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1.
Pain Ther ; 13(4): 691-717, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38748200

RESUMO

INTRODUCTION: Tension-type headache (TTH) is common but challenging to manage due to limited effectiveness of conventional treatments. This study examines six complementary and alternative medicine (CAM) interventions through network meta-analysis to identify effective TTH management strategies. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, OVID, CNKI, Wanfang, VIP, and CBM databases for randomized controlled trials on CAM for TTH treatment. Headache frequency and intensity were the primary outcomes. Methodological quality was evaluated on the basis of the Cochrane risk of bias tool. We used R software to conduct this Bayesian network meta-analysis. We used mean difference (MD) with 95% credible intervals (CI) to calculate the continuous outcomes and analyzed the percentages of the surface under the cumulative ranking (SUCRA) curve. RESULTS: In total, 32 randomized controlled trials (RCTs) with 2405 participants were analyzed. For reducing headache intensity, the network meta-analysis shows that acupuncture therapy combined with traditional Chinese medicine (AT_TCM), manual therapy (MT), psychological treatment (PT), and traditional Chinese medicine combined with acupuncture and manual therapy (TCM_AT_MT) are superior to Western medicine (WM). In the SUCRA curve, TCM_AT_MT is the best for reducing headache frequency (HF). CONCLUSIONS: This review, assessed as low-quality evidence by GRADE, cautiously suggests potential benefits of PT over other CAM interventions for TTH and indicates TCM_AT_MT might better reduce HF. It proposes that combining CAM interventions could enhance outcomes. Due to the preliminary nature of these findings, further high-quality RCTs are essential to confirm these suggestions and provide clearer clinical guidance. PROSPERO REGISTRATION NUMBER: CRD42021252073.

2.
Eur J Obstet Gynecol Reprod Biol ; 297: 91-95, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38603985

RESUMO

OBJECTIVES: To evaluate the the diagnostic yield of chromosomal microarray analysis (CMA) in fetuses with isolated CPC (iCPC). METHODS: A total of 315 fetuses with iCPC (iCPC group) and 364 fetuses without abnormal ultrasound findings (control group) were recruited between July 2014 to March 2018. RESULTS: The overall diagnostic yield of chromosomal abnormalities by CMA and karyotyping in iCPC group was up to 4.1 %, higher than 1.4 % in the control group, p < 0.05. The detection rate of pathogenic or likely pathogenic copy number variants (CNVs) with clinical significance by CMA in iCPC group (1.3 %) was higher than in control group (0 %), p < 0.05. According to the type of chromosome abnormalities, the missed diagnosis rate of non-invasive prenatal testing (NIPT) was 1.6 % in our study. CONCLUSIONS: The presence of iCPC on ultrasound examination suggests a potential indication for genetic counseling. Karyotyping and chromosomal microarray analysis may be considered for fetuses with iCPC. It is important to be aware of the limitations of non-invasive prenatal testing, as there is a possibility of residual risk.


Assuntos
Aberrações Cromossômicas , Cariotipagem , Análise em Microsséries , Humanos , Feminino , Cariotipagem/métodos , Gravidez , Estudos Retrospectivos , Análise em Microsséries/métodos , Estudos de Casos e Controles , Adulto , Aberrações Cromossômicas/embriologia , Diagnóstico Pré-Natal/métodos , Ultrassonografia Pré-Natal , Plexo Corióideo/diagnóstico por imagem
3.
Growth Factors ; 42(1): 13-23, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37932893

RESUMO

Danggui blood-supplementing decoction (DBsD) is an herbal preparation treating several diseases including stroke. The present study sought to investigate the potential mechanism of DBsD in ischaemic stroke (IS) using network pharmacology, molecular docking, and cell experiment. Based on the protein-protein (PPI) network analysis, MAPK1 (0.51, 12), KNG1 (0.57, 28), and TNF (0.64, 39) were found with relatively good performance in degree and closeness centrality. The functional enrichment analysis revealed that DBsD contributed to IS-related biological processes, molecule function, and presynaptic/postsynaptic cellular components. Pathway enrichment indicated that DBsD might protect IS by modulating multi-signalling pathways including the sphingolipid signalling pathway. Molecular docking verified the stigmasterol-KNG1, bifendate-TNF, and formononetin-MAPK1 pairs. Cell experiments confirmed the involvement of KNG1 and sphingolipid signalling pathway in hippocampal neuronal cell apoptosis. This study showed that DBsD can protect neuronal cell injury after IS through multiple components, multiple targets, and multiple pathways.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Isquemia Encefálica/tratamento farmacológico , Esfingolipídeos
4.
FASEB J ; 38(1): e23369, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38100642

RESUMO

The human cardiovascular system has evolved to accommodate the gravity of Earth. Microgravity during spaceflight has been shown to induce vascular remodeling, leading to a decline in vascular function. The underlying mechanisms are not yet fully understood. Our previous study demonstrated that miR-214 plays a critical role in angiotensin II-induced vascular remodeling by reducing the levels of Smad7 and increasing the phosphorylation of Smad3. However, its role in vascular remodeling evoked by microgravity is not yet known. This study aimed to determine the contribution of miR-214 to the regulation of microgravity-induced vascular remodeling. The results of our study revealed that miR-214 expression was increased in the forebody arteries of both mice and monkeys after simulated microgravity treatment. In vitro, rotation-simulated microgravity-induced VSMC migration, hypertrophy, fibrosis, and inflammation were repressed by miR-214 knockout (KO) in VSMCs. Additionally, miR-214 KO increased the level of Smad7 and decreased the phosphorylation of Smad3, leading to a decrease in downstream gene expression. Furthermore, miR-214 cKO protected against simulated microgravity induced the decline in aorta function and the increase in stiffness. Histological analysis showed that miR-214 cKO inhibited the increases in vascular medial thickness that occurred after simulated microgravity treatment. Altogether, these results demonstrate that miR-214 has potential as a therapeutic target for the treatment of vascular remodeling caused by simulated microgravity.


Assuntos
MicroRNAs , Ausência de Peso , Humanos , Camundongos , Animais , Músculo Liso Vascular/metabolismo , MicroRNAs/metabolismo , Remodelação Vascular/genética , Aorta/metabolismo , Miócitos de Músculo Liso/metabolismo
5.
iScience ; 26(12): 108556, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38125015

RESUMO

Spaceflight is physically demanding and can negatively affect astronauts' health. It has been shown that the human gut microbiota and cardiac function are affected by spaceflight and simulated spaceflight. This study investigated the effects of the gut microbiota on simulated spaceflight-induced cardiac remodeling using 10° of head-down bed rest (HDBR) in rhesus macaques and 30° of hindlimb unloading (HU) in mice. The gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR in macaques and HU in mice, cardiac remodeling in control mice was affected by the gut microbiota of HU mice and that of HU mice was protected by the gut microbiota of control mice, and there was a correlation between cardiac remodeling and the gut microbial-derived metabolite trimethylamine N-oxide. These findings suggest that spaceflight can affect cardiac remodeling by modulating the gut microbiota and fecal metabolites.

6.
Biosens Bioelectron ; 242: 115750, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37844387

RESUMO

MicroRNAs (miRNA) are the potential biomarker for breast cancer, a biosensor for detecting miRNA-21 was successfully prepared by covalently linking carbohydrazide (CON4H6) and tris (4,4 '- dicarboxylic acid-2,2' - bipyridyl) ruthenium dichloride (Ru (dcbpy)32+) as a self-enhanced emitter (Ru-CON4H6). The biosensor was prepared by coating the electrode with mesoporous silica encapsulated Ru-CON4H6 as luminophores (RMSNs) to covalently link a couple of DNA strands (Q1-H2). The RMSNs coated electrode exhibited strong ECL emission due to the intramolecular electron transfer between the electrochemically oxidized Ru (dcbpy)32+ and co-reactant CON4H6. In the presence of target miRNA-21 and an assistant hairpin H1, H2 could be released from the surface through a strand displacement reaction (SDR), and the reserved Q1 could form G-quadruplex upon the addition of K+. The formed G-quadruplex then interacted with Q2-Fc in the presence of Mg2+ to form a DNA complex on the biosensor surface, which quenched the nano-matrixes propped self-enhanced ECL emission through the electron exchange between Fc and electrode or oxidized ECL intermediates. Under optimal conditions, the ECL decrease showed a correlation with target concentration, leading to a biosensing method for sensitive detection of miRNA-21. The proposed ECL method demonstrated a detectable concentration range from 0.1 fM to 1 nM along with a detection limit of 0.03 fM, good accuracy, and acceptable reproducibility, showing that the self-enhanced ECL biosensing strategy supported by nano-matrix provided a new way for the ultrasensitive detection of miRNA, and promoted the development of breast cancer diagnosis.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , MicroRNAs , Humanos , Feminino , MicroRNAs/química , Técnicas Eletroquímicas , Reprodutibilidade dos Testes , Medições Luminescentes/métodos , Técnicas Biossensoriais/métodos , Neoplasias da Mama/diagnóstico , DNA , Limite de Detecção
7.
Bone Res ; 11(1): 53, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872163

RESUMO

Bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation and osteoblast function play critical roles in bone formation, which is a highly regulated process. Long noncoding RNAs (lncRNAs) perform diverse functions in a variety of biological processes, including BMSC osteogenic differentiation. Although several studies have reported that HOX transcript antisense RNA (HOTAIR) is involved in BMSC osteogenic differentiation, its effect on bone formation in vivo remains unclear. Here, by constructing transgenic mice with BMSC (Prx1-HOTAIR)- and osteoblast (Bglap-HOTAIR)-specific overexpression of HOTAIR, we found that Prx1-HOTAIR and Bglap-HOTAIR transgenic mice show different bone phenotypes in vivo. Specifically, Prx1-HOTAIR mice showed delayed bone formation, while Bglap-HOTAIR mice showed increased bone formation. HOTAIR inhibits BMSC osteogenic differentiation but promotes osteoblast function in vitro. Furthermore, we identified that HOTAIR is mainly located in the nucleus of BMSCs and in the cytoplasm of osteoblasts. HOTAIR displays a nucleocytoplasmic translocation pattern during BMSC osteogenic differentiation. We first identified that the RNA-binding protein human antigen R (HuR) is responsible for HOTAIR nucleocytoplasmic translocation. HOTAIR is essential for osteoblast function, and cytoplasmic HOTAIR binds to miR-214 and acts as a ceRNA to increase Atf4 protein levels and osteoblast function. Bglap-HOTAIR mice, but not Prx1-HOTAIR mice, showed alleviation of bone loss induced by unloading. This study reveals the importance of temporal and spatial regulation of HOTAIR in BMSC osteogenic differentiation and bone formation, which provides new insights into precise regulation as a target for bone loss.


Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Humanos , Camundongos , Osso e Ossos/metabolismo , Diferenciação Celular/genética , Camundongos Transgênicos , MicroRNAs/genética , Osteogênese/genética , RNA Longo não Codificante/genética
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(10): 1306-1311, 2023 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-37730237

RESUMO

OBJECTIVE: To assess the value of using flat-sided culture tubes for preparing chromosomes through chorionic villi (CV) and amniotic fluid (AF) cell cultures during prenatal diagnosis. METHODS: From February to March 2020, 157 CV samples and 147 AF samples subjected to prenatal diagnosis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region were selected as the study subjects. For each sample, one flat-sided tube and one flask culture were set up by following the standard protocols. The methods were evaluated by comparing the cell growth, experimental process, quality of chromosome preparation and costs. RESULTS: The success rates for the culturing of CV and AF samples by the flat-sided culture tube method were 97.45% (153/157) and 97.96% (144/147), respectively. By contrast, the success rates for the conventional flask method were 98.72% (155/157) for CV and 98.64% (145/147) for AF samples. No significant difference was found between the two methods (P > 0.05). The average harvest time required by the flat-sided culture tube method was 8.45 days for CV and 9.43 days for AF cultures, whilst the average harvest time for conventional flask method was 9.05 days and 9.54 days, respectively. The flat-sided culture tube method for CV had required significantly shorter average harvest time than the conventional method (P < 0.001). No statistical significant difference was found in the average harvest time for AF by the two methods (P > 0.05). The conventional culturing method had required three containers with two sample transfers. By contrast, the flat-sided culture tube method was carried out in one tube without any sample transfer. The average total amount of medium used was 3.91 mL for each flat-sided culture tube and 6.26 mL for each conventional flask. CONCLUSION: The flat-sided culture tube method can provide a simple, cost-effective and error-reducing procedure for the CV and AF samples culture during prenatal diagnosis.


Assuntos
Amostra da Vilosidade Coriônica , Diagnóstico Pré-Natal , Criança , Feminino , Gravidez , Humanos , China , Líquido Amniótico , Proliferação de Células
10.
Front Med (Lausanne) ; 10: 1114362, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37358994

RESUMO

Introduction: Malignant skin lesions pose a great threat to the health of patients. Due to the limitations of existing diagnostic techniques, such as poor accuracy and invasive operations, malignant skin lesions are highly similar to other skin lesions, with low diagnostic efficiency and high misdiagnosis rates. Automatic medical image classification using computer algorithms can effectively improve clinical diagnostic efficiency. However, existing clinical datasets are sparse and clinical images have complex backgrounds, problems with noise interference such as light changes and shadows, hair occlusions, etc. In addition, existing classification models lack the ability to focus on lesion regions in complex backgrounds. Methods: In this paper, we propose a DBN (double branch network) based on a two-branch network model that uses a backbone with the same structure as the original network branches and the fused network branches. The feature maps of each layer of the original network branch are extracted by our proposed CFEBlock (Common Feature Extraction Block), the common features of the feature maps between adjacent layers are extracted, and then these features are combined with the feature maps of the corresponding layers of the fusion network branch by FusionBlock, and finally the total prediction results are obtained by weighting the prediction results of both branches. In addition, we constructed a new dataset CSLI (Clinical Skin Lesion Images) by combining the publicly available dataset PAD-UFES-20 with our collected dataset, the CSLI dataset contains 3361 clinical dermatology images for six disease categories: actinic keratosis (730), cutaneous basal cell carcinoma (1136), malignant melanoma (170) cutaneous melanocytic nevus (391), squamous cell carcinoma (298) and seborrheic keratosis (636). Results: We divided the CSLI dataset into a training set, a validation set and a test set, and performed accuracy, precision, sensitivity, specificity, f1score, balanced accuracy, AUC summary, visualisation of different model training, ROC curves and confusion matrix for various diseases, ultimately showing that the network performed well overall on the test data. Discussion: The DBN contains two identical feature extraction network branches, a structure that allows shallow feature maps for image classification to be used with deeper feature maps for information transfer between them in both directions, providing greater flexibility and accuracy and enhancing the network's ability to focus on lesion regions. In addition, the dual branch structure of DBN provides more possibilities for model structure modification and feature transfer, and has great potential for development.

11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(5): 538-542, 2023 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-37102285

RESUMO

OBJECTIVE: To explore the genetic etiology of 5 cases of monochorionic-diamniotic (MCDA) with genetic discordance. METHODS: 148 cases of MCDA twins who were diagnosed by amniocentesis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 2016 to June 2020 were selected as the study subjects. Relevant clinical data of the pregnant women were collected, and amniotic fluid samples of the twins were collected separately. Chromosomal karyotyping analysis and single nucleotide polymorphism array (SNP array) assay were carried out. RESULTS: The results of chromosomal karyotyping analysis showed that 5 of the MCDA twins had inconsistent chromosome karyotypes, with an incidence of 3.4% (5/148). SNP array assay showed that 3 fetuses were mosaics. CONCLUSION: Genetic discordance occurs among MCDA twins, and prenatal counseling for such cases should be given by doctors with experience in medical genetics and fetal medicine, and personalized clinical management should be recommended.


Assuntos
Amniocentese , Gêmeos , Criança , Gravidez , Feminino , Humanos , China , Gêmeos/genética , Cariotipagem , Feto , Gêmeos Monozigóticos/genética , Ultrassonografia Pré-Natal , Estudos Retrospectivos
12.
Commun Biol ; 6(1): 407, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-37055517

RESUMO

Mechanical force loading is essential for maintaining bone homeostasis, and unloading exposure can lead to bone loss. Osteoclasts are the only bone resorbing cells and play a crucial role in bone remodeling. The molecular mechanisms underlying mechanical stimulation-induced changes in osteoclast function remain to be fully elucidated. Our previous research found Ca2+-activated Cl- channel Anoctamin 1 (Ano1) was an essential regulator for osteoclast function. Here, we report that Ano1 mediates osteoclast responses to mechanical stimulation. In vitro, osteoclast activities are obviously affected by mechanical stress, which is accompanied by the changes of Ano1 levels, intracellular Cl- concentration and Ca2+ downstream signaling. Ano1 knockout or calcium binding mutants blunts the response of osteoclast to mechanical stimulation. In vivo, Ano1 knockout in osteoclast blunts loading induced osteoclast inhibition and unloading induced bone loss and. These results demonstrate that Ano1 plays an important role in mechanical stimulation induced osteoclast activity changes.


Assuntos
Canais de Cloreto , Osteoclastos , Anoctamina-1/genética , Anoctamina-1/metabolismo , Canais de Cloreto/genética , Osteoclastos/metabolismo , Transdução de Sinais/fisiologia
13.
Clin Lab ; 69(3)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36912299

RESUMO

BACKGROUND: Trisomy 18 syndrome, also called Edwards syndrome, is the second most common autosomal trisomy after trisomy 21 that is caused by the presence of an extra copy of chromosome 18. Approximately 50% of infants with trisomy 18 cannot survive for more than 1 week and about 5 - 10% of children die within 1 year after birth. The aim of this study is to describe a 4-year-old female patient of mosaic trisomy 18 with normal prenatal ultrasound findings and maternal serum markers and to investigate the relationship between the percentage of trisomic cells and the major clinical phenotypes combined with other nine patients through a review of the literature. METHODS: The patient's peripheral blood was examined by cytogenetic G-banding technique. RESULTS: The cytogenetics results reported following the ISCN 2020 guideline as mos 47,XX,+18[87]/46,XX[13]. CONCLUSIONS: There is little correlation between various phenotypes of mosaic trisomy 18 and the percentage of trisomy cells in the patient's peripheral leukocytes. Although most of fetuses with mosaic trisomy 18 have abnormal ultrasound findings, it is necessary to highlight the possibility of normal findings during the pregnancy.


Assuntos
Amniocentese , Diagnóstico Pré-Natal , Gravidez , Feminino , Humanos , Amniocentese/métodos , Síndrome da Trissomía do Cromossomo 18 , Trissomia , Mosaicismo , Fenótipo
15.
J Clin Pharm Ther ; 47(12): 1952-1965, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36452989

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The management of biological agents during pregnancy poses challenges as maternal and infant safety must be addressed. This study aims to compare the recommendations of existing guidelines on managing the use of biologics during pregnancy, lactation for patients with inflammatory bowel disease, and the influence on neonatal vaccination. METHODS: The PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database and China Biomedical Database were systematically searched from the inception date to 11 May 2022, to screen all relevant guidelines. Quality assessment was performed using the guideline methodology reporting tool AGREE II. RESULTS AND DISCUSSION: Fourteen guidelines and consensus statements with detailed recommendations were included. All guidance documents cover management comments during pregnancy, and most consider that biologics can be given safely during pregnancy but require suspension at the right time to protect the foetus. However, the roles of vedolizumab and ustekinumab are disputed. Five documents guide lactation and the use of most biologics during lactation is safe, but no guidelines recommend vedolizumab. Six papers provide recommendations for newborns' vaccination, suggesting a delay in infants' live vaccination schedule if their mothers are treated with biologics. WHAT IS NEW AND CONCLUSION: Our study concluded that future guidelines could consider incorporating newer, more robust evidence to update recommendations. The development of future guidelines needs to consider the involvement of multidisciplinary experts, adequately report on the evidence retrieval process, and provide strategies for implementation. Besides, more research is needed to explore the use of biologics during pregnancy and lactation in patients with inflammatory bowel disease.


Assuntos
Produtos Biológicos , Doenças Inflamatórias Intestinais , Gravidez , Feminino , Humanos , Recém-Nascido , Produtos Biológicos/uso terapêutico , Lactação , Fatores Biológicos , China , Doenças Inflamatórias Intestinais/tratamento farmacológico
16.
Nature ; 610(7931): 308-312, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36163288

RESUMO

Exploring the subsurface structure and stratification of Mars advances our understanding of Martian geology, hydrological evolution and palaeoclimatic changes, and has been a main task for past and continuing Mars exploration missions1-10. Utopia Planitia, the smooth plains of volcanic and sedimentary strata that infilled the Utopia impact crater, has been a prime target for such exploration as it is inferred to have hosted an ancient ocean on Mars11-13. However, 45 years have passed since Viking-2 provided ground-based detection results. Here we report an in situ ground-penetrating radar survey of Martian subsurface structure in a southern marginal area of Utopia Planitia conducted by the Zhurong rover of the Tianwen-1 mission. A detailed subsurface image profile is constructed along the roughly 1,171 m traverse of the rover, showing an approximately 70-m-thick, multi-layered structure below a less than 10-m-thick regolith. Although alternative models deserve further scrutiny, the new radar image suggests the occurrence of episodic hydraulic flooding sedimentation that is interpreted to represent the basin infilling of Utopia Planitia during the Late Hesperian to Amazonian. While no direct evidence for the existence of liquid water was found within the radar detection depth range, we cannot rule out the presence of saline ice in the subsurface of the landing area.

17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(8): 842-847, 2022 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-35929933

RESUMO

OBJECTIVE: To assess the value of chromosomal karyotyping analysis and single nucleotide polymorphism-based microarray (SNP-array) for the detection of chromosomal mosaicisms in amniotic fluid samples. METHODS: Seventy four pregnant women with fetal mosaicisms detected by both methods were retrospectively analyzed. RESULTS: Among the 74 mosaicisms, 12 were pseudo and 62 were true mosaicisms, which included 1 Robertsonian translocation, 3 deletions, 4 supernumerary markers, 19 autosomal aneuploidy mosaicisms, 30 sex chromosome aneuploidy mosaicisms and 5 isometric chromosome mosaicisms. CONCLUSION: Chromosome karyotyping analysis and SNP-array have their own advantages and limitations for the diagnosis of mosaicisms. When the two methods have yielded inconsistent results, fluorescence in situ hybridization may be used for further verification.


Assuntos
Mosaicismo , Diagnóstico Pré-Natal , Aneuploidia , Aberrações Cromossômicas , Feminino , Humanos , Hibridização in Situ Fluorescente , Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Retrospectivos , Aberrações dos Cromossomos Sexuais
18.
Acta Biochim Pol ; 69(2): 327-333, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35675627

RESUMO

OBJECTIVE: This study aimed to identify novel prognostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) using bioinformatics analyzes. METHODS: Clinical information, microRNAs (miRNAs), and genes expression profile data from PDAC cases were downloaded from the Cancer Genome Atlas (TCGA) database. The potential prognostic risk miRNAs and genes were screened using the Elastic Net Cox proportional risk regression hazards (EN-COX) model. The receiver operating characteristic (ROC) curve and the Kaplan-Meier (KM) curve were used to identify miRNAs and genes of significant prognostic risk. Furthermore, significant prognostic risk miRNAs were functional enrichment analyses based on their target genes. Furthermore, the survival analyzes of the hub genes were validated through OncoLnc. RESULTS: Complete clinical records and expression data of 797 miRNAs and 19969 genes from 137 PDAC cases were obtained, of which 59 potential prognostic risk factors, including 54 genes and 5 miRNAs, were selected by EN-COX analyzes. A total of 17 significant prognostic risk markers were identified (all P<0.05), including 16 genes and 1 miRNA (miRNA-125a). The miRNA-125a target genes were found in the MiRWalk database and the function enrichment analyzes were performed in the the DAVID website. Furthermore, according to data from the Oncomine and Human Protein Atlas (HPA) databases, the mRNA and protein level of frizzled class receptor 8 (FZD8) were overexpressed in pancreatic cancer tissues compared to the corresponding noncancer normal tissues (P<0.001). However, both glutathione S-transferase mu 4 (GSTM4) and inducible T cell costimulator ligand (ICOSLG) were negatively regulated in tissues of pancreatic cancer tissues (P<0.001). Finally, survival analysis was used to validate these factors by the OncoLnc database, and the results revealed that overexpression of ICOSLG was associated with a better prognosis (P=0.025). CONCLUSIONS: This study showed that the expression levels of FZD8, GSTM4 and ICOSLG were significantly different between PDAC and non-tumor tissues, especially ICOSLG, which could be a prognostic indicator and therapeutic target for PDAC.


Assuntos
Carcinoma Ductal Pancreático , MicroRNAs , Neoplasias Pancreáticas , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Neoplasias Pancreáticas
19.
Front Bioeng Biotechnol ; 10: 850303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528209

RESUMO

As hematopoietic stem cells can differentiate into all hematopoietic lineages, mitigating the damage to hematopoietic stem cells is important for recovery from overdose radiation injury. Cells in bone marrow microenvironment are essential for hematopoietic stem cells maintenance and protection, and many of the paracrine mediators have been discovered in shaping hematopoietic function. Several recent reports support exosomes as effective regulators of hematopoietic stem cells, but the role of osteoblast derived exosomes in hematopoietic stem cells protection is less understood. Here, we investigated that osteoblast derived exosomes could alleviate radiation damage to hematopoietic stem cells. We show that intravenous injection of osteoblast derived exosomes promoted WBC, lymphocyte, monocyte and hematopoietic stem cells recovery after irradiation significantly. By sequencing osteoblast derived exosomes derived miRNAs and verified in vitro, we identified miR-21 is involved in hematopoietic stem cells protection via targeting PDCD4. Collectively, our data demonstrate that osteoblast derived exosomes derived miR-21 is a resultful regulator to radio-protection of hematopoietic stem cells and provide a new strategy for reducing radiation induced hematopoietic injury.

20.
Nat Commun ; 13(1): 2899, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610255

RESUMO

Osteoclast over-activation leads to bone loss and chloride homeostasis is fundamental importance for osteoclast function. The calcium-activated chloride channel Anoctamin 1 (also known as TMEM16A) is an important chloride channel involved in many physiological processes. However, its role in osteoclast remains unresolved. Here, we identified the existence of Anoctamin 1 in osteoclast and show that its expression positively correlates with osteoclast activity. Osteoclast-specific Anoctamin 1 knockout mice exhibit increased bone mass and decreased bone resorption. Mechanistically, Anoctamin 1 deletion increases intracellular Cl- concentration, decreases H+ secretion and reduces bone resorption. Notably, Anoctamin 1 physically interacts with RANK and this interaction is dependent upon Anoctamin 1 channel activity, jointly promoting RANKL-induced downstream signaling pathways. Anoctamin 1 protein levels are substantially increased in osteoporosis patients and this closely correlates with osteoclast activity. Finally, Anoctamin 1 deletion significantly alleviates ovariectomy induced osteoporosis. These results collectively establish Anoctamin 1 as an essential regulator in osteoclast function and suggest a potential therapeutic target for osteoporosis.


Assuntos
Anoctamina-1/metabolismo , Reabsorção Óssea , Osteoporose , Animais , Reabsorção Óssea/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Osteoporose/metabolismo , Ovariectomia , Ligante RANK/genética , Ligante RANK/metabolismo
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