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1.
Curr Biol ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34610275

RESUMO

In most tetrapod vertebrates, limb skeletal progenitors condense with postaxial dominance. Posterior elements (such as ulna and fibula) appear prior to their anterior counterparts (radius and tibia), followed by digit-appearance order with continuing postaxial polarity. The only exceptions are urodele amphibians (salamanders), whose limb elements develop with preaxial polarity and who are also notable for their unique ability to regenerate complete limbs as adults. The mechanistic basis for this preaxial dominance has remained an enigma and has even been proposed to relate to the acquisition of novel genes involved in regeneration. However, recent fossil evidence suggests that preaxial polarity represents an ancestral rather than derived state. Here, we report that 5'Hoxd (Hoxd11-d13) gene deletion in mouse is atavistic and uncovers an underlying preaxial polarity in mammalian limb formation. We demonstrate this shift from postaxial to preaxial dominance in mouse results from excess Gli3 repressor (Gli3R) activity due to the loss of 5'Hoxd-Gli3 antagonism and is associated with cell-cycle changes promoting precocious cell-cycle exit in the anterior limb bud. We further show that Gli3 knockdown in axolotl results in a shift to postaxial dominant limb skeleton formation, as well as expanded paddle-shaped limb-bud morphology and ensuing polydactyly. Evolutionary changes in Gli3R activity level, which also played a key role in the fin-to-limb transition, appear to be fundamental to the shift from preaxial to postaxial polarity in formation of the tetrapod limb skeleton.

2.
Front Physiol ; 12: 730196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646156

RESUMO

The follicle is the functional unit of the ovary, which is composed of three types of cells: oocytes, granulosa cells, and theca cells. Ovarian follicle development and the subsequent ovulation process are coordinated by highly complex interplay between endocrine, paracrine, and autocrine signals, which coordinate steroidogenesis and gametogenesis. Follicle development is regulated mainly by three organs, the hypothalamus, anterior pituitary, and gonad, which make up the hypothalamic-pituitary-gonadal axis. Steroid hormones and their receptors play pivotal roles in follicle development and participate in a series of classical signaling pathways. In this review, we summarize and compare the role of classical signaling pathways, such as the WNT, insulin, Notch, and Hedgehog pathways, in ovarian follicle development and the underlying regulatory mechanism. We have also found that these four signaling pathways all interact with FOXO3, a transcription factor that is widely known to be under control of the PI3K/AKT signaling pathway and has been implicated as a major signaling pathway in the regulation of dormancy and initial follicular activation in the ovary. Although some of these interactions with FOXO3 have not been verified in ovarian follicle cells, there is a high possibility that FOXO3 plays a core role in follicular development and is regulated by classical signaling pathways. In this review, we present these signaling pathways from a comprehensive perspective to obtain a better understanding of the follicular development process.

3.
Brain Res Bull ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34678443

RESUMO

Bone is the main supporting structure of the body and the main organ involved in body movement and calcium and phosphorus metabolism. Recent studies have shown that bone is also a potential new endocrine organ that participates in the physiological and pathophysiological processes of the cardiovascular, digestive, and endocrine systems through various bioactive cytokines secreted by bone cells and bone marrow. Bone-derived active cytokines can also directly act on the central nervous system and regulate brain function and individual behavior. The bidirectional regulation of the bone-brain axis has gradually attracted attention in the field of neuroscience. This paper reviews the regulatory effects of bone-derived active cytokines and bone-derived cells on individual brain function and brain diseases, as well as the occurrence and development of related neuropsychiatric diseases. The central regulatory mechanism function is briefly introduced, which will broaden the scope for mechanistic research and help establish prevention and treatment strategies for neuropsychiatric diseases based on the bone-brain axis.

5.
Nature ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34552241

RESUMO

Glutamate-gated kainate receptors are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission at the postsynapse and modulate transmitter release at the presynapse1-7. In the brain, the trafficking, gating kinetics and pharmacology of kainate receptors are tightly regulated by neuropilin and tolloid-like (NETO) proteins8-11. Here we report cryo-electron microscopy structures of homotetrameric GluK2 in complex with NETO2 at inhibited and desensitized states, illustrating variable stoichiometry of GluK2-NETO2 complexes, with one or two NETO2 subunits associating with GluK2. We find that NETO2 accesses only two broad faces of kainate receptors, intermolecularly crosslinking the lower lobe of ATDA/C, the upper lobe of LBDB/D and the lower lobe of LBDA/C, illustrating how NETO2 regulates receptor-gating kinetics. The transmembrane helix of NETO2 is positioned proximal to the selectivity filter and competes with the amphiphilic H1 helix after M4 for interaction with an intracellular cap domain formed by the M1-M2 linkers of the receptor, revealing how rectification is regulated by NETO2.

6.
Brain Res Bull ; 176: 174-183, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34478811

RESUMO

Aryl Hydrocarbon Receptor (AHR) is a ligand-activated transcription factor expressed in various brain regions. However, little is known about the role of AHR during neuroinflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Here, mice were sacrificed at day 4, day 6 and day 8 respectively after MPTP or saline treatment. Behavioral tests, Tyrosine hydroxylase (TH) expression, glial reaction, and AHR expression and activation were then assayed. As expected, mice treated with MPTP showed apparent behavioral dysfunctions and significantly reduced TH content. Immunofluorescence (IF) labeling showed an increased trend of phosphorylated AHR activation in the Substantia Nigra pars compacta (SNpc) and striatum after MPTP treatment. Western blot analysis demonstrated that MPTP treatment induced a significantly increased level of AHR at each time point tested, with the highest level observed at day 6 in the striatum. To determine exactly the AHR activation in relation to changes of glial cell reactivity, double IF labeling was performed for either IBA1 (microglia marker) and p-AHR, or GFAP (astrocyte marker) and p-AHR. The results demonstrated that MPTP treatment not only increases the number of p-AHR-positive IBA1-expressing cells in the striatum and the SNpc, but also increases that of p-AHR-positive GFAP-expressing cells in the striatum. Intriguingly, the increase of the number of cells co-expressing both p-AHR and IBA1 was highest at day 4 in response to MPTP in the striatum and at day 8 in the SNpc. The number of cells co-expressing both p-AHR and GFAP was increased at days 4, 6 and 8 in the striatum. In conclusion, our study suggests that AHR activation may facilitate PD diagnosis and serve as a target for the treatment of PD.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34569360

RESUMO

PURPOSE: The flow velocity of visceral arteries was measured by 2D PCMRI to produce the patient-specific flow BC imposed on the outlets of visceral arteries in CFD simulation. This modified method aimed to improve the CFD accuracy in the abdominal aorta and visceral arteries. METHODS: A volunteer underwent non-contrast-enhanced MRA to scan the abdominal aorta and visceral arteries, and 2D PCMRI to obtain the flow velocity of the aforementioned vessels. The three-dimensional geometric model was reconstructed using the MRI scan data of the abdominal aorta and visceral arteries. The flow waveforms measured by 2D PCMRI were processed and then imposed on the aortic inlet and the outlets of all visceral arteries as the flow BC. The RCR parameters of the three elements Windkessel model were modulated and imposed on the aortic outlet. CFD simulation was run in the open-source software: svSolver. The same volunteer underwent 4D flow MRI to compare the flow field with those extracted from CFD results. RESULTS: Four specific time points in a cardiac cycle and three cross-sectional planes of aorta were selected to analyze the flow field, pressure and wall shear stress (WSS) from CFD. The flow waveforms and streamlines of CFD agreed with those of 4D flow MRI. The pressure waveforms, pressure distribution and WSS distribution from CFD conformed with the physiological condition of human body. CONCLUSION: These results suggest this modified CFD method may yield reasonable flow field, pressure and WSS in the abdominal aorta and visceral arteries.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34585471

RESUMO

Conformational distributions and mutual interconversions of thermally activated delayed fluorescence (TADF) emitters significantly affect the exciton utlization. However, their influence of photophysics in amorphous film states are still underdevelopment due to the lack of a suitable quantitative analysis method. Herein, by using temperature dependent time-resolved photoluminescence spectroscopy, we quantitatively measured the relative populations of the conformations of a TADF emitter for the first time which not only help deepen the understanding of conformational distributions of TADF emitters, but also provide an aspect to analyze the overall properties of organic amorphous films for other applications. In terms of conformational distribution aspect, we further propose a new concept of "self-doping" for realizing high-efficiency nondoped OLEDs. Interestingly, this "compositionally" pure film actually behaves as a film with dopant (quasi-equatorial form) in a matrix (quasi-axial form). The concentration-induced quenching that may seriously occur at high concentrations is thus expected to be effectively relieved. The "self-doping" OLED by using newly developed TADF emitter TP2P-PXZ as a neat emitting layer, realizes a high maximum external quantum efficiency of 25.4% and neglectable efficiency roll-off. This demonstrates high-performance in doped OLEDs can indeed be achieved with the present "self-doping" emitting layer based on one single compound.

10.
Elife ; 102021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544549

RESUMO

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.


Assuntos
Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/imunologia , Vacinas Bacterianas/administração & dosagem , Infecções por Klebsiella/prevenção & controle , Klebsiella pneumoniae/imunologia , Macrófagos Alveolares/efeitos dos fármacos , Pneumonia Bacteriana/prevenção & controle , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/imunologia , Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/microbiologia , Administração Intranasal , Transferência Adotiva , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Proteínas de Homeodomínio/genética , Imunidade Inata/efeitos dos fármacos , Infecções por Klebsiella/imunologia , Infecções por Klebsiella/microbiologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Macrófagos Alveolares/transplante , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/microbiologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Fatores de Tempo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Vacinação , Vacinas de Produtos Inativados/administração & dosagem
11.
Mater Sci Eng C Mater Biol Appl ; 128: 112326, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474877

RESUMO

Bone defects remain a challenging problem for doctors and patients in clinical practice. Processed pyritum is a traditional Chinese medicine that is often used to clinically treat bone fractures. It contains mainly Fe, Zn, Cu, Mn, and other elements. In this study, we added the extract of processed pyritum to ß-tricalcium phosphate and produced a porous composite TPP (TCP/processed pyritum) scaffold using digital light processing (DLP) 3D printing technology. Scanning electron microscopy (SEM) analysis revealed that TPP scaffolds contained interconnected pore structures. When compared with TCP scaffolds (1.35 ± 0.15 MPa), TPP scaffolds (5.50 ± 0.24 MPa) have stronger mechanical strength and can effectively induce osteoblast proliferation, differentiation, and mineralization in vitro. Meanwhile, the in vivo study showed that the TPP scaffold had better osteogenic capacity than the TCP scaffold. Furthermore, the TPP scaffold had good biosafety after implantation. In summary, the TPP scaffold is a promising biomaterial for the clinical treatment of bone defects.


Assuntos
Fosfatos de Cálcio , Tecidos Suporte , Humanos , Porosidade , Impressão Tridimensional
12.
Front Physiol ; 12: 724470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483973

RESUMO

Cardiac fibrosis is evident even in the situation without a significant cardiomyocyte loss in diabetic cardiomyopathy and a high glucose (HG) level independently activates the cardiac fibroblasts (CFs) and promotes cell proliferation. Mitochondrial respiration and glycolysis, which are key for cell proliferation and the mitochondria-associated membranes (MAMs), are critically involved in this process. However, the roles and the underlying mechanism of MAMs in the proliferation of HG-induced CFs are largely unknown. The proliferation and apoptosis of CFs responding to HG treatment were evaluated. The MAMs were quantified, and the mitochondrial respiration and cellular glycolytic levels were determined using the Seahorse XF analyzer. The changes of signal transducer and activator of transcription 3 (STAT3) and mitofusin-2 (MFN2) in responding to HG were also determined, the effects of which on cell proliferation, MAMs, and mitochondrial respiration were assessed. The effects of STAT3 on MFN2 transcription was determined by the dual-luciferase reporter assay (DLRA) and chromatin immunoprecipitation (CHIP). HG-induced CFs proliferation increased the glycolytic levels and adenosine triphosphate (ATP) production, while mitochondrial respiration was inhibited. The MAMs and MFN2 expressions were significantly reduced on the HG treatment, and the restoration of MFN2 expression counteracted the effects of HG on cell proliferation, mitochondrial respiration of the MAMs, glycolytic levels, and ATP production. The mitochondrial STAT3 contents were not changed by HG, but the levels of phosphorylated STAT3 and nuclear STAT3 were increased. The inhibition of STAT3 reversed the reduction of MFN2 levels induced by HG. The DLRA and CHIP directly demonstrated the negative regulation of MFN2 by STAT3 at the transcription levels via interacting with the sequences in the MFN2 promoter region locating at about -400 bp counting from the start site of transcription. The present study demonstrated that the HG independently induced CFs proliferation via promoting STAT3 translocation to the nucleus, which switched the mitochondrial respiration to glycolysis to produce ATP by inhibiting MAMs in an MFN2-depression manner.

13.
Curr Med Imaging ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34488589

RESUMO

BACKGROUND: Scapula is a small irregular-shaped flat bone, which may suffer from a variety of tumors or tumor-like lesions. Because the imaging manifestations are complex and changeable, correct imaging diagnosis is difficult. INTRODUCTION: At present, there are few related radiology literatures, and it is necessary to fully analyze the imaging signs of different types of benign and malignant tumors in scapula to guide clinical treatment. This study was to investigate clinical and imaging presentations of tumors and tumor-like lesions in the scapula so as to increase the diagnostic accuracy of diseases in the scapula. METHODS: Patients with scapular tumors confirmed by pathology were enrolled. The imaging and clinical data were analyzed. RESULT: Among 108 patients, benign tumors were in 53 (49.1%) cases, intermediate in seven (6.5%), and malignant in 48 (44.4%) involving 16 diseases. Osteochondroma was the first benign tumors in 45 cases accounting for 84.9% of all benign scapular tumors followed by chondroma in four cases (7.5%). The intermediate tumors were mainly eosinophilic granuloma in four cases. Metastatic tumors were the commonest malignant tumor (27 cases or 56.2% of all malignant tumors), followed by chondrosarcoma (in 13 cases). Except for the one case of chondroblastoma in which the lesion involved the glenoid cavity, all the other cartilaginous tumors were located in the scapular body and processes. The type of lesions in the bony processes is the same as in the scapular body, the common lesions in the central area of body were malignant tumors, and the commonest lesions in the glenoid area were metastasis. Common imaging features of malignant scapular tumors were ill-defined margins, cortical destruction and soft tissue involvement. The imaging features of chondrosarcoma lack specificity except calcification. Benign lesions usually had clear boundary and marginal sclerosis. CONCLUSION: A wide variety of benign and malignant tumors may occur in the scapula with mostly cartilaginous and metastatic tumors, and the location and distribution of lesions are similar in the scapula to those in the long bones.

14.
Water Environ Res ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551458

RESUMO

Eutrophication of water constitutes a serious threat to global water quality. Light intensity and water disturbance are important factors affecting the growth of algae and the release of algal toxins. In this study, algal growth indicators, algal enzyme systems and algal toxin release in Microcystis aeruginosa under different light intensities and water disturbances were determined. The results showed that 2,500 lx and 120 rpm were the optimal conditions for the growth of M. aeruginosa. The growth of algal cells was inhibited by high light intensity and high water disturbance. However, the optimal conditions for algal growth were not favorable conditions for the release of algal toxin. The highest concentration of microcystin-LR (MC-LR), observed at 4,500 lx and 80 rpm, was 198.1 µg/L, while the highest single cell toxin production reached up to 10.49 × 10-9 µg/cell at 7,000 lx and 120 rpm. Redundancy analysis results showed that the concentration of MC-LR was positively correlated with algal cell density and antioxidant enzyme activities (superoxide dismutase, catalase, peroxidase, and malondialdehyde (MDA)), and negatively correlated with the total nitrogen and total phosphorus consumption rates and MDA. Single cell toxin production was negatively correlated with algal cell density and antioxidant enzyme activity, but positively correlated with MDA content.

15.
iScience ; 24(9): 103002, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34505012

RESUMO

Urbanization is a pressing challenge for earth's humans because it is changing not only natural environments but also agricultural lands. Yet, the consequences of cropland loss on pest insect populations that largely depend on these habitats remain largely unclear. We used a 17-year data set to investigate the dynamics of three moth pest species (i.e., striped stem borer, yellow stem borer, and pink stem borer) and their driving forces across the largest mega-urban region of China. Total abundance of three pest species is declined by about 80%, which was strongly associated with cropland loss during rapid urbanization. Our findings indicate that not only the increasing conversion of natural areas to human-dominated landscapes but also that of agricultural lands to urban landscapes can be critical to insect populations. It is therefore essential to monitor and understand the insect dynamics in rapidly urbanizing regions, which are currently found in many developing countries worldwide.

16.
BMC Cardiovasc Disord ; 21(1): 417, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470611

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), but few studies have been conducted to identify CVD risk in COPD patients. This study was to develop a predictive model of CVD in COPD patients based on the National Health and Nutrition Examination Survey (NHANES) database. METHODS: A total of 3,226 COPD patients were retrieved from NHANES 2007-2012, dividing into the training (n = 2351) and testing (n = 895) sets. The prediction models were conducted using the multivariable logistic regression and random forest analyses, respectively. Receiver operating characteristic (ROC) curves, area under the curves (AUC) and internal validation were used to assess the predictive performance of models. RESULTS: The logistic regression model for predicting the risk of CVD was developed regarding age, gender, body mass index (BMI), high-density lipoprotein (HDL), glycosylated hemoglobin (HbA1c), family history of heart disease, and stayed overnight in the hospital due to illness last year, which the AUC of the internal validation was 0.741. According to the random forest analysis, the important variables-associated with CVD risk were screened including smoking (NNAL and cotinine), HbA1c, HDL, age, gender, diastolic blood pressure, poverty income ratio, BMI, systolic blood pressure, and sedentary activity per day. The AUC of the internal validation was 0.984, indicating the random forest model for predicting the CVD risk in COPD cases was superior to the logistic regression model. CONCLUSION: The random forest model performed better predictive effectiveness for the cardiovascular risk among COPD patients, which may be useful for clinicians to guide the clinical practice.

17.
Exp Neurol ; 345: 113842, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34403688

RESUMO

SARM1 is an inducible NAD+ hydrolase that is the central executioner of pathological axon loss. Recently, we elucidated the molecular mechanism of SARM1 activation, demonstrating that SARM1 is a metabolic sensor regulated by the levels of NAD+ and its precursor, nicotinamide mononucleotide (NMN), via their competitive binding to an allosteric site within the SARM1 N-terminal ARM domain. In healthy neurons with abundant NAD+, binding of NAD+ blocks access of NMN to this allosteric site. However, with injury or disease the levels of the NAD+ biosynthetic enzyme NMNAT2 drop, increasing the NMN/ NAD+ ratio and thereby promoting NMN binding to the SARM1 allosteric site, which in turn induces a conformational change activating the SARM1 NAD+ hydrolase. Hence, NAD+ metabolites both regulate the activation of SARM1 and, in turn, are regulated by the SARM1 NAD+ hydrolase. This dual upstream and downstream role for NAD+ metabolites in SARM1 function has hindered mechanistic understanding of axoprotective mechanisms that manipulate the NAD+ metabolome. Here we reevaluate two methods that potently block axon degeneration via modulation of NAD+ related metabolites, 1) the administration of the NMN biosynthesis inhibitor FK866 in conjunction with the NAD+ precursor nicotinic acid riboside (NaR) and 2) the neuronal expression of the bacterial enzyme NMN deamidase. We find that these approaches not only lead to a decrease in the levels of the SARM1 activator NMN, but also an increase in the levels of the NAD+ precursor nicotinic acid mononucleotide (NaMN). We show that NaMN inhibits SARM1 activation, and demonstrate that this NaMN-mediated inhibition is important for the long-term axon protection induced by these treatments. Analysis of the NaMN-ARM domain co-crystal structure shows that NaMN competes with NMN for binding to the SARM1 allosteric site and promotes the open, autoinhibited configuration of SARM1 ARM domain. Together, these results demonstrate that the SARM1 allosteric pocket can bind a diverse set of metabolites including NMN, NAD+, and NaMN to monitor cellular NAD+ homeostasis and regulate SARM1 NAD+ hydrolase activity. The relative promiscuity of the allosteric site may enable the development of potent pharmacological inhibitors of SARM1 activation for the treatment of neurodegenerative disorders.

18.
Biomed Mater ; 16(5)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34375969

RESUMO

Combating bacteria while promoting tissue regeneration is an aim of highest priority for employing biomaterials in orthopedics that often embroiled with pre-operative contamination. Through simulating a surgical site infection environment and an infected implant site, we showcase the ability of a functionally modified hydroxyapatite, Ag,Si-HA that permits preferential adhesion of human bone marrow derived mesenchymal stem cells (BMSCs) over co-cultured bacterial pathogen,Pseudomonas aeruginosa, by displaying immediate suppression and killing of the bacteria present with minimum cytotoxicity for 28 d. And, at the same time, Ag,Si-HA stimulates BMSCs towards osteogenic differentiation despite being within the contaminated milieu. These findings provide well-defined requirements for incorporating antibacterial properties to biomaterials in managing pre-operative contamination. In addition, it highlights the dual positive attributes of Ag,Si-HA as an effective antibacterial biomaterial and at the same time, promotes bone tissue regeneration.

19.
Eur J Med Genet ; 64(11): 104324, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34461324

RESUMO

Epidermolytic ichthyosis and epidermolytic nevi share the same histopathological features of epidermolytic hyperkeratosis, characterized by distinctive vacuolar degeneration and hypergranulosis of the superficial epidermis. Both are caused by pathogenic variants in either of two keratin genes KRT1or KRT10, with epidermolytic ichthyosis presenting as a generalized phenotype and epidermolytic nevi presenting as a mosaic phenotype. We report a boy who presented as epidermolytic ichthyosis, with diffuse erythema, superficial erosions and flaccid blisters at birth progressing to generalized ichthyosis. He was found to have inherited a novel KRT1 variant from his mother who presented with extensive epidermolytic nevi or mosaic form of epidermolytic ichthyosis, with extensive, linear and Blaschkoid verrucous, hyperkeratotic plaques over the trunk and limbs. This case highlights the importance of recognising post-zygotic mosaicism which might be transmitted to a child, and the different presentations for germline and mosaic carriers.

20.
Front Neurosci ; 15: 688727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366776

RESUMO

Purpose of the Review: Nowadays, the incidence of schizophrenia is noticeably increased. If left undiagnosed and untreated, it will lead to impaired social functions, repeated hospital admissions, decline in quality of life and life expectancy. However, the diagnosis of schizophrenia is complicated and challenging. Both genetic and environmental factors are considered as important contributors to the development and progression of this disorder. The environmental factors have been linked to changes in gene expression through epigenetic modulations, which have raised more and more research interests in recent years. This review article is to summarize the current findings and understanding of epigenetic modulation associated with pathogenesis of schizophrenia, aiming to provide useful information for further research in developing biomarkers for schizophrenia. Recent Findings: Three major types of epigenetic modulations have been described in this article. Firstly, both DNA hypermethylation and hypomethylated have been associated with schizophrenia via analyzing post-mortem brain tissues and peripheral blood of patients. Specific changes of non-coding RNAs, particularly microRNAs and long-chain non-coding RNAs, have been observed in central and peripheral samples of schizophrenia patients, indicating their significant diagnostic value for the disease, and may also potentially predict treatment response. The correlation between histone modification and schizophrenia, however, is largely unclear. Summary: Epigenetic modulations, including DNA methylation, ncRNA transcriptional regulation and histone modification, play an important role in the pathogenesis of schizophrenia. Therefore, tests of these epigenetic alterations may be utilized to assist in the diagnosis and determination of strategies of individualized treatment in clinical practice.

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