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INTRODUCTION: Premature ovarian insufficiency (POI) is one of the causes of female infertility. Unexplained POI is increasingly affecting women in their reproductive years. However, the etiology of POI is diverse and remains elusive. We and others have shown that brain-derived neurotrophic factor (BDNF) plays an important role in adult ovarian function. Here, we report on a novel role of BDNF in the Developmental Origins of POI. METHODS: Placental BDNF knockout mice were created using CRISPR/CAS9. Homozygous knockout (cKO(HO)) mice didn't survive, while heterozygous knockout (cKO(HE)) mice did. BDNF reduction in cKO(HE) mice was confirmed via immunohistochemistry and Western blots. Ovaries were collected from cKO(HE) mice at various ages, analyzing ovarian metrics, FSH expression, and litter sizes. In one-month-old mice, oocyte numbers were assessed using super-ovulation, and oocyte gene expression was analyzed with smart RNAseq. Ovaries of P7 mice were studied with SEM, and gene expression was confirmed with RT-qPCR. Alkaline phosphatase staining at E11.5 and immunofluorescence for cyclinD1 assessed germ cell number and cell proliferation. RESULTS: cKO(HE) mice had decreased ovarian function and litter size in adulthood. They were insensitive to ovulation induction drugs manifested by lower oocyte release after superovulation in one-month-old cKO(HE) mice. The transcriptome and SEM results indicate that mitochondria-mediated cell death or aging might occur in cKO(HE) ovaries. Decreased placental BDNF led to diminished primordial germ cell proliferation at E11.5 and ovarian reserve which may underlie POI in adulthood. CONCLUSION: The current results showed decreased placental BDNF diminished primordial germ cell proliferation in female fetuses during pregnancy and POI in adulthood. Our findings can provide insights into understanding the underlying mechanisms of POI.
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Fator Neurotrófico Derivado do Encéfalo , Camundongos Knockout , Placenta , Insuficiência Ovariana Primária , Animais , Insuficiência Ovariana Primária/metabolismo , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Feminino , Camundongos , Gravidez , Placenta/metabolismo , Ovário/metabolismo , Ovário/patologia , Modelos Animais de Doenças , Oócitos/metabolismoRESUMO
BACKGROUND: A chronic condition that significantly reduces a child's quality of life is allergic rhinitis (AR). The environment and allergens that the body is regularly exposed to can cause inflammatory and immunological reactions, which can change the expression of certain genes Epigenetic changes are closely linked to the onset and severity of allergy disorders according to mounting amounts of data. Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot be converted into polypeptides. The three main categories of ncRNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). NcRNAs play a crucial role in controlling gene expression and contribute to the development of numerous human diseases. METHODS: Articles are selected based on Pubmed's literature review and the author's personal knowledge. The largest and highest quality studies were included. The search selection is not standardized. RESULTS: Recent findings indicate that various categories of ncRNAs play distinct yet interconnected roles and actively contribute to intricate gene regulatory networks. CONCLUSION: This article demonstrates the significance and progress of ncRNAs in children's AR. The database covers three key areas: miRNAs, lncRNAs, and circRNAs. Additionally, potential avenues for future research to facilitate the practical application of ncRNAs as therapeutic targets and biomarkers will be explore.
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RNA não Traduzido , Rinite Alérgica , Humanos , Rinite Alérgica/genética , Rinite Alérgica/imunologia , Criança , RNA não Traduzido/genética , MicroRNAs/genética , Biomarcadores/metabolismoRESUMO
Tumor dormancy is the underpinning for cancer relapse and chemoresistance, leading to massive cancer-related death in colorectal cancer (CRC). However, our comprehension of the mechanisms dictating tumor dormancy and strategies for eliminating dormant tumor cells remains restricted. In this study, we identified that collagen XVII (COL17A1), a hemidesmosomal transmembrane protein, can promote the dormancy of CRC cells. The upregulation of COL17A1 was observed to prolong quiescence periods and diminish drug susceptibility of CRC cells. Mechanistically, COL17A1 acts as a scaffold, enhancing the crosstalk between mTORC2 and Akt, thereby instigating the mTORC2-mediated dormant signaling. Notably, the activation of mTORC2 is contingent upon the intracellular domain of COL17A1, regardless of its ectodomain shedding. Our findings underscore a pivotal role of the COL17A1-mTORC2 axis in CRC dormancy, suggesting that mTORC2-specific inhibitors may hold therapeutic prospects for the eradication of dormant tumor cells.
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Colágeno Tipo XVII , Neoplasias Colorretais , Alvo Mecanístico do Complexo 2 de Rapamicina , Colágenos não Fibrilares , Transdução de Sinais , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Colágenos não Fibrilares/metabolismo , Colágenos não Fibrilares/genética , Linhagem Celular Tumoral , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Autoantígenos/metabolismo , Camundongos , Camundongos Nus , Proliferação de Células , Camundongos Endogâmicos BALB CRESUMO
A vasculature network supplies blood to feather buds in the developing skin. Does the vasculature network during early skin development form by sequential sprouting from the central vasculature or does local vasculogenesis occur first that then connect with the central vascular tree? Using transgenic Japanese quail Tg(TIE1p.H2B-eYFP), we observe that vascular progenitor cells appear after feather primordia formation. The vasculature then radiates out from each bud and connects with primordial vessels from neighboring buds. Later they connect with the central vasculature. Epithelial-mesenchymal recombination shows local vasculature is patterned by the epithelium, which expresses FGF2 and VEGF. Perturbing noggin expression leads to abnormal vascularization. To study endothelial origin, we compare transcriptomes of TIE1p.H2B-eYFP+ cells collected from the skin and aorta. Endothelial cells from the skin more closely resemble skin dermal cells than those from the aorta. The results show developing chicken skin vasculature is assembled by (1) physiological vasculogenesis from the peripheral tissue, and (2) subsequently connects with the central vasculature. The work implies mesenchymal plasticity and convergent differentiation play significant roles in development, and such processes may be re-activated during adult regeneration. SUMMARY STATEMENT: We show the vasculature network in the chicken skin is assembled using existing feather buds as the template, and endothelia are derived from local bud dermis and central vasculature.
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Ambient fine particular matter (PM2.5) exposure has been associated with numerous adverse effects including triggering functional disorders of the placenta and inducing immune imbalance in offspring. However, how maternal PM2.5 exposure impacts immune development during early life is not fully understood. In the current study, we exposed mice with low-, middle-, and high-dose PM2.5 during pregnancy to investigate the potential link between the transcriptional changes in the placenta and immune imbalance in mice offspring induced by PM2.5 exposures. Using flow cytometry, we found that the proportions of B cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and macrophage (Mφ) cells were altered in the blood of PM2.5-exposed mice pups but not dendritic cells (DCs) and natural killer cells (NKs). Using bulk RNA sequencing, we found that PM2.5 exposure altered the transcriptional profile which indicated an inhibition of the complement and coagulation cascades in the placenta. Weighted gene co-expression network analysis (WGCNA) revealed the potential crosstalk between the perturbation of placental gene expression and the changes of immune cell subsets in pups on postnatal day 10 (PND10). Specifically, WGCNA identified a cluster of genes including Defb15, Defb20, Defb25, Cst8, Cst12, and Adam7 that might regulate the core immune cell types in PND10 pups. Although the underlying mechanisms of how maternal PM2.5 exposure induces peripheral lymphocyte disturbance in offspring still remain much unknown, our findings here shed light on the potential role of placental dysfunction in these adverse effects.
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Material Particulado , Placenta , Humanos , Gravidez , Feminino , Camundongos , Animais , Material Particulado/toxicidade , Material Particulado/metabolismo , Transcriptoma , Linfócitos T CD8-Positivos/metabolismo , Exposição Materna/efeitos adversos , HomeostaseRESUMO
Stable emulsions can have numerous negative impacts on both the oil industry and the environment. This study focuses on the synthesis of two ionic liquids (via. PPBD and PPBH) with four hydrophobic branches and four ionic centers that can effectively treat oil-water emulsions at a low temperature of 40 °C. Their chemical structure was explored using Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance hydrogen spectra (1H NMR). The effect of temperature, PPBD and PPBH concentration, oil-water ratio, salinity and pH value on the demulsification efficiency (DE) of W/O emulsion was studied detailly and several commercial demulsifiers were also used for comparison. Results revealed that by adding 250 mg/L of PPBH in an E30 emulsion and leaving it for 120 min at 40 °C, the DE could reach 96.34%. Meanwhile, in an E30 emulsion (oil-water mass ratio of 3:7) with 250 mg/L of PPBD, the DE of 95.23% could be obtained at 40 °C for 360 min. Especially, the DE of PPBH could reach 100% in an E70 emulsion (oil-water mass ratio of 7:3) at the same conditions. Additionally, the demulsifier (PPBH) exhibited excellent salt resistance and outperformed some commonly used commercial demulsifiers. Several methods were utilized to investigate the potential demulsification mechanism, including measuring interfacial tension (IFT), three-phase contact angle (CA), droplet contact time, zeta potential, and observing samples under optical microscopy.
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Líquidos Iônicos , Emulsões , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Baixa , Íons , ÁguaRESUMO
Our previous studies found that Zinc-finger protein 382 (ZNF382) played as a tumor suppressor gene in esophageal and gastric cancers, and a positive correlation between the high expression of ZNF382 and better outcome in breast cancer patients. However, the biological roles and mechanisms of ZNF382 in breast cancer remains unclear. We detected ZNF382 expression by reverse-transcription PCR (RT-PCR) and real-time quantitative PCR (qRT-PCR) in breast cancer cells and tissues, and explored the impacts and mechanisms of ectopic ZNF382 expression in breast cancer cells in vitro and in vivo, respectively. Our results revealed that ZNF382 was significantly down-regulated in breast cancer tissues compared with adjacent non-cancer tissues. Restoration of ZNF382 expression in silenced breast cancer cells not only inhibited tumor cell colony formation, viability, migration and invasion, and epithelial-mesenchymal-transition (EMT), but also induced apoptosis and G0/G1 arrest. In conclusion, ZNF382 could induce G0/G1 cell cycle arrest through inhibiting CDC25A signaling, and, inhibit cell migration, invasion and EMT by antagonizing ZEB1 signaling in breast cancer cells.
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BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in ovarian function including follicle development and oocyte maturation, and embryonic development. However, whether BDNF treatment can reimpose ovarian aging and impaired fertility remains elusive. In this study, we investigated the reproductive outcomes of BDNF treatment and potential mechanisms in aged mice. METHOD: "Aged" mice (35-37 weeks old, n = 68) were treated with recombinant human BDNF protein (rhBDNF, 1 µg/200 µL) through daily intraperitoneal (IP) injection for 10 days with/without ovulation induction. Reproductive age mice (8-10 weeks old, n = 28) were treated with ANA 12 (a selective BDNF receptor, TrkB antagonist) through daily IP injection for 5 days with/without ovulation induction. Ovarian function was assessed by ovarian weight, number of follicles, and sex hormone productions. Following induction of ovulation, the number of total oocytes or abnormal oocytes, and blastocyst formation were assessed. Reproductive functions of the mice were evaluated, including pregnancy rate, mating duration for conception, implantation sites, litter size, and weight of offspring. Finally, the molecular mechanism of the effects of BDNF on ovarian cell functions in mice were examined by Western blot and immunofluorescence. RESULTS: rhBDNF treatment increased the ovarian weight, number of follicles, number and quality of oocytes including increased blastocysts formation, blood estrogen levels, and pregnancy rate in 35-37-week-old mice. Conversely, BDNF receptor antagonist, ANA 12, treatment decreased the ovarian volume and number of antral follicles and increased the proportion of abnormal oocytes in 8-10-week-old mice. We further demonstrated that BDNF treatment promoted ovarian cell proliferation as well as activation of TrkB and cyclinD1-creb signalling. CONCLUSION: We demonstrated that ten consecutive days of daily IP injection of rhBDNF rescued ovarian function in aged mice. Our results further indicate that TrkB and cyclin D1-creb signaling may underlie the BDNF function in ovaries. Targeting BDNF-TrkB signaling is a potential novel therapeutic strategy to reverse ovarian aging.
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Fator Neurotrófico Derivado do Encéfalo , Ovário , Animais , Feminino , Humanos , Camundongos , Gravidez , Envelhecimento , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células , Oócitos/metabolismo , Folículo Ovariano/metabolismo , Ovário/metabolismoRESUMO
The association between exposure to particulate matter (PM) during pregnancy and abnormal birth outcomes is still inconclusive. This study aims to provide more evidence for this public health concern by investigating birth outcomes and the growth of offspring in mice exposed to PM during pregnancy. C57BL/6 J pregnant mice were exposed to PM via nasal drip at three doses or solvent control. The dam weight gain was recorded during pregnancy. The number of pups, pup weight, and placental weight were recorded at embryonic day 18.5 (E18.5) necropsy. For mice that gave birth naturally, we calculated the gestation length and measured the body weight of offspring once a week from the 1st to the 6th week after birth. The results showed that there were no significant differences in maternal body weight gain, conception rate, pregnancy duration, and litter size among different groups. There were no significant differences in fetal weight, placental weight, and fetal/placental weight ratio at E18.5. Weight gain in offspring was reduced after birth. The average body weight of offspring in the high-dose group was significantly lower than that in the control group at weeks 5 in female pups. There were no significant differences in the body weight of male offspring among groups from 1st to the 6th. Together, our study indicated that maternal exposure to PM did not significantly impact birth outcomes of C57BL/6 J mice but affected growth trajectories in offspring after birth in a dose- and fetal sex-dependent manner.
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Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Humanos , Gravidez , Feminino , Camundongos , Masculino , Animais , Exposição Materna/efeitos adversos , Material Particulado/toxicidade , Placenta , Camundongos Endogâmicos C57BL , Aumento de Peso , Peso ao NascerRESUMO
Hyperphosphatemia can occur as a result of reduced phosphate (Pi) excretion in cases of kidney dysfunction, which can induce muscle wasting and suppress myogenic differentiation. Higher Pi suppresses myogenic differentiation and promotes muscle atrophy through canonical (oxidative stress-mediated) and noncanonical (p62-mediated) activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. However, the crosstalk between myogenin and Nrf2/p62 and potential drug(s) for the regulation of myogenin expression needed to be addressed. In this study, we further identified that myogenin may negatively regulate Nrf2 and p62 protein levels in the mouse C2C12 muscle cell line. In the drug screening analysis, we identified N-acetylcysteine, metformin, phenformin, berberine, 4-chloro-3-ethylphenol, cilostazol, and cilomilast as ameliorating the induction of Nrf2 and p62 expression and reduction in myogenin expression that occur due to high Pi. We further elucidated that doxorubicin and hydrogen peroxide reduced the amount of myogenin protein mediated through the Kelch-like ECH-associated protein 1/Nrf2 pathway, differently from the mechanism of high Pi. The dual functional roles of L-ascorbic acid (L-AA) were found to be dependent on the working concentration, where concentrations below 1 mM L-AA reversed the effect of high Pi on myogenin and those above 1 mM L-AA had a similar effect of high Pi on myogenin when used alone. L-AA exacerbated the effect of hydrogen peroxide on myogenin protein and had no further effect of doxorubicin on myogenin protein. In summary, our results further our understanding of the crosstalk between myogenin and Nrf2, with the identification and verification of several potential drugs that can be applied in rescuing the decline of myogenin due to high Pi in muscle cells.
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Peróxido de Hidrogênio , Fator 2 Relacionado a NF-E2 , Animais , Camundongos , Ácido Ascórbico/farmacologia , Doxorrubicina/farmacologia , Peróxido de Hidrogênio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Atrofia Muscular/metabolismo , Miogenina/genética , Miogenina/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais/fisiologiaRESUMO
It is well understood that exposure to particulate matter (PM) can have adverse effects on the nervous system. When pregnant women are exposed to PM, their fetuses are also affected through the placenta. However, the mechanisms by which fetal brain development is regulated between mother and fetus remain unclear. C57BL/6J pregnant mice were exposed to PM at embryonic day (E) 2.5, 5.5, 8.5, 11.5, 14.5, and 17.5 via nasal drip at three doses (3, 6, 12 mg/kg of body weight) or PBS control. Neurobehavioral changes in the offspring were examined at 5-6-week-old by open field test (OFT) and elevated plus maze (EPM). The maternal and fetal brain and placenta were collected at E18.5, and molecular signal changes were explored using transcriptome analysis. We found that both male and female low-dose pups and male middle-dose pups traveled a significantly longer distance than controls in EPM tests. Both male and female low-dose pups showed a higher frequency of entering the center area and female low-dose pups exhibited a higher percentage of distance moved in the center area than controls in OFT tests. Gene expression in the maternal brain, fetal brain, and placenta at E18.5 was altered. Differentially expressed genes were enriched in the neuroactive ligand-receptor interaction pathway in all three tissue types. Pathway analysis revealed that the PI3K-Akt and PKC signaling was dysregulated in the fetal brain in the high-dose group compared with the control group. The pathways play a role in neuronal survival and apoptosis. Furthermore, there is a dose-dependent increase in Caspase-6, neuronal apoptosis and neurodegeneration biomarker, levels in E18.5 fetal brain (P = 0.06). In conclusion, our study demonstrated that prenatal PM exposure enhanced exploration and locomotor activity in adolescent offspring and altered molecular events in maternal brain, fetal brain, and placenta. The connections of these changes warrant further investigations.
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Material Particulado , Efeitos Tardios da Exposição Pré-Natal , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Desenvolvimento Fetal/fisiologia , Masculino , Exposição Materna/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Material Particulado/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
PURPOSE: To determine the sensitivity of a noncontrast T1 dispersion cardiovascular magnetic resonance technique for detecting diffuse fibrosis in hypertrophic cardiomyopathy (HCM). METHODS: Thirty-two adult HCM patients and ten age- and gender-matched healthy volunteers were prospectively included in this study. Patients and controls underwent cine, T1ρ-mapping, and pre- and post-contrast T1-mapping imaging using a 3-T magnetic resonance system. Myocardial extracellular volume fraction (ECV) maps were obtained using pre- and post-contrast T1 maps to determine reference values for diffuse fibrosis. Myocardial T1ρ and T1ρ dispersion maps called myocardial fibrosis index (mFI) maps provided 570 myocardial segments for Pearson or Spearman correlation analysis. The left ventricle myocardia of the HCM patients were divided into 16 segments that were further classified as either normal-thickness myocardium (<15 mm) (HCM-N) or hypertrophic myocardium (≥15 mm) (HCM-H). RESULTS: ECV and mFI values increased progressively on a per-segment basis from healthy controls to the HCM-N group and then to the HCM-H group (ECV: 27.4 ± 2.8% vs. 31.1 ± 4.2% vs. 37.6 ± 6.9%, respectively [P < 0.0001]; mFI: 6.1 ± 0.9 ms vs. 8 ± 1.9 ms vs. 11 ± 3.3 ms, respectively [P < 0.0001]). There was a strong positive correlation between the segmented ECV and the mFI (r = 0.878). The mFI was equally or significantly better than the ECV for differentiating fibrosis content in HCM-N and HCM-H according to their receiver operating characteristic curves. CONCLUSION: A T1ρ dispersion imaging mFI can sensitively detect diffuse myocardial fibrosis in HCM, even in HCM-N.
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Cardiomiopatias , Cardiomiopatia Hipertrófica , Adulto , Cardiomiopatias/patologia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/patologia , Meios de Contraste , Fibrose , Humanos , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Miocárdio/patologia , Valor Preditivo dos TestesRESUMO
Background: The histologic classification of lung adenocarcinoma (LUAD) was mainly divided into three pathological subtype groups: the low-grade predominant subtype group (lepidic), the intermediate-grade predominant subtype group (papillary and acinar), and the high-grade predominant subtype group (micropapillary and solid). Previous studies have focused on the prognostic impact of predominant subtypes of lung adenocarcinoma. In this investigation, we investigated the effect of the second predominant subtype on prognosis. Methods: The data of LUAD postoperative patients were retrospectively collected. Exclusion criteria included cases in which the pathologic results revealed a single characteristic, the presence of invasive mucinous LUAD, or if the first predominant and the second predominant groups could not be distinguished. Categorical variables were compared with the two-tailed Pearson χ2 test and continuous variables with the Student's t-test. Follow-up was conducted by telephone and other methods. Independent prognostic factors of the second major subtype were determined by the Kaplan-Meier method and log-rank test. The Cox proportional risk regression model was used to analyze the possible prognostic factors. Results: Among 293 patients, the mean age was 61.9 years and 47.1% were male. The results revealed that when the predominant group was the low-grade group, the second predominant groups had no significant influence on overall survival (OS) (P=0.15) but significantly influenced disease free survival (DFS) (P=0.037). Subsequently, when the predominant group was the intermediate-grade group, the second predominant groups significantly influenced OS (P=0.024) but had no significant influence on DFS (P=0.3). Moreover, when the predominant group was the high-grade group, the second predominant groups significantly influenced OS (P=0.033) but had no significant influence on DFS (P=0.31). Conclusions: The independent prognostic effect of the second predominant group was not identified for OS and DFS of lung adenocarcinoma. The effects of the second predominant subtype groups on OS and DFS were not evenly distributed among different predominant subtype groups, and the low-grade second predominant subtype exhibited some protective effects on the middle-grade predominant subtypes.
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BACKGROUND AND PURPOSE: Conventional cardiac magnetic resonance (CCMR) imaging is usually performed with breath-holding (BH), which is adverse in patients with BH limitations. We explored the ability of a free-breathing CMR (fCMR) protocol to prognosticate in patients with coronary heart diseases (CHD) and limited BH ability. METHODS: Sixty-seven patients with CHD and limited BH abilities were prospectively enrolled in this study. All patients underwent comprehensive fCMR imaging at 3.0 T. The fCMR protocols included compressed sensing (CS) single-shot cine acceleration imaging, and motion-corrected (MOCO), single-shot late gadolinium enhancement (LGE) imaging. Image quality (IQ) of the cine and LGE images was evaluated based on the 5-point Likert scale. The value of fMRI in providing a prognosis in patients with CHD was assessed. Statistical methods included the T test, Mann-Whitney test, Kappa test, Kaplan-Meier curve, Log-rank test, Cox proportional hazard regression analysis, and receiver operating characteristic curves. RESULTS: All IQ scores of the short axis CS-cine and both the short and long axes MOCO LGE images were ≥ 3 points. Over a median follow-up of 31 months (range 3.8-38.2), 25 major adverse cardiovascular events (MACE) occurred. In the univariate analysis, infarction size (IS), left ventricular ejection fraction (LVEF), 3D-Global peak longitudinal strain (3D-GPLS), heart failure classification were significantly associated with MACE. When the significantly univariate MACE predictors, added to the multivariate analysis, which showed IS (HR 1.02; 95% CI 1.00-1.05; p = 0.048) and heart failure with preserved EF (HR 0.20; 95% CI 0.04-0.98; p = 0.048) correlated positively with MACE. The optimal cutoff value for LVEF, 3D-GPLS, and IS in predicting MACE was 34.2%, - 5.7%, and 26.1% respectively, with a sensitivity of 90.5%, 64%, and 96.0% and specificity of 72%, 95.2%, and 85.7% respectively. CONCLUSIONS: The fCMR protocol can be used to make prognostic assessments in patients with CHD and BH limitations by calculating IS and LVEF.
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Suspensão da Respiração , Doença das Coronárias/diagnóstico por imagem , Pulmão/fisiopatologia , Imagem Cinética por Ressonância Magnética , Idoso , Meios de Contraste , Doença das Coronárias/fisiopatologia , Feminino , Gadolínio DTPA , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Volume Sistólico , Função Ventricular EsquerdaRESUMO
How dermis maintains tissue homeostasis in cyclic growth and wounding is a fundamental unsolved question. Here, we study how dermal components of feather follicles undergo physiological (molting) and plucking injury-induced regeneration in chickens. Proliferation analyses reveal quiescent, transient-amplifying (TA) and long-term label-retaining dermal cell (LRDC) states. During the growth phase, LRDCs are activated to make new dermal components with distinct cellular flows. Dermal TA cells, enriched in the proximal follicle, generate both peripheral pulp, which extends distally to expand the epithelial-mesenchymal interactive interface for barb patterning, and central pulp, which provides nutrition. Entering the resting phase, LRDCs, accompanying collar bulge epidermal label-retaining cells, descend to the apical dermal papilla. In the next cycle, these apical dermal papilla LRDCs are re-activated to become new pulp progenitor TA cells. In the growth phase, lower dermal sheath can generate dermal papilla and pulp. Transcriptome analyses identify marker genes and highlight molecular signaling associated with dermal specification. We compare the cyclic topological changes with those of the hair follicle, a convergently evolved follicle configuration. This work presents a model for analyzing homeostasis and tissue remodeling of mesenchymal progenitors.
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Galinhas/fisiologia , Derme/fisiologia , Células Epidérmicas/fisiologia , Plumas/fisiologia , Folículo Piloso/fisiologia , Regeneração/fisiologia , Células-Tronco/fisiologia , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Cabelo/fisiologia , Muda/fisiologia , Transdução de Sinais/fisiologiaRESUMO
Background: Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that have become globally ubiquitous in humans and the environment. In utero PFAS exposure is associated with neurodevelopmental effects; however, the mechanism is poorly understood. Brain-derived neurotrophic factor (BDNF) signaling is critical to fetal neurodevelopment during pregnancy and maintains important regulatory roles later in life. This study aims to characterize placental BDNF signaling and investigate whether PFAS exposure disrupts the signaling pathway in placental trophoblast cells. Methods: The expression and localization of BDNF receptors-p75NTR and TrkB-in first trimester and term human placentas and trophoblast cells were investigated by immunofluorescence staining. To assess the effects of PFAS exposure on the BDNF pathway, BeWo cells were treated with PFAS mixtures that mimicked blood levels in a highly exposed population and major PFAS compounds in the mixture at 0.01, 0.1, 1, and 10 µM concentrations. Changes in pro-BDNF levels and phosphorylation of TrkB receptors were examined by Western blot. Results: In first trimester human placentas, TrkB and p75NTR receptors were primarily localized to syncytiotrophoblast and cytotrophoblast cells. At term, TrkB and p75NTR receptors were primarily observed in the placental villous stroma. TrkB receptor staining in trophoblasts was reduced at term, while p75NTR receptor staining was negative. TrkB receptors were confined to the nuclear and perinuclear spaces, and phosphorylation occurred at the Tyr816 residue in BeWo cells. Exposure to PFOS, PFOA, PFBS, and the six-PFAS mixture did not significantly affect BDNF levels or activation (phosphorylation) of TrkB. Treating cells with 1 µM and 10 µM of PFNA resulted in increased TrkB phosphorylation compared to unexposed controls, but BDNF levels were unchanged. Conclusions: BDNF receptors are present in different regions of human placental villi, indicating diverse functions of BDNF signaling in placental development. Our findings suggest that the BDNF pathway in placental trophoblast cells is not disrupted by exposures to PFOS, PFOA, PFBS, and a PFAS mixture, but may be affected by PFNA exposures. Further investigation is needed on how PFAS affects other critical signaling pathways during fetal neurodevelopment.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fluorocarbonos/toxicidade , Trofoblastos/efeitos dos fármacos , Feminino , Humanos , Exposição Materna/efeitos adversos , Glicoproteínas de Membrana/metabolismo , Fosforilação , Placenta/efeitos dos fármacos , Placenta/metabolismo , Placentação/efeitos dos fármacos , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Primeiro Trimestre da Gravidez/metabolismo , Receptor trkB/metabolismo , Transdução de Sinais/efeitos dos fármacos , Trofoblastos/metabolismo , Células Tumorais CultivadasRESUMO
The association between molecular chirality and helical characteristics known as the chirality-helicity equivalence is determined for the first time by quantifying a chirality-helicity measure consistent with photoexcitation circular dichroism experiments. This is demonstrated using a formally achiral SN 2 reaction and a chiral SN 2 reaction. Both the achiral and chiral SN 2 reactions possess significant values of the chirality-helicity measure and display a Walden inversion, i. e. an inversion of the chirality between the reactant and product. We also track the chirality-helicity measure along the reaction path and discover the presence of chirality at the transition state and two intermediate structures for both reactions. We demonstrate the need for the chirality-helicity measure to differentiate between steric effects due to eclipsed conformations and chiral behaviors in formally achiral species. We explain the significance of this work for asymmetric synthetic reactions including the intermediate structures where the Cahn-Ingold-Prelog (CIP) rules cannot be used.