundwater depths on soil microbiota and multifunctionality in a semi-arid region. Three groundwater depth levels were studied, with different soil quality and soil moisture at each level. The deep groundwater treatment had negative impacts on diversity, network complexity of microbiota, and the relationships among microbial phylum unites. Increasing groundwater depth also changed composition of soil microbiota, reducing the relative abundance of dominant phyla including Proteobacteria and Ascomycota. Increasing groundwater depth led to changes in microbial community characteristics, which are strongly related to alterations in soil multifunctionality. Overall, our results suggest that groundwater depth had a strongly effect on soil microbiota and functionality.
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Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease without long-term effective therapy. This study aims to evaluate the efficacy and safety of botulinum toxin A (BoNT/A) plus Sapylin, which might modulate the immune response of the bladder in the treatment of IC/BPS patients. We retrospectively investigated the clinical outcomes among 34 patients who accepted repeated Sapylin instillations after 200 U of BoNT/A submucosally injected into bladder walls (Mix group) and 28 patients who received BoNT/A alone (Control group). Each of the bladder walls (left, right, anterior and posterior) was injected six times with 8 U of BoNT/A per injection. The primary outcome measure was the global response assessment. The results showed that at 6 months post-injection, the response rate in the Mix group was remarkably higher than that in the Control group (58.8% vs. 28.6%, p < 0.05). The mean effective duration of the responders in the Mix group was apparently better than that in the Control group (27.5 (range 0-89) vs. 4.9 (range 0-11) months, p < 0.05). None of the patients experienced serious adverse events. In conclusion, repeated intravesical instillations of Sapylin after BoNT/A injection can produce significantly better clinical outcomes than BoNT/A alone in IC/PBS patients.
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Toxinas Botulínicas Tipo A , Cistite Intersticial , Humanos , Toxinas Botulínicas Tipo A/efeitos adversos , Cistite Intersticial/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Administração IntravesicalRESUMO
OBJECTIVE: To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD). METHODS: The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA. RESULTS: Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P<0.05 or P<0.01), and led to neuronal repair in the hippocampus. There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups, nor between the 4-VO+TAK-242 and 4-VO+EA groups (P>0.05). CONCLUSIONS: EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.
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Demência Vascular , Eletroacupuntura , Animais , Demência Vascular/terapia , Hipocampo/metabolismo , Imunidade , Fator 88 de Diferenciação Mieloide , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 4 Toll-Like/metabolismoRESUMO
(1) Purpose: The purpose of this study was to evaluate the prognostic capacity of the pathological N status (pN), lymph node ratio (LNR), and the log odds of positive lymph nodes (LODDS), and to build a prognostic nomogram to predict overall survival (OS) for bladder cancer patients treated by radical cystectomy. (2) Methods: The clinical and pathological characteristics of 10,938 patients with bladder cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017. The predictive capacity was assessed by univariate and multivariate Cox regression analyses, the area under the receiver operating characteristic curve (AUC), and C-index. Calibration curves, decision curve analysis (DCA), and risk-grouping were utilized to evaluate the predictive accuracy and discriminative ability of the nomogram. (3) Results: LODDS was an independent risk factor for bladder cancer (all p < 0.001) and demonstrated the highest values of C-index and AUC. The values of AUCs in the training cohort were 0.747, 0.743, and 0.735 for predicting 1-, 3-, and 5-year OS, respectively. Calibration curves and DCA curves suggested the excellent clinical application value of our nomogram. (4) Conclusions: LODDS is a better predictive indicator for bladder cancer patients compared to pN and LNR. The LODDS-incorporated nomogram has excellent accuracy and promising clinical application value for non-metastatic bladder cancer after radical cystectomy.
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Nomogramas , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Metástase Linfática/patologia , Estadiamento de Neoplasias , Linfonodos/cirurgia , Linfonodos/patologia , Cistectomia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
The spread of the novel coronavirus COVID-19 resulted in unprecedented worldwide countermeasures such as lockdowns and suspensions of all retail, recreational, and religious activities for the majority of 2020. Nonetheless, no adequate scientific data have been provided thus far about the impact of COVID-19 on driving behavior and road safety, especially in Malaysia. This study examined the effect of COVID-19 on driving behavior using naturalistic driving data. This was accomplished by comparing the driving behaviors of the same drivers in three periods: before COVID-19 lockdown, during COVID-19 lockdown, and after COVID-19 lockdown. Thirty people were previously recruited in 2019 to drive an instrumental vehicle on a 25 km route while recording their driving data such as speed, acceleration, deceleration, distance to vehicle ahead, and steering. The data acquisition system incorporated various sensors such as an OBDII reader, a lidar, two ultrasonic sensors, an IMU, and a GPS. The same individuals were contacted again in 2020 to drive the same vehicle on the same route in order to capture their driving behavior during the COVID-19 lockdown. Participants were approached once again in 2022 to repeat the procedure in order to capture their driving behavior after the COVID-19 lockdown. Such valuable and trustworthy data enable the assessment of changes in driving behavior throughout the three time periods. Results showed that drivers committed more violations during the COVID-19 lockdown, with young drivers in particular being most affected by the traffic restrictions, driving significantly faster and performing more aggressive steering behaviors during the COVID-19 lockdown than any other time. Furthermore, the locations where the most speeding offenses were committed are highlighted in order to provide lawmakers with guidance on how to improve traffic safety in those areas, in addition to various recommendations on how to manage traffic during future lockdowns.
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Condução de Veículo , COVID-19 , Acidentes de Trânsito , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Humanos , Malásia/epidemiologiaRESUMO
BACKGROUND: Alzheimer's disease (AD), with cognitive impairment as the main clinical manifestation, is a progressive neurodegenerative disease. The assembly of amyloid-ß (Aß) as senile plaques is one of the most well-known histopathological alterations in AD. Several studies reported that cognitive training reduced Aß deposition and delayed memory loss. However, the long-term benefits of spatial training and the underlying neurobiological mechanisms have not yet been elucidated. OBJECTIVE: To explore the long-term effects of spatial training on AD-related pathogenic processes in APP/PS1 mice. METHODS: We used Morris water maze (MWM), Open Field, Barnes Maze, western blotting, qPCR, and immunofluorescence. RESULTS: One-month MWM training in APP/PS1 mice at 2.5 months of age could attenuate Aß deposition and decrease the expression of ß-secretase (BACE1) and amyloid-ß protein precursor (AßPP) with long-term effects. Simultaneously, regular spatial training increased the expression of synapse-related proteins in the hippocampus. Moreover, MWM training increased adult hippocampal neurogenesis in AD model mice. Nonetheless, cognitive deficits in APP/PS1 transgenic mice at 7 months of age were not attenuated by MWM training at an early stage. CONCLUSION: Our study demonstrates that MWM training alleviates amyloid plaque burden and adult hippocampal neurogenesis deficits with long-term effects in AD model mice.