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1.
Sci Rep ; 13(1): 1522, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707533

RESUMO

To investigate the application of combined audiological examination and a self-reported symptoms survey in the evaluation of hyperacusis. Patients who visited the outpatient department of Otolaryngology Head and Neck Surgery and Otological medicine, Affiliated Hospital of Southwest Medical University, from January 2019 to March 2021 were divided into a hyperacusis group and a normal control group. We measured the loudness discomfort level (LDL) and hearing threshold (HT) of the subjects and investigated their self-reported symptoms. We compared the demographic characteristics, loudness discomfort level, and hearing threshold of the two groups and analyzed the self-reported symptoms and audiological characteristics of hyperacusis. We considered 87 subjects, comprising 40 patients with hyperacusis and 47 healthy individuals. Among the hyperacusis patients, bilateral disease was predominant. Among them, 33 were females, 23 had hearing loss, and 20 had tinnitus. Patients are mainly in the 21-60 age group. Patients with hyperacusis had low discomfort thresholds at all frequencies except 500 Hz (P ≤ 0.05, mean LDL decreased by 6.14-1.37 dB HL for all frequencies). The incidences of feeling upset, pain, and anxiety or fear were 95%, 65%, and 82.5%, respectively, in patients with hyperacusis. The severity of symptoms varies between patients with hyperacusis and healthy individuals. A combination of LDL measurements and self-reported symptom surveys allows for an accurate and comprehensive assessment of hyperacusis.Trial registration: This study was retrospectively registered (TRN: ChiCTR2100047391) on June 13, 2021.


Assuntos
Audiologia , Zumbido , Feminino , Humanos , Masculino , Hiperacusia/diagnóstico , Autorrelato , Audição , Zumbido/diagnóstico , Zumbido/epidemiologia , Pacientes Ambulatoriais
2.
Neural Regen Res ; 18(3): 594-602, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018183

RESUMO

Dysregulation of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels alters neuronal excitability. However, the role of HCN channels in status epilepticus is not fully understood. In this study, we established rat models of pentylenetetrazole-induced status epilepticus. We performed western blot assays and immunofluorescence staining. Our results showed that HCN1 channel protein expression, particularly HCN1 surface protein, was significantly decreased in the hippocampal CA1 region, whereas the expression of HCN2 channel protein was unchanged. Moreover, metabolic glutamate receptor 1 (mGluR1) protein expression was increased after status epilepticus. The mGluR1 agonist (RS)-3,5-dihydroxyphenylglycine injected intracerebroventricularly increased the sensitivity and severity of pentylenetetrazole-induced status epilepticus, whereas application of the mGluR1 antagonist (+)-2-methyl-4-carboxyphenylglycine (LY367385) alleviated the severity of pentylenetetrazole-induced status epilepticus. The results from double immunofluorescence labeling revealed that mGluR1 and HCN1 were co-localized in the CA1 region. Subsequently, a protein kinase A inhibitor (H89) administered intraperitoneally successfully reversed HCN1 channel inhibition, thereby suppressing the severity and prolonging the latency of pentylenetetrazole-induced status epilepticus. Furthermore, H89 reduced the level of mGluR1, downregulated cyclic adenosine monophosphate (cAMP)/protein kinase A expression, significantly increased tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) (1a-4) expression, and restored TRIP8b (1b-2) levels. TRIP8b (1a-4) and TRIP8b (1b-2) are subunits of Rab8b interacting protein that regulate HCN1 surface protein.

3.
Genomics ; 115(1): 110540, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36563917

RESUMO

Non-coding RNAs (ncRNAs) induced competing endogenous RNAs (ceRNA) play crucial roles in various biological process by regulating target gene expression. However, the studies of ceRNA networks in the regulation of ovarian ovulation processing of chicken remains deficient compared to that in mammals. Our present study revealed that circEML1 was differential expressed in hen's ovarian tissues at different ages (15 W/20 W/30 W/68 W) and identified as a loop structure from EML1 pre-mRNA, which promoted the expressions of CYP19A1/StAR and E2/P4 secretion in follicular granulosa cells (GCs). Furthermore, circEML1 could serve as a sponge of gga-miR-449a and also found that IGF2BP3 was targeted by gga-miR-449a to co-participate in the steroidogenesis, which possibly act the regulatory role via mTOR/p38MAPK pathways. Meanwhile, in the rescue experiment, gga-miR-449a could reverse the promoting role of circEML1 to IGF2BP3 and steroidogenesis. Eventually, this study suggested that circEML1/gga-miR-449a/IGF2BP3 axis exerted an important role in the steroidogenesis in GCs of chicken.


Assuntos
Galinhas , MicroRNAs , Animais , Feminino , Galinhas/genética , Galinhas/metabolismo , Células da Granulosa , Mamíferos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Ovário/metabolismo , Esteroides/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo
4.
Eur J Pharmacol ; : 175446, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36470443

RESUMO

Cerebral amyloid angiopathy (CAA) is characterized by the cerebrovascular amyloid-ß (Aß) accumulation, and always accompanied by Alzheimer's disease (AD). The mechanisms revealing CAA pathogenesis are still unclear, and it is challenging to develop an efficient therapeutic strategy for its treatment. Vascular endothelial growth factor (VEGF) and its receptors including VEGFR-1,-2,-3 activation are involved in Aß processing, and modulate numerous cellular events associated with central nervous system (CNS) diseases. In the present study, we attempted to explore the regulatory function of fruquintinib (also named as HMPL-013), a highly selective inhibitor of VEGFR-1,-2,-3 tyrosine kinases, on CAA progression in Tg-SwDI mice. Here, we found that HMPL-013-rich diet consumption for 12 months significantly improved the behavioral performances and cerebral blood flow (CBF) of Tg-SwDI mice compared with the vehicle group. Importantly, HMPL-013 administration considerably reduced Aß1-40 and Aß1-42 burden in cortex and hippocampus of Tg-SwDI mice through regulating Aß metabolism process. Congo red staining confirmed Aß deposition in vessel walls, reflecting CAA formation, which was, however, strongly ameliorated after HMPL-013 treatment. Neuron death, aberrant glial activation and pro-inflammatory response in brain tissues of Tg-SwDI mice were dramatically alleviated after HMPL-013 consumption. More studies showed that the protective effects of HMPL-013 against CAA might be partially attributed to its regulation on the expression of genes associated with blood vasculature. Intriguingly, VEGF and phosphorylated VEGFR-1,-2 protein expression levels were remarkably decreased by HMPL-013 in cortex and hippocampus of Tg-SwDI mice, which were validated in HMPL-013-treated brain vascular endothelial cells (BVECs) under hypoxia. Finally, we found that VEGF-induced human umbilical vein endothelial cells (HUVEC) proliferation and tube formation were strongly abolished upon HMPL-013 exposure. Collectively, all these findings demonstrated that oral administration of HMPL-013 had therapeutic potential against CAA by reducing Aß deposition, inflammation and neuron death via suppressing VEGF/VEGFR-1,-2 signaling.

5.
Mol Divers ; 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36576665

RESUMO

Alzheimer's disease is the most common neurodegenerative disease. Acanthopanax senticosus, also known as Ciwujia or Siberian ginseng in Chinese, has a wide range of antioxidant and anti-inflammatory activities. The study aims to explore the action mechanism of A. senticosus against Alzheimer's disease using network pharmacology and molecular docking. The active ingredients and targets of A. senticosus were searched through the ETCM database, and Alzheimer's disease-related targets were obtained through the OMIM and GeneCards databases. The Cytoscape 3.7.2 software was used to construct a "drug-component-target" relationship network, and the target genes of A. senticosus against Alzheimer's disease were imported into the String database to establish a protein interaction (PPI) network. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes gene enrichment analyses were performed through the Metascape database to obtain potential pathways of action of A. senticosus for the treatment of Alzheimer's disease, and the ability of these active ingredients to bind to core targets was then verified by molecular docking. 51 active ingredients were screened from A. senticosus, and 88 effective targets for Alzheimer's disease were screened. Topological and pathway-enrichment analyses revealed that A. senticosus could play a beneficial role in the treatment of Alzheimer's disease by regulating apoptosis and inflammation. Molecular docking results showed that Ciwujianoside B, Chiisanoside, and Ciwujianoside D1 had strong binding abilities to key target proteins (TNFα, IL1ß, and CASP3). Collectively, A. senticosus is feasible in the treatment of Alzheimer's disease.

6.
Front Plant Sci ; 13: 1013331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388515

RESUMO

Exploring the diversity and formation mechanism of under-ground bud banks is essential for understanding the renewal of plant populations and community succession. However, there are few studies on the response of bud bank size and composition to different degradation gradients in alpine meadows. In view of this, we investigated the size and composition of bud bank under four degradation gradients (non-degraded:ND, lightly degraded:LD, moderately degraded:MD, and heavily degraded:HD) caused by overgrazing in a typical alpine meadow in Tibet, China, using a unit area excavation sampling method, and analyzed the correlation between above-ground plant community composition and bud bank density. Our results showed that: (i) in the ND alpine meadow, rhizome buds were dominant, in the LD, tiller buds were dominant, and in the MD, root-sprouting buds were dominant; (ii) total bud bank and cyperaceae bud density decreased with increasing degradation gradient, the density of leguminosae was insignificant in each degradation gradient, and the density of gramineae and forb were dominant in LD and MD meadows, respectively; (iii) total bud bank density was significantly and positively correlated with total above-ground biomass in the LD gradient, tiller bud density was significantly positively correlated with the species diversity index of above-ground vegetation under the ND gradient, rhizome bud density was significantly and positively correlated with total above-ground biomass in the LD gradient, and root-sprouting density was significantly negatively correlated with total above-ground biomass in ND meadows, but was significantly positively correlated with the species diversity index of the LD gradient. Therefore, our research shows that rhizome buds are more important in ND meadow habitats, tiller buds are more important in LD meadow habitats, and root-sprouting buds are more important in MD meadows. The response of bud banks to degradation gradient varies with different types of bud banks and different functional groups of plants, and the survival strategy of bud banks is of great value for community restoration and regeneration, which should be paid more attention to in subsequent alpine meadow research.

7.
Antibodies (Basel) ; 11(4)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36412839

RESUMO

Since the first approval of the anti-CD3 recombinant monoclonal antibody (mAb), muromonab-CD3, a mouse antibody for the prevention of transplant rejection, by the US Food and Drug Administration (FDA) in 1986, mAb therapeutics have become increasingly important to medical care. A wealth of information about mAbs regarding their structure, stability, post-translation modifications, and the relationship between modification and function has been reported. Yet, substantial resources are still required throughout development and commercialization to have appropriate control strategies to maintain consistent product quality, safety, and efficacy. A typical feature of mAbs is charge heterogeneity, which stems from a variety of modifications, including modifications that are common to many mAbs or unique to a specific molecule or process. Charge heterogeneity is highly sensitive to process changes and thus a good indicator of a robust process. It is a high-risk quality attribute that could potentially fail the specification and comparability required for batch disposition. Failure to meet product specifications or comparability can substantially affect clinical development timelines. To mitigate these risks, the general rule is to maintain a comparable charge profile when process changes are inevitably introduced during development and even after commercialization. Otherwise, new peaks or varied levels of acidic and basic species must be justified based on scientific knowledge and clinical experience for a specific molecule. Here, we summarize the current understanding of mAb charge variants and outline risk-based control strategies to support process development and ultimately commercialization.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36334061

RESUMO

OBJECTIVE: To compare the recurrence rate and risk factors between conservative surgery followed by medical treatments and conservative surgery-only in patients with focal adenomyosis. METHODS: This retrospective study was conducted in a single teaching hospital from May 2011 to October 2016. All eligible patients were identified into three groups: surgery-only group, surgery combined with gonadotropin-releasing hormone agonist (GnRHa), and a levonorgestrel-releasing intrauterine system (LNG-IUS) group. The recurrence rate and risk factors were compared among groups using Kaplan-Meier and Cox proportional hazards analyses. Receiver operating characteristic (ROC) curve analysis was applied to determine a cut-off value for identifying recurrence-related risk factors. RESULTS: A total of 249 postoperative patients with adenomyosis were included in the final analysis with a mean of 41 months of follow up. The recurrence rate at the long-term follow up was significantly lower in intervention groups than in the surgery-only group (P = 0.011). The Cox proportional hazards and ROC analyses showed that a menstrual cycle longer than 26 days (P = 0.026), diameter of lesions <6 cm (P = 0.030), and combination treatment using GnRHa (P = 0.039) or LNG-IUS (P = 0.007) were protective against relapse. The risk of recurrence was lower in patients with anterior (P = 0.034) or fundus (P = 0.038) adenomyosis. CONCLUSION: Postoperative therapy using GnRHa or LNG-IUS decreases the long-term relapse rate in women undergoing conservative surgery.

9.
Biochem Biophys Res Commun ; 636(Pt 1): 170-177, 2022 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-36334441

RESUMO

NSCs play an essential role in the regeneration process of the central nervous system. However, due to the influence of the harsh pathological microenvironment, the viability of neural stem cells is limited, and the therapeutic effect needs improvement. Previous studies have found that stem cells overexpressing ciliary neurotrophic factor (CNTF) have apparent therapeutic effects on remyelination, but the specific mechanism of action still needs to be further explored. We found that astrocytes, the most numerous groups in the CNS, exhibited a pathological role in the experimental autoimmune encephalomyelitis model, but after stimulation with CNTF-NSCs, a phenotypic switch occurred and induced the neurotrophic factor cardiotrophin-like cytokine 1 (Clcf1) production. Mechanistically, Clcf1 can significantly promote the differentiation of oligodendrocyte precursor cells (OPCs), and the advanced effect can attenuate by the Clcf1 antibody. Therefore, this study was conducted to investigate the pathway by which CNTF-NSCs exert their therapeutic effects by affecting astrocytes. It is expected to identify a potential therapeutic factor, Clcf1, for the treatment of demyelinating diseases.


Assuntos
Células-Tronco Neurais , Células Precursoras de Oligodendrócitos , Fator Neurotrófico Ciliar/farmacologia , Células Precursoras de Oligodendrócitos/metabolismo , Astrócitos/metabolismo , Diferenciação Celular , Células-Tronco Neurais/metabolismo , Oligodendroglia
10.
Int J Womens Health ; 14: 1489-1497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36317008

RESUMO

This paper reports two cases of postpartum pulmonary embolism in Taicang First People's Hospital affiliated to Soochow University. They share many similarities in age, fertilization way, birthing method, incidence of pulmonary embolism, treatment and prognosis. The main purpose is to inspire the current maternal PTE risk assessment, diagnosis and treatment, as well as to explore the existing limitations and problems.

11.
Genet Sel Evol ; 54(1): 69, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273127

RESUMO

BACKGROUND: At the beginning of genomic selection, some Chinese companies genotyped pigs with different single nucleotide polymorphism (SNP) arrays. The obtained genomic data are then combined and to do this, several imputation strategies have been developed. Usually, only additive genetic effects are considered in genetic evaluations. However, dominance effects that may be important for some traits can be fitted in a mixed linear model as either 'classical' or 'genotypic' dominance effects. Their influence on genomic evaluation has rarely been studied. Thus, the objectives of this study were to use a dataset from Canadian Yorkshire pigs to (1) compare different strategies to combine data from two SNP arrays (Affymetrix 55K and Illumina 42K) and identify the most appropriate strategy for genomic evaluation and (2) evaluate the impact of dominance effects (classical' and 'genotypic') and inbreeding depression effects on genomic predictive abilities for average daily gain (ADG), backfat thickness (BF), loin muscle depth (LMD), days to 100 kg (AGE100), and the total number of piglets born (TNB) at first parity. RESULTS: The reliabilities obtained with the additive genomic models showed that the strategy used to combine data from two SNP arrays had little impact on genomic evaluations. Models with classical or genotypic dominance effect showed similar predictive abilities for all traits. For ADG, BF, LMD, and AGE100, dominance effects accounted for a small proportion (2 to 11%) of the total genetic variance, whereas for TNB, dominance effects accounted for 11 to 20%. For all traits, the predictive abilities of the models increased significantly when genomic inbreeding depression effects were included in the model. However, the inclusion of dominance effects did not change the predictive ability for any trait except for TNB. CONCLUSIONS: Our study shows that it is feasible to combine data from different SNP arrays for genomic evaluation, and that all combination methods result in similar accuracies. Regardless of how dominance effects are fitted in the genomic model, there is no impact on genetic evaluation. Models including inbreeding depression effects outperform a model with only additive effects, even if the trait is not strongly affected by dominant genes.


Assuntos
Depressão por Endogamia , Gravidez , Feminino , Suínos/genética , Animais , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Canadá , Genômica/métodos
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(5): 815-820, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36224683

RESUMO

Objective: To analyze the effects of bone marrow mesenchyml stem cells (BMSCs) on bone alkaline phosphatase (BALP)/C-terminal telopeptide of type-Ⅰ collagen (CTX-1) expression and mechanical dynamics in rats with osteoporotic (OP) vertebral fracture. Methods: A total of 60 female Sprague-Dawley rats were evenly divided into three groups, a control group that received sham operation (sham group), a group consisting of rats with OP vertebral fracture (OP group), and the last group consisting of OP vertebral fracture rats given BMSCs treatment (BMSCs group). Comparison of the three groups of animals was made in terms of bone dynamic change, bone quantitative broadband ultrasound attenuation (BUA) measurement, and bone mineral density (BMD). HE staining was done to examine the bone histological morphological parameters of the vertebral body. Serum CTX-1 and BALP levels were determined by ELISA. Results: Mechanical comparison showed that there were significant differences in mechanical changes of L 5 vertebra body and right femur among the three experimental groups ( P<0.05). The elastic modulus and maximum load of the OP group significantly decreased compared with those of the sham group ( P<0.05). After the intervention, the maximum load and elastic modulus of the BMSCs group were significantly higher than those of the OP group ( P<0.05). Compared with the sham group, BUA and BMD values in the OP group were significantly downregulated ( P<0.05). After intervention, BUA and BMD of the BMSCs group were significantly higher than those of the OP group and were comparable to those of the sham group ( P<0.05). Compared with the sham group, the number of trabeculae in the OP group was significantly fewer, and the distribution of trabeculae was disorderly and lacked regularity. Compared with the OP group, there were more trabeculae in the BMSCs group, and their distribution was more regular. Compared with sham group, bone histological morphological parameters of the vertebral body of rats in the OP group were significantly changed--mean trabecular plate thickness (MTPT) and trabecular bone volume (TBV) parameters were significantly decreased, while mineral apposition rate (MAR) and trabecula bone surface (TRS) parameters were significantly upregulated (all P<0.05). After the experimental intervention, bone histological morphological parameters of the vertebral body in the BMSCs group showed significant improvement compared with those of the OP group ( P<0.05). Compared with the sham group, serum BALP content in the OP group was greatly decreased, while the CTX-1 level was upregulated ( P<0.05). After the intervention, the BMSCs group had higher serum BALP content than that of the OP group and substantially lower CTX-1 content than that of the OP group ( P<0.05). Conclusion: BMSCs can improve the mechanical changes in rats with OP vertebral fracture, and can increase the maximum load and elastic modulus of bone tissue. In addition, BMSCs can upregulate the expression of BALP in serum and downregulate the expression of CTX-1, thus helping rats with OP vertebral fracture heal early.


Assuntos
Colágeno Tipo I , Células-Tronco Mesenquimais , Fragmentos de Peptídeos , Fraturas da Coluna Vertebral , Animais , Feminino , Ratos , Fosfatase Alcalina , Densidade Óssea , Colágeno Tipo I/metabolismo , Ovariectomia , Fragmentos de Peptídeos/metabolismo , Ratos Sprague-Dawley , Coluna Vertebral
13.
Lifestyle Genom ; 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36183698

RESUMO

INTRODUCTION: The prevalence of colon cancer remains high across the world. The early diagnosis of colon cancer is challenging. Moreover, patients with colon cancer frequently suffer from poor prognoses. METHODS: Differentially expressed genes (DEGs) in colon cancer were acquired based on TCGA-COAD dataset screening. DEGs were input into the Connectivity Map (CMap) database to screen small molecule compounds with the potential to reverse colon cancer pathological function. Glycitein ranked first among the screened small molecule compounds. We downloaded the main targets of glycitein from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database and constructed protein-protein interaction (PPI) networks of those which were closely related to targets by Search Tool for the Retrieval of Interaction Gene/Proteins (STRING). Five potential targets of glycitein for treating colon cancer were identified (CCNA2, ESR1, ESR2, MAPK14, and PTGS2). These targets were used as seeds for random walk with restart (RWR) analysis of PPI networks. Then, the interaction network of glycitein-colon cancer-related genes was constructed based on the top 50 genes in affinity coefficients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the potential genes targeted by glycitein in colon cancer treatment and those were closely bound up with targets. RESULTS: GO analysis demonstrated that the enrichment of these genes was primarily discovered in biological functions including regulation of fibroblast proliferation, response to oxygen levels, and epithelial cell proliferation. KEGG analysis results illustrated that the signaling pathways where these genes were mostly involved consisted of the mitogen-activated protein kinases signaling pathway, the phosphatidylinositol-3-kinase-Akt signaling pathway, and the p53 signaling pathway. Finally, stable binding of glycitein to five potential targets in colon cancer was verified by molecular docking. CONCLUSION: This study elucidated the key targets and main pathways of glycitein on the basis of network pharmacology and preliminarily analyzed molecular mechanisms in the treatment of colon cancer. A scientific basis is provided for glycitein application in treating colon cancer.

14.
Exp Eye Res ; 224: 109264, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36162459

RESUMO

Diabetic retinopathy (DR) is one of the common systemic complications of diabetes. Epithelial-mesenchymal transition (EMT) is required for DR progression. Previous studies have explored that circular RNAs (circRNAs) are crucial for DR development. Herein, we focused on the biological functions of circSCMH1 in DR. RT-qPCR determined the expression of circSCMH1, miR-200a-3p and ZEB1. EMT-related proteins were measured by Western blot. Gene combinations were validated by RIP and dual luciferase reporter assays. CCK-8, EdU, TUNEL staining and Transwell analysis were used to assess the cellular function. FISH analysis assessed the localization of circSCMH1 and miR-200a-3p. HE staining was used to detect retinal structures in a mouse DR model. High-glucose (HG) significantly increased circSCMH1 expression in ARPE-19 cells. Additionally, circSCMH1 silencing repressed proliferation, migration, and EMT in HG cells. Mechanistically, circSCMH1 positively regulated ZEB1 expression via targeting miR-200a-3p. Furthermore, circSCMH1 was observed to induce HG cell growth and EMT by regulating the miR-200a-3p/ZEB1 axis. Finally, we verified that downregulation of circSCMH1 or ZEB1 alleviated EMT in the retina of diabetic mice. These findings have implications for new therapeutic targets for DR.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , MicroRNAs , RNA Circular , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Animais , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Diabetes Mellitus Experimental/genética , Retinopatia Diabética/genética , Transição Epitelial-Mesenquimal/genética , Glucose , MicroRNAs/genética , MicroRNAs/metabolismo , Retina/metabolismo , RNA Circular/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
15.
Adv Clin Exp Med ; 31(11): 1215-1229, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36047895

RESUMO

BACKGROUND: Diabetes mellitus (DM) often causes stenosis and occlusion of hindlimb blood vessels, which are also the main cause for hindlimb ischemia in elderly people. OBJECTIVES: To investigate the therapeutic effect of endothelial progenitor cell (EPC) transplantation on diabetic hindlimb ischemia. MATERIAL AND METHODS: Endothelial progenitor cells were separated, labeled with PKH-26 and transplanted into rat models (107 cells/100 g). Dichlorodihydrofluorescein diacetate (DCFH-DA) was used to detect any oxidative stress. Streptozotocin (STZ) was injected to establish a diabetic rat model and hindlimb ischemia model was established via operation. Western blotting was used to detect total ß-catenin (T-ß-catenin) and non-phospho-ß-catenin (NP-ß-catenin) levels. The malondialdehyde (MDA), superoxide dismutase (SOD), Wnt3a, Wnt5a and Wnt7a levels were detected using enzyme-linked immunosorbent assay (ELISA). Oxidative stress was measured using DCFH-DA and dihydroethidium (DHE). The endothelial biomarker CD31 was observed to highlight vessels, and PKH-26 to trace migration/adhesion of EPCs. RESULTS: Endothelial progenitor cells were successfully isolated and identified, and diabetic hindlimb ischemic rat models were created. Tempol remarkably improved blood flow in diabetic hindlimb ischemic rats compared to DM+EPCs rats at 14 days (p < 0.001) and 28 days post-operation (p < 0.001). High oxidative stress was observed in diabetic hindlimb ischemic rats. Tempol significantly inhibited oxidative stress levels in diabetic hindlimb ischemic rats. Furthermore, Tempol significantly promoted angiogenesis in diabetic hindlimb ischemic rats compared to DM+EPCs rats. The ß-catenin inhibitor, XAV (DM+EPCs+Tempol+XAV group), significantly suppressed blood flow recovery and angiogenesis in diabetic hindlimb ischemic rats when compared to the DM+EPCs+Tempol group at 14 days (p = 0.026) and 28 days (p < 0.001). The XAV remarkably reduced T-ß-catenin (p < 0.001) and N-ß-catenin (p = 0.030) levels in Tempol-treated diabetic hindlimb ischemic rats, as compared to the DM+EPCs+Tempol group. The Wnt5a participated in the pathology of diabetic hindlimb ischemia. CONCLUSIONS: There are high oxidative stress levels in both EPCs in high-glucose environments and diabetic hindlimb ischemia, which can lead to limited blood flow recovery. The high oxidative stress caused the inhibition of Wnt/ß-catenin signaling pathway, leading to limited blood flow recovery in diabetic hindlimb ischemia. At the same time, Wnt5a participated in the EPC-mediated blood flow recovery.


Assuntos
Diabetes Mellitus , Células Progenitoras Endoteliais , Ratos , Animais , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , beta Catenina/metabolismo , Via de Sinalização Wnt , Neovascularização Fisiológica/fisiologia , Membro Posterior/irrigação sanguínea , Isquemia , Estresse Oxidativo , Diabetes Mellitus/metabolismo , Neovascularização Patológica/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-35914036

RESUMO

Generalization to out-of-distribution (OOD) data is a capability natural to humans yet challenging for machines to reproduce. This is because most learning algorithms strongly rely on the i.i.d. assumption on source/target data, which is often violated in practice due to domain shift. Domain generalization (DG) aims to achieve OOD generalization by using only source data for model learning. Over the last ten years, research in DG has made great progress, leading to a broad spectrum of methodologies, e.g., those based on domain alignment, meta-learning, data augmentation, or ensemble learning, to name a few; DG has also been studied in various application areas including computer vision, speech recognition, natural language processing, medical imaging, and reinforcement learning. In this paper, for the first time a comprehensive literature review in DG is provided to summarize the developments over the past decade. Specifically, we first cover the background by formally defining DG and relating it to other relevant fields like domain adaptation and transfer learning. Then, we conduct a thorough review into existing methods and theories. Finally, we conclude this survey with insights and discussions on future research directions.

17.
Front Plant Sci ; 13: 951003, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035662

RESUMO

Rhododendron (Ericaceae) not only has ornamental value, but also has great medicinal and edible values. Many Rhododendron species are native to acid soils where aluminum (Al) toxicity limits plant productivity and species distribution. However, it remains unknown how Rhododendron adapts to acid soils. Here, we investigated the physiological and molecular mechanisms of Al tolerance in Rhododendron yunnanense Franch. We found that the shoots of R. yunnanense Franch did not accumulate Al after exposure of seedlings to 50 µM Al for 7 days but predominantly accumulated in roots, suggesting that root Al immobilization contributes to its high Al tolerance. Whole-genome de novo transcriptome analysis was carried out for R. yunnanense Franch root apex in response to 6 h of 50 µM Al stress. A total of 443,639 unigenes were identified, among which 1,354 and 3,413 were up- and down-regulated, respectively, by 6 h of 50 µM Al treatment. Both Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that genes involved in "ribosome" and "cytoskeleton" are overrepresented. Additionally, we identified Al-tolerance homologous genes including a tonoplast-localized ABC transporter RyALS3; 1. Overexpression of RyALS3; 1 in tobacco plants confers transgenic plants higher Al tolerance. However, root Al content was not different between wild-type plants and transgenic plants, suggesting that RyALS3; 1 is responsible for Al compartmentalization within vacuoles. Taken together, integrative transcriptome, physiological, and molecular analyses revealed that high Al tolerance in R. yunnanense Franch is associated with ALS3; 1-mediated Al immobilization in roots.

18.
Oxid Med Cell Longev ; 2022: 2405943, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910848

RESUMO

Background: Ferroptosis is a nonapoptotic form of programmed cell death, which may be related to the occurrence and development of sepsis-induced acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). Mucin 1 (MUC1) is a kind of macromolecule transmembrane glycoprotein. Previous studies have shown that MUC1 could relieve ALI in sepsis and predict whether sepsis patients would develop into ARDS. However, the role of MUC1 in the ferroptosis of sepsis-induced ALI/ARDS remains unclear. Materials and Methods: Sera samples from 50 patients with sepsis/septic shock were used to detect iron metabolism-related markers. Western blot and qRT-PCR were conducted to detect the expression levels of ferroptosis-related genes. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate inflammatory factors. Transmission electron microscopy (TEM) was used to assess morphological changes of cells. Results: The results showed that the iron metabolism-related indicators in sepsis-induced ARDS patients changed significantly, suggesting the iron metabolism disorder. The expression levels of ferroptosis-related genes in lung tissues of sepsis had marked changes, and the lipid peroxidation levels increased, while Ferrostatin-1 (Fer-1) could reverse the above results, which confirmed the occurrence of ferroptosis. In terms of mechanism studies, inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3ß, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. Besides, inhibiting MUC1 reversed the alleviating effect of vitamin E on ALI caused by sepsis, increased the aggregation of inflammatory cells in lung tissues, and aggravated alveolar injury and edema. Conclusions: Our study was the first to explore the changes of iron metabolism indicators in ALI/ARDS of sepsis, clarify the important role of ferroptosis in ALI/ARDS induced by sepsis, and reveal the effects and specific mechanisms of MUC1 in regulating ferroptosis, as well as the sensitization on vitamin E.


Assuntos
Lesão Pulmonar Aguda , Ferroptose , Mucina-1 , Sepse , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Ferroptose/genética , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Ferro/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Mucina-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Síndrome do Desconforto Respiratório , Sepse/complicações , Sepse/tratamento farmacológico , Vitamina E/metabolismo
19.
Ann Transl Med ; 10(14): 781, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35965826

RESUMO

Background: Existing scoring systems have limitations in predicting the in-hospital mortality of adult sepsis patients. We aimed to develop and validate a novel risk score for predicting the in-hospital mortality of adult sepsis patients. Methods: The clinical data of 1,335 adult sepsis inpatients were retrospectively analyzed. Enrolled patients were randomly divided into a modeling group and a validation group at a 3:2 ratio. The modeling group (n=801) was used to develop the risk score by univariate and multivariate logistic regression analyses. The score's performance was validated in the validation group (n=534). We classified patients into four risk levels according to the novel risk score. Results: Age, central vein catheterization, mechanical ventilation, vasopressin, Charlson comorbidity index (CCI), respiratory rate (RR), heart rate (HR), Glasgow coma scale (GCS) score, platelet (PLT), hematocrit (HCT), aspartate aminotransferase (AST), and activated partial thrombin time (APTT) were independent risk factors for in-hospital death in adult sepsis patients. Continuous variables were converted into classified variables to develop the risk score, with a total score of 39 points. Adult sepsis patients with low, lower medium, higher medium, and high risk levels had in-hospital mortality rates of 9.8%, 24.7%, 55.8%, and 83.5%, respectively. Conclusions: Compared with the Acute Physiology and Chronic Health Evaluation II scoring system (APACHE II) and the Modified Early Warning Score (MEWS), the novel risk score showed good predictive performance for in-hospital mortality in adult sepsis patients.

20.
Dalton Trans ; 51(33): 12484-12493, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35916573

RESUMO

A series of tetranuclear coordination clusters [Ln4L2(HL)2(µ3-OH)2(NO3)2](NO3)2 [Ln = Dy (1·3CH3CN·5H2O), Gd (2·4CH3CN·5H2O), H2L = 6,6'-dimethoxy-2,2'-[2,2-dimethylpropane-1,3-diylbis-(nitrilomethylidyne)] diphenol] and dinuclear complexes [LnZnL(NO3)3(H2O)]·2CH3CN [Ln = Dy (3), Er (4), Yb (5), Lu (6)] were prepared and characterized. Static magnetic measurements revealed the presence of ferromagnetic interactions between the Dy(III) ions and weak antiferromagnetic couplings between the Gd(III) ions in 1 and 2. Dynamic magnetic studies showed that complexes 1 and 3 exhibit slow magnetic relaxation under a zero static field as expected for single molecule magnet (SMM) behavior, whereas complex 4 is a field-induced SMM. Clear hysteresis loops were observed for 1 and 3 at 2 K, verifying their SMM behavior. Luminescence investigations demonstrated that complexes 1 and 2 show ligand-based emission and can act as luminescence thermometers below 100 K, whereas complexes 3 and 5 display the characteristic emission of lanthanide ions. From the high-resolution emission spectra of 3 and 5, the energy gaps between the ground state and excited states of Dy(III) and Yb(III) ions were determined.

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