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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 893-898, 2024 Aug 15.
Artículo en Chino | MEDLINE | ID: mdl-39148397

RESUMEN

Pharyngitis can be caused by various pathogens, including viruses and bacteria. Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis. However, distinguishing GAS pharyngitis from other types of upper respiratory tract infections is challenging in clinical settings. This often leads to empirical treatments and, consequently, the overuse of antimicrobial drugs. With the advancement of antimicrobial drug management and healthcare payment reform initiatives in China, reducing unnecessary testing and prescriptions of antimicrobial drugs is imperative. To promote standardized diagnosis and treatment of GAS pharyngitis, this article reviews various international guidelines on the clinical diagnosis and differential diagnosis of GAS pharyngitis, particularly focusing on clinical scoring systems guiding laboratory testing and antimicrobial treatment decisions for GAS pharyngitis and their application recommendations, providing a reference for domestic researchers and clinical practitioners.


Asunto(s)
Faringitis , Infecciones Estreptocócicas , Streptococcus pyogenes , Humanos , Faringitis/microbiología , Faringitis/tratamiento farmacológico , Faringitis/diagnóstico , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/tratamiento farmacológico
3.
Braz J Infect Dis ; 28(2): 103734, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38471654

RESUMEN

BACKGROUND: Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. METHODS: S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). RESULTS: The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). CONCLUSIONS: Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae.


Asunto(s)
Antibacterianos , Pacientes Internos , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Pacientes Ambulatorios , Infecciones Neumocócicas , Serogrupo , Streptococcus pneumoniae , Humanos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/aislamiento & purificación , Streptococcus pneumoniae/genética , Preescolar , Pacientes Ambulatorios/estadística & datos numéricos , Lactante , Antibacterianos/farmacología , Masculino , Femenino , Pacientes Internos/estadística & datos numéricos , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/epidemiología , Hospitales Pediátricos , Farmacorresistencia Bacteriana , Beijing/epidemiología , Serotipificación , Vacunas Neumococicas/inmunología
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(1): 92-97, 2024 Jan 15.
Artículo en Chino | MEDLINE | ID: mdl-38269466

RESUMEN

-lactams, including penicillin, have been used for over 80 years in the treatment of group A Streptococcus (GAS) infections. Although -lactam-resistant GAS strains have not been identified in vitro tests, clinical treatment failures have been reported since the 1950s. The mechanism underlying the clinical failure of -lactam treatment in GAS infections remains unclear. Previous research has suggested that -lactam resistance in GAS in vivo is associated with reduced drug susceptibility of strains, bacterial inoculation effects, biofilm formation, the effect of coexisting bacteria, bacterial persistence, and bacterial internalization into host cells. This article reviews the main reports on -lactam treatment failure in GAS infections and analyzes the possible mechanisms of -lactam resistance in vivo. The findings aim to contribute to future research and clinical approaches in the field.


Asunto(s)
Lactamas , Infecciones Estreptocócicas , Humanos , Penicilinas , Infecciones Estreptocócicas/tratamiento farmacológico , Insuficiencia del Tratamiento
5.
Journal of Practical Radiology ; (12): 111-114, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1020169

RESUMEN

Objective To explore the short-term and long-term curative effect of different polyvinyl alcohol(PVA)embolic agents combined with coaxial microcatheter embolization on massive hemoptysis.Methods According to different embolization agents,60 patients with massive hemoptysis were divided into polyvinyl alcohol embolization microsphere group(microsphere group,32 cases,polyvinyl alco-hol embolization microsphere+coaxial microcatheter embolization)and polyvinyl alcohol foam embolization microparticle group(micropar-ticle group,28 cases,polyvinyl alcohol foam embolization microparticle+coaxial microcatheter embolization).The curative effect,coagula-tion indexes,hemoptysis volume,incidence of complications and recurrence rate of hemoptysis were compared between the two groups.Results The difference in the response rates to treatment between the two groups was not statistically significant(P>0.05).Hemoptysis volume was significantly less in the microsphere group than that in the microparticle group(P<0.05).There was no significant difference in the incidence of complications between the two groups(P>0.05).The recurrence rate of hemoptysis was lower in the microsphere group than that in the microparticle group(3.03%vs 21.43%)(P<0.05).Conclusion The curative effect of both polyvinyl alcohol embolization microsphere and foam embolization microparticle combined with coaxial microcatheter embolization is highly effective on massive hemoptysis.The long-term prognosis of polyvinyl alcohol embolization microsphere combined with coaxial microcatheter embolization is better.

6.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1036491

RESUMEN

Traumatic fractures and stress fractures are common orthopedic diseases, and there is great potential in researching bone turnover, repair, and promotion of fracture healing. Basic medical experiments often use animal models of long bone fractures in limbs to study the mechanisms of various interventions on fracture healing. Fracture healing is a complex process influenced by multiple factors and involves multiple molecules and pathways. Therefore, to explore the mechanisms more deeply, accelerate the translation of results, and improve the clinical efficacy, it is particularly important to choose the appropriate animal fracture modeling methods in experimental research. Based on this, this paper conducts a literature review of animal species and modeling methods commonly used for long bone fracture models in experimental research. It summarizes five methods: bone defect method, physical impact method, mechanical bending method, open osteotomy method, and drilling method. A side-by-side comparison of their advantages, disadvantages, and scope of application is made, aiming to provide suitable fracture models for studying the mechanisms of fracture healing interventions.

7.
Acta Pharmaceutica Sinica ; (12): 279-288, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1016653

RESUMEN

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

8.
International Eye Science ; (12): 420-426, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1011394

RESUMEN

Ocular diseases pose a significant challenge to global health. The field of metabolomics, which involves the systematic identification and quantification of metabolites within a biological system, has emerged as a promising research approach for unraveling disease mechanisms and discovering novel biomarkers. Through its application, metabolomics has yielded valuable knowledge pertaining to the initiation and advancement of various ocular diseases. This review presents an overview of metabolomics and examines recent research progess in four ocular diseases, specifically diabetic retinopathy, age-related macular degeneration, glaucoma, and dry eye, summarizing potential biomarkers and metabolic pathways associated with these diseases. Additionally, this review offers insights into the future prospects of utilizing metabolomics for the management and treatment of ocular diseases.

9.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1009899

RESUMEN

-lactams, including penicillin, have been used for over 80 years in the treatment of group A Streptococcus (GAS) infections. Although -lactam-resistant GAS strains have not been identified in vitro tests, clinical treatment failures have been reported since the 1950s. The mechanism underlying the clinical failure of -lactam treatment in GAS infections remains unclear. Previous research has suggested that -lactam resistance in GAS in vivo is associated with reduced drug susceptibility of strains, bacterial inoculation effects, biofilm formation, the effect of coexisting bacteria, bacterial persistence, and bacterial internalization into host cells. This article reviews the main reports on -lactam treatment failure in GAS infections and analyzes the possible mechanisms of -lactam resistance in vivo. The findings aim to contribute to future research and clinical approaches in the field.


Asunto(s)
Humanos , Lactamas , Penicilinas , Infecciones Estreptocócicas/tratamiento farmacológico , Insuficiencia del Tratamiento
10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1024127

RESUMEN

Objective To clarify the high-touch surface in oral diagnosis and treatment procedures,provide basis and guidance for cleaning and disinfection.Methods The direct observation method was used to investigate the tou-ch time and frequency of environmental surfaces in 7 outpatient departments of a tertiary stomatology hospitals in Beijing.The average touch frequency,95%confidence interval and cumulative touch rate were calculated.Results In oral diagnosis and treatment procedures,the average touch frequency of the environmental surface was 26.75 times per procedure,with the highest in endodontics(46.25 times per procedure)and the lowest in the oral mucosal specialty(10.19 times per procedure).The high-touch surface consisted of the shadowless lamp handle,manipula-tion panel and handle on dental unit(doctor's side),computer keyboard and mouse,handle and line front end of three way syringe,as well as dental high speed handpiece and line front end,with average touch frequencies of 3.99,3.85,2.65,1.86,and 1.40 times per procedure.The high-touch surface in all stomatology specialties in-cluded the manipulation panel and handle on dental unit(doctor's side),75%of specialties included computer key-board and mouse,and the shadowless lamp handle has the highest touch frequency in 50%of specialties.The ave-rage touch frequency of the environmental surface was highest(113.50 times per procedure)during crown prepara-tion procedure,and the lowest(8.50 times per procedure)during the orthodontic consultations.Conclusion The high-touch surface of different dental specialties and different diagnosis and treatment procedures are different.Me-dical institutions should take corresponding cleaning,disinfection and management measures according to the actual situation of high-touch surface in stomatology departments,so as to effectively improve the quality of environmental cleaning and disinfection.

11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1024504

RESUMEN

Objectives:To investigate the short-term efficacy of oblique lateral interbody fusion(OLIF)in treating mild-to-moderate lumbar spinal stenosis(LSS).Methods:35 patients with mild-o-moderate LSS treated with OLIF between May 2018 and May 2020 were analyzed retrospectively,including 25 males and 10 females,aged 50-74(60.3±10.7)years old.The patients were followed up for 12-28(18.3±3.7)months.The operative time,intraoperative bleeding,and complications were recorded;At preoperation,1 week,and 3,6 and 12 months after surgery,the visual analogue scale(VAS)for lumbar and leg pain and Oswestry disability index(ODI)were compared to evaluate clinical efficacy;And lumbar X-ray,CT,and MRI were performed at the same time to measure and evaluate the height of the intervertebral space,size of intervertebral foramen,area of dural sac and sagittal diameter,lordotic angle of intervertebral space,lordotic angle of lumbar spine,and their respective differences between before and after operation,as well as between each postoperative time point were analyzed;The complications and fusion conditions at each time point were also documented.Results:The operative time was 30-100(70.5±20.3)min,and intraoperative bleeding was 20-120(60.3±20.2)mL.The lumbar and leg pain VAS scores and ODI at postoperative 1 week,and 3,6 and 12 months were signif-icantly improved compared with those before operation,and the differences were statistically significant(P<0.05),while there was no statistical significance when compared pairwisely between postoperative time points(P>0.05).At postoperative 1 week,and 3,6 and 12 months,the intervertebral space height,intervertebral lor-dotic angle and lumbar lordotic angle,left and right intervertebral foramina sizes,dural sac areas,and sagittal diameters increased significantly compared with those before operation,with statistically significance(P<0.05),and no statistical difference was found when compared pairwisely between postoperative time points for each imaging parameter(P>0.05).According to the CT image evaluation 1 year after operation,the overall fusion rate was 94.2%(33/35 cases).No serious complications such as nerve and vascular injury occurred;3 cases of postoperative hip flexion weakness and anterior thigh numbness were relieved after 1 month of symptomatic treatment with conservative therapy;2 cases of fusion device sinking of end-plate cutting were revised in the second stage and underwent posterior muscular gap approach internal fixation.Conclusions:OLIF has satisfactory short-term clinical efficacy in the treatment of mild-to-moderate LSS.

12.
Chinese Critical Care Medicine ; (12): 142-146, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1025363

RESUMEN

Objective:To investigate the clinical practicability of positive end-expiratory pressure (PEEP) titrated by lung stretch index (SI) in patients with acute respiratory distress syndrome (ARDS).Methods:A parallel randomized controlled trial was conducted. Patients with moderate to severe ARDS who required mechanical ventilation admitted to the department of critical care medicine of General Hospital of the Yangtze River Shipping from August 2022 to February 2023 were enrolled. They were randomly divide into SI guided PEEP titration group (SI group) and pressure-volume curve (P-V curve) inspiratory low inflection point (LIP) guided PEEP titration group (LIP group). All patients were ventilated in a supine position after admission, with the head of the bed raised by 30°. The primary disease was actively treated, prone position ventilation for 12 h/d, and lung protective ventilation strategies such as controlled lung expansion were used for lung recruitment. On this basis, mechanical ventilation parameters were titrated with SI in the SI group; the LIP group titrated mechanical ventilation parameters with P-V curve inspiratory LIP+2 cmH 2O (1 cmH 2O ≈ 0.098 kPa). The oxygenation index (PaO 2/FiO 2), and respiratory mechanics indicators such as lung dynamic compliance (Cdyn), peak airway pressure (Pip) were monitored before recruitment maneuver and after 1, 3, and 5 days of treatment. The therapeutic effect of the two groups was compared. Results:There were 41 patients in the SI group and 40 patients in the LIP group. There was no significant difference in general information such as gender, age, and disease type between the two groups. The mechanical ventilation time and the length of intensive care unit (ICU) stay in the SI group were significantly shorter than those in the LIP group (days: 9.47±3.36 vs. 14.68±5.52, 22.27±4.68 vs. 27.57±9.52, both P < 0.05). Although the 28-day mortality of the SI group was lower than that of the LIP group, the difference was not statistically significant [19.5% (8/41) vs. 35.0% (14/40), P > 0.05]. On the fifth day, the PaO 2/FiO 2 was higher in SI group [mmHg (1 mmHg≈0.133 kPa): 225.57±47.85 vs. 198.32±31.59, P < 0.05], the Cdyn was higher in SI group (mL/cmH 2O: 47.39±6.71 vs. 35.88±5.35, P < 0.01), the Pip was lower in SI group (mmHg: 35.85±5.77 vs. 43.87±6.68, P < 0.05). The Kaplan-Meier survival curve showed no statistically significant difference in the 28 days cumulative survival rate between the two groups (Log-Rank: χ2 = 2.348, P = 0.125). Conclusion:The application of SI titration with PEEP in the treatment of ARDS patients may improve their prognosis.

13.
Braz. j. infect. dis ; 28(2): 103734, 2024. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1557300

RESUMEN

Abstract Background Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. Methods S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). Results The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). Conclusions Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae.

14.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(5): 534-540, 2023 May 15.
Artículo en Chino | MEDLINE | ID: mdl-37272182

RESUMEN

Currently, the main strategy for preventing neonatal group B Streptococcus (GBS) infection is prenatal screening combined with intrapartum antibiotic prophylaxis, which has effectively reduced the incidence of neonatal GBS early-onset disease. However, the burden of GBS infection is still significant. The intrapartum antibiotic prophylaxis strategy has limitations such as inducing antibiotic resistance and inability to effectively prevent GBS late-onset disease. It is crucial to develop and evaluate other prevention strategies, while paying close attention to assessing penicillin allergy in pregnant women and how to prevent GBS infection in neonates with negative maternal GBS screening. In recent years, there has been some progress in GBS vaccines and related immunological research, and the use of specific vaccines is expected to significantly reduce GBS infection in neonates.


Asunto(s)
Complicaciones Infecciosas del Embarazo , Infecciones Estreptocócicas , Femenino , Humanos , Recién Nacido , Embarazo , Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus agalactiae
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(4): 333-338, 2023 Apr 15.
Artículo en Chino | MEDLINE | ID: mdl-37073835

RESUMEN

At the end of 2022, the World Health Organization reported an increase in group A Streptococcus (GAS) infections, such as scarlet fever, in multiple countries. The outbreak primarily affected children under 10 years old, and the number of deaths was higher than anticipated, causing international concern. This paper reviews the current state of the GAS disease outbreak, its causes, and response measures. The authors aim to draw attention from clinical workers in China and increase their awareness and vigilance regarding this epidemic. Healthcare workers should be aware of the potential epidemiological changes in infectious diseases that may arise after the optimization of control measures for coronavirus disease 2019 to ensure children's health.


Asunto(s)
Epidemias , Infecciones Estreptocócicas , Streptococcus pyogenes , Niño , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Brotes de Enfermedades , Epidemias/estadística & datos numéricos , Escarlatina/epidemiología , Infecciones Estreptocócicas/epidemiología , Europa (Continente)/epidemiología , Américas/epidemiología
17.
Front Cell Infect Microbiol ; 13: 1110652, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36844410

RESUMEN

Objective: This study aims to analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from children aged 8 days to 7 years in Urumqi, China, between 2014 to 2021, during which PCV13 was introduced in the private sector's immunization program and COVID-19 control was administrated in the last 2 years. Methods: Serotypes of S. pneumoniae isolates were determined by Quellung reaction, and their susceptibility against 14 antimicrobials were tested. According to the start year of PCV13 administration (2017) and COVID-19 control (2020), the study period was divided into three stages: 2014-2015, 2018-2019, and 2020-2021. Results: A total of 317 isolates were involved in this study. The most common serotypes were type 19F (34.4%), followed by 19A (15.8%), 23F (11.7%), 6B (11.4%), and 6A(5.0%). The coverage rate of both PCV13 and PCV15 was 83.0%. The coverage of PCV20 was a little higher at 85.2%. The resistance rate against penicillin was 28.6% according to the breakpoints of oral penicillin, which would reach up to 91.8% based on the breakpoints of parenteral penicillin for meningitis. The resistance rates to erythromycin, clindamycin, tetracycline, and sulfamethoxazole-trimethoprim were 95.9%, 90.2%, 88.9%, and 78.8%, respectively. The PCV13 isolate was more resistant to penicillin than the non-PCV13 ones. There was not any significant change found in the serotype distribution since the PCV13 introduction and the COVID-19 control. The resistance rate against oral penicillin slightly elevated to 34.5% in 2018-2019 from 30.7% in 2014-2015 and then decreased significantly to 18.1% in 2020-2021 (χ 2 = 7.716, P < 0.05), while the resistance rate to ceftriaxone (non-meningitis) continuously declined from 16.0% in 2014-2015 to 1.4% in 2018-2019 and 0% in 2020-2021 (Fisher = 24.463, P < 0.01). Conclusion: The common serotypes of S. pneumoniae isolated from children in Urumqi were types 19F, 19A, 23F, 6B, and 6A, which we found to have no marked change since the PCV13 introduction and the COVID-19 control However, the resistance rate to oral penicillin and ceftriaxone significantly declined in the COVID-19 control stage.


Asunto(s)
Antiinfecciosos , COVID-19 , Infecciones Neumocócicas , Niño , Humanos , Lactante , Streptococcus pneumoniae , Antibacterianos/farmacología , Serogrupo , Ceftriaxona , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Farmacorresistencia Bacteriana , COVID-19/epidemiología , Penicilinas , China/epidemiología , Vacunas Neumococicas , Serotipificación
18.
Eur J Pharmacol ; 942: 175494, 2023 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-36657656

RESUMEN

Cardiac fibrosis remains an unresolved problem in heart disease. Its etiology is directly caused by the activation and proliferation of cardiac fibroblasts (CFs). However, there is limited information regarding the biological role of cardiac fibroblasts in cardiac fibrosis. Herein, we screened out a gene, IGFBP3, whose expression significantly increased in TGF-ß1-stimulated human primary CFs by mining RNA-Seq data for differential and WGCNA. We verified the IGFBP3's expression in transverse aortic constriction (TAC) surgery, isoproterenol (ISO)-induced cardiac fibrosis models, and TGFß1-stimulated mouse primary CFs. We also found that the knockdown of IGFBP3 could inhibit the migration and proliferation ability of CFs. Furthermore, we found that aberrant N6-methyladenosine(m6A) mRNA modifications in the animal model and activated CFs may regulate the expression of IGFBP3 in developing cardiac fibrosis. Silencing METTL3 could downregulate the expression of IGFBP3 and inhibit the activation of CFs and the degree of cardiac fibrosis both in vitro and in vivo. Indeed, we also verified the expression of METTL3 and IGFBP3 in the atrial tissues of patients with atrial fibrillation (AF). Thus, METTL3 may regulate IGFBP3's expression and CFs activation via RNA epigenetic modifications, laying the foundation for a specific and novel therapeutic target in cardiac fibrosis.


Asunto(s)
Cardiomiopatías , Animales , Humanos , Ratones , Cardiomiopatías/metabolismo , Proliferación Celular/genética , Epigénesis Genética , Fibroblastos/metabolismo , Fibrosis , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Miocardio/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
19.
Eur J Pharmacol ; 938: 175398, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36455647

RESUMEN

Cardiac fibroblasts (CFs) drive extracellular matrix remodeling after inflammatory injury, leading to cardiac fibrosis and diastolic dysfunction. Recent studies described the role of epigenetics in cardiac fibrosis. Nevertheless, detailed reports on epigenetics regulating CFs pyroptosis and describing their implication in cardiac fibrosis are still unclear. Here, we found that DNMT3A reduces the expression of lncRNA Neat1 and promotes the NLRP3 axis leading to CFs pyroptosis, using cultured cells, animal models, and clinical samples to shed light on the underlying mechanism. We report that pyroptosis-related genes are increased explicitly in cardiac fibrosis tissue and LPS-treated CFs, while lncRNA Neat1 decreased. Mechanistically, we show that loss of DNMT3A or overexpression of lncRNA Neat1 in CFs after LPS treatment significantly enhances CFs pyroptosis and the production of pyroptosis-related markers in vitro. It has been demonstrated that DNMT3A can decrease lncRNA Neat1, promoting NLRP3 axis activation in CFs treated with LPS. In sum, this study is the first to identify that DNMT3A methylation decreases the expression of lncRNA Neat1 and promotes CFs pyroptosis and cardiac fibrosis, suggesting that DNMT3A and NEAT1 may function as an anti-fibrotic therapy target in cardiac fibrosis.


Asunto(s)
Cardiomiopatías , MicroARNs , ARN Largo no Codificante , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Piroptosis/genética , Lipopolisacáridos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fibrosis , Fibroblastos/metabolismo , Cardiomiopatías/metabolismo , Epigénesis Genética , MicroARNs/genética
20.
Chinese Journal of Burns ; (6): 25-34, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-971146

RESUMEN

Objective: To explore the effects of porcine urinary bladder matrix (UBM) on the motility and polarization of bone marrow-derived macrophages in mice, so as to provide evidence for the rational selection of stent in clinical wound repair. Methods: The method of experimental research was used. The microstructure of porcine UBM and absorbable dressing was observed under scanning electron microscope. Polyacrylamide gel electrophoresis was used to observe the protein distribution of the two stent extracts. The primary macrophages were induced from bone marrow-derived cells isolated from six 6-8-week-old male C57BL/6J mice (mouse age, sex, and strain, the same below) and identified. Three batches of macrophages were divided into porcine UBM extract group and absorbable dressing extract group. The cells in each group were cultured with Dulbecco's modified Eagle medium/F12 medium containing the corresponding extracts. The cell migration rate was detected and calculated on 1, 3, and 7 d after scratching by scratch test. The number of migrated cells at 12 and 24 h of culture was detected by Transwell experiment. The percentages of CD206 and CD86 positive cells at 24 h of culture was detected by flow cytometer. The numbers of sample in the above cell experiments were all 3. An incision was prepared on the left and right back of twelve mice, respectively. The left incision of each mouse was included in porcine UBM group and the right incision was included in absorbable dressing group, and the corresponding stents were implanted into the incisions respectively. On post operation day (POD) 7 and 14, the number of inflammatory cells infiltrated in the stent was detected by hematoxylin-eosin staining; the number of F4/80, transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and matrix metalloprotein-9 (MMP-9) positive cells and type Ⅰ collagen deposition in stents were observed by immunohistochemistry; the percentages of F4/80, CD86, and CD206 positive cells were observed by immunofluorescence staining. The numbers of sample in the above animal experiments were all 6. Data were statistically analyzed with analysis of variance for factorial design, analysis of variance for repeated measurement, and independent sample t test. Results: Porcine UBM has a dense basement membrane structure on one side and porous propria containing a fibrous structures on the other. Both sides of the absorbable dressing had three-dimensional porous structure. In the molecular weight range of (50-70)×103, multiple non-type Ⅰ collagen bands appeared in the lanes of porcine UBM extract, while no obvious bands appeared in the lanes of absorbable dressing extract. It had been identified that mouse bone marrow-derived cells had been successfully induced into macrophages. The cell migration rates in porcine UBM extract group were significantly higher than those in absorbable dressing extract group on 1, 3, and 7 d after scratching (with t values of 15.31, 19.76, and 20.58, respectively, P<0.05). The numbers of migrated cells in porcine UBM extract group were significantly more than those in absorbable dressing extract group at 12 and 24 h of culture (with t values of 12.20 and 33.26, respectively, P<0.05). At 24 h of culture, the percentage of CD86 positive cells in porcine UBM extract group ((1.27±0.19)%) was significantly lower than (7.34±0.14)% in absorbable dressing extract group (t=17.03, P<0.05);the percentage of CD206 positive cells in porcine UBM extract group was (73.4±0.7)%, significantly higher than (32.2±0.5)% in absorbable dressing extract group (t=119.10, P<0.05). On POD 7 and 14, the numbers of inflammatory cells infiltrated in the stents in porcine UBM group was significantly more than those in absorbable dressing group (with t values of 6.58 and 10.70, respectively, P<0.05). On POD 7 and 14, the numbers of F4/80, TGF-β1, VEGF, and MMP-9 positive cells in the stents in porcine UBM group were significantly more than those in absorbable dressing group (with t values of 46.11, 40.69, 13.90, 14.15, 19.79, 32.93, 12.16, and 13.21, respectively, P<0.05); type Ⅰ collagen deposition in the stents in porcine UBM group was more pronounced than that in absorbable dressing group; the percentages of CD206 positive cells in the stents in porcine UBM group were significantly higher than those in absorbable dressing group (with t values of 5.05 and 4.13, respectively, P<0.05), while the percentages of CD86 positive cells were significantly lower than those in absorbable dressing group (with t values of 20.90 and 19.64, respectively, P<0.05), and more M2-type macrophages were seen in the stents in porcine UBM group and more M1-type macrophages were seen in the stents in absorbable dressing group. Conclusions: Porcine UBM can enhance macrophage motility, induce M2 polarization and paracrine function, create a microenvironment containing growth factors such as TGF-β1 and MMP-9 tissue remodeling molecules, and promote tissue regeneration and extracellular matrix remodeling in mice.


Asunto(s)
Ratones , Masculino , Animales , Porcinos , Factor A de Crecimiento Endotelial Vascular , Vejiga Urinaria , Metaloproteinasa 9 de la Matriz , Ratones Endogámicos C57BL , Macrófagos , Colágeno
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