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Cerebral ischemic preconditioning (CIP) has been shown to improve brain ischemic tolerance against subsequent lethal ischemia. Reactive astrocytes play important roles in cerebral ischemia-reperfusion. Recent studies have shown that reactive astrocytes can be polarized into neurotoxic A1 phenotype (C3d) and neuroprotective A2 phenotype (S100A10). However, their role in CIP remains unclear. Here, we focused on the role of N-myc downstream-regulated gene 2 (NDRG2) in regulating the transformation of A1/A2 astrocytes and promoting to brain ischemic tolerance induced by CIP. A Sprague Dawley rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was used. Rats were divided into the following six groups: (1) sham group; (2) CIP group: left middle cerebral artery was blocked for 10 min; (3) MCAO/R group: left middle cerebral artery was blocked for 90 min; (4) CIP + MCAO/R group: CIP was performed 72 h before MCAO/R; (5) AAV-NDRG2 + CIP + MCAO/R group: adeno-associated virus (AAV) carrying NDRG2 was administered 14 days before CIP + MCAO/R; (6) AAV-Ctrl + CIP + MCAO/R group: empty control group. The rats were subjected to neurological evaluation 24 h after the above treatments, and then were sacrificed for 2, 3, 5-triphenyltetraolium chloride staining, thionin staining, immunofluorescence and western blot analysis. In CIP + MCAO/R group, the neurological deficit scores decreased, infarct volume reduced, and neuronal density increased compared with MCAO/R group. Notably, CIP significantly increased S100A10 expression and the number of S100A10+/GFAP+ cells, and also increased NDRG2 expression. MCAO/R significantly decreased S100A10 expression and the number of S100A10+/GFAP+ cells yet increased C3d expression and the number of C3d+/GFAP+ cells and NDRG2 expression, and these trends were reversed by CIP + MCAO/R. Furthermore, over-expression of NDRG2 before CIP + MCAO/R, the C3d expression and the number of C3d+/GFAP+ cells increased, while S100A10 expression and the number of S100A10+/GFAP+ cells decreased. Meanwhile, over-expression of NDRG2 blocked the CIP-induced brain ischemic tolerance. Taken together, these results suggest that CIP exerts neuroprotective effects against ischemic injury by suppressing A1 astrocyte polarization and promoting A2 astrocyte polarization via inhibiting NDRG2 expression.
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Astrocitos , Isquemia Encefálica , Infarto de la Arteria Cerebral Media , Precondicionamiento Isquémico , Ratas Sprague-Dawley , Animales , Precondicionamiento Isquémico/métodos , Masculino , Astrocitos/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Isquemia Encefálica/metabolismo , Ratas , Proteínas del Tejido NerviosoRESUMEN
Neuroinflammation is a significant pathological event involving the neurodegenerative process associated with many neurological disorders. Diagnosis and treatment of neuroinflammation in its early stage are essential for the prevention and management of neurological diseases. Herein, we designed macrophage membrane-coated photoacoustic (PA) probes (MSINPs), with targeting specificities based on naturally existing target-ligand interactions for the early diagnosis of neuroinflammation. The second near-infrared dye, IR1061, was doped into silica as the core and was encapsulated with a macrophage membrane. In vitro as well as in vivo, the MSINPs could target inflammatory cells via the inflammation chemotactic effect. PA imaging was used to trace the MSINPs in a neuroinflammation mouse model and showed a great targeted effect of MSINPs in the prefrontal cortex. Therefore, the biomimetic nanoprobe prepared in this study offers a new strategy for PA molecular imaging of neuroinflammation, which can enhance our understanding of the evolution of neuroinflammation in specific brain regions.
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Nanopartículas , Técnicas Fotoacústicas , Animales , Ratones , Enfermedades Neuroinflamatorias , Técnicas Fotoacústicas/métodos , Biomimética , Imagen ÓpticaRESUMEN
OBJECTIVES: To locate the most valuable sites for shear wave elastography (SWE) evaluation and to develop a clinically applicable scoring system based on SWE for systemic sclerosis (SSc) and to verify the accuracy for detection and subdivision and the correlation by modified Rodnan total skin score (mRTSS). METHODS: SSc patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) and symptomatic other rheumatic diseases (ORD) patients were included in this cross-sectional study. We assessed the skin stiffness at forehead, chest, abdomen, and bilateral fingers, hands, forearm, arms, thighs, legs, and feet, by palpation and SWE. Logistic regression was used to screen the most valuable sites for detection of SSc and subdivision of lcSSc and dcSSc, on which a scoring system was developed and verified. RESULTS: A total of 49 lcSSc, 51 dcSSc, and 36 ORD patients were included. The SWE-derived scoring system, including finger, hand, foot, arm, chest, and abdomen, reached a sensitivity and specificity of 80.0% and 94.4%, respectively, for diagnosing SSc at the cut-off value >24. The scoring system, including arm, chest, and abdomen, reached a sensitivity of 72.5% and specificity of 98.0% for subdividing dcSSc at the cut-off value >11. The kappa coefficient between the SWE-derived diagnosis and clinical diagnosis was 0.636 (P<0.001). The SWE-derived total scores of six sites had a strong correlation with mRTSS (r=0.757, p<0.001). CONCLUSIONS: The SWE-derived scoring system can be valuable in detection and evaluation of SSc in clinical application.
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Diagnóstico por Imagen de Elasticidad , Índice de Severidad de la Enfermedad , Humanos , Femenino , Persona de Mediana Edad , Masculino , Diagnóstico por Imagen de Elasticidad/métodos , Estudios Transversales , Adulto , Reproducibilidad de los Resultados , Piel/diagnóstico por imagen , Piel/patología , Esclerodermia Difusa/diagnóstico por imagen , Anciano , Valor Predictivo de las Pruebas , Esclerodermia Limitada/diagnóstico por imagen , Esclerodermia Sistémica/diagnóstico por imagenRESUMEN
This study focuses on the diffusion patterns of principal ore-forming elements (Pb and Zn) and associated elements (Cd, Cu, Cr, and As) in lead-zinc ore. Sampling points in upwind and downwind directions of lead-zinc ore areas at various densities (1 N/km2 - 4 N/km2) were categorized. This study analyzed the statistical relationship between the content of PTEs in the soil around lead-zinc ore and the source strength and dominant wind direction, constructed one-dimensional and two-dimensional diffusion model, and simulated the EER scope caused by PTEs. The findings indicate that: (1) concerning source strength, the content of PTEs in soils of high-density ore aggregation areas is significantly higher than in low-density ore aggregation areas. However, the impact of source strength decreases with decreasing ore grade, with a difference in Pb content of 1.71 times among principal ore-forming elements and almost consistent Cd content among associated elements. (2) Regarding the transport pathways, for most PTEs, the inverse proportion coefficients downwind are higher than upwind, approximately 1.18-3.63 times, indicating greater migration distances of PTEs downwind due to atmospheric dispersion. (3) By establishing a two-dimensional risk diffusion model, the study simulates the maximum radius of risk diffusion (r = 5.7 km), the 50% probability radius (r = 3.1 km), and the minimum radius (r = 0.8 km) based on the maximum, median, and minimum values statistically obtained from the EER. This study provides a scientific basis for implementing preventive measures for PTEs accumulation in soil within different pollution ranges. Different risk prevention and control measures should be adopted for PTEs accumulation in soil within the three ranges after cutting off pollution sources. Subsequent research should further investigate the impact and contribution of atmospheric transmission and surface runoff on the diffusion of PTEs in areas with high risk near lead-zinc ore.
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Monitoreo del Ambiente , Minería , Contaminantes del Suelo , Contaminantes del Suelo/análisis , Difusión , Suelo/química , Plomo/análisis , Modelos Teóricos , Viento , Zinc/análisisRESUMEN
BACKGROUND: To investigate the correlation between subclavian steal syndrome and posterior circulation infarction using magnetic resonance imaging. METHODS: A total of 294 patients diagnosed with subclavian steal syndrome using carotid Doppler ultrasonography were retrospectively included. According to the magnetic resonance imaging results, they were divided into posterior circulation infarction group and nonposterior circulation infarction group. Clinical indicators and carotid Doppler ultrasound parameters of patients were collected, and they were screened to establish a multiple logistic regression model. Receiver operating characteristic curve analysis of the established multiple logistic regression model was performed, and the area under the curve was calculated to evaluate the predictive efficiency of the model. RESULTS: After statistical analysis of all parameters of the 2 groups of patients, a total of 10 parameters were included in multiple logistic regression to establish a model. The results showed a correlation between posterior circulation infarction and subclavian artery occlusion, grade III subclavian steal syndrome, gender, vulnerable plaques, National Institutes of Health Stroke Scale score, and age. After the receiver operating characteristic curve analysis of the model, the area under the curve for the multiple logistic regression model was 0.773. CONCLUSIONS: The multiparameter composite model based on clinical baseline data and carotid Doppler ultrasonography parameters can effectively predict posterior circulation infarction and offer novel insight for clinical diagnosis.
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Long noncoding RNAs (lncRNAs) are important regulators of bone metabolism. In this study, lncRNA microarray analysis was used to identify differentially expressed lncRNAs in differentiated osteoclasts. lncRNA-Gm5532 is highly expressed during osteoclast differentiation. lncRNA-Gm5532 knockdown impairs osteoclast formation and bone resorption. Mechanistic experiments show that lncRNA-Gm5532 functions as a competing endogenous RNA (ceRNA) and acts as a sponge for miR-125a-3p, which promotes TNF receptor-associated factor 6 (TRAF6) expression. miR-125a-3p mimics suppress osteoclast differentiation and TAK1/NF-κB/MAPK signaling. The miR-125a-3p inhibitor reverses the negative effects of siGm5532 on osteoclast differentiation. In summary, our study reveals that lncRNA-Gm5532 functions as an activator in osteoclast differentiation by targeting the miR-125a-3p/TRAF6 axis, making it a novel biomarker and potential therapeutic target for osteoporosis.
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Resorción Ósea , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/metabolismo , Osteoclastos/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Resorción Ósea/genética , Resorción Ósea/metabolismoRESUMEN
OBJECTIVES: Psoriatic arthritis (PsA) is the most prevalent coexisting condition associated with psoriasis. Early-stage PsA patients always present unspecific and subtle clinical manifestations causing delayed diagnosis and leading to unfavorable health outcomes. The application of ultrasound enables precise identification of inflammatory changes in musculoskeletal structures. Hence, we constructed ultrasound models to aid early diagnosis of PsA. METHODS: This is a cross-sectional study carried out in the Department of Dermatology at West China Hospital (October 2018-April 2021). All participants underwent thorough ultrasound examinations. Participants were classified into the under 45 group (18 ≤ age ≤ 45) and over 45 group (age > 45) and then randomly grouped into derivation and test cohort (7:3). Univariable logistic regression, least absolute shrinkage and selection operator, and multivariable logistic regression visualized by nomogram were conducted in order. Receiver operating characteristic (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were performed for model verification. RESULTS: A total of 1256 participants were included, with 767 participants in the under 45 group and 489 in the over 45 group. Eleven and sixteen independent ultrasonic variables were finally selected to construct the under 45 and over 45 model with the area under the ROC of 0.83 (95%CI: 0.78-0.87) and 0.83 (95%CI: 0.78-0.88) in derivation cohort, respectively. The DCA and CICA analyses showed good clinical utility of the two models. CONCLUSION: The implementation of the ultrasound models could streamline the diagnostic process for PsA in psoriasis patients, leading to expedited evaluations while maintaining diagnostic accuracy.
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Sepsis has a systemic inflammatory response syndrome caused by infection. While neutrophils play contradictory roles in different stages of sepsis. Neutrophils have been proven to play an antibacterial role by producing neutrophil extracellular traps (NETs). Although the NET is beneficial to bacteria resistance, abnormal NET increases tissue damage. The complement C5a receptor 1 (C5ar1) is a gene related to strong inflammatory reactions and is found to be associated with inflammatory factors. This study found that there were 45 down-regulated genes and 704 up-regulated genes in sepsis rats by transcriptome sequencing. And those genes were significantly related to inflammation and immunity by GO and KEGG enrichment analysis involving the chemokine signaling pathway, the Toll-like receptor (TLR) signaling pathway, and the Fc gamma R-mediated phagocytosis. Additionally, the C5ar1 gene was significantly upregulated with interesting potential in sepsis and used for further study. This study used cecum ligation and puncture (CLP) rats that were respectively injected intravenously with PBS or the lentivirus vector to explore the effect of C5ar1 on CLP rats. It demonstrated that silenced- C5ar1 inhibited the ALT, AST, BUN, and CREA levels, improved the lung and spleen injury, and reduced the TNF-α, IL-6, IL-1ß, IL-10, cf-DNA, and cfDNA/MPO levels. Additionally, silenced C5ar1 inhibited the TLR2, TLR4, and peptidylarginine deiminase 4 expression levels, which suggested the improvement of silenced C5ar1 on sepsis via inhibiting NETs and the TLR signaling pathway. This study provides a basis and new direction for the study of treatment on sepsis.
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Trampas Extracelulares , Sepsis , Ratas , Animales , Neutrófilos/metabolismo , Inflamación/metabolismo , Pulmón , Sepsis/genética , Sepsis/complicacionesRESUMEN
BACKGROUND: Hemophilia B is an X-linked bleeding disorder caused by a mutation in the gene responsible for encoding coagulation factor IX (FIX). Gene therapy offers promising potential for curing this disease. However, the current method of relatively high dosage of virus injection carries inherent risks. The purpose of this study was to introduce a novel scAAV-DJ/8-LP1-hFIXco vector transduced human umbilical cord blood derived mesenchymal stem cells (HUCMSCs) as an alternative cell-based gene therapy to conventional gene therapy for Hemophilia B. METHODS: The LP1-hFIXco gene structure was designed by us through searching the literature from NCBI and the scAAV-DJ/8-LP1-hFIXco vector was constructed by a commercial company. The HUCMSCs were cultivated in routine approach and transduced with scAAV-DJ/8-LP1-hFIXco vector. The human FIX activation system was employed for detection of hFIXco activity. The RNA and protein expression levels of the hFIXco were evaluated using PCR and western blot techniques. In animal studies, both NSG and F9-KO mice were used for the experiment, in which clotting time was utilized as a parameter for bleeding assessment. The immunohistochemical analysis was used to assess the distribution of HUCMSCs in mouse tissue sections. The safety for tumorigenicity of this cell-based gene therapy was evaluated by pathological observation after hematoxylin-eosin staining. RESULTS: The transduction of HUCMSCs with the scAAV-DJ/8-LP1-hFIXco vector results in consistent and sustainable secretion of human FIXco during 5 months period both in vitro and in mouse model. The secretion level (hFIXco activity: 97.1 ± 2.3% at day 7 to 48.8 ± 4.5% at 5 months) was comparable to that observed following intravenous injection with a high dose of the viral vector (hFIXco activity: 95.2 ± 2.2% to 40.8 ± 4.3%). After a 5-month observation period, no clonal expansions of the transduced cells in tissues were observed in any of the mice studied. CONCLUSIONS: We have discovered a novel and safer HUCMSCs mediated approach potentially effective for gene therapy in hemophilia B.
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Factor IX , Terapia Genética , Vectores Genéticos , Hemofilia B , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Terapia Genética/métodos , Animales , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Hemofilia B/terapia , Hemofilia B/genética , Ratones , Factor IX/genética , Factor IX/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Transducción Genética , Cordón Umbilical/citología , Ratones Noqueados , Sangre Fetal/citología , Sangre Fetal/metabolismoRESUMEN
Advances in computer image recognition have significantly impacted many industries, including healthcare, security and autonomous systems. This paper aims to explore the potential of improving image algorithms to enhance computer image recognition. Specifically, we will focus on regression methods as a means to improve the accuracy and efficiency of identifying images. In this study, we will analyze various regression techniques and their applications in computer image recognition, as well as the resulting performance improvements through detailed examples and data analysis. This paper deals with the problems related to visual image processing in outdoor unstructured environment. Finally, the heterogeneous patterns are converted into the same pattern, and the heterogeneous patterns are extracted from the fusion features of data modes. The simulation results show that the perception ability and recognition ability of outdoor image recognition in complex environment are improved.
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BACKGROUND: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy accounts for the majority of membranous nephropathy; however, few studies have determined the prognostic impact and clinical application of renal pathologic change on this disease. METHODS: A retrospective cohort study of 262 patients with PLA2R-associated membranous nephropathy was conducted. The total renal chronicity score calculated according to the degree of glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis was applied to evaluate renal chronicity. Baseline bias was adjusted by inverse probability weight when assessing the prognostic impact of chronicity, and multiple parameters were used to evaluate the application value of renal chronicity. RESULTS: During a median follow-up of 24.5 months, renal outcome (kidney function deterioration and/or end-stage kidney disease) was observed in 22 (8.40%) patients. Not only did a higher total renal chronicity score independently predict renal outcome [odds ratio (OR): 1.562, 95% confidence interval (CI) 1.073-2.273, P = 0.020], but non-minimal chronicity was also an independent risk factor for renal outcome (OR: 3.170, 95% CI 1.040-9.659, P = 0.042). Moreover, the membranous nephropathy risk classification in the Kidney Disease: Improving Global Outcomes (KDIGO) guideline integrated with non-minimal chronicity showed improvements in categorical net reclassification (0.174, 95% CI 0.012-0.335, P = 0.035), continuous net reclassification (0.462, 95% CI 0.087-0.838, P = 0.016), and integrated discrimination (0.019, 95% CI 0.003-0.035, P = 0.020) compared to the original classification. CONCLUSIONS: Renal chronicity is closely associated with renal outcomes in PLA2R-associated membranous nephropathy, and combining the KDIGO risk classification with chronicity scores may provide a more accurate prognostic prediction.
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Glomerulonefritis Membranosa , Receptores de Fosfolipasa A2 , Humanos , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Pronóstico , Riñón/fisiopatología , Riñón/patología , Factores de Riesgo , Fallo Renal Crónico/etiología , Valor Predictivo de las Pruebas , Progresión de la Enfermedad , Atrofia , Fibrosis , Biopsia , Índice de Severidad de la EnfermedadRESUMEN
Autophagy activation can alleviate sepsis-induced organ injuries. Rapamycin (Rap) has emerged as an autophagy regulator in multiple forms of organ injuries. This study aimed to assess whether Rap protects rats from cecal ligation and puncture (CLP)-induced sepsis through autophagy-mediated inactivation of the NLRP3 inflammasome. Rats were allocated to the sham, CLP, Rap (10 mg/kg), or 3-Methyladenine (3-MA) (15 mg/kg) groups. A rat CLP model was established. The survival of rats and lung wet-to-dry weight ratio in each group was assessed. Blood biochemical indexes and oxidative stress-related factors were analyzed with an automatic biochemical analyzer. The bacterial counts of blood and organs were monitored. The degrees of myeloperoxidase of the ileum, inflammation-related indexes, and pathological changes in the tissues were detected by ELISA and hematoxylin-eosin staining. The levels of NLRP3 inflammasome and autophagy-related factors were analyzed by Western blot. Rap increased the survival and SOD activity, and repressed ALT, AST, BUN, SCr, MDA, and inflammation-related marker levels in CLP rats, it also restrained the bacterial counts of blood, lung, liver, and kidney in CLP rats; the effects of 3-MA on CLP rats on the above-mentioned indicators were opposite to those of Rap. Additionally, Rap alleviated the pathological injury of the lung, liver, and kidney, which was the opposite to the effect of 3-MA on CLP rats. Furthermore, Rap mitigated the ASC, Pro-caspase 1, and NLRP3 levels and increased the Beclin-1 levels and the LC3II/LC3I ratio in the organ tissues. Collectively, autophagy activation can mitigate organ damage by suppressing the NLRP3 inflammasome in sepsis rats.
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Autofagia , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas Sprague-Dawley , Sepsis , Sirolimus , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Autofagia/efectos de los fármacos , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Sepsis/patología , Sirolimus/farmacología , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Masculino , Ratas , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
Microwave technology offers a rapid and uniform heating method. This study investigated how microwave pretreatment affects the aroma precursors and flavor of fragrant rapeseed oils (FROs). Microwave pretreatment led to decreased levels of polyunsaturated fatty acids, sugars, protein-bound amino acids, and glucosinolates. Using gas chromatography-mass spectrometry, we identified 66 volatile compounds in the oil samples. Among these, based on odor activity values (OAV ≥ 1), we found 9 aldehydes, 1 ketone, 6 pyrazines, 1 isothiocyanate, and 7 nitriles as the key aroma-active compounds, contributing fatty-like, nutty-like, and pungent-like odors, respectively. The electronic nose results highlighted W5S and W1W as primary sensors for determining the flavor profiles of FROs. Notably, aroma-active pyrazines exhibited strong negative correlations with sucrose, cysteine, lysine, and isoleucine. This research provides essential insights for enhancing the aroma of FROs.
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Purpose: To evaluate the impact of surgical compliance on overall survival (OS) and cancer-specific survival (CSS) in ovarian cancer patients and identify factors influencing surgical compliance. Materials and methods: Data from patients with ovarian cancer in the SEER database (2004-2015) were analyzed to compare the characteristics of patients with high and low surgical compliance. Kaplan-Meier curves and Cox regression models were used to assess the impact of surgical compliance on survival outcomes. Nomograms incorporating surgical compliance and independent prognostic factors were constructed to predict OS and CSS and were validated using internal validation sets. Predictive accuracy was evaluated using Harrell's concordance index (C-index), decision curve analysis (DCA), receiver operating characteristic (ROC) curves, and calibration plots. Binary logistic regression analysis identified factors significantly affecting surgical compliance, and propensity score matching (PSM) was used to adjust for confounders. Results: Among the 41,859 patients, 783 (1.87 %) demonstrated poor surgical compliance, while 41,076 (98.13 %) exhibited good compliance. Surgical compliance has emerged as an independent prognostic indicator for ovarian cancer. Patients with high compliance had significantly better OS and CSS rates (P < 0.0001). The prognostic models were internally validated and showed strong discriminative and calibration capabilities. Factors affecting compliance included older age, advanced pathological stage, metastasis, elevated CA-125 levels, and lower income. After PSM, Kaplan-Meier analysis revealed significantly improved survival in patients with good compliance (P < 0.0001). Conclusion: Surgical compliance is a pivotal and independent predictor of overall and cancer-specific survival in patients undergoing OC. Factors contributing to lower surgical compliance include advanced age, later tumor stage, metastatic spread, elevated CA-125 levels, and reduced family income.
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PURPOSE: To investigate intraindividual cardiac structural and functional changes before and after COVID-19 infection in a previously healthy population with a 3T cardiac magnetic resonance (CMR). MATERIALS AND METHODS: A total of 39 unhospitalized patients with COVID-19 were recruited. They participated in our previous study as non-COVID-19 healthy volunteers undergoing baseline CMR examination and were recruited to perform a repeated CMR examination after confirmed COVID-19 infection in December 2022. The CMR parameters were measured and compared between before and after COVID-19 infection with paired t tests. The laboratory measures including myocardial enzymes and inflammatory indicators were also collected when performing repeated CMR. RESULTS: The median duration was 393 days from the first to second CMR and 26 days from clinical symptoms onset to the second CMR. Four patients (10.3%, 4/39) had the same late gadolinium enhancement pattern at baseline and repeated CMR and 5 female patients (12.8%, 5/39) had myocardial T2 ratio >2 (2.07 to 2.27) but with normal T2 value in post-COVID-19 CMR. All other CMR parameters were in normal ranges before and after COVID-19 infection. Between before and after the COVID-19 infection, there were no significant differences in cardiac structure, function, and tissue characterization, no matter with or without symptoms (fatigue, chest discomfort, palpitations, shortness of breath, and insomnia/sleep disorders) (all P >0.05). The laboratory measures at repeated CMR were in normal ranges in all participants. CONCLUSIONS: These intraindividual CMR studies showed unhospitalized patients with COVID-19 with normal myocardial enzymes had no measurable CMR abnormalities, which can help alleviate wide social concerns about COVID-19-related myocarditis.
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COVID-19 , Miocarditis , Humanos , Femenino , Medios de Contraste , COVID-19/diagnóstico por imagen , COVID-19/patología , Imagen por Resonancia Cinemagnética , Gadolinio , Imagen por Resonancia Magnética , Miocardio/patología , Espectroscopía de Resonancia Magnética , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Premature ovarian insufficiency (POI) is a severe disorder leading to female infertility. Genetic mutations are important factors causing POI. TP63-truncating mutation has been reported to cause POI by increasing germ cell apoptosis, however what factors mediate this apoptosis remains unclear. METHODS: Ninety-three patients with POI were recruited from Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Whole-exome sequencing (WES) was performed for each patient. Sanger sequencing was used to confirm potential causative genetic variants. A minigene assay was performed to determine splicing effects of TP63 variants. A TP63-truncating plasmid was constructed. Real-time quantitative PCR, western blot analyses, dual luciferase reporter assays, immunofluorescence staining, and cell apoptosis assays were used to study the underlying mechanism of a TP63-truncating mutation causing POI. RESULTS: By WES of 93 sporadic patients with POI, we found a 14-bp deletion covering the splice site in the TP63 gene. A minigene assay demonstrated that the 14-bp deletion variant led to exon 13 skipping during TP63 mRNA splicing, resulting in the generation of a truncated TP63 protein (TP63-mut). Overexpression of TP63-mut accelerated cell apoptosis. Mechanistically, the TP63-mut protein could bind to the promoter region of CLCA2 and activate the transcription of CLCA2 several times compared to that of the TP63 wild-type protein. Silencing CLCA2 using a specific small interfering RNA (siRNA) or inhibiting the Ataxia Telangiectasia Mutated (ATM) pathway using the KU55933 inhibitor attenuated cell apoptosis caused by TP63-mut protein expression. CONCLUSION: Our findings revealed a crucial role for CLCA2 in mediating apoptosis in POI pathogenesis, and suggested that CLCA2 is a potential therapeutic target for POI.
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Menopausia Prematura , Insuficiencia Ovárica Primaria , Factores de Transcripción , Proteínas Supresoras de Tumor , Femenino , Humanos , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Exones , Menopausia Prematura/genética , Mutación , Insuficiencia Ovárica Primaria/genética , Insuficiencia Ovárica Primaria/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Activación Transcripcional , Proteínas Supresoras de Tumor/genéticaRESUMEN
Pelvic masses frequently originate from the pelvic cavity and are often associated with uterine, ovarian, or intestinal disorders. This report describes the case of a patient with a pelvic mass diagnosed as a retroperitoneal dermoid cyst at our hospital. We analyzed this case and conducted a literature review, to mitigate the risk of misdiagnosis and enhance the treatment of retroperitoneal masses.
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Adenomioma , Quiste Dermoide , Neoplasias Retroperitoneales , Neoplasias Uterinas , Humanos , Femenino , Quiste Dermoide/cirugía , Quiste Dermoide/complicaciones , Quiste Dermoide/diagnóstico , Quiste Dermoide/patología , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/complicaciones , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/diagnóstico , Neoplasias Retroperitoneales/cirugía , Neoplasias Uterinas/patología , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/diagnóstico por imagen , Adenomioma/patología , Adenomioma/cirugía , Adenomioma/complicaciones , Adenomioma/diagnóstico , Adenomioma/diagnóstico por imagen , Tomografía Computarizada por Rayos X , AdultoRESUMEN
Artificial peroxisomes (AP) with enzyme-mimetic catalytic activity and recruitment ability have drawn a great deal of attention in fabricating protocell systems for scavenging reactive oxygen species (ROS), modulating the inflammatory microenvironment, and reprogramming macrophages, which is of great potential in treating inflammatory diseases such as rheumatoid arthritis (RA). Herein, a macrophage membrane-cloaked Cu-coordinated polyphthalocyanine-based AP (CuAP) is prepared with a macrocyclic conjugated polymerized network and embedded Cu-single atomic active center, which mimics the catalytic activity and coordination environment of natural superoxide dismutase and catalase, possesses the inflammatory recruitment ability of macrophages, and performs photoacoustic imaging (PAI)-guided treatment. The results of both in vitro cellular and in vivo animal experiments demonstrated that the CuAP under ultrasound and microbubbles could efficiently scavenge excess ROS in cells and tissues, modulate microenvironmental inflammatory cytokines such as interleukin-1ß, tumor necrosis factor-α, and arginase-1, and reprogram macrophages by polarization of M1 (proinflammatory phenotype) to M2 (anti-inflammatory phenotype). We believe this study offers a proof of concept for engineering multifaceted AP and a promising approach for a PAI-guided treatment platform for RA.
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Artritis Reumatoide , Macrófagos , Técnicas Fotoacústicas , Animales , Macrófagos/metabolismo , Ratones , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/terapia , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Humanos , Cobre/química , Cobre/farmacologíaRESUMEN
OBJECTIVE: To screen interleukin (IL)-1ß secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice. METHODS: THP-1 cell line was differentiated to obtain human THP-1-derived macrophages, and the primary macrophages were obtained from human peripheral blood. FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice. The macrophages in abdominal cavity and bone marrow of mice were cultivated. The cells were treated with ABCC1/MRP1, ABCG2/BCRP, ABCB1/P-gp, OATP1B1, and MATE transporter inhibitors, then stimulated by lipopolysaccharide and adenosine triphosphate. The secretion level of IL-1ß was detected by ELISA, Western blot, and immunofluorescence. RESULTS: After inhibiting ABCC1/MRP1 transporter, the secretion of IL-1ß decreased significantly, while inhibition of the other 4 transporters had no effect. In animal experiment, the level of IL-1ß secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group (P < 0.05). CONCLUSION: ABCC1/MRP1 transporter is a newly discovered IL-1ß secretion pathway, which is expected to become a new target for solving clinical problems such as cytokine release syndrome.
Asunto(s)
Regulación hacia Abajo , Interleucina-1beta , Macrófagos , Ratones Noqueados , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Animales , Humanos , Ratones , Interleucina-1beta/metabolismo , Lipopolisacáridos , Macrófagos/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Células THP-1RESUMEN
The Alpinia oxyphylla fruit (AOF) is a popular condiment and traditional Chinese medicine in Asia, known for its neuroprotective compound nootkatone. However, there has not been a comprehensive study of its flavor or the relationship between sensory and bioactive compounds. To address this issue, we examined AOF's microstructure, flavor, and metabolomic profiles during fruit maturation. The key markers used to distinguish samples included fruit expansion, testa pigmentation, aril liquefaction, oil cell expansion, peel spiciness, aril sweetness, and seed bitterness. A full-spectrum metabolomic analysis, combining a nontargeted metabolomics approach for volatile compounds and a widely targeted metabolomics approach for nonvolatile compounds, identified 1,448 metabolites, including 1,410 differentially accumulated metabolites (DAMs). Notably, 31 DAMs, including nootkatone, were associated with spicy peel, sweet aril, and bitter seeds. Correlational analysis indicated that bitterness intensity is an easy-to-use biomarker for nootkatone content in seeds. KEGG enrichment analysis linked peel spiciness to phenylpropanoid and capsaicin biosynthesis, seed bitterness to terpenoid (especially nootkatone) biosynthesis, and aril sweetness to starch and sucrose metabolism. This investigation advances the understanding of AOF's complex flavor chemistry and underlying bioactive principle, encapsulating the essence of the adage: "no bitterness, no intelligence" within the realm of phytochemistry.