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STUDY QUESTION: Does the transfer of single low-grade blastocysts result in acceptable reproductive and perinatal outcomes compared to the transfer of single good-grade blastocysts? SUMMARY ANSWER: The transfer of single low-grade blastocysts resulted in a reduced live birth rate of around 30% (14% for very low-grade blastocysts) compared to 44% for single good-grade blastocysts, but does not lead to more adverse perinatal outcomes. WHAT IS KNOWN ALREADY: It is known that low-grade blastocysts can result in live births. However, the current studies are limited by relatively small sample sizes and single-centre designs. Furthermore, evidence on perinatal outcomes after transferring low-grade blastocysts is limited. STUDY DESIGN, SIZE, DURATION: We conducted a multi-centre, multi-national retrospective cohort study of 10 018 women undergoing 10 964 single blastocyst transfer cycles between 2009 and 2020 from 14 clinics across Australia, China, and New Zealand. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blastocysts were graded individually based on assessment of the morphology and development of the inner cell mass (ICM) and trophectoderm (TE), and were grouped into three quality categories: good- (AB, AB, or BA), moderate- (BB), and low-grade (grade C for ICM or TE) blastocysts. CC blastocysts were individually grouped as very low-grade blastocysts. Logistic regression with generalized estimating equation was used to analyse the association between blastocyst quality and live birth as well as other reproductive outcomes. Binomial, multinomial logistic, or linear regression was used to investigate the association between blastocyst quality and perinatal outcomes. Odds ratio (OR), adjusted OR (aOR), adjusted regression coefficient, and their 95% CIs are presented. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: There were 4386 good-grade blastocysts, 3735 moderate-grade blastocysts, and 2843 low-grade blastocysts were included in the analysis, for which the live birth rates were 44.4%, 38.6%, and 30.2%, respectively. Compared to good-grade blastocysts, the live birth rate of low-grade blastocysts was significantly lower (aOR of 0.48 (0.41-0.55)). Very low-grade blastocysts were associated with an even lower live birth rate (aOR 0.30 (0.18-0.52)) and their absolute live birth rate was 13.7%. There were 4132 singleton live births included in the analysis of perinatal outcomes. Compared with good-grade blastocysts, low-grade blastocysts had comparable preterm birth rates (<37 weeks, aOR 1.00 (0.65-1.54)), birthweight Z-scores (adjusted regression coefficient 0.02 (0.09-0.14)), and rates of very low birth weight (<1500 g, aOR 0.84 (0.22-3.25)), low birth weight (1500-2500 g, aOR 0.96 (0.56-1.65)), high birth weight (>4500 g, aOR 0.93 (0.37-2.32)), small for gestational age (aOR 1.63 (0.91-2.93)), and large for gestational age (aOR 1.28 (0.97-1.70)). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the retrospective design, residual confounding could not be excluded. In addition, the number of events for some perinatal outcomes was small. Between-operator and between-laboratory variations in blastocyst assessment were difficult to control. WIDER IMPLICATIONS OF THE FINDINGS: Patients undergoing IVF should be informed that low-grade blastocysts result in a lower live birth rate, however they do not increase the risk of adverse perinatal outcomes. Further research should focus on the criteria for embryos that should not be transferred and on the follow-up of long-term outcomes of offspring. STUDY FUNDING/COMPETING INTEREST(S): H.Z. is supported by a Monash Research Scholarship. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437). R.W. is supported by an NHMRC Emerging Leadership Investigator grant (2009767). B.W.J.M. reports consultancy, travel support, and research funding from Merck. The other authors do not have competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.
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Nascimento Prematuro , Gravidez , Humanos , Recém-Nascido , Feminino , Estudos Retrospectivos , Transferência Embrionária/métodos , Nascido Vivo , Peso ao Nascer , BlastocistoRESUMO
Flavonoids and their methylated derivatives have immense market potential in the food and biomedical industries due to their multiple beneficial effects, such as antimicrobial, anti-inflammatory, and anticancer activities. The biological synthesis of flavonoids and their derivatives is often accomplished via the use of genetically modified microorganisms to ensure large-scale production. Therefore, it is pivotal to understand the properties of O-methyltransferases (OMTs) that mediate the methylation of flavonoids. However, the properties of these OMTs are governed by their: sources, substrate specificity, amino acid residues in the active sites, and the intricate mechanism. In order to obtain a clue for the selection of suitable OMTs for the biosynthesis of a target methylated flavonoid, we made a comprehensive review of the currently reported results, with a particular focus on their comparative regioselectivity for different flavonoid substrates. Additionally, the possible mechanisms for the diversity of this class of enzymes were explored using molecular simulation technology. Finally, major gaps in our understanding and areas for future studies were discussed. The findings of this study may be useful in selecting genes that encode OMTs and designing enzyme-based processes for synthesizing O-methylated flavonoids.
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Fungi-mediated synthesis of Gold nanoparticles (AuNPs) has advantages in: high efficiency, low energy consumption, no need for extra capping and stabilizing agents, simple operation, and easy isolation and purification. Many fungi have been found to synthesize AuNPs inside cells or outside cells, providing different composition and properties of particles when different fungi species or reaction conditions are used. This is good to produce AuNPs with different properties, but may cause challenges to precisely control the particle shape, size, and activities. Besides, low concentrations of substrate and fungal biomass are needed to synthesize small-size particles, limiting the yield of AuNPs in a large scale. To find clues for the development methods to solve these challenges, the reported mechanisms of the fungi-mediated synthesis of AuNPs were summarized. The mechanisms of intracellular AuNPs synthesis are dependent on gold ions absorption by the fungal cell wall via proteins, polysaccharides, or electric absorption, and the reduction of gold ions via enzymes, proteins, and other cytoplasmic redox mediators in the cytoplasm or cell wall. The extracellular synthesis of AuNPs is mainly due to the metabolites outside fungal cells, including proteins, peptides, enzymes, and phenolic metabolites. These mechanisms cause the great diversity of the produced AuNPs in functional groups, element composition, shapes, sizes, and properties. Many methods have been developed to improve the synthesis efficiency by changing: chloroauric acid concentrations, reaction temperature, pH, fungal mass, and reaction time. However, future studies are still required to precisely control the: shape, size, composition, and properties of fungal AuNPs.
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Fatigue has many negative effects on human health. As such, it is desirable to develop anti-fatigue foods and understand the mechanisms of their action. Based on a comprehensive review of the literature, this article discusses the important roles of gut microbiota in fatigue and anti-fatigue. Studies have shown that an increase in pathogenic bacteria and a decrease in beneficial bacteria co-exist when fatigue is present in both rodents and humans, whereas changes in gut microbiota were reported after intervention with anti-fatigue foods. The roles of gut microbiota in the activities of anti-fatigue foods can also be explained in the causes and the effects of fatigue. Among the causes of fatigue, the accumulation of lactic acid, decrease of energy, and reduction of central nervous system function were related to gut microbiota metabolism. Among the harmful effects of fatigue, oxidative stress, inflammation, and intestinal barrier dysfunction were related to gut microbiota dysbiosis. Furthermore, gut microbiota, together with anti-fatigue foods, can inhibit pathogen growth, convert foods into highly anti-oxidative or anti-inflammatory products, produce short-chain fatty acids, maintain intestinal barrier integrity, inhibit intestinal inflammation, and stimulate the production of neurotransmitters that regulate the central nervous system. Therefore, it is believed that gut microbiota play important roles in the activities of anti-fatigue foods and may provide new insights on the development of anti-fatigue foods.
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Gastroenteropatias , Microbioma Gastrointestinal , Humanos , Intestinos/microbiologia , Inflamação , Bactérias/metabolismo , DisbioseRESUMO
Obesity is a serious health problem in modern life and increases the risk of many comorbidities including iron dyshomeostasis. In contrast to malnourished anemia, obesity-related iron dyshomeostasis is mainly caused by excessive fat accumulation, inflammation, and disordered gut microbiota. In obesity, iron dyshomeostasis also induces disorders associated with gut microbiota, neurodegenerative injury, oxidative damage, and fat accumulation in the liver. Selenium deficiency is often accompanied by obesity or iron deficiency, and selenium supplementation has been shown to alleviate obesity and overcome iron deficiency. Selenium inhibits fat accumulation and exhibits anti-inflammatory activity. It regulates gut microbiota, prevents neurodegenerative injury, alleviates oxidative damage to the body, and ameliorates hepatic fat accumulation. These effects theoretically meet the requirements for the inhibition of factors underlying obesity-related iron dyshomeostasis. Selenium supplementation may have a potential role in the alleviation of obesity-related iron dyshomeostasis. This review verifies this hypothesis in theory. All the currently reported causes and results of obesity-related iron dyshomeostasis are reviewed comprehensively, together with the effects of selenium. The challenges and strategies of selenium supplementation are also discussed. The findings demonstrate the possibility of selenium-containing drugs or functional foods in alleviating obesity-related iron dyshomeostasis.
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Deficiências de Ferro , Selênio , Humanos , Ferro , Selênio/farmacologia , Selênio/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológico , Fígado , Dieta HiperlipídicaRESUMO
BACKGROUND: Charlson Comorbidity Index (CCI) is positively associated with all-cause readmission in patients with heart failure (HF) in western countries. However, there is a scarcity of strong scientific evidence supporting the correlation in China. This study aimed at testing this hypothesis in Chinese. METHODS: We conducted a secondary analysis of 1,946 patients with HF in Zigong Fourth People's Hospital in China between December 2016 to June 2019. Logistic regression models were used to study the hypotheses, with adjustments for the four regression models. We also explore the linear trend and possible nonlinear relationship between CCI and readmission within six months. We further conducted subgroup analysis and tests for interaction to examine the possible interaction between CCI and the endpoint. Additionally, CCI alone and several combinations of variables based on CCI were used to predict the endpoint. Under the curve (AUC), sensitivity and specificity were reported to evaluate the performance of the predicted model. RESULTS: In the adjusted II model, CCI was an independent prognostic factor for readmission within six months in patients with HF (OR = 1.14, 95% CI: 1.03-1.26, P = 0.011). Trend tests revealed that there was a significant linear trend for the association. A nonlinear association was identified between them and the inflection point of CCI was 1. Subgroup analyses and tests for interaction indicated that cystatin played an interactive role in the association. ROC analysis indicated neither CCI alone nor combinations of variables based on CCI were adequate for prediction. CONCLUSION: CCI was independently positively correlated with readmission within six months in patients with HF in Chinese population. However, CCI has limited value on predicting readmission within six months in patients with HF.
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Insuficiência Cardíaca , Readmissão do Paciente , Humanos , Estudos Retrospectivos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , China/epidemiologia , ComorbidadeRESUMO
In this work, a lateral flow immunoassay (LFIA) with peptide functionalized gold nanoparticles (termed as biotin-ppeptide-AuNPs) has been developed for rapid, semi-quantitative detection of PTP1B activity without using any sophisticated equipment. In this method, the anti-phosphotyrosine (anti-pY) monoclonal antibody and streptavidin were used as test line and control line, respectively. The biotin-ppeptide-AuNPs contain 10% biotinylated peptide ligand carry a motif SDGHEpYIYVDP with pY (phosphotyrosine) and 90% pentapeptide (CALNN) ligand, which are used as PTP1B substrates and LFIA labelling probes. The experimental results demonstrate that the as-proposed LFIA with biotin-ppeptide-AuNPs exhibits a wide linear range (from 50 ng/mL to 10 µg/mL), a relatively low limit of detection (LOD, 44 ng/mL), and good specificity. In addition, the LFIA with biotin-ppeptide-AuNPs has been successfully used to evaluate activity levels of PTP1B in four cell lysates and the detection results exhibit a consistent trend with that of commercial kit.
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Ouro , Nanopartículas Metálicas , Biotina , Imunoensaio/métodos , Ligantes , Limite de Detecção , Peptídeos , Proteína Tirosina Fosfatase não Receptora Tipo 1RESUMO
Porcine circovirus 3 (PCV3) is a newly emerging virus and has been found associated with porcine dermatitis and nephropathy syndrome in pigs. Compared with PCV2, research into PCV3 cap gene sequencing is deficient. To investigate the prevalence and genotype distribution of PCV3, we collected 1291 samples from 211 pig farms throughout 15 provinces and municipalities. 312 out of 1291 samples were tested positive by PCR. We further sequenced and analyzed 164 PCR-positive samples. The majority (61.8%) of isolates we sequenced belong to genotype PCV3c. PCV3c is also the dominant genotype in Hubei, Hunan, Hebei province and Chongqing city. We found 3 sites under positive selection and located in predicted epitope peptide, revealing that the pig's immunity may be a reason those sites are undergoing highly positive selection.
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Infecções por Circoviridae , Circovirus , Doenças dos Suínos , Suínos , Animais , Circovirus/genética , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/veterinária , Cidades , Doenças dos Suínos/epidemiologia , Filogenia , China/epidemiologiaRESUMO
OBJECTIVE: Nonsyndromic cleft lip and/or cleft palate (NSCL/P) is an isolated phenotype of orofacial clefts with skewed sex ratio in prevalence. This study aims to identify differentially expressed genes (DEGs) and microRNAs (DEMs) of NSCL/P by integrated bioinformatics analysis, revealing mechanisms for sexual dimorphism in prevalence. MATERIALS AND METHODS: First, we downloaded the expression profile data from Gene Expression Omnibus database to identify DEGs and DEMs. Second, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses performed DEGs' functions. Then, clustered DEGs were identified through protein-protein interaction networks. Combining clustered DEGs with key genes searched in GeneCards enlarged NSCL/P-related genes. Moreover, the genes were linked by transcription factors (TFs). Subsequently, connected by the above TFs, DEMs and genes were used to establish the miRNA-TF-messenger RNA (mRNA) regulatory networks. RESULTS: The DEGs in sex-ignored group, female-only group, and male-only group were obtained, respectively. Among the DEMs, miR-378 was downregulated in females but upregulated in males. In female-only group, the miRNA-TF-mRNA regulatory networks showed miR-378-SP1-POLE2/CDK6/EZR regulatory axis was found to be key candidates of NSCL/P. CONCLUSIONS: Our findings suggest that different expression of miR-378 is consistent with the skewed sex ratio in the prevalence of NSCL/P.
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Fenda Labial , Fissura Palatina , MicroRNAs , Fenda Labial/genética , Fissura Palatina/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Prevalência , Razão de MasculinidadeRESUMO
Although recent studies have revealed that germline stem cells (GSCs) exist in the mouse postnatal ovary, how to efficiently obtain GSCs for regenerating neo-oogenesis is still a technical challenge. Here, we report that using in situ tissue culture we can efficiently accumulate large amounts of proliferating germ-like cells from mouse postnatal ovaries. Usually, more than 10,000 germ-like cells can be derived from one ovary by this method, and over 20% of these cells can grow into germ-like cells with self-renewal, which thus can serve as a good cell pool to isolate GSCs by other cell assorting methods such as FACS. This method is simple and time-saving, which should be useful for in future studies on mouse GSCs.
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Células Germinativas/citologia , Ovário/citologia , Células-Tronco/citologia , Técnicas de Cultura de Tecidos , Animais , Proliferação de Células , Feminino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Oxymatrine is a quinazine alkaloid extracted from Sophora flavescens with various therapeutic effects such as organ- and tissue-protective, anti-inflammatory, anti-cancer, and anti-viral effects. In this review, we summarize the protective effects of oxymatrine on damaged organs and tissues by analyzing both in vivo and in vitro studies. The mechanisms of protective effects of oxymatrine are mainly related to its anti-inflammatory, anti-oxidative stress, anti- or pro-apoptotic, anti-fibrotic, metabolism-regulation, and anti-nociceptive functions. In addition, a variety of signal pathways, cells, and molecules are influenced by oxymatrine, and by these comprehensive actions, maximum therapeutic effects can be achieved. Furthermore, we summarize the protective effects in clinical studies and adverse effects of oxymatrine. It is believed that through more in-depth animal experiments and standardized clinical research, oxymatrine holds a bright future in the process of organ and tissue protection and has a significant therapeutic promise to translate from bench to bedside.
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Alcaloides/farmacologia , Substâncias Protetoras/farmacologia , Quinolizinas/farmacologia , Alcaloides/química , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Fibrose , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Quinolizinas/química , Sophora/químicaRESUMO
BACKGROUND: Atherosclerosis (AS) is a common pathological basis of various cardiovascular and cerebrovascular diseases. Plaque formation is initiated and triggered by vascular smooth musclecells (VSMCs) migration in vascular wall, which gradually aggravates atherosclerosis progression. Absent in melanoma 2 (AIM2), a member of HIN-200 family, plays an important role in activating inflammasome. However, the role of AIM2 in atherosclerotic plaque progression outside of the inflammasome has not yet been reported. METHODS: The potential effect and the underlying mechanism of AIM2 were investigated in apoliporotein E-deficient (ApoE-/-) mice. Murine AIM2 lentivirus, shRNA-AIM2 lentivirus and null lentivirus were constructed and injected intravenously into ApoE-/- mice, which were fed on a high fat diet. The specific mechanism of AIM2 in vascular smooth cells (VSMCs) was explored in vitro. RESULTS: Results showed the aortic atherosclerotic lesion area was larger with AIM2 over-expression, and the number of smooth muscle cells was enhanced in line with the increased AIM2 levels. AIM2 overexpression also induced the increasing expression of MMP2. In vitro studies revealed that different levels of ox-LDL increased AIM2 expression in a time-dependent manner. Transwell showed that AIM2 mediated migration in VSMCs. The expression of AIM2 can be inhibited when the ROS inhibitor was used. Additionally, the overexpression and inhibition of AIM2 significantly affects HG-induced migration and TGF-ß/SMAD signaling pathway in VSMCs. CONCLUSION: Thus, we demonstrated that AIM2 could promote the progression of atherosclerotic plaque by increasing migration in VSMCs.
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Doenças da Aorta/fisiopatologia , Aterosclerose/fisiopatologia , Movimento Celular , Proteínas de Ligação a DNA/metabolismo , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/metabolismo , Animais , Doenças da Aorta/patologia , Aterosclerose/patologia , Masculino , Camundongos , Camundongos Knockout , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of both hospital and community infections globally. It's important to illuminate the differences between community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA), but there have been confusions on the definition, especially for the MRSA isolates identified within 48 h of admission. This study aimed to determine the molecular characteristics and virulence genes profile of CA and HA-MRSA isolates identified less than 48 h after hospital admission in our region. METHODS: A total 62 MRSA isolates identified within 48 h after admission and the clinical data were collected. Antimicrobial susceptibility test (AST) of collected isolates were performed according to the guidelines of Clinical and Laboratory Standards Institute (CLSI) 2015, and staphylococcal cassette chromosome mec (SCCmec) typing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and virulence gene profiling were performed to explore the molecular diversity. RESULTS: SCCmec III and sequence type (ST) 239 were the most prevalent SCCmec type and ST in both CA and HA-MRSA groups. HA-MRSA group had higher prevalence of SCCmec III (87.2 %) and ST239 (79.5 %) compared with CA-MRSA (60.9 and 43.4 %, both P < 0.001), while the frequency of SCCmec IV (26.0 %) and ST59 (21.7 %) were higher in CA-MRSA than its counterpart (P < 0.001 and P = 0.003). MRSA-ST239-III was the predominant type in this study (61.3 %, 38/62), especially in HA-MRSA group (76.9 %, 30/39). However, CA-MRSA strains exhibited more diversity in genotypes in this study. Meanwhile, CA-MRSA tended to have lower resistant percentage to non-ß-lactams antibiotics but more virulence genes carriage, especially the staphylococcal enterotoxins (SE) genes. Notably, seb gene was only detected in CA-MRSA isolates (52.2 %), likely a significant marker for CA-MRSA isolates. Panton-Valentine leukocidin gene (PVL) was highly detected in both groups, while appeared no significantly different between CA-MRSA (47.8 %) and HA-MRSA (43.6 %). CONCLUSIONS: Our findings support a difference in the molecular epidemiology and virulence genes profile of CA-MRSA and HA-MRSA. Furthermore, this study indicates a possible transmission from HA-MRSA to CA-MRSA, which may cause the overlap of the definition.
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Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/genética , Fatores de Virulência/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Eletroforese em Gel de Campo Pulsado , Feminino , Hospitais , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Virulência/genética , Adulto JovemRESUMO
OBJECTIVE: We present a prenatal diagnosis strategy of using Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) for the detection of maternal uniparental disomy 15/trisomy 15 (UPD(15) mat/T15) mosaicism. CASE REPORT: A 43-year-old woman underwent amniocentesis at 19 weeks of gestation due to a high risk of trisomy 15 (T15) as indicated by non-invasive prenatal testing (NIPT). Cytogenetic analysis revealed a karyotype of 46, XX of cultured amniocytes. Further analysis using copy number variation sequencing (CNV-seq) analysis showed 55 % T15 mosaicism. The second amniocentesis was performed and showed a karyotype of 46, XX and 26 % T15 mosaicism by interphase fluorescence in situ hybridization (FISH). MS-MLPA analysis of uncultured amniocytes showed that the copy number ratio of 15q11-13 ranged from 1.3 to 1.5, and the percentage of methylation was between 70 % and 100 %. MS-MLPA assay of cultured amniocytes showed a copy number ratio of 1 and a methylation percentage of 100 %. Therefore, this fetus was identified to be an UPD(15) mat/T15 mosaicism. The parents decided to terminate the pregnancy. CONCLUSION: MS-MLPA can be used in combination with karyotype and CNV-seq for prenatal diagnosis of NIPT high-risk T15 to avoid missed diagnosis of UPD(15) mat/T15 mosaicism.
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Síndrome de Prader-Willi , Dissomia Uniparental , Gravidez , Feminino , Humanos , Adulto , Hibridização in Situ Fluorescente , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Reação em Cadeia da Polimerase Multiplex , Trissomia/diagnóstico , Trissomia/genética , Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Amniocentese , Mosaicismo , Hibridização Genômica Comparativa , Cromossomos Humanos Par 15RESUMO
OBJECTIVE: This study aimed to develop and validate an eMCI-CHD tool based on clinical data to predict mild cognitive impairment (MCI) risk in patients with coronary heart disease (CHD). METHODS: This cross-sectional study prospectively collected data from 400 patients with coronary heart disease (aged 55-90 years, 62% men) from July 2022 to September 2023 and randomized (7:3 ratio) them into training and validation sets. After determining the modeling variables through least absolute shrinkage and selection operator regression analysis, four ML classifiers were developed: logistic regression, extreme gradient boosting (XGBoost), support vector machine, and random forest. The performance of the models was evaluated using area under the ROC curve, accuracy, sensitivity, specificity, and F1 score. Decision curve analysis was used to assess the clinical performance of the established models. The SHapley Additive exPlanations (SHAP) method was applied to determine the significance of the features, the predictive model was visualized with a nomogram, and an online web-based calculator for predicting CHD-MCI risk scores was developed. RESULTS: Of 400 CHD patients (average age 70.86 ± 8.74 years), 220 (55%) had MCI. The XGBoost model demonstrated superior performance (AUC: 0.86, accuracy: 78.57%, sensitivity: 0.74, specificity: 0.84, F1: 0.79) and underwent validation. An online tool (https://mr.cscps.com.cn/mci/index.html) with seven predictive variables (APOE gene typing, age, education, TyG index, NT-proBNP, C-reactive protein, and occupation) assessed MCI risk in CHD patients. CONCLUSION: This study highlights the potential for predicting MCI risk among CHD patients using an ML model-driven nomogram and risk scoring tool based on clinical data.
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BACKGROUND: The Zhizi Chuanxiong herb pair (ZCHP) can delay pathological progression of atherosclerosis (AS); however, its pharmacological mechanism remains unclear because of its complex components. The purpose of current study is to systematically investigate the anti-AS mechanism of ZCHP. METHODS: The databases of TCMSP, STITCH, SwissTargetPrediction, BATMAN-TCM, and ETCM were searched to predict the potential targets of ZCHP components. Disease targets associated with AS was retrieved from the GEO database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses were executed using DAVID 6.8. Molecular docking method was employed to evaluate the core target binding to blood components, and animal experiments were performed to test action mechanism. RESULTS: A ZCHP-components-targets-AS network was constructed by using Cytoscape, included 11 main components and 52 candidate targets. Crucial genes were shown in the protein-protein interaction network, including TNF, IL-1ß, IGF1, MMP9, COL1A1, CCR5, HMOX1, PTGS1, SELE, and SYK. KEGG enrichment illustrated that the NF-κB, Fc epsilon RI, and TNF signaling pathways were important for AS treatment. These results were validated by molecular docking. In ApoE-/- mice, ZCHP significantly reduced intima-media thickness, pulse wave velocity, plaque area, and serum lipid levels while increasing the difference between the end-diastolic and end-systolic diameters. Furthermore, ZCHP significantly decreased the mRNA and protein levels of TNF-α and IL-1ß, suppressed NF-κB activation, and inhibited the M1 macrophage polarization marker CD86 in ApoE-/- mice. CONCLUSION: This study combining network pharmacology, molecular biology, and animal experiments showed that ZCHP can alleviate AS by suppressing the TNF/NF-κB axis and M1 macrophage polarization.
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Background: Polycystic ovary syndrome with insulin resistance (PCOS-IR) is the most common endocrine and metabolic disease in women of reproductive age, and low fertility in PCOS patients may be associated with oocyte quality; however, the molecular mechanism through which PCOS-IR affects oocyte quality remains unknown. Methods: A total of 22 women with PCOS-IR and 23 women without polycystic ovary syndrome (control) who underwent in vitro fertilization and embryo transfer were recruited, and clinical information pertaining to oocyte quality was analyzed. Lipid components of follicular fluid (FF) were detected using high-coverage targeted lipidomics, which identified 344 lipid species belonging to 19 lipid classes. The exact lipid species associated with oocyte quality were identified. Results: The number (rate) of two pronuclear (2PN) zygotes, the number (rate) of 2PN cleaved embryos, and the number of high-quality embryos were significantly lower in the PCOS-IR group. A total of 19 individual lipid classes and 344 lipid species were identified and quantified. The concentrations of the 19 lipid species in the normal follicular fluid (control) ranged between 10-3 mol/L and 10-9 mol/L. In addition, 39 lipid species were significantly reduced in the PCOS-IR group, among which plasmalogens were positively correlated with oocyte quality. Conclusions: This study measured the levels of various lipids in follicular fluid, identified a significantly altered lipid profile in the FF of PCOS-IR patients, and established a correlation between poor oocyte quality and plasmalogens in PCOS-IR patients. These findings have contributed to the development of plasmalogen replacement therapy to enhance oocyte quality and have improved culture medium formulations for oocyte in vitro maturation (IVM).
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Fertilização in vitro , Líquido Folicular , Resistência à Insulina , Lipidômica , Oócitos , Plasmalogênios , Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/metabolismo , Líquido Folicular/metabolismo , Líquido Folicular/química , Oócitos/metabolismo , Adulto , Lipidômica/métodos , Plasmalogênios/metabolismo , Plasmalogênios/análise , Fertilização in vitro/métodos , Lipídeos/análise , Infertilidade Feminina/metabolismo , Metabolismo dos Lipídeos/fisiologia , Transferência Embrionária , Estudos de Casos e ControlesRESUMO
Introduction: Type 2 diabetes mellitus (T2DM) is a major cause of atherosclerosis (AS). However, definitive evidence regarding the common molecular mechanisms underlying these two diseases are lacking. This study aimed to investigate the mechanisms underlying the association between T2DM and AS. Methods: The gene expression profiles of T2DM (GSE159984) and AS (GSE100927) were obtained from the Gene Expression Omnibus, after which overlapping differentially expressed gene identification, bioinformatics enrichment analyses, protein-protein interaction network construction, and core genes identification were performed. We confirmed the discriminatory capacity of core genes using receiver operating curve analysis. We further identified transcription factors using TRRUST database to build a transcription factor-mRNA regulatory network. Finally, the immune infiltration and the correlation between core genes and differential infiltrating immune cells were analyzed. Results: A total of 27 overlapping differentially expressed genes were identified under the two-stress conditions. Functional analyses revealed that immune responses and transcriptional regulation may be involved in the potential pathogenesis. After protein-protein interaction network deconstruction, external datasets, and qRT-PCR experimental validation, four core genes (IL1B, C1QA, CCR5, and MSR1) were identified. ROC analysis further showed the reliable value of these core genes. Four common differential infiltrating immune cells (B cells, CD4+ T cells, regulatory T cells, and M2 macrophages) between T2DM and AS datasets were selected based on immune cell infiltration. A significant correlation between core genes and common differential immune cells. Additionally, five transcription factors (RELA, NFκB1, JUN, YY1, and SPI1) regulating the transcription of core genes were mined using upstream gene regulator analysis. Discussion: In this study, common target genes and co-immune infiltration landscapes were identified between T2DM and AS. The relationship among five transcription factors, four core genes, and four immune cells profiles may be crucial to understanding T2DM complicated with AS pathogenesis and therapeutic direction.
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Aterosclerose , Biomarcadores , Biologia Computacional , Diabetes Mellitus Tipo 2 , Mapas de Interação de Proteínas , Humanos , Biologia Computacional/métodos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Aterosclerose/genética , Aterosclerose/imunologia , Biomarcadores/metabolismo , Mapas de Interação de Proteínas/genética , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , TranscriptomaRESUMO
PURPOSE: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. STUDY DESIGN AND METHODS: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. RESULTS: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. CONCLUSIONS: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. TRIAL REGISTRY: https://www.chictr.org.cn/showproj.html?proj=166181.
Assuntos
Senilidade Prematura , Medicamentos de Ervas Chinesas , Qualidade de Vida , Humanos , Método Duplo-Cego , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Pessoa de Meia-Idade , Feminino , Idoso , Senilidade Prematura/tratamento farmacológico , Adulto , Telomerase , Força da Mão , Estudos Prospectivos , Telômero/efeitos dos fármacosRESUMO
Background: Growing observational studies have shown that abnormal systemic iron status is associated with Coronary heart disease (CHD). However, these results from observational studies was not entirely consistent.It remains unclear whether this relationship represents causality.It is necessary to explore the causal relationship between iron status and CHD and related cardiovascular diseases (CVD). Objective: We aimed to investigate the potential casual relationship between serum iron status and CHD and related CVD using a two-sample Mendelian randomization (MR) approach. Methods: Genetic statistics for single nucleotide polymorphisms (SNPs) between four iron status parameters were identified in a large-scale genome-wide association study (GWAS) conducted by the Iron Status Genetics organization. Three independent single nucleotide polymorphisms (SNPs) (rs1800562, rs1799945, and rs855791) aligned with four iron status biomarkers were used as instrumental variables. CHD and related CVD genetic statistics We used publicly available summary-level GWAS data. Five different MR methods random effects inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and Wald ratio were used to explore the causal relationship between serum iron status and CHD and related CVD. Results: In the MR analysis, we found that the causal effect of serum iron (OR = 0.995, 95% CI = 0.992-0.998, p = 0.002) was negatively associated with the odds of coronary atherosclerosis (AS). Transferrin saturation (TS) (OR = 0.885, 95% CI = 0.797-0.982, p = 0.02) was negatively associated with the odds of Myocardial infarction (MI). Conclusion: This MR analysis provides evidence for a causal relationship between whole-body iron status and CHD development. Our study suggests that a high iron status may be associated with a reduced risk of developing CHD.