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1.
Front Endocrinol (Lausanne) ; 12: 671225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630317

RESUMO

Background: Laparoscopic ovarian cystectomy is established as the standard surgical approach for the treatment of benign ovarian cysts. However, previous studies have shown that potential fertility can be directly impaired by laparoscopic ovarian cystectomy, diminished ovarian reserve (DOR), and even premature ovarian failure. Therefore, fertility-preserving interventions are required for benign gynecologic diseases. However, there are still little data on the time period required for recovery of ovarian reserve after the laparoscopic unilateral ovarian cystectomy, which is very important for the individualization of treatment protocols. This study aimed at investigating the time needed for the ovarian reserve to recover after laparoscopic unilateral ovarian non-endometriotic cystectomy. Materials and Methods: Sixty-seven patients with unilateral ovarian non-endometriotic cyst from Zhoupu and Punan Hospitals who underwent laparoscopic unilateral ovarian cystectomy were recruited as a postoperative observation group (POG). Also, 69 healthy age-matched women without ovarian cyst who did not undergo surgery were recruited as a referent group (RFG). Ovarian reserve with the serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2) levels, ovarian arterial resistance index (OARI), and antral follicle counts (AFCs) were measured on the third to fifth days of the same menstrual cycle. A postoperative 6-month follow-up of cases was performed. Results: Compared with RFG, AFC of cyst side in the POG group showed no difference in the first, third, and sixth postoperative month (F = 0.03, F = 0.02, F = 0.55, respectively; p = 0.873, p = 0.878, p = 0.460, respectively). The OARI of cyst side in the POG group revealed no differences in the first, third, and sixth postoperative month (F = 0.73, F = 3.57, F = 1.75, respectively; p = 0.395, p = 0.061, p = 0.701, respectively). In the first month, the postoperative AMH levels significantly declined, reaching 1.88 ng/ml [interquartile range (IQR): 1.61-2.16 ng/ml] in POG and 2.57 ng/ml (IQR: 2.32-2.83 ng/ml) in RFG (F = 13.43, p = 0.000). For the data of AMH levels stratified by age, the same trend was observed between less than 25 and more than 26 years old. At this same time interval, the postoperative rate of decline was significantly lower compared to the preoperative one in POG (32.75%). The same trend was observed between the POG and RFG groups (26.67%). Conclusions: The optimal time for recovery of ovarian reserve after laparoscopic unilateral ovarian cystectomy is estimated to be 6 months.

2.
J Cell Biol ; 220(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34623380

RESUMO

In eukaryote cells, lipid droplets (LDs) are key intracellular organelles that dynamically regulate cellular energy homeostasis. LDs originate from the ER and continuously contact the ER during their growth. How the ER affects LD growth is largely unknown. Here, we show that RNAi knockdown of acs-1, encoding an acyl-CoA synthetase required for the biosynthesis of monomethyl branched-chain fatty acids C15iso and C17iso, remarkably prevented LD growth in Caenorhabditis elegans. Dietary C17iso, or complex lipids with C17iso including phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol, could fully restore the LD growth in the acs-1RNAi worms. Mechanistically, C17iso may incorporate into phospholipids to ensure the membrane integrity of the ER so as to maintain the function of ER-resident enzymes such as SCD/stearoyl-CoA desaturase and DGAT2/diacylglycerol acyltransferase for appropriate lipid synthesis and LD growth. Collectively, our work uncovers a unique fatty acid, C17iso, as the side chain of phospholipids for determining the ER homeostasis for LD growth in an intact organism, C. elegans.

3.
Food Funct ; 12(19): 9273-9285, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606538

RESUMO

This study aimed to explore the protection mechanism of a debranched corn starch/konjac glucomannan (DCSK) composite against type 2 diabetes (T2D) related to dyslipidemia and gut microbiota in mice fed on a high-fat diet (HFD). The results showed that the consumption of DCSK led to a significant improvement in the biochemical parameters and physiological indices associated with T2D in the HFD group, including the decrease in blood glucose, triglyceride, total cholesterol, and high-density lipoprotein cholesterol levels, as well as the suppression of the oxidative stress of the liver and kidneys. Furthermore, the health of the intestinal microbiota in the HFD-fed mice was altered dramatically after DCSK consumption. Metabolomics revealed 13 differential metabolites strongly linked to DCSK intervention, and DCSK supplementation regulated amino acid metabolism, nucleotide metabolism, and lipid metabolism. These findings demonstrated that DCSK has an outstanding ability to improve hyperglycemia, hyperlipidemia, and gut microbiota associated with T2D.

4.
J Clin Ultrasound ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34669189

RESUMO

As a bridge between the heart and the arteries, the aorta plays an important role in the cardiovascular system. The morbidity and mortality of aortic disease are extremely high, which is a serious threat to human life. The biomechanical abnormality of the aorta is an important factor of a series of pathological changes in the aortic wall. At present, there are many imaging methods to evaluate the biomechanics of the aorta, which will benefit to the early diagnosis and treatment of aortic disease. In this review, we describe the application of various imaging methods and parameters in aortic disease.

5.
J Fungi (Basel) ; 7(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34682279

RESUMO

Magnaporthe oryzae, a fungal pathogen that causes rice blast, which is the most destructive disease of rice worldwide, has the potential to perform both asexual and sexual reproduction. MAT loci, consisting of MAT genes, were deemed to determine the mating types of M. oryzae strains. However, investigation was rarely performed on the development and molecular mechanisms of the sexual reproduction of the fungus. In the present work, we analyzed the roles of two MAT loci and five individual MAT genes in the sex determination, sexual development and pathogenicity of M. oryzae. Both of the MAT1-1 and MAT1-2 loci are required for sex determination and the development of sexual structures. MAT1-1-1, MAT1-1-3 and MAT1-2-1 genes are crucial for the formation of perithecium. MAT1-1-2 impacts the generation of asci and ascospores, while MAT1-2-2 is dispensable for sexual development. A GFP fusion experiment indicated that the protein of MAT1-1-3 is distributed in the nucleus. However, all of the MAT loci or MAT genes are dispensable for vegetative growth, asexual reproduction, pathogenicity and pathogenicity-related developments of the fungus, suggesting that sexual reproduction is regulated relatively independently in the development of the fungus. The data and methods of this work may be helpful to further understand the life cycle and the variation of the fungus.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34639607

RESUMO

BACKGROUND: Previous studies have examined the association between socioeconomic status and prosocial behavior, but the underlying mechanism between them is unclear. The present study aimed to examine the serially mediating roles of community identity and perceived control in this relationship. METHODS: Using the convenient sampling technique, a total of 477 Chinese adults from Chinese communities, and ranging in age from 20 to 65 completed the questionnaires for objective socioeconomic status, the MacArthur scale of subjective socioeconomic status, an eight-item community identity scale, the perceived control scale, and a prosocial tendencies measure. Bivariate correlation analysis and regression analysis were used to examine the relationships among the major variables. RESULTS: Socioeconomic status was positively associated with prosocial behavior. It was also found that community identity and perceived control played mediating roles between socioeconomic status and prosocial behavior, respectively. In addition, community identity and perceived control also had a serially mediating role in the relationship. CONCLUSIONS: Community identity and perceived control played a serially mediating role in the association between socioeconomic status and prosocial behavior. The findings in the present study contribute to understanding the underlying mechanism in the association between socioeconomic status and prosocial behavior among adults, and have important implications for interventions aimed at improving prosocial behavior in lower-status individuals.


Assuntos
Altruísmo , Classe Social , Adulto , Humanos , Inquéritos e Questionários
7.
Ecotoxicol Environ Saf ; 227: 112888, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34649136

RESUMO

Heavy metals (HMs) contamination in agricultural soils is a major concern for global food safety and human health. Although, various in-situ and ex-situ remediation methods have been used for the treatment of HMs contaminated soils, however, they also have many drawbacks viz., capital investment, toxicity, and environmental health hazards. Consequently, there is an urgent need to develop a novel method to ameliorate the toxicity of HMs in agricultural soils. In recent years, nanoparticles (NPs) have gained significant attention due to their potential applications in the environment and agriculture fields. Nanoremediation employs NPs that effectively reduce the contents of toxic HMs in the soil-plant system. Several studies have reported that the application of NPs in HMs-polluted soils, which reduced plant-available HMs concentration soils. However, the long-term efficiency of NPs immobilization is still unclear. Here, we provide details about the toxicity of HMs to environmental systems and potential applications NPs to alleviate the accumulation of HMs in agricultural soils. Finally, we present the mechanistic route of HMs-toxicity alleviation in plants by NPs application as well as their long-term efficiency and future prospects.

8.
Expert Opin Biol Ther ; : 1-9, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34607519

RESUMO

BACKGROUND: Perjeta® is a recombinant, humanized monoclonal antibody that has been marketed and approved for the targeted therapy of human epidermal growth factor receptor (HER2) positive breast cancer in the United States. This study compared the bioequivalence, immunogenicity, and safety of pertuzumab injection (a biosimilar of Perjeta® produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Perjeta® (produced by Roche Pharma AG) in healthy Chinese males. RESEARCH DESIGN AND METHODS: Healthy Chinese male subjects (N = 87) were randomly given intravenous injection of 5 mg/kg pertuzumab or Perjeta® at a 1:1 ratio. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay, and primary pharmacokinetic parameters were statistically analyzed. We detected the levels of anti-drug antibody (ADA) and neutralizing antibody (nAb) to evaluate drug immunogenicity and safety of the drugs throughout the study. RESULTS: The geometric mean ratios of AUC0-t, Cmax, and AUC0-∞ for pertuzumab and Perjeta® were 100.42%, 96.71%, and 101.47%, respectively. The 90% CIs were all within 80%-125%, meeting the bioequivalence standards. The levels of ADA and nAb were similar. In addition, both had good safety in the study. CONCLUSION: The study shows that pertuzumab injection and Perjeta® had similar bioequivalence, immunogenicity, and safety.

9.
Carbohydr Polym ; 273: 118612, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34561010

RESUMO

Herein, a ß-1,3-d-glucan based microcarrier, yeast cell wall microparticles (YPs), was used to develop a food-source-based nano-in-micro oral delivery system for ulcerative colitis (UC) treatment. Briefly, lactoferrin (Lf), which targets intestinal epithelial cells, was used to encapsulate emodin (EMO) to form nanoparticles (EMO-NPs), and then loaded into YPs with the natural macrophages targeting ability, forming a final formula with two outer-inner targeting layers (EMO-NYPs). These dual-targeting strategy could enhance the dual-effects of EMO in anti-inflammatory and mucosal repair effects respectively. As expected, cell uptake assessment confirmed that EMO-NPs and EMO-NYPs could target on the Lf and dection-1 receptors on the membranes of Caco-2 cells and macrophages, respectively. Importantly, EMO-NYPs showed the best anti-UC effects compared to EMO-NPs and free EMO, by inhibiting NF-κB pathway to anti-inflammation and promoting intestinal mucosa repair via MLCK/pMLC2 pathway. The results show that EMO-NYPs are a promising food-based oral delivery system in anti-UC.

10.
Insects ; 12(9)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34564252

RESUMO

Small interfering RNAs (siRNAs) are non-coding RNAs with a length of 21~23 nucleotides (nt) and present in almost all eukaryotes. The formation of siRNA is a highly conserved post-transcriptional gene-silencing mechanism mediated by key proteins, including Dicer2, Argonaute2 (Ago2) and R2D2. R2D2 has been identified as a double-stranded RNA (dsRNA)-binding protein and reported as an integral component of the siRNA pathway in Drosophila. However, the involvement of R2D2 in the siRNA pathway of Locusta migratoria is still unknown. In the present study, we identified an LmR2D2 gene from the transcriptome of L. migratoria. It consists of a 954-bp open reading frame that encodes a protein of 318 amino acid residues. Further sequence analysis revealed that LmR2D2 possesses two tandem dsRNA-binding domains (dsRBD) at the N-terminus. Analysis of the developmental expression profile of LmR2D2 indicated that its transcript level was stable in third-instar nymphs of L. migratoria, whereas the tissue-dependent expression profile exhibited high levels of expression of LmR2D2 in the testis and ovary. When LmR2D2 was silenced by RNAi, the RNAi efficiency against Lmß-tubulin as a marker gene was significantly diminished, as indicated by the 37.7% increased Lmß-tubulin transcript level. Additionally, the prokaryotic expression system was used to obtain the LmR2D2 supernatant protein. By incubating the LmR2D2 protein with biotin-dsRNA, we found that LmR2D2 can bind to dsRNA in vitro, which supports our conclusion that LmR2D2 plays an essential role in the siRNA pathway of L. migratoria.

11.
Photodiagnosis Photodyn Ther ; 36: 102516, 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34469794

RESUMO

BACKGROUND AND AIM: It is generally believed that bacteria can not develop resistance to antimicrobial photodynamic therapy (aPDT). This work employed a polymyxin-resistant Escherichia coli clinical isolate (E15017) to study whether it could become resistant to aPDT mediated by haematoporphyrin monomethyl ether (HMME) via consecutive photodynamic treatments at sub-lethal condition. METHODS: The sub-lethal and lethal photodynamic treatment conditions for E15017 were determined by colony forming units (CFU) assay. Bacterial cells of E15017 were treated with 20 cycles of repeated sub-lethal HMME-mediated aPDT, and subsequently subjected to aPDT at lethal condition. The antibiotic susceptibility, zeta-potential and membrane integrity of sub-lethal aPDT treated E15017 cells were also investigated. RESULTS: After 20 cycles of repeated HMME-mediated aPDT treatments at sub-lethal condition, E15017 cells didn't become more resistant to aPDT. Sub-lethal HMME-mediated aPDT decreased the MIC values of E15017 to ceftazidime and polymyxin E by 4 and 2-fold, respectively, and increased the electronegativity of bacterial surface and affected the bacterial membrane integrity. CONCLUSIONS: The results obtained in this study confirmed that antibiotic-resistant bacteria could not develop resistance to aPDT, and HMME-mediated aPDT is an attractive potential treatment for MDR E. coli caused infections.

12.
Nat Commun ; 12(1): 5416, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518544

RESUMO

Hypoxia is the most prominent feature in human solid tumors and induces activation of hypoxia-inducible factors and their downstream genes to promote cancer progression. However, whether and how hypoxia regulates overall mRNA homeostasis is unclear. Here we show that hypoxia inhibits global-mRNA decay in cancer cells. Mechanistically, hypoxia induces the interaction of AGO2 with LUBAC, the linear ubiquitin chain assembly complex, which co-localizes with miRNA-induced silencing complex and in turn catalyzes AGO2 occurring Met1-linked linear ubiquitination (M1-Ubi). A series of biochemical experiments reveal that M1-Ubi of AGO2 restrains miRNA-mediated gene silencing. Moreover, combination analyses of the AGO2-associated mRNA transcriptome by RIP-Seq and the mRNA transcriptome by RNA-Seq confirm that AGO2 M1-Ubi interferes miRNA-targeted mRNA recruiting to AGO2, and thereby facilitates accumulation of global mRNAs. By this mechanism, short-term hypoxia may protect overall mRNAs and enhances stress tolerance, whereas long-term hypoxia in tumor cells results in seriously changing the entire gene expression profile to drive cell malignant evolution.


Assuntos
Proteínas Argonauta/genética , Regulação Neoplásica da Expressão Gênica , Homeostase/genética , Metionina/genética , RNA Mensageiro/genética , Ubiquitinação , Células A549 , Proteínas Argonauta/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Inativação Gênica , Células HEK293 , Células HeLa , Humanos , Hipóxia , Metionina/metabolismo , MicroRNAs/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Células PC-3 , Estabilidade de RNA/genética , RNA Mensageiro/metabolismo
13.
Biomed Res Int ; 2021: 4156162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513990

RESUMO

Methods: A total of 121 patients with moderate to severe ARDS admitted to the intensive care unit (ICU) from June 2017 to April 2020 and treated with invasive mechanical ventilation were sequentially included in this study. Their general information was collected, and MP was recorded at 0 h, 24 h, 48 h, and 72 h after admission to the ICU. Professionally trained researchers performed the LUS assessments. Patients were divided into the death and survival groups according to their 28-day prognosis. The trend of MP and LUS at the four time points was analyzed. A receiver operating characteristic curve (ROC) was used to analyze the predictive value of MP and LUS scores at 0 h and 72 h for the prognosis (28-day mortality rate) of patients with moderate to severe ARDS. Results: 121 patients were included in the analysis, of which 73 were male and 48 were female. When patients entered the ICU, their oxygenation index (t: 30885, P < 0.01), APACHE II score (t: 2.105, P < 0.05), and SOFA score (t: 4.134, P < 0.001) were higher in the death group than the survival group. The death group had significantly higher MP and LUS at each time point (0 h, 24 h, 48 h, and 72 h) compared to the survival group (all P < 0.05). There was a significant upward trend over time in the MP and LUS of the death group, contrasting to a significant downward trend in the survival group (all P < 0.05). The Pearson correlation analysis showed that MP and LUS were significantly positively correlated at each time point (r values: 0 h: 0.3027; 24 h: 0.3705; 48 h: 0.3902; 72 h: 0.5916; all P < 0.01). The ROC curves showed that MP and LUS at 72 h were of significant value in predicting the prognosis of ARDS patients, with areas under the curve of 0.866 ± 0.032 and 0.839 ± 0.037, respectively. Conclusion: There was a significant correlation between the MP and LUS of ARDS patients at four time points from 0 to 72 h, which has a clinical value in evaluating severity and prognosis.


Assuntos
Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/fisiopatologia , Adulto , Idoso , China , Feminino , Humanos , Unidades de Terapia Intensiva , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Respiração Artificial , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Índice de Gravidade de Doença , Ultrassonografia/métodos
14.
Mol Med Rep ; 24(6)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34590152

RESUMO

Acute lung injury (ALI) is a respiratory tract disease characterized by increased alveolar/capillary permeability, lung inflammation and structural damage to lung tissues, which can progress and transform into acute respiratory distress syndrome (ARDS). Although there are several treatment strategies available to manage this condition, there is still no specific cure for ALI. Aldo­keto reductase family 1 member C1 (AKR1C1) is a member of the aldo­keto reductase superfamily, and is a well­known Nrf2 target gene and an oxidative stress gene. The aim of the present study was to investigate the effects of AKR1C1 on a lipopolysaccharide (LPS)­induced ALI model. After mice received LPS treatment, the mRNA expression levels of AKR1C1 in the bronchoalveolar lavage fluid and serum were measured using reverse transcription­quantitative PCR and its relationship with the inflammatory factors and malondialdehyde levels were determined using correlation analysis. Next, AKR1C1 was overexpressed or knocked out in mice, and subsequently ALI was induced in mice using LPS. The severity of ALI, oxidative stress and inflammation in the lungs were measured, and the potential involvement of the Janus kinase 2 (JAK2)/signal transduction activator of transcription 3 (STAT3) signaling pathway was assessed by measuring the changes of lung injury parameters after the agonists of JAK2/STAT3 pathway, including interleukin (IL)­6 and colivelin, were administrated to mice. The results revealed that AKR1C1 expression was decreased in the LPS­induced ALI mouse model. AKR1C1 expression was inversely correlated with serum tumor necrosis factor­α, IL­6 and malondialdehyde levels, and positively correlated with serum IL­10 levels. AKR1C1 overexpression significantly attenuated lung injury, as shown by the changes in Evans blue leakage in the lung, lung wet/dry weight ratio, PaO2/FIO2 ratio, survival rate of mice and histological lung changes. In addition, the JAK2/STAT3 signaling pathway was significantly deactivated by AKR1C1+/+. When AKR1C1+/+ mice were treated with JAK2/STAT3 agonists, the effects of AKR1C1 overexpression on lung injury and oxidative stress were abolished. In conclusion, AKR1C1 may protect against oxidative stress and serve as a negative regulator of inflammation in ALI/ARDS. In addition, the JAK2/STAT3 signaling pathway could participate in the protective effects of AKR1C1 against ALI.

15.
Front Psychol ; 12: 723171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539525

RESUMO

This study examined the influence of the formative feedback types of teachers on creativity in Science, Technology, Engineering, Art, Mathematics (STEAM) education. Participants were 90 undergraduate students who were randomly assigned to the teacher opinions feedback group, the teacher suggestion feedback group, or the non-feedback group, and took part in three courses of STEAM education of 3D-printing technology. Before and after each course, they were asked to fill out the Eugene Creativity Test. The results showed that compare with the teacher opinions feedback group and the non-feedback group, the participants in the teacher suggestion feedback group showed a higher score on the creativity scale. This suggests that the teacher suggestion feedback can be useful for improving the creativity in STEAM education.

16.
Abdom Radiol (NY) ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476534

RESUMO

PURPOSE: To study the clinical efficacy and safety of transarterial chemoembolization with drug-eluting beads (DEB-TACE) among women with advanced-stage or recurrent cervical cancer. METHODS: This retrospective cohort study enrolled women with cervical cancer who were treated by DEB-TACE between April 3, 2017 and July 12, 2021. Inclusion criteria were pathologic diagnosis of cervical cancer, II-IVa period, being aged 18 to 80 years, patient's inclination of treatment with DEB-TACE, and complete clinicopathologic data. Direct medical cost, hospital stay, resection frequency, treatment responses, adverse events, overall survival, and progression-free survival were investigated. RESULTS: A total of 16 women with cervical cancer were treated by DEB-TACE. DEB-TACE was successfully performed in all patients, with no major complications or adverse events. A total of 10 minor complications were observed in 9 women (56.3%) after the procedure. Seven (43.8%) women experienced mild to moderate post-embolization pain. The tumors decreased 3 and 6 months after the treatment. The frequency of complete response, partial response, stable disease, and progressive disease was 1 (40%), 3 (40%), 12 (15%), and 0 (0%), respectively, resulting in an objective response rate of 25.0% and a disease control rate of 100.0% after 1 month. The median hospital stay was 9.5 days, and the direct medical cost was 5.9 × 104 ¥. The median follow-up time was 4.1 months (interquartile range 2.6-23.7 months). The median overall survival was 19.1 months, and the 1- and 3-year survival rate was 64.9% and 46.4%, respectively. CONCLUSION: DEB-TACE with diamminedichloroplatinum-preloaded beads may be an effective and safe treatment for women with advanced-stage or recurrent cervical cancer.

17.
Front Neurol ; 12: 695696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557143

RESUMO

Background: Plasma-based biomarkers would be potential biomarkers for early diagnosis of Alzheimer's disease (AD) because they are more available and cost-effective than cerebrospinal fluid (CSF) or neuroimaging. Therefore, we aimed to evaluate whether phosphorylated tau181 (p-tau181) in plasma could be an accurate AD predictor. Methods: Participants from the ADNI database included 185 cognitively unimpaired subjects with negative Aß (CU-), 66 subjects with pre-clinical AD (CU with positive Aß), 164 subjects with mild cognitive impairment with negative Aß (MCI-), 254 subjects with prodromal AD (MCI with positive Aß), and 98 subjects with dementia. Multiple linear regression models, linear mixed-effects models, and local regression were used to explore cross-sectional and longitudinal associations of plasma p-tau181 with cognition, neuroimaging, or CSF biomarkers adjusted for age, sex, education, and APOE genotype. Besides, Kaplan-Meier and adjusted Cox-regression model were performed to predict the risk of progression to dementia. Receiver operating characteristic analyses were performed to evaluate the predictive value of p-tau181. Results: Plasma p-tau181 level was highest in AD dementia, followed by prodromal AD and pre-clinical AD. In pre-clinical AD, plasma p-tau181 was negatively associated with hippocampal volume (ß = -0.031, p-value = 0.017). In prodromal AD, plasma p-tau181 was associated with decreased global cognition, executive function, memory, language, and visuospatial functioning (ß range -0.119 to -0.273, p-value < 0.05) and correlated with hippocampal volume (ß = -0.028, p-value < 0.005) and white matter hyperintensity volume (WMH) volume (ß = 0.02, p-value = 0.01). In AD dementia, increased plasma p-tau181 was associated with worse memory. In the whole group, baseline plasma p-tau181 was significantly associated with longitudinal increases in multiple neuropsychological test z-scores and correlated with AD-related CSF biomarkers and hippocampal volume (p-value < 0.05). Meanwhile, CU or MCI with high plasma p-tau181 carried a higher risk of progression to dementia. The area under the curve (AUC) of the adjusted model (age, sex, education, APOE genotype, and plasma p-tau181) was 0.78; that of additionally included CSF biomarkers was 0.84. Conclusions: Plasma p-tau181 level is related to multiple AD-associated cognitive domains and AD-related CSF biomarkers at the clinical stages of AD. Moreover, plasma p-tau181 level is related to the change rates of cognitive decline and hippocampal atrophy. Thus, this study confirms the utility of plasma p-tau181 as a non-invasive biomarker for early detection and prediction of AD.

18.
Comput Math Methods Med ; 2021: 6415275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422094

RESUMO

Objective: To explore the protective effects and mechanism of mild hypothermia treatment in the treatment of myocardial ischemia-reperfusion injury. Material and Methods. A total of 20 Sprague-Dawley (SD) rats were assigned to 4 groups: the blank control group, sham operation group, ischemia reperfusion group, and mild hypothermia therapy group (each n = 5). Some indexes were detected. In addition, myocardial cell models of oxygen-glucose deprivation/reoxygenation injury (OGD) were established. The expression of mRNA IL-6 and TNF-α and the key enzyme levels of apoptosis (cleaved-Caspase-3) and the NLRP3 inflammasome/p53 signaling pathway in the models were determined. Results: The expression of serum IL-6 and TNF-α in the mild hypothermia therapy group was significantly lower than that in the ischemia reperfusion group. The mild hypothermia therapy group also showed a significantly lower TUNEL cell count and NLRP3 and p53 phosphorylation levels than the ischemia reperfusion group (all p < 0.05). The in vitro mild hypothermia + OGD group also showed significantly lower mRNA expression of IL-6 and TNF-α and levels of cleaved Caspase-3, NLRP3, and phosphorylated p53 protein than the OGD group (all p < 0.05). Conclusion: In conclusion, mild hypothermia therapy can inhibit the apoptosis and myocardial inflammation of cells induced by MI/R injury in rats and inhibiting the activity of the NLRP3 inflammasome pathway and p53 signaling pathway may be the mechanism.

19.
Oxid Med Cell Longev ; 2021: 3154501, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422207

RESUMO

Sick sinus syndrome (SSS) is a disease with bradycardia or arrhythmia. The pathological mechanism of SSS is mainly due to the abnormal conduction function of the sinoatrial node (SAN) caused by interstitial lesions or fibrosis of the SAN or surrounding tissues, SAN pacing dysfunction, and SAN impulse conduction accompanied by SAN fibrosis. Tongyang Huoxue Decoction (TYHX) is widely used in SSS treatment and amelioration of SAN fibrosis. It has a variety of active ingredients to regulate the redox balance and mitochondrial quality control. This study mainly discusses the mechanism of TYHX in ameliorating calcium homeostasis disorder and redox imbalance of sinoatrial node cells (SANCs) and clarifies the protective mechanism of TYHX on the activity of SANCs. The activity of SANCs was determined by CCK-8 and the TUNEL method. The levels of apoptosis, ROS, and calcium release were analyzed by flow cytometry and immunofluorescence. The mRNA and protein levels of calcium channel regulatory molecules and mitochondrial quality control-related molecules were detected by real-time quantitative PCR and Western Blot. The level of calcium release was detected by laser confocal. It was found that after H/R treatment, the viability of SANCs decreased significantly, the levels of apoptosis and ROS increased, and the cells showed calcium overload, redox imbalance, and mitochondrial dysfunction. After treatment with TYHX, the cell survival level was improved, calcium overload and oxidative stress were inhibited, and mitochondrial energy metabolism and mitochondrial function were restored. However, after the SANCs were treated with siRNA (si-ß-tubulin), the regulation of TYHX on calcium homeostasis and redox balance was counteracted. These results suggest that ß-tubulin interacts with the regulation of mitochondrial function and calcium release. TYHX may regulate mitochondrial quality control, maintain calcium homeostasis and redox balance, and protect SANCs through ß-tubulin. The regulation mechanism of TYHX on mitochondrial quality control may also become a new target for SSS treatment.

20.
In Vivo ; 35(5): 2521-2529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410938

RESUMO

BACKGROUND/AIM: High-flow nasal cannula (HFNC), a new method for postoperative oxygenation, has increasingly received attention during postoperative care. However, its importance for obese patients undergoing cardiac surgery remains controversial. This systematic review and meta-analysis compared and evaluated HFNC and conventional oxygen therapy (COT) in this patient group. MATERIALS AND METHODS: Literature was retrieved by searching eight public databases. Randomized controlled trials (RCTs) were selected. RevMan 5.3 was used to analyze the results and any potential bias. The primary outcome included atelectasis score at 24 h postoperatively. The secondary outcomes included PaO2/FiO2 (ratio), dyspnea score at 24 h postoperatively, intensive care unit (ICU) length of stay, and reintubation. RESULTS: The search strategy yielded 382 studies after duplicates were removed. Finally, 3 RCTs with a total of 526 patients were included in the present study. Compared with COT, there was no significant difference in atelectasis score, dyspnea score, reintubation, and ICU length of stay. CONCLUSION: For obese patients undergoing cardiac surgery, postoperative use of HFNC can maintain patient's oxygenation. Additional clinical studies are needed to investigate the role of HFNC in this patient group.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Insuficiência Respiratória , Cânula , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Tempo de Internação , Obesidade/complicações , Obesidade/terapia , Oxigênio , Oxigenoterapia , Insuficiência Respiratória/terapia
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