ABSTRACT
PURPOSE: Two-dimensional speckle tracking echocardiography is a novel ultrasound technique, which can detect early subclinical myocardial dysfunction with high sensitivity. The purpose of this study was to explore the value of speckle tracking echocardiography in the evaluation of subclinical myocardial injury in patients with Cushing's syndrome. METHODS: 35 patients with Cushing's syndrome and 29 healthy controls matched for age, sex, BMI, and systolic blood pressure were included in the study. All subjects were assessed using both conventional Doppler echocardiography and speckle tracking echocardiography. Among patients, they were further divided into inactive group (n = 7) and active group (n = 28) based on cortisol levels. Trend analysis was used among patients in different disease activity. Correlation analysis and linear regression analysis were used to explore influence factors related to subclinical myocardial dysfunction. RESULTS: Left ventricular ejection fraction value showed no statistical difference between patients Cushing's syndrome and control group. However, GLS and LVSD, show significant differences in Cushing's syndrome group. Also, among active Cushing's syndrome group, inactive Cushing's syndrome group and control group, GLS (-15.4 ± 3.0 vs -18.1 ± 3.1 vs-19.4 ± 2.4, P < 0001) and LVSD (48.9 ± 21.5 vs 43.5 ± 17.9 vs 28.5 ± 8.3, P < 0001) changed significantly with the disease activity status. In addition, GLS and LVSD were both linearly corrected with 24-hour urinary cortisol level. CONCLUSION: GLS and LVSD are sensitive parameters in detecting and monitoring subclinical myocardial systolic dysfunction in patients with Cushing's syndrome. Myocardial injury is linearly correlated with cortisol level, which can be partially reversed after the biochemical control of cortisol.
ABSTRACT
During pregnancy, germline development is vital for maintaining the continuation of species. Recent studies have shown increased pregnancy risks in COVID-19 patients at the perinatal stage. However, the potential consequence of infection for reproductive quality in developing fetuses remains unclear. Here, we analyze the transcriptome and DNA methylome of the fetal germline following maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We find that infection at early gestational age, a critical period of human primordial germ cell specification and epigenetic reprogramming, trivially affects fetal germ cell (FGC) development. Additionally, FGC-niche communications are not compromised by maternal infection. Strikingly, both general and SARS-CoV-2-specific immune pathways are greatly activated in gonadal niche cells to protect FGCs from maternal infection. Notably, there occurs an "in advance" development tendency in FGCs after maternal infection. Our study provides insights into the impacts of maternal SARS-CoV-2 infection on fetal germline development and serves as potential clinical guidance for future pandemics.
Subject(s)
COVID-19 , Fetus , Germ Cells , SARS-CoV-2 , Humans , Female , COVID-19/virology , COVID-19/immunology , COVID-19/pathology , Pregnancy , Germ Cells/virology , Fetus/virology , Pregnancy Complications, Infectious/virology , Pregnancy Complications, Infectious/pathology , Gonads/virology , Transcriptome/genetics , Male , DNA Methylation/genetics , Epigenesis, GeneticABSTRACT
The quantitative analysis of multicomponents by single-marker(QAMS) was established for 13 chemical components of Epimedii Folium, including neoglycolic acid, chlorogenic acid, cryo-chlorogenic acid, magnolidine, hypericin, epimedin A, epimedin B, epimedin C, icariin, baohuoside â ¡, sagittatoside A, icariin subside â , and baohuoside â , so as to investigate the feasibility and accuracy of this method in evaluating the quality of Epimedii Folium materials from different origins and different varieties. Through the scientific and accurate investigation of the experimental method, the external standard method was used to determine the content of 13 chemical components in epimedium brevieornu. At the same time, icariin was used as the internal standard, and the relative correction factors of icariin with neoglycolic acid, chlorogenic acid, cryo-chlorogenic acid, magnolidine, hypericin, epimedin A, epimedin B, epimedin C, icariin, baohuoside â ¡, sagittatoside A, icariin subside â , and baohuoside â were established, respectively. The contens of neoglycolic acid, chlorogenic acid, cryo-chlorogenic acid, magnolidine, hypericin, epimedin A, epimedin B, epimedin C, icariin, baohuoside â ¡, sagittatoside A, icariin subside â , and baohuosideâ in Epimedii Folium were calculated by QAMS. Finally, the difference between the measured value and the calculated value was compared to verify the accuracy and scientific nature of QAMS in the determination. The relative correction factor of each component had better repeatability, and there was no significant difference between the results of the external standard method and those of QAMS. With icariin as the internal standard, QAMS simultaneously determining neoglycolic acid, chlorogenic acid, cryo-chlorogenic acid, magnolidine, hypericin, epimedin A, epimedin B, epimedin C, icariin, baohuoside â ¡, sagittatoside A, icariin subside â , and baohuoside â can be used for quantitative analysis of Epimedii Folium.
Subject(s)
Anthracenes , Drugs, Chinese Herbal , Epimedium , Perylene/analogs & derivatives , Chromatography, High Pressure Liquid/methods , Chlorogenic Acid , Flavonoids/analysis , Drugs, Chinese Herbal/chemistry , Epimedium/chemistryABSTRACT
The market value of tea is largely dependent on the tea species and cultivar. Therefore, it is important to develop efficient molecular markers covering the entire tea genome that can be used for the identification of tea varieties, marker-assisted breeding, and mapping important quantitative trait loci for beneficial traits. In this study, genome-wide molecular markers based on intron length polymorphism (ILP) were developed for tea trees. A total of 479, 1393, and 1342 tea ILP markers were identified using the PCR method in silico from the 'Shuchazao' scaffold genome, the chromosome-level genome of 'Longjing 43', and the ancient tea DASZ chromosome-level genome, respectively. A total of 230 tea ILP markers were used to amplify six tea tree species. Among these, 213 pairs of primers successfully characterize products in all six species, with 112 primer pairs exhibiting polymorphism. The polymorphism rate of primer pairs increased with the improvement in reference genome assembly quality level. The cross-species transferability analysis of 35 primer pairs of tea ILP markers showed an average amplification rate of 85.17% through 11 species in 6 families, with high transferability in Camellia reticulata and tobacco. We also used 40 pairs of tea ILP primers to evaluate the genetic diversity and population structure of C. tetracocca with 176 plants from Puan County, Guizhou Province, China. These genome-wide markers will be a valuable resource for genetic diversity analysis, marker-assisted breeding, and variety identification in tea, providing important information for the tea industry.
Subject(s)
Camellia sinensis , Humans , Introns/genetics , Camellia sinensis/genetics , Genetic Markers , Genome, Plant , Plant Breeding , TeaABSTRACT
PURPOSE: Despite the involvement of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) in the proliferation and metastasis of diverse tumor types, its biological functions and related molecular mechanisms in anaplastic thyroid carcinoma (ATC) remain largely unclear. METHODS: Datasets from the Gene Expression Omnibus, the Cancer Genome Atlas and immunohistochemistry (IHC) analyses were employed to measure the expression level of PFKFB3 in ATC. A series of assays were performed to analyze the role of PFKFB3 and its inhibitor KAN0438757 in ATC cell proliferation and migration. Furthermore, Western blotting (WB), IHC and luciferase reporter assay were conducted to investigate the potential mechanisms underlying the involvement of PFKFB3 and KAN0438757 in ATC. Additionally, we established a subcutaneous xenograft tumor model in nude mice to evaluate the in vivo tumor growth. RESULTS: PFKFB3 exhibited a significant increase in its expression level in ATC tissues. The overexpression of PFKFB3 resulted in the stimulation of ATC cell proliferation and migration. Furthermore, this overexpression was associated with the elevated expression levels of p-AKT (ser473), p-GSK3α/ß (ser21/9), nuclear ß-catenin, fibronectin1 (FN1), matrix metallopeptidase 9 (MMP-9) and cyclin D1. It also promoted the nuclear translocation of ß-catenin and the transcription of downstream molecules. Conversely, contrasting results were observed with the downregulation or KAN0438757-mediated inhibition of PFKFB3 in ATC cells. The selective AKT inhibitor MK2206 was noted to reverse the increased expression of p-AKT (ser473) and p-GSK3α/ß (ser21/9) induced by PFKFB3 overexpression. The level of lactate was increased in PFKFB3-overexpressing ATC cells, while the presence of KAN0438757 inhibited lactate production. Moreover, the simultaneous use of PFKFB3 downregulation and KAN0438757 was found to suppress subcutaneous tumor growth in vivo. CONCLUSION: PFKFB3 can enhance ATC cell proliferation and migration via the WNT/ß-catenin signaling pathway and plays a crucial role in the regulation of aerobic glycolysis in ATC cells.
Subject(s)
Phosphofructokinase-2 , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Wnt Signaling Pathway , Animals , Humans , Mice , Cell Line, Tumor , Cell Movement , Cell Proliferation , Mice, Nude , Phosphofructokinase-2/metabolism , Phosphofructokinase-2/genetics , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Carcinoma, Anaplastic/metabolism , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolismABSTRACT
Recurrent miscarriages (RM) generally refer to two or more consecutive pregnancy losses. The risk of miscarriages grows with its frequency of occurrences, so as the future obstetric complications or longer-term health problems for patients. Most previous researches sought to discover the etiology of RM by making comparisons between patients with RM and fertile women. Our study collected decidua tissues from patients with RM and single miscarriage (SM) for transcriptome sequencing analysis and aimed at identifying vital factors contributing to additional miscarriages after previous miscarriage. Between the RM and SM group, a total of 122 differentially expressed genes (DEGs) were detected and pathways associated with cell adhesion and ECM remodeling were particularly enriched in the RM group, which indicated abnormally activated fibrogenesis process. Particularly, the enhancement of ITGB6, EGFLAM and COL3A1 in the RM group were validated by RT-qPCR. Our study discovered that fibrogenesis, which might be caused by intrauterine manipulation, could lead to recurrent miscarriages after a previous miscarriage. Therefore, we encourage higher attention to thorough prevention and prompt remedies towards fibrotic disorders related diseases.
Subject(s)
Abortion, Habitual , Pregnancy , Humans , Female , Abortion, Habitual/genetics , Gene Expression ProfilingABSTRACT
Selinexor is a nuclear exportin-1 (XPO1) inhibitor that has been approved for the treatment of multiple myeloma patients. However, sustained use of selinexor may result in some undesirable consequences. Furthermore, selinexor has moderate inter-patient variability. Herein, we developed an ultrahigh-performance liquid chromatography tandem mass spectrometry method for measuring selinexor levels in human plasma ranging from 1 to 1000 ng mL-1. Furthermore, the developed approach was validated in accordance with FDA criteria. The established approach demonstrated inter-day and intra-day precision, expressed as the relative standard deviation, of less than 8%, with accuracies of less than 6%, expressed as relative error. The results showed that the protein depletion was quite complete for selinexor extraction, with recoveries ranging from 85.89 to 108.38%. The validated method facilitates the quantitation of selinexor in multiple myeloma patients. The selinexor plasma concentration exhibits obvious inter-patient' variability after administration. Thus, it is necessary to make a personalized prescription through therapeutic drug monitoring. Furthermore, the change in platelet counts before and after selinexor treatment was shown to be related to the plasma concentration at 3 h after administration, which provides the basis for therapeutic drug monitoring sampling time points and a method for predicting the occurrence of thrombocytopenia. In conclusion, the developed method can be used for the quantification of the plasma concentration of selinexor, and it is of great significance to conduct therapeutic drug monitoring for patients taking selinexor in order to enhance therapeutic effects and prevent the occurrence of adverse reactions.
Subject(s)
Hydrazines , Multiple Myeloma , Triazoles , Humans , Multiple Myeloma/drug therapy , Multiple Myeloma/metabolism , Tandem Mass Spectrometry/methods , Chromatography, Liquid/methods , ChinaSubject(s)
COVID-19 , Pregnancy Complications, Infectious , Pregnancy , Female , Humans , Placentation , Placenta , SARS-CoV-2ABSTRACT
Drugs acting on dopamine D2 receptors are widely used for the treatment of several neuropsychiatric disorders, including schizophrenia and depression. Social deficits are a core symptom of these disorders. Pharmacological manipulation of dopamine D2 receptors (Drd2), a Gi-coupled subtype of dopamine receptors, in the medial prefrontal cortex (mPFC) has shown that Drd2 is implicated in social behaviors. However, the type of neurons expressing Drd2 in the mPFC and the underlying circuit mechanism regulating social behaviors remain largely unknown. Here, we show that Drd2 were mainly expressed in pyramidal neurons in the mPFC and that the activation of the Gi-pathway in Drd2+ pyramidal neurons impaired social behavior in male mice. In contrast, the knockdown of D2R in pyramidal neurons in the mPFC enhanced social approach behaviors in male mice and selectively facilitated the activation of mPFC neurons projecting to the nucleus accumbens (NAc) during social interaction. Remarkably, optogenetic activation of mPFC-to-NAc-projecting neurons mimicked the effects of conditional D2R knockdown on social behaviors. Altogether, these results demonstrate a cell type-specific role for Drd2 in the mPFC in regulating social behavior, which may be mediated by the mPFC-to-NAc pathway.
Subject(s)
Pyramidal Cells , Receptors, Dopamine D2 , Mice , Male , Animals , Receptors, Dopamine D2/metabolism , Pyramidal Cells/physiology , Neurons/metabolism , Prefrontal Cortex/metabolism , Nucleus Accumbens/physiology , Social BehaviorABSTRACT
Severe endometrial injury caused by invasive uterine operation and/or endometritis often results in intrauterine adhesions (IUAs), which are named Asherman's syndrome (AS), further leading to menstrual disorders, infertility and severe complications during pregnancy and delivery. IUAs or AS has been a challenging medical problem. Stem cells are a promising therapeutic modality for endometrial regeneration in patients with refractory AS. Here, we developed a new system of adipose-derived mesenchymal stem cells (ADMSCs) implantation on silk fibroin/polycaprolactone (SF/PCL) electrospun nanofibers (ADMSCs-SF/PCL) and used it in the damaged endometrium of a rat model. After SF/PCL enhanced the proliferation of transplanted ADMSCs, the results showed that the ADMSCs-SF/PCL system could recover morphology, promote regeneration of the glands and angiogenesis by increasing CD31 expression, and reverse endometrial fibrosis by decreasing TGF-ß/Smad expression. In addition, the ADMSCs-SF/PCL system also increased the expression of differentiation and decidualization markers, including HOXA11, HAND2 and FOXO1. Most importantly, the ADMSCs-SF/PCL system could remodel the special immune microenvironment, resulting in dominant NK infiltration and a normal Th1/Th2 bias in the endometrium. Moreover, this treatment had a lower but more persistent effect than estrogen. Thus, the ADMSCs-SF/PCL system enhanced endometrial restoration, suggesting a promising strategy for damaged endometrial regeneration and immune microenvironment remodeling.
ABSTRACT
OBJECT: Mycobacterium tuberculosis (MTB) is a bacterium that can cause zoonoses by aerosol transmission. Tuberculosis (TB) caused by MTB heavily burdens world public health security. Developing efficient, specific, convenient, and inexpensive MTB assays are essential for preventing and controlling TB. METHODS: In this study, we established a specific detection method for MTB using the Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) system, combined with recombinase mediated isothermal nucleic acid amplification (RAA) to improve the sensitivity of the detection system and achieve "two-level" amplification of the detection signal. The sensitivity and specificity of RAA combined with the CRISPR/Cas system were analyzed. Using BACTEC 960 culture as the gold standard for detecting MTB, we established the TB-CRISPR technique by testing 504 samples from patients with suspected TB. RESULTS: MTB H37Ra could be seen as low as 3.13 CFU/mL by the CRISPR-Cas12a system targeting IS6110. With BACTEC960 culture (120 positives and 384 negatives) as the gold standard, the sensitivity of the TB-CRISPR technique was 0.883 (0.809-0.932), and the specificity was 0.940 (0.910-0.961). According to the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) reached 0.944 (0.914-0.975) within 95% CI. The positive likelihood ratio (PLR) was 14.747 (9.870-22.035), and the negative likelihood ratio (NLR) was 0.124 (0.076-0.203). The positive predictive value (PPV) was 0.822 (0.742-0.881), and the negative predictive value (NPV) was 0.963 (0.937-0.979). CONCLUSION: TB-CRISPR plays an essential role in the molecular diagnosis of TB. The whole detection time is less than 1.5 h. It is easy to operate and does not need complex instruments. It is of great significance for the rapid detection of MTB and the clinical diagnosis of TB.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Humans , Mycobacterium tuberculosis/genetics , Tuberculosis, Pulmonary/diagnosis , CRISPR-Cas Systems , Tuberculosis/diagnosis , Tuberculosis/microbiology , Sensitivity and SpecificityABSTRACT
Long non-coding RNAs (lncRNAs) play crucial regulatory roles in various cellular processes, including gene expression, chromatin remodeling, and protein localization. Dysregulation of lncRNAs has been linked to several diseases, making it essential to understand their functions in disease mechanisms and therapeutic strategies. However, traditional experimental methods for studying lncRNA function are time-consuming, expensive, and offer limited insights. In recent years, computational methods have emerged as valuable tools for predicting lncRNA functions and their associations with diseases. However, many existing methods focus on constructing separate networks for lncRNA and disease similarity, resulting in information loss and insufficient processing capacity for isolated nodes. To address this, we developed 'RGLD' by combining Random Walk with restarting (RWR), Graph Neural Network (GNN), and Graph Attention Networks (GAT) to predict lncRNA-disease associations in a heterogeneous network. RGLD achieved an impressive AUC of 0.88, outperforming other methods. It can also predict novel associations between lncRNAs and diseases. RGLD identified HOTAIR, MEG3, and PVT1 as lncRNAs associated with uterine fibroids. Biological experiments directly or indirectly verified the involvement of these three lncRNAs in uterine fibroids, validating the accuracy of RGLD's predictions. Furthermore, we extensively discussed the functions of the target genes regulated by these lncRNAs in uterine fibroids, providing evidence for their role in the development and progression of the disease.
Subject(s)
Leiomyoma , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Computational Biology/methods , Neural Networks, Computer , Leiomyoma/genetics , AlgorithmsABSTRACT
BACKGROUND: In recent years, minimally invasive and non-invasive rejuvenation methods have been welcomed. PRP has been used widely for skin rejuvenation, but there are few studies on PRP for lip rejuvenation. OBJECTIVE: The objective of this study was to investigate the preliminary effects of PRP for lip rejuvenation. METHODS: Between October 2018 and April 2023, 15 participants with lip aging (1 male, 14 females; range 27-58 years) were treated with PRP. The follow-up time was 3 to 24months. After 3 to 6 times treatments, beauty seekers and experienced physicians jointly evaluated effectiveness of treatment. The assessment included improvements in the colour, wrinkles, and skin texture of the lips before and after treatment. RESULTS: According to the beauty seekers and Surgeons 'evaluation, the aging characteristics of the lips of the 15 beauty seekers have been improved to varying degrees. The most obvious improvement was that the color of the lips which became more vivid. There was no swelling, bruising, scar hyperplasia and other complications. A participant was evaluated using the VISIA skin detector. The patient's lip color and discoloration improved after treatment. Of the 15 participants treated. 3 participants experienced mild pain or discomfort during the injection process. There was no swelling, bruising, scar hyperplasia and other complications. CONCLUSION: The results of this study revealed promising evidence of PRP as an effective option on lip rejuvenation. However, large, multi-center, controlled, long term, pilot studies are required to confirm the preliminary results of our study.
Subject(s)
Cosmetic Techniques , Platelet-Rich Plasma , Skin Aging , Female , Humans , Male , Lip , Rejuvenation , Face , Cicatrix , HyperplasiaABSTRACT
As a promising cost-effective nanozyme, MoS2 nanosheets (NSs) have been considered as a good candidate for the enzyme-like catalysis. However, their catalytic activity is still restricted by the insufficient active sites and poor conductivity, and thus, the comprehensive performances are still unsatisfactory. To address these issues, herein, we design and fabricate an intelligent tubular nanostructure of hierarchical hollow nanotubes, which are assembled by NiSx/MoS2 NSs encapsulated into N-doped carbon microtubes (NiSx/MoS2@NCMTs). The N-doped carbon microtubes (NCMTs) serve as a conductive skeleton, integrating with NiSx/MoS2 NSs and ensuring their well-distribution, thereby maximally exposing more active sites. Additionally, the tube-like structure is favorable for increasing the mass transfusion to ensure their excellent catalytic performance. Profiting from their component and structural advantages, the obtained NiSx/MoS2@NCMTs exhibit a surprisingly enhanced enzyme-like activity. Based on these, a facile colorimetric sensing platform to detect H2O2 and GSH has been developed. This proposed approach can be expected to synthesize a series of tubular heterostructured MoS2-based composites, which will be widely applied in catalysis, energy storage, disease diagnosis, etc.
ABSTRACT
Quercetin-3,4'-O-diglucoside (Q3,4'G), among the major dietary flavonoids, is superior to quercetin aglycone or quercetin monoglucoside in solubility. However, its low content in nature makes it hard to be prepared in large quantities by traditional extraction methods. In the present study, the F378S mutant of UGT78D2 (78D2_F378S) derived from Arabidopsis thaliana with improved regioselectivity and the V371A mutant of UGT73G1 (73G1_V371A) derived from Allium cepa were adopted to realize a two-step continuous glycosylation of quercetin to produce Q3,4'G. The mutation S31D was introduced to the sucrose synthase from Micractinium conductrix with enhanced activity, which was responsible for regenerating UDP-glucose by coupling with 78D2_F378S and 73G1_V371A. Using the aforementioned enzymes, prepared from the three-enzyme co-expression strain, 4.4 ± 0.03 g/L (7.0 ± 0.05 mM, yield 21.2%) Q3,4'G was produced from 10 g/L quercetin after reaction for 24 h at 45 °C.
Subject(s)
Arabidopsis , Quercetin , Glycosyltransferases/genetics , Glucosides , Onions/genetics , Arabidopsis/geneticsABSTRACT
The gastrointestinal (GI) tract is more vulnerable to effects by the outside environment, and experiences oxidative stress. A wide diversity of GI disorders can be partially attributed to oxidative stress. However, the mechanism of oxidative stress-caused GI pathological changes is not clear. In the present study, human gastric epithelial cells (hGECs) were treated with hydrogen peroxide (H2O2), and oxidative stress was determined. The effect of oxidative stress on the levels of some antioxidative enzymes, proliferation, nuclear DNA damage, apoptosis, expression of ten-eleven translocation (TET), and level of DNA methylation was determined in these cells. The results showed that H2O2 treatment caused oxidative stress, increased the levels of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA), decreased the level of glutathione (GSH), inhibited proliferation, caused nuclear DNA damage and apoptosis, upregulated the expression of TET1 gene, and ultimately led to active DNA demethylation in hGECs. The present study presents a mechanism by which oxidative stress induces active DNA demethylation in hGECs. We propose that TET inhibitors can be used to restore the oxidative stress-induced DNA demethylation, and thus inhibit possible malignant transformation of GI cells.
Subject(s)
DNA Demethylation , Hydrogen Peroxide , Humans , Up-Regulation , Hydrogen Peroxide/toxicity , Hydrogen Peroxide/metabolism , Oxidative Stress , Antioxidants/pharmacology , Superoxide Dismutase/metabolism , Apoptosis/genetics , Glutathione/metabolism , Epithelial Cells , Mixed Function Oxygenases/genetics , Mixed Function Oxygenases/metabolism , Mixed Function Oxygenases/pharmacology , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolismABSTRACT
High concentrations of antioxidants can exert pro-oxidative effects, elevate the level of intracellular reactive oxygen species (ROS), and cause oxidative stress in cells. We previously found that high concentrations of curcumin, a natural polyphenol antioxidant, elevated ROS levels and upregulated the expression of histone deacetylase 1 (HDAC1) in human gastric cancer cells (hGCCs); however, its potential mechanisms and subsequent functions have not been elucidated. In the present study, we treated hGCCs with high concentrations of curcumin, detected several indicators of oxidative stress, and investigated the mechanism of curcumin-treatment-mediated HDAC1 upregulation and its effect on histone acetylation. The results showed that curcumin treatment caused oxidative stress in hGCCs and upregulated HDAC1/2 expression via the forkhead box O (FOXO) signaling pathway, ultimately leading to the deacetylation of histones in hGCCs. Moreover, HDAC1/2 mediates the deacetylation of FOXOs and promotes their transcription activities, implying a positive feedback loop between FOXOs and HDAC1/2. These findings present a mechanism by which oxidative stress induces histone deacetylation in hGCCs.
Subject(s)
Curcumin , Histones , Humans , Histones/metabolism , Reactive Oxygen Species/metabolism , Oxidative Stress , Signal Transduction , AcetylationABSTRACT
Posterior reversible encephalopathy syndrome is a clinical-neuroradiological syndrome with typical neuroimaging features of posterior cerebral white matter changes that are usually reversible. However, there are only few reports of burns with posterior reversible encephalopathy syndrome in the literature. Hence, it is a clinical entity that many burn medicine physicians may be unfamiliar with. We report a case of severe burns complicated by posterior reversible encephalopathy syndrome in a 14-month-old male patient. On the eighth day of hospitalization, the child had persistent fever, occasional convulsions, eyes staring to the right, and high-pitched cry. Magnetic resonance imaging on day 10 showed the diagnosis is posterior reversible encephalopathy syndrome. We used hormone therapy to reduce cerebral oedema, oxcarbazepine to control convulsions, and multiple other drugs and physical measures to treat fever. The symptoms, signs, and imaging abnormalities of his posterior reversible encephalopathy syndrome were rapidly reversed in a short period of time. At the 1-year follow-up, the patient had recovered completely with no residual neurological signs and symptoms. To our knowledge, the patient may be the youngest recorded patient with both burns and posterior reversible encephalopathy syndrome. Careful observation, computed tomography, and magnetic resonance imaging can achieve early detection, early diagnosis, and early treatment of posterior reversible encephalopathy syndrome, which facilitates the achievement of desired therapeutic results. Further investigation is required to determine whether burns can serve as an independent posterior reversible encephalopathy syndrome causative factor and clarify the underlying pathogenesis mechanism.
ABSTRACT
AIM: To report the safety, efficacy, and accuracy of small-incision lenticule extraction (SMILE) or femtosecond-assisted laser in situ keratomileusis (FS-LASIK) for the correction of myopia or myopic astigmatism in patients with deep corneal opacity denoted by anterior segment optical coherence tomography (AS-OCT). METHODS: Four patients with monocular corneal opacity (3 due to mechanical injury, 1 due to a firecracker wound) were recruited and treated with refractive surgery (3 for SMILE, 1 for FS-LASIK combined with limbal relaxing incision (LRI). Preoperative ocular manifestations, surgical details, postoperative visual outcomes, corneal opacity parameters, and corneal topography were analyzed. RESULTS: Preoperatively, spherical diopter ranged from -3.0 D to -4.75 D with cylinder ranging from -0.75 to -5.0 D, and corrected distance visual acuity (CDVA) ranging from 20/25 to 20/20. One eye's corneal opacity was located in the central zone and three were in the mid-peripheral optical zone. Three patients underwent uneventful SMILE in both eyes, whilst one patient underwent FS-LASIK for high astigmatism in both eyes and LRI in the right eye. CDVA of the eye with corneal opacity ranged from 20/22 to 20/20 one to six weeks postoperatively. Two patients achieved better CDVA and no patients lost Snellen lines. The postoperative diopter was within ±0.75 D for all eyes. Significant edema existed above the corneal opacity in one eye and dissipated soon. No eccentric corneal topography or morphological anomaly of the corneal cap or flap was observed. CONCLUSION: The cases demonstrate that SMILE or FS-LASIK is safe and effective to treat myopic astigmatism combined with deep corneal opacity lesions after comprehensive preoperative evaluation and appropriate candidate selection. FS-LASIK combined with LRI is also sufficient for correcting high astigmatism due to corneal scarring.
ABSTRACT
Pterygium is a common ocular disease with a high recurrence rate, characterized by hyperplasia of subconjunctival fibrovascular tissue. Autophagy, an important process to maintain cellular homeostasis, participates in the pathogenic fibrosis of different organs. However, the exact role of autophagy in pterygium pathogenesis remains unknown. Here, we found that autophagic activity was decreased in human pterygium tissues compared with adjacent normal conjunctival tissues. The in vitro model of fibrosis was successfully established using human primary conjunctival fibroblasts (ConFB) treated with transforming growth factor-ß1 (TGF-ß1), evidenced by increased fibrotic level and strong proliferative and invasive capabilities. The autophagic activity was suppressed during TGF-ß1- or ultraviolet-induced fibrosis of ConFB. Activating autophagy dramatically retarded the fibrotic progress of ConFB, while blocking autophagy exacerbated this process. Furthermore, SQSTM1, the main cargo receptor of selective autophagy, was found to significantly promote the fibrosis of ConFB through activating the PKCι-NF-κB signaling pathway. Knockdown of SQSTM1, PKCι, or p65 in ConFB delayed TGF-ß1-induced fibrosis. Overexpression of SQSTM1 drastically abrogated the inhibitory effect of rapamycin or serum starvation on TGF-ß1-induced fibrosis. Collectively, our data suggested that autophagy impairment of human ConFB facilitates fibrosis via activating the SQSTM1-PKCι-NF-κB signaling cascades. This work was contributory to elucidating the mechanism of autophagy underlying pterygium occurrence.