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1.
BMC Womens Health ; 24(1): 386, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38961373

ABSTRACT

BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.


Subject(s)
Endometriosis , Fibrinogen , Neutrophils , Humans , Female , Endometriosis/blood , Endometriosis/complications , Endometriosis/diagnosis , Adult , Retrospective Studies , Case-Control Studies , Fibrinogen/analysis , Partial Thromboplastin Time , Blood Coagulation/physiology , Severity of Illness Index , CA-125 Antigen/blood , ROC Curve , Lymphocytes , Biomarkers/blood
2.
Front Med (Lausanne) ; 11: 1362108, 2024.
Article in English | MEDLINE | ID: mdl-38966527

ABSTRACT

Background: Central retinal vein occlusion (CRVO) is a rare adverse effect related to the use of tyrosine kinase inhibitors (TKIs) in patients with metastatic malignancies, which has only been reported in several case reports. Case presentation: We reported the case series of three CRVO patients on regular regimens of TKIs as part of targeted therapies for metastatic malignancies, all of whom were otherwise healthy with no or well-controlled systemic conditions. All these patients received injections of intravitreal dexamethasone implant (IDI) and achieved a fluid-free macula at the end of the visit. In addition, we reviewed the existing literature on this subject and present here an updated analysis of the related TKIs, ocular presentation, treatment, and prognosis. Conclusion: All patients diagnosed with CRVO on TKIs received dexamethasone implant treatment and obtained a fluid-free macula. We would like to raise awareness among our colleague oncologists about the possibility of CRVO related to TKI use and the necessity for patients to be screened regularly by a retinal specialist.

3.
Cell Death Dis ; 15(6): 393, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834627

ABSTRACT

Myocardial infarction (MI) is one of the leading causes of heart failure with highly complicated pathogeneses. miR-654-3p has been recognized as a pivotal regulator of controlling cell survival. However, the function of miR-654-3p in cardiomyocytes and MI has yet to be reported. This study aimed to identify the role of miR-654-3p in the regulation of myocardial infarction. To understand the contribution of miR-654-3p on heart function, we generated cardiac-specific knockdown and overexpression mice using AAV9 technology in MI injury. Mechanically, we combined cellular and molecular techniques, pharmaceutical treatment, RNA sequencing, and functional testing to elucidate the potential pathological mechanisms. We identified that mice subjected to MI decreased the expression of miR-654-3p in the border and infarcted area. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. Furthermore, we found a deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death but not other programmed cell death. Intriguingly, miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Cardiac elevating miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Using RNA sequence and molecular biological approaches, we found overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function. Our finding identified the character of miR-654-3p in protecting against MI damage by mediating pyroptosis and mitochondrial metabolism. These findings provide a new mechanism for miR-654-3p involvement in the pathogenesis of MI and reveal novel therapeutic targets. miR-654-3p expression was decreased after MI. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. The deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death. miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Overexpression of miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function.


Subject(s)
MicroRNAs , Mitochondria , Myocardial Infarction , Myocytes, Cardiac , Pyroptosis , Animals , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardial Infarction/genetics , MicroRNAs/metabolism , MicroRNAs/genetics , Pyroptosis/genetics , Mice , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Mitochondria/metabolism , Mice, Inbred C57BL , Male , Disease Models, Animal , Humans
4.
J Cell Mol Med ; 28(8): 1-11, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38526036

ABSTRACT

Dysregulated angiogenesis leads to neovascularization, which can promote or exacerbate various diseases. Previous studies have proved that NEDD4L plays an important role in hypertension and atherosclerosis. Hence, we hypothesized that NEDD4L may be a critical regulator of endothelial cell (EC) function. This study aimed to define the role of NEDD4L in regulating EC angiogenesis and elucidate their underlying mechanisms. Loss- and gain-of-function of NEDD4L detected the angiogenesis and mobility role in human umbilical vein endothelial cells (HUVECs) using Matrigel tube formation assay, cell proliferation and migration. Pharmacological pathway inhibitors and western blot were used to determine the underlying mechanism of NEDD4L-regulated endothelial functions. Knockdown of NEDD4L suppressed tube formation, cell proliferation and cell migration in HUVECs, whereas NEDD4L overexpression promoted these functions. Moreover, NEDD4L-regulated angiogenesis and cell progression are associated with the phosphorylation of Akt, Erk1/2 and eNOS and the expression of VEGFR2 and cyclin D1 and D3. Mechanically, further evidence was confirmed by using Akt blocker MK-2206, Erk1/2 blocker U0126 and eNOS blocker L-NAME. Overexpression NEDD4L-promoted angiogenesis, cell migration and cell proliferation were restrained by these inhibitors. In addition, overexpression NEDD4L-promoted cell cycle-related proteins cyclin D1 and D3 were also suppressed by Akt blocker MK-2206, Erk1/2 blocker U0126 and eNOS blocker L-NAME. Our results demonstrated a novel finding that NEDD4L promotes angiogenesis and cell progression by regulating the Akt/Erk/eNOS pathways.


Subject(s)
Butadienes , Cyclin D1 , Nitriles , Signal Transduction , Humans , Human Umbilical Vein Endothelial Cells/metabolism , Cyclin D1/metabolism , Proto-Oncogene Proteins c-akt/metabolism , NG-Nitroarginine Methyl Ester , Angiogenesis , Neovascularization, Physiologic/genetics , Cell Proliferation , Cell Movement/genetics
5.
Eur Arch Otorhinolaryngol ; 281(7): 3615-3623, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38341822

ABSTRACT

PURPOSE: Chronic rhinosinusitis (CRS) is a common disease that affects patients' quality of life (QoL). We aim to explore which symptoms bothered the patient most. METHODS: This is a cross-sectional study of CRS patients 2 years after endoscopic sinus surgery (ESS). The main observation indicators were SNOT-22 and visual analog scale (VAS) scores. The patients were grouped according to clinical control standard of EPOS 2020. Patients' symptom scores and postoperative medication were used for analysis. RESULTS: A total of 276 patients were included, among them, uncontrolled patients accounted for 23.9%, sense of taste/smell, fatigue, lacking of a good night's sleep, reduced concentration and reduced productivity were the most serious symptoms that troubled them. VAS and SNOT-22 scores were significantly different among all groups (P = 0.000), and had clinical significance for the diagnosis of clinical uncontrolled patients (both P < 0.0001). Furthermore, the duration of corticosteroids use and nasal saline irrigation in uncontrolled patients was significantly longer than that in other patients (P < 0.05). CONCLUSION: There are significant differences in the QoL of CRS patients with different clinical control, sleep and psychological disorders are main symptoms that affect the QoL of CRS patients, and more targeted management of sleep/psychological issues may be needed especially for uncontrolled patients.


Subject(s)
Quality of Life , Rhinitis , Sinusitis , Sleep Wake Disorders , Humans , Sinusitis/psychology , Sinusitis/surgery , Sinusitis/complications , Rhinitis/psychology , Rhinitis/surgery , Rhinitis/complications , Male , Female , Cross-Sectional Studies , Chronic Disease , Middle Aged , Adult , Sleep Wake Disorders/psychology , Sleep Wake Disorders/etiology , Endoscopy , Mental Disorders/psychology , Mental Disorders/epidemiology , Aged , Rhinosinusitis
6.
Microbiol Res ; 282: 127648, 2024 May.
Article in English | MEDLINE | ID: mdl-38367479

ABSTRACT

Ligilactobacillus murinus, a member of the Ligilactobacillus genus, holds significant potential as a probiotic. While research on Ligilactobacillus murinus has been relatively limited compared to well-studied probiotic lactic acid bacteria such as Limosilactobacillus reuteri and Lactobacillus gasseri, a mounting body of evidence highlights its extensive involvement in host intestinal metabolism and immune activities. Moreover, its abundance exhibits a close correlation with intestinal health. Notably, beyond the intestinal context, Ligilactobacillus murinus is gaining recognition for its contributions to metabolism and regulation in the oral cavity, lungs, and vagina. As such, Ligilactobacillus murinus emerges as a potential probiotic candidate with a pivotal role in supporting host well-being. This review delves into studies elucidating the multifaceted roles of Ligilactobacillus murinus. It also examines its medicinal potential and associated challenges, underscoring the imperative to delve deeper into unraveling the mechanisms of its actions and exploring its health applications.


Subject(s)
Lactobacillus , Probiotics , Female , Humans , Lactobacillus/genetics , Intestines/microbiology , Vagina/microbiology
7.
Nat Med ; 30(2): 584-594, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38177850

ABSTRACT

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.


Subject(s)
Deep Learning , Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/diagnosis , Blindness
8.
Neurochem Res ; 49(3): 670-683, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38015410

ABSTRACT

White matter dysplasia (WMD) in preterm infants due to intrauterine inflammation is caused by excessive apoptosis of oligodendrocyte precursor cells (OPCs). In recent years, studies have found that excessive autophagy and apoptosis are highly interconnected and important in infection and inflammatory diseases in general. Therefore, in this study, we aimed to confirm whether regulation of autophagy by using the Akt phosphorylation agonist SC79 can inhibit abnormal apoptosis of OPCs and promote myelin maturation and white matter development in neonatal rats with WMD. We investigated the effect of inflammation on oligodendrocyte development in P0 neonatal rats by intracerebellar injection of LPS, and collected brain tissue at P2 and P5. Immunohistochemical and immunofluorescence staining were used to evaluate white matter damage, while immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling analysis (TUNEL), and western blotting were used to evaluate autophagy and apoptosis. First, we observed that white matter development was arrested and white matter fiber maturation was impaired in LPS-inflicted pups compared with those in the sham-operated group. Second, treatment with SC79 reduced the levels of LC3II, caspase 3, caspase 9, and Bax/Bcl-2 and increased the levels of p62, p-Akt, and p-mTOR in the brain tissue of neonatal rats. Finally, SC79 treatment inhibited OPC apoptosis by increasing the binding of Beclin 1 to Bcl-2, which promoted OPC differentiation and maturation. However, the opposite results were observed after rapamycin administration. Taken together, our results suggest that SC79 can inhibit the abnormal apoptosis of OPCs caused by excessive autophagy through the Akt/mTOR pathway and that SC79 is a potential therapeutic agent for WMD in preterm infants.


Subject(s)
Oligodendrocyte Precursor Cells , White Matter , Humans , Infant, Newborn , Rats , Animals , White Matter/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Oligodendrocyte Precursor Cells/metabolism , Lipopolysaccharides/pharmacology , Infant, Premature , Apoptosis , TOR Serine-Threonine Kinases/metabolism , Autophagy , Inflammation , Proto-Oncogene Proteins c-bcl-2/metabolism
10.
Neurol Sci ; 45(2): 431-453, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37843692

ABSTRACT

Freezing of gait (FoG) is one of the most distressing symptoms of Parkinson's Disease (PD), commonly occurring in patients at middle and late stages of the disease. Automatic and accurate FoG detection and prediction have emerged as a promising tool for long-term monitoring of PD and implementation of gait assistance systems. This paper reviews the recent development of FoG detection and prediction using wearable sensors, with attention on identifying knowledge gaps that need to be filled in future research. This review searched the PubMed and Web of Science databases to collect studies that detect or predict FoG with wearable sensors. After screening, 89 of 270 articles were included. The data description, extracted features, detection/prediction methods, and classification performance were extracted from the articles. As the number of papers of this area is increasing, the performance has been steadily improved. However, small datasets and inconsistent evaluation processes still hinder the application of FoG detection and prediction with wearable sensors in clinical practice.


Subject(s)
Gait Disorders, Neurologic , Parkinson Disease , Wearable Electronic Devices , Humans , Parkinson Disease/complications , Parkinson Disease/diagnosis , Gait Disorders, Neurologic/diagnosis , Gait Disorders, Neurologic/etiology , Gait/physiology
11.
Medicine (Baltimore) ; 102(43): e35546, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37904471

ABSTRACT

The effectiveness of filtered air tamponade for superior retinal breaks was well established. This study was performed to compare the treatment efficacy of pars plana vitrectomies (PPV) with filtered air and silicone oil (SO) for patients with rhegmatogenous retinal detachment (RRD) caused by superior breaks with no or mild proliferative vitreoretinopathy. Patients of RRD with superior breaks who underwent PPV with filtered air (Group A) and SO (Group S) tamponade were reviewed retrospectively. Age, gender, laterality, lens status, duration of symptoms, macular status, proliferative vitreoretinopathy grade, use of perfluorocarbon liquid, early and late postoperative complications, follow-up duration were acquired. The primary anatomic reattachment after the first surgery and the final rate of successful reattachment was compared as the main outcome. Secondary outcomes were long-term postoperative best-corrected visual acuity (BCVA), rate of deferred cataract removal, surgical complications and total surgery number. The primary anatomic success rate was 88% (14/16 eyes) in Group A and 100% (16/16 eyes) in group S, which was not significantly different (P = .484). Both groups achieved 100% final anatomic success. The rate of cataract removal was 57.1% and 100% (P = .016), and the duration from first surgery to cataract surgery was 231.38 ±â€…241.23 and 156.36 ±â€…110.09 days (P = .428) for group A and group S, respectively. The rate of postoperative epiretinal membrane was 21.4% vs 25.0% (P = 1.000). Postoperative BCVA was associated with preoperative BCVA after multiple linear analysis. The primary and final anatomic success rate for PPV with air tamponade and SO in treating RRD with superior breaks were not statistically different. The rate of deferred cataract removal was higher in patients with SO as tamponade.


Subject(s)
Cataract , Retinal Detachment , Vitreoretinopathy, Proliferative , Humans , Retinal Detachment/etiology , Vitreoretinopathy, Proliferative/complications , Vitreoretinopathy, Proliferative/surgery , Vitrectomy/adverse effects , Retrospective Studies , Visual Acuity , Treatment Outcome , Silicone Oils , Cataract/complications
12.
ACS Appl Mater Interfaces ; 15(37): 43845-43858, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37690049

ABSTRACT

Cobalt is an alternative catalyst for furfural hydrogenation but suffers from the strong binding of H and furan ring on the surface, resulting in low catalytic activity and chemoselectivity. Herein, by constructing a Pd-Co interface in cobalt oxide-supported Pd catalysts to tailor the d-band center of Co, the concerted effort of Pd and Co boosts the catalytic performance for the hydroconversion of furfural to cyclopentanone and cyclopentanol. The increased dispersion of Pd on acid etching Co3O4 promotes the reduction of Co3+ to Co0 by enhancing hydrogen spillover, favoring the creation of the Pd-Co interface. Both experimental and theoretical calculations demonstrate that the electron transfer from Pd to Co at the interface results in the downshift of the d-band center of Co atoms, accompanied by the destabilization of H and furan ring adsorption on the Co surface, respectively. The former improves the furfural hydrogenation with TOF on Co elevating from 0.20 to 0.62 s-1, and the latter facilitates the desorption of formed furfuryl alcohol from the Co surface for subsequently hydrogenative rearrangement of the furan ring to cyclopentanone on acid sites. The resultant Pd/Co3O4-6 catalyst delivers superior activity with a 99% furfural conversion and 85% overall selectivity toward cyclopentanone/cyclopentanol. We anticipate that such a concept of tailoring the d-band center of Co via interface engineering provides novel insight and feasible approach for the design of highly efficient catalysts for furfural hydroconversion and beyond.

13.
Rheumatol Ther ; 10(6): 1609-1622, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37768505

ABSTRACT

INTRODUCTION: Baricitinib, a JAK1/JAK2 inhibitor, is approved for treatment of moderate-to-severe rheumatoid arthritis (RA) in China. This single-arm, prospective, multi-center, post-marketing safety study (PMSS) evaluated the safety and effectiveness of baricitinib in Chinese patients. METHODS: This study included adult patients with moderate-to-severe active RA who received baricitinib over periods of approximately 12 and 24 weeks. The primary endpoint was safety, defined as week 12 adverse event (AE)/serious AE incidence. Secondary endpoints were week 24 safety and effectiveness (disease activity score with 28 joints/C-reactive protein [DAS28-CRP] and simplified/Clinical Disease Activity Index [SDAI/CDAI]). RESULTS: Safety analyses included 667 patients (female, 82.3%; mean age, 53.3 years; mean RA duration, 86.9 months); 106/667 (15.9%) were 65-74 years old and 19/667 (2.8%) were ≥ 75 years old; 87.0% received baricitinib 2 mg QD. Total exposure was 262.1 patient-years (PY). At week 12, AEs had occurred in 214 (32.1%; exposure-adjusted incidence rate [EAIR], 172.5 per 100 PY) patients (serious AEs: 22 [3.3%; EAIR, 15.0]). At week 24, AEs had occurred in 250 (37.5%; EAIR, 125.9) patients (serious AEs: 28 [4.2%; EAIR, 10.9]). Two patients (0.3%) died (of pneumonia and unknown cause); EAIR for death, 0.77. Serious infection occurred in 1.2% of patients (EAIR, 3.1). Hepatotoxicity occurred in 3.4% of patients (EAIR, 9.0). No patients met potential Hy's law laboratory criteria (alanine/aspartate aminotransferases ≥ 3 × upper limit of normal (ULN) and total bilirubin ≥ 2 × ULN). Malignancy occurred in one patient. No patients experienced venous thromboembolism (VTE) or major adverse cardiovascular events (MACE). At week 24, 52.4%, 27.5%, and 27.6% of patients achieved remission per DAS28-CRP, SDAI, and CDAI, respectively. CONCLUSIONS: This PMSS investigated the safety and effectiveness of baricitinib in clinical practice in China. No VTE/MACE or new safety signals were reported and there was promising effectiveness, supporting the use of baricitinib in Chinese patients with moderate-to-severe active RA. TRIAL REGISTRATION: EU PAS Register: EUPAS34213.

14.
Inflammation ; 46(6): 2386-2401, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37556072

ABSTRACT

Nuclear factor e2-related factor 2 (Nrf2) plays a key role in cellular resistance to oxidative stress injury. Oxidative stress injury, caused by Nrf2 imbalance, results in increased pyroptosis, DNA damage, and inflammatory activation, which may lead to the arrest of alveolar development and bronchopulmonary dysplasia (BPD) in premature infants under hyperoxic conditions. We established a BPD mouse model to investigate the effects of tert-butylhydroquinone (TBHQ), an Nrf2 activator, on oxidative stress injury, pyroptosis, NLRP3 inflammasome activation, and alveolar development. TBHQ reduced abnormal cell death in the lung tissue of BPD mice and restored the number and normal structure of the alveoli. TBHQ administration activated the Nrf2/heme oxygenase-1 (HO-1) signaling pathway, resulting in the decrease in the following: reactive oxygen species (ROS), activation of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, and IL-18 and IL-1ß expression and activation, as well as inhibition of pyroptosis. In contrast, after Nrf2 gene knockout in BPD mice, there was more severe oxidative stress injury and cell death in the lungs, there were TUNEL + and NLRP3 + co-positive cells in the alveoli, the pyroptosis was significantly increased, and the development of alveoli was significantly blocked. We demonstrated that TBHQ may promote alveolar development by enhancing Nrf2-induced antioxidation in the lung tissue of BPD mice and that the decrease in the NLRP3 inflammasome and pyroptosis caused by Nrf2 activation may be the underlying mechanism. These results suggest that TBHQ is a promising treatment for lung injury in premature infants with hyperoxia.


Subject(s)
Bronchopulmonary Dysplasia , Hyperoxia , Lung Injury , Humans , Mice , Animals , Infant, Newborn , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NF-E2-Related Factor 2/metabolism , Bronchopulmonary Dysplasia/drug therapy , Lung Injury/drug therapy , Pyroptosis , Hyperoxia/complications , Disease Models, Animal
15.
Stem Cell Rev Rep ; 19(7): 2481-2496, 2023 10.
Article in English | MEDLINE | ID: mdl-37535186

ABSTRACT

BACKGROUND: Protection of cardiac function following myocardial infarction was largely enhanced by bradykinin-pretreated cardiac-specific c-kit+ (BK-c-kit+) cells, even without significant engraftment, indicating that paracrine actions of BK-c-kit+ cells play a pivotal role in angiogenesis. Nevertheless, the active components of the paracrine actions of BK-c-kit+ cells and the underlying mechanisms remain unknown. This study aimed to define the active components of exosomes from BK-c-kit+ cells and elucidate their underlying protective mechanisms. METHODS: Matrigel tube formation assay, cell cycle, and mobility in human umbilical vein endothelial cells (HUVECs) and hindlimb ischemia (HLI) in mice were applied to determine the angiogenic effect of condition medium (CM) and exosomes. Proteome profiler, microRNA sponge, Due-luciferase assay, microRNA-sequencing, qRT-PCR, and Western blot were used to determine the underlying mechanism of the angiogenic effect of exosomes from BK-c-kit+. RESULTS: As a result, BK-c-kit+ CM and exosomes promoted tube formation in HUVECs and the repair of HLI in mice. Angiogenesis-related proteomic profiling and microRNA sequencing revealed highly enriched miR-3059-5p as a key angiogenic component of BK-c-kit+ exosomes. Meanwhile, loss- and gain-of-function experiments revealed that the promotion of angiogenesis by miR-3059-5p was mainly through suppression of TNFSF15-inhibited effects on vascular tube formation, cell proliferation and cell migration. Moreover, enhanced angiogenesis of miR-3059-5p-inhibited TNFSF15 has been associated with Akt/Erk1/2/Smad2/3-modulated signaling pathway. CONCLUSION: Our results demonstrated a novel finding that BK-c-kit+ cells enrich exosomal miR-3059-5p to suppress TNFSF15 and promote angiogenesis against hindlimb ischemia in mice.


Subject(s)
Bradykinin , MicroRNAs , Humans , Mice , Animals , Bradykinin/metabolism , Proteomics , Neovascularization, Physiologic/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Ischemia/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Hindlimb/metabolism , Tumor Necrosis Factor Ligand Superfamily Member 15/metabolism
16.
Nat Plants ; 9(3): 442-459, 2023 03.
Article in English | MEDLINE | ID: mdl-36879016

ABSTRACT

Although a conserved SAGA complex containing the histone acetyltransferase GCN5 is known to mediate histone acetylation and transcriptional activation in eukaryotes, how to maintain different levels of histone acetylation and transcription at the whole-genome level remains to be determined. Here we identify and characterize a plant-specific GCN5-containing complex, which we term PAGA, in Arabidopsis thaliana and Oryza sativa. In Arabidopsis, the PAGA complex consists of two conserved subunits (GCN5 and ADA2A) and four plant-specific subunits (SPC, ING1, SDRL and EAF6). We find that PAGA and SAGA can independently mediate moderate and high levels of histone acetylation, respectively, thereby promoting transcriptional activation. Moreover, PAGA and SAGA can also repress gene transcription via the antagonistic effect between PAGA and SAGA. Unlike SAGA, which regulates multiple biological processes, PAGA is specifically involved in plant height and branch growth by regulating the transcription of hormone biosynthesis and response related genes. These results reveal how PAGA and SAGA cooperate to regulate histone acetylation, transcription and development. Given that the PAGA mutants show semi-dwarf and increased branching phenotypes without reduction in seed yield, the PAGA mutations could potentially be used for crop improvement.


Subject(s)
Histone Acetyltransferases , Histones , Histones/metabolism , Histone Acetyltransferases/genetics , Histone Acetyltransferases/metabolism , Cell Nucleus/metabolism , Plants/genetics , Transcription, Genetic , Plant Development , Acetylation
17.
Allergol Immunopathol (Madr) ; 51(2): 17-26, 2023.
Article in English | MEDLINE | ID: mdl-36916084

ABSTRACT

BACKGROUND: Sepsis is a life-threatening disease with dominant mortality. Its early diagnosis and treatment can improve prognosis and reduce mortality. Long noncoding RNAs (lncRNAs) ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) is dysregulated and is involved in the progression of various diseases. Nevertheless, the role of ATP2B1-AS1 in sepsis remains unclear. METHODS: A human monocytic cell line, THP-1 cells, was stimulated to induce a model of sepsis in vitro. The levels of ATP2B1-AS1, miR-23a-3p, and TLR4 were assessed by real-time quantitative polymerase chain reaction. The role of ATP2B1-AS1 in cell apoptosis and inflammation was explored by flow cytometry, Western blot analysis and enzyme-linked immunosorbent serologic assay. The binding sites between ATP2B1-AS1 and miR-23a-3p, and between miR-23a-3p and TLR4 were predicted by BiBiServ and the Encyclopedia of RNA Interactomes (ENCORI) online sites, respectively, and confirmed by the luciferase assay. RESULTS: The level of ATP2B1-AS1 was increased in lipopolysaccharide (LPS)-treated THP-1 cells. LPS increased apoptosis ratio, relative protein expressions of pro-apoptotic factors, and relative messenger RNA (mRNA) level and concentrations of pro-inflammatory cytokines, but decreased the relative expression of anti-apoptosis protein and relative mRNA level and concentrations of anti-inflammatory factor. All these alterations were reversed with transfection of shATP2B1-AS1 into THP-1 cells. Moreover, ATP2B1-AS1 directly bound miR-23a-3p and negatively modulated the level of miR-23a-3p. Meanwhile, TLR4 was directly targeted by miR-23a-3p, and negatively and positively modulated by miR-23a-3p and ATP2B1-AS1, respectively. CONCLUSION: ATP2B1-AS1 aggravated apoptosis and inflammation by modulating miR-23a-3p/TLR4 axis in LPS-treated THP-1 cells.


Subject(s)
MicroRNAs , Sepsis , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Lipopolysaccharides , Inflammation/metabolism , Cell Proliferation/genetics , Plasma Membrane Calcium-Transporting ATPases/metabolism
18.
Ann Transl Med ; 11(4): 179, 2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36923079

ABSTRACT

Background: Laryngeal carcinoma is one of the most common types of head and neck tumors. The mortality rate in patients with laryngeal cancer has not declined in recent years. Previous studies have shown that laryngeal cancer mortality is related to the extent of laryngeal cancer, the proportion of lymph node metastases, treatment modalities, and postoperative lifestyle habits. Thus, early identifying patients at high risk of laryngeal cancer-specific death is of great clinical importance. However, in the presence of competing risk, the existing survival models based on Cox proportional hazards model may be biased in estimating tumor-specific mortality. In this study, we developed and validated a nomogram based on competitive risk analysis for patients with laryngeal cancer. Methods: We used SEER*Stat (Version 4.6.1) software to identify patients in the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with laryngeal cancer between 2000 and 2019 as study subjects. The collected data included demographic data, the primary site of laryngeal cancer, the histological type of tumor, tumor size, and other variables. After excluding cases with missing information, the entire cohort was randomly split into a training cohort and a validation cohort at a 7:3 ratio. The training cohort was used in building the model while the validation cohort was used to validate the model. Univariate and multivariate Fine&Gray regression analyses were used to screen statistically significant variables, and the model performance was measured by establishing a consistency index, receiver operating characteristic curve (ROC), and calibration curves. Results: After excluding cases with missing information, 3,805 patients (2,264 in the training cohort and 1,141 in the validation cohort) were included in the study and followed for a median of 16 months. A total of 411 died of laryngeal cancer, and 2,104 patients died from other causes. Among 3,805 patients, the vast majority was male (80.9%), and Caucasian (77.2%), and aged 60-80 years old (58.4%). Conclusions: Advanced age and keratinized SCC are risk factors for laryngeal cancer-specific death. These high-risk patients should be given more attention and closer monitoring in clinical practice.

19.
Allergol. immunopatol ; 51(2): 17-26, 01 mar. 2023. graf
Article in English | IBECS | ID: ibc-216795

ABSTRACT

Background: Sepsis is a life-threatening disease with dominant mortality. Its early diagnosis and treatment can improve prognosis and reduce mortality. Long noncoding RNAs (lncRNAs) ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) is dysregulated and is involved in the progression of various diseases. Nevertheless, the role of ATP2B1-AS1 in sepsis remains unclear. Methods: A human monocytic cell line, THP-1 cells, was stimulated to induce a model of sepsis in vitro. The levels of ATP2B1-AS1, miR-23a-3p, and TLR4 were assessed by real-time quantitative polymerase chain reaction. The role of ATP2B1-AS1 in cell apoptosis and inflammation was explored by flow cytometry, Western blot analysis and enzyme-linked immunosorbent serologic assay. The binding sites between ATP2B1-AS1 and miR-23a-3p, and between miR-23a-3p and TLR4 were predicted by BiBiServ and the Encyclopedia of RNA Interactomes (ENCORI) online sites, respectively, and confirmed by the luciferase assay. Results: The level of ATP2B1-AS1 was increased in lipopolysaccharide (LPS)-treated THP-1 cells. LPS increased apoptosis ratio, relative protein expressions of pro-apoptotic factors, and relative messenger RNA (mRNA) level and concentrations of pro-inflammatory cytokines, but decreased the relative expression of anti-apoptosis protein and relative mRNA level and concentrations of anti-inflammatory factor. All these alterations were reversed with transfection of shATP2B1-AS1 into THP-1 cells. Moreover, ATP2B1-AS1 directly bound miR-23a-3p and negatively modulated the level of miR-23a-3p. Meanwhile, TLR4 was directly targeted by miR-23a-3p, and negatively and positively modulated by miR-23a-3p and ATP2B1-AS1, respectively. Conclusion: ATP2B1-AS1 aggravated apoptosis and inflammation by modulating miR-23a-3p/TLR4 axis in LPS-treated THP-1 cells (AU)


Subject(s)
Humans , Apoptosis , Sepsis/pathology , Inflammation/pathology , Toll-Like Receptor 4/metabolism , Cells, Cultured , Transfection , Flow Cytometry , Blotting, Western , Enzyme-Linked Immunosorbent Assay
20.
Comput Biol Med ; 155: 106661, 2023 03.
Article in English | MEDLINE | ID: mdl-36827789

ABSTRACT

PROPOSE: Multimodal registration of 2D Ultrasound (US) and 3D Magnetic Resonance (MR) for fusion navigation can improve the intraoperative detection accuracy of lesion. However, multimodal registration remains a challenge because of the poor US image quality. In the study, a weighted self-similarity structure vector (WSSV) is proposed to registrate multimodal images. METHOD: The self-similarity structure vector utilizes the normalized distance of symmetrically located patches in the neighborhood to describe the local structure information. The texture weights are extracted using the local standard deviation to reduce the speckle interference in the US images. The multimodal similarity metric is constructed by combining a self-similarity structure vector with a texture weight map. RESULTS: Experiments were performed on US and MR images of the liver from 88 groups of data including 8 patients and 80 simulated samples. The average target registration error was reduced from 14.91 ± 3.86 mm to 4.95 ± 2.23 mm using the WSSV-based method. CONCLUSIONS: The experimental results show that the WSSV-based registration method could robustly align the US and MR images of the liver. With further acceleration, the registration framework can be potentially applied in time-sensitive clinical settings, such as US-MR image registration in image-guided surgery.


Subject(s)
Algorithms , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Ultrasonography/methods , Liver/diagnostic imaging , Imaging, Three-Dimensional/methods
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