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1.
Sci Adv ; 10(14): eadk5229, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38569034

RESUMEN

The origin of the cosmic magnetic field remains an unsolved mystery, relying not only on specific dynamo processes but also on the seed field to be amplified. Recently, the diffuse radio emission and Faraday rotation observations reveal that there has been a microgauss-level magnetic field in intracluster medium in the early universe, which places strong constraints on the strength of the initial field and implies the underlying kinetic effects; the commonly believed Biermann battery can only provide extremely weak seed of 10-21 G. Here, we present evidence for the spontaneous Weibel-type magnetogenesis in laser-produced weakly collisional plasma with the three-dimensional synchronous proton radiography, where the distribution anisotropy directly arises from the temperature gradient, even without the commonly considered interpenetrating plasmas or shear flows. This field can achieve sufficient strength and is sensitive to Coulomb collision. Our results demonstrate the importance of kinetics in magnetogenesis in weakly collisional astrophysical scenarios.

3.
Diagn Pathol ; 18(1): 56, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37118812

RESUMEN

Germ cell tumours with somatic-type solid malignancy (GCT-STM) are a rare disease of the mediastinum. Recently, a cohort of vasculogenic mesenchymal tumour (VMT)-nonseminoma cases with different prognoses were recognized and reported. Here, we report a case of mediastinal high-grade VMT with a seminoma. A 16-year-old male had a fever, chest tightness and fatigue. Chest CT showed a 7.5 cm×5.3 cm solid mass in the right anterior mediastinum. The serum levels of alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (ß-HCG) and carcinoembryonic antigen (CEA) were within the normal range. Tumorectomy was performed. The tumour was irregular, and no capsule was found. The cut surface was greyish white and greyish brown with medium consistency. There were foci of bleeding and necrosis. Microscopic histology showed prominent vascular proliferation, which was lined by mildly atypical endothelial cells in a cellular stroma with significant cytologic atypia. The vascular spectrum varied from crevice-like or antler-like thin- to thick-walled vessels. Beyond the tumour area, inside the remnant thymus tissues, there were small clusters of polygonal tumour cells with clear cytoplasm, distinct cell membranes, and round to polygonal nuclei with prominent nucleoli that were positive for Oct4, PLAP, SALL4 and CD117. The patient did not receive any treatments pre- or postoperation, and his condition was stable without progression after 14 months of follow-up evaluation. Here, we added a new entity of GCT-STM of the mediastinum composed of VMT and seminoma. A better understanding of the pathological features of GCT-VMT could help pathologists improve their awareness of these rare diseases.


Asunto(s)
Neoplasias del Mediastino , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Adolescente , Seminoma/patología , Mediastino/patología , Células Endoteliales/patología , Neoplasias Testiculares/cirugía , Neoplasias Testiculares/patología , Neoplasias del Mediastino/patología
4.
Biomed Pharmacother ; 159: 114099, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36641923

RESUMEN

Intervertebral disc degeneration (IVDD), a common cartilage-degenerative disease, is considered the main cause of low back pain (LBP). Owing to the complex aetiology and pathophysiology of IVDD, its molecular mechanisms and definitive treatment of IVDD remain unclear. As an evolutionarily and functionally conserved signalling pathway, Hippo-YAP/TAZ signalling plays a crucial role in IVDD progression. In this review, we discuss the regulation of Hippo-YAP/TAZ signalling and summarise the recent research progress on its role in cartilage homeostasis and IVDD. We also discuss the current application and future prospects of IVDD treatments based on Hippo-YAP/TAZ signalling.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Humanos , Vía de Señalización Hippo , Transducción de Señal , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ
5.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-984767

RESUMEN

Objective: To analyze the association between sleep duration and cognitive function of the elderly in six provinces of China. Methods: Based on the cross-sectional survey data of the elderly from the Healthy Ageing Assessment Cohort Study in 2019, 4 644 participants' sociodemographic and economic indicators, lifestyle, prevalence of major chronic diseases, and sleep status, including night-time sleep duration, daytime sleep duration and insomnia, were collected by questionnaires. Cognitive function was evaluated by the Mini-Mental State Examination. Multivariate logistic regression was used to analyze the association between night-time sleep duration, daytime sleep duration and cognitive function. Results: The mean age of 4 644 respondents was (72.3±5.7) years, and 2 111 of them were males (45.5%). The mean total daily sleep time of the elderly was (7.9±1.9) hours, and the proportion of those who slept less than 7.0, 7.0-8.9 and≥9.0 hours was 24.1% (1 119), 42.1% (1 954) and 33.8% (1 571), respectively. The mean sleep time at night was (6.9±1.7) hours. About 23.7% (1 102) of the elderly did not sleep during the day, and the mean duration of the elderly who slept during the day was (78±51) minutes. Among the elderly with insomnia, 47.9% were still satisfied with their sleep quality. The mean value of MMSE score of 4 644 respondents was (24.5±5.3), and the cognitive impairment rate was 28.3% (1 316). The results of multivariate logistic regression model analysis showed that the OR (95%CI) value of the risk of cognitive impairment in older people who did not sleep, slept for 31 to 60 minutes and slept more than one hour was 1.473 (1.139 to 1.904), 1.277 (1.001 to 1.629) and 1.496 (1.160 to 1.928), respectively, compared with those who slept for 1 to 30 minutes during the daytime. Compared with those who slept for 7.0‒8.9 hours at night, the OR (95%CI) value of the risk of cognitive impairment in older people who slept more than 9.0 hours was 1.239 (1.011 to 1.519). Conclusion: The cognitive function is related to sleep duration in the Chinese elderly.


Asunto(s)
Masculino , Humanos , Anciano , Femenino , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Estudios Transversales , Estudios de Cohortes , Sueño , Trastornos del Sueño-Vigilia , Cognición , China/epidemiología
6.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1009837

RESUMEN

OBJECTIVES@#To explore the effects of somatostatin on the levels of gastrointestinal hormones and clinical outcomes in critically ill infants after gastrointestinal surgery.@*METHODS@#Using a random number table method, critically ill infants after gastrointestinal surgery who were admitted to the Intensive Care Unit of Xuzhou Children's Hospital from June 2019 to June 2021 were randomly divided into an observation group (29 cases) and a control group (30 cases). The control group received routine treatment such as anti-infection and hemostasis after surgery, while the observation group received somatostatin in addition to the routine treatment [3.5 μg/(kg·h) infusion for 7 days]. The levels of serum gastrin (GAS), motilin (MTL), insulin, and glucagon-like peptide-1 (GLP-1) before surgery, on the 3rd day after surgery, and on the 7th day after surgery were compared between the two groups. The recovery progress and incidence of complications after surgery were also compared between the two groups.@*RESULTS@#There was no significant difference in the levels of serum GAS, MTL, insulin, and GLP-1 between the two groups before surgery (P>0.05). On the 3rd and 7th day after surgery, the levels of serum GAS, MTL, insulin, and GLP-1 in the observation group were higher than those in the control group (P<0.05). In the observation group, the levels of GAS, MTL, insulin, and GLP-1 on the 7th day after surgery were higher than those before surgery and on the 3rd day after surgery (P<0.05), and the levels on the 3rd day after surgery were higher than those before surgery (P<0.05). There was no significant difference in the levels of serum GAS, MTL, and insulin before surgery, on the 3rd day after surgery, and on the 7th day after surgery in the control group (P>0.05). The level of GLP-1 on the 7th day after surgery was higher than that before surgery and on the 3rd day after surgery (P<0.05), and the level on the 3rd day after surgery was higher than that before surgery (P<0.05) in the control group. The observation group had shorter first time of anal exhaust, recovery time of bowel sounds, and first time of defecation after surgery compared to the control group (P<0.05). The incidence of complications after surgery in the observation group was lower than that in the control group (10% vs 33%, P<0.05).@*CONCLUSIONS@#Somatostatin can increase the levels of serum GAS, MTL, insulin, and GLP-1 in critically ill infants after gastrointestinal surgery, promote the recovery of gastrointestinal function, and reduce the incidence of postoperative complications.


Asunto(s)
Humanos , Lactante , Enfermedad Crítica , Procedimientos Quirúrgicos del Sistema Digestivo , Péptido 1 Similar al Glucagón , Insulina , Estudios Prospectivos , Somatostatina/uso terapéutico
7.
Acta Pharmaceutica Sinica ; (12): 2942-2951, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-999063

RESUMEN

Psoriasis is a chronic, recurrent, and inflammatory skin disease induced by multiple factors. Its typical clinical manifestation is scaly erythema or plaques, which can cause various complications such as metabolic syndrome, cardiovascular disease, and inflammatory arthritis, seriously affecting the quality of life of patients. A deep understanding of the pathogenesis of psoriasis is helpful to discover new therapeutic targets and develop effective new therapeutic drugs, thus having important clinical significance. This manuscript reviews the new advances in the pathogenesis and drug research of psoriasis in recent years.

8.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-996877

RESUMEN

@#As the indications for transcatheter aortic valve replacement (TAVR) expand, multi-valve lesions are becoming more common in clinical practice. Moderate to severe atrioventricular regurgitation, particularly when persistent after TAVR, significantly increases the risk of adverse events. Therefore, many studies have evaluated factors that contribute to the improvement of atrioventricular regurgitation. However, this field remains controversial due to the heterogeneity of retrospective studies and the lack of randomized controlled trials. Despite advances in atrioventricular valve intervention techniques, evidence for atrioventricular regurgitation intervention after TAVR is still scarce. The management decision for atrioventricular regurgitation in patients who underwent TAVR is complex and must take into account the severity of valve disease, anatomical characteristics, quality of life, and procedural complexity. We conducted a review of atrioventricular regurgitation in patients who have received TAVR in hope that it will help decision-making in clinical practice.

9.
Chinese Journal of Radiology ; (12): 684-688, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-992998

RESUMEN

Objective:To evaluate the influence of different detector widths and signal acquisition positions of wide-detector CT in different scanning modes on CT number and noise, and to provide a basis for reasonable selection of scanning modes and related parameters in clinical practice.Methods:The body dose phantom was scanned by GE Revolution CT. The scan was performed with detector widths of 40, 80 and 160 mm in sequential scanning mode and with detector width/pitch combinations of 40 mm/0.516, 40 mm/0.984, 80 mm/0.508 and 80 mm/0.992 in spiral scanning mode. The phantom was placed at the central and peripheral of the selected detector widths, and the adjacent positions between two axial scans. The images of the phantom were evaluated subjectively and the CT numbers and SDs were measured. The differences between the measured values at different imaging parameters were compared. The multi-group Friedman test was used to compare CT numbers and SD under different scanning parameters in sequential scanning mode, and the Wilcoxon test was used to compare CT numbers and SD in spiral scanning mode.Results:There was no statistically significant difference in the geometric shapes of the phantom images obtained at any combination of parameters. In sequential scanning mode, the differences at different detector widths were statistically significant (χ 2=14.00, P=0.001) with CT numbers at 40 mm and 160 mm greater than CT numbers at 80 mm ( P<0.05). The differences at different signal acquisition positions were statistically significant (χ 2=12.04, P=0.002) with CT numbers at peripheral and adjacent greater than CT numbers at central ( P<0.05). In spiral scanning mode CT numbers at detector width at 80 mm were greater than CT numbers at 40 mm ( Z=-2.10, P=0.036). For SD, the differences at different detector widths were statistically significant in sequential scanning modes (χ 2=8.17, P=0.017) with SD at 160 mm greater than SD at 80 mm ( P<0.05). The differences at different signal acquisition positions were statistically significant (χ 2=13.50, P=0.001) with SD at peripheral greater than SD at central ( P<0.05). In spiral scanning mode SDs at pitches 0.984 and 0.992 were greater than SDs at 0.516 and 0.508 ( Z=-2.66, P=0.008). There were no significant differences among other groups. Conclusion:The selection of scanning mode, detector width and signal acquisition position of wide-detector CT will affect the image CT numbers and SDs.

10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-992536

RESUMEN

Objective:To investigate the diagnostic value of neutrophil CD64 index (nCD64) in disseminated nontuberculous mycobacteria (NTM) infection.Methods:Thirty-six patients with NTM infection from January 2020 to June 2021 in Huashan Hospital, Fudan University were included. Patients were classified into groups of disseminated infection and focal infection according to their medical history and discharge diagnosis. The expressions of nCD64 in patients with focal infection and disseminated infection before treatment were collected and analyzed. Statistical analysis was performed using the Mann-Whitney U test, and the diagnostic value of nCD64 for disseminated NTM infection was analyzed using the receiver operator characteristic curve (ROC curve). Results:Among the 36 patients with NTM infection, 18 cases were focal infection (due to the low white blood cell count of the patient with myelodysplastic syndrome, the detection results were biased, which were excluded from the subsequent analysis) and 18 cases were disseminated infection. The expression of nCD64 in focal infection was 0.72(0.50, 1.55), and that in disseminated infection was 13.63(6.77, 32.31). The difference was statistically significant ( U=15.50, P<0.001). Using focal infection as a control, the area under the ROC curve for the operational characteristics of the subjects was 0.949 3 for disseminated NTM infection. The diagnostic cut-off value of nCD64 was 3.06, with the sensitivity and specificity of the disseminated NTM infection were 88.89% and 100.00%, respectively. Conclusions:In patients with NTM infection before effective treatment, the diagnostic cut-off value of nCD64 of 3.06 has high sensitivity and specificity, which is useful for the aided diagnosis of disseminated NTM infection.

11.
Chinese Pharmacological Bulletin ; (12): 594-598, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013821

RESUMEN

Aim To construct and identify a new time-specific NLRP3 point mutation transgenic mouse model by Cre-LoxP system. Methods Cre-LoxP system was used to generate NL-RP3

12.
Chinese Pharmacological Bulletin ; (12): 1195-1199, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013796

RESUMEN

Aim To establish stable and reliable animal models of Blau syndrome (BS) in vivo. Methods C57BL/6J mice were intraperitoneally injected with muramyl dipeptide (MDP) or L18-MDP to induce systemic inflammatory model of BS. Meanwhile, positive drug etanercept (ETN) was set to investigate the response of the model to evaluate effectiveness. SD rats were intravitrealiy injected with MDP to establish BS-associated uveitis model. Serum levels of TNF-a, IL-6 and IL-8 were detected by enzyme linked immunosorbent assay (ELISA). Histopathologic al changes of rat eyeballs were detected by HE staining and the expressions of p65, p-ERK, p-p38, p-JNK, TNF-a, IL-6 and IL-8 in vitreous were determined by immunohistochem-istry (IHC) staining. Results The serum level of TNF-a in mice increased after intraperitoneal injection of MDP (P < 0.05), and increased significantly after L18-MDP injection (P < 0.01). Meanwhile, the levels of IL-6 and IL-8 were also markedly induced by L18-MDP (P < 0. 01, P < 0. 01). ETN treatment evidently inhibited the increased levels of these above cytokines induced by L18-MDP (P < 0. 05, P < 0. 01). After the intravitreous injection of MDP in SD rats, there were numerous inflammatory cells infiltrated in retina and vitreous, and the retina was seriously damaged. The staining levels of p65, p-ERK, p-p38, p-JNK, TNF-a, IL-6 and IL-8 in eyeball tissues were significantly enhanced. Conclusions The systemic animal model of BS can be successfully established by intraperitoneal injection of L18-MDP in C57BL/6J mice, and the good BS-relat-ed uveitis can be induced by intravitreous injection of MDP in SD rats, which provides the simple, convenient, repeatable and i-deal animal models for exploring the pathogenesis of BS and e-valuating the efficacy of drugs.

13.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1007877

RESUMEN

OBJECTIVE@#To evaluate the effect of intense pulsed light (IPL) in the treatment of chronic hordeolum.@*METHODS@#Patients with chronic hordeolum who underwent IPL treatment were enrolled in this study. According to the severity of hordeolum, the patients were treated with IPL 3 to 5 times. Patients' satisfaction and visual analog scale scores for ocular discomfort symptoms before and after treatment were collected. The number, congestion, long diameter, short diameter and area of nodules were also recorded and measured. Finally, eyelid margin signs, meibum quality, meibomian gland expressibility, meibomian gland dropout, tear meniscus height, and corneal fluorescein staining were scored.@*RESULTS@#20 patients were enrolled in this study. The eyelid margins were congestive and swollen, with blunt rounding or irregularity. The meibum was cloudy or toothpaste-like. The meibomian gland expressibility, meibomian gland dropout and tear meniscus height were reduced. The cornea showed scattered fluorescein staining. After treatment, score of visual analog scale, congestion and size of nodules were significantly reduced. Eyelid margin signs, meibum quality, meibomian gland expressibility, tear meniscus height and corneal fluorescein staining scores were improved. Meibomian gland dropout had no significant change. No side effects occurred during treatment.@*CONCLUSIONS@#IPL is beneficial for the treatment of chronic hordeolum.


Asunto(s)
Humanos , Orzuelo , Glándulas Tarsales , Lágrimas , Fluoresceínas
14.
Chinese Medical Journal ; (24): 2712-2721, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1007683

RESUMEN

BACKGROUND@#Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.@*METHODS@#We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs.@*RESULTS@#The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1 , while those in TNENs were in MEN1, MLL2, APC, RB1 , and TSC2 . Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling.@*CONCLUSION@#We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.


Asunto(s)
Humanos , Timoma , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , China , Neoplasias del Timo/patología , Pronóstico , Tumores Neuroendocrinos/patología , Mutación/genética
15.
Acta Physiologica Sinica ; (6): 317-327, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-981008

RESUMEN

The present study aimed to investigate the protective effect of S-propargyl-cysteine (SPRC) on atherosclerosis progression in mice. A mouse model of vulnerable atherosclerotic plaque was created in ApoE-/- mice by carotid artery tandem stenosis (TS) combined with a Western diet. Macrophotography, lipid profiles, and inflammatory markers were measured to evaluate the antiatherosclerotic effects of SPRC compared to atorvastatin as a control. Histopathological analysis was performed to assess the plaque stability. To explore the protective mechanism of SPRC, human umbilical vein endothelial cells (HUVECs) were cultured in vitro and challenged with oxidized low-density lipoprotein (ox-LDL). Cell viability was determined with a Cell Counting Kit-8 (CCK-8). Endothelial nitric oxide synthase (eNOS) phosphorylation and mRNA expression were detected by Western blot and RT-qPCR respectively. The results showed that the lesion area quantified by en face photographs of the aortic arch and carotid artery was significantly less, plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced, plaque collagen content was increased and matrix metalloproteinase-9 (MMP-9) was decreased in 80 mg/kg per day SPRC-treated mice compared with model mice. These findings support the role of SPRC in plaque stabilization. In vitro studies revealed that 100 μmol/L SPRC increased the cell viability and the phosphorylation level of eNOS after ox-LDL challenge. These results suggest that SPRC delays the progression of atherosclerosis and enhances plaque stability. The protective effect may be at least partially related to the increased phosphorylation of eNOS in endothelial cells.


Asunto(s)
Animales , Humanos , Ratones , Aterosclerosis , Colesterol/metabolismo , Cisteína/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Lipoproteínas LDL/farmacología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación , Placa Aterosclerótica/patología
16.
Acta Pharmaceutica Sinica ; (12): 899-908, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-978773

RESUMEN

Nucleotide-binding oligomerization domain containing protein 2 (NOD2) is a member of intracellular pattern recognition receptor. After being activated, it will induce the release of inflammatory factors through a series of signal cascade transduction, thus playing an important role in the innate immune response. The abnormal NOD2 signaling pathway is involved in the occurrence and development of many diseases, especially the single nucleotide polymorphisms (SNPs) of the NOD2 gene have been identified to be closely associated with autoinflammatory diseases (AIDs). Therefore, inhibitors targeting NOD2 pathway have great potential in the treatment of inflammatory immune diseases. This review presents the recent progress of NOD2 receptor-mediated signal transduction pathways and its regulation mechanisms, the relationship between NOD2 and AIDs, and the inhibitors of NOD2 pathway.

17.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-973179

RESUMEN

@#Multi-leaf collimators are devices to block rays from medical linear accelerators, which directly affect doses to targets and organs at risk by adjusting field shape and dose distribution in radiation therapy. As multi-leaf collimators are diversified in structure, there has been growing research on dosimetric comparison of various multi-leaf collimators. In this paper, we introduced the classifications of multi-leaf collimators according to their basic components, as well as the hardware structure and design features of the products of main accelerator manufacturers, including Varian’s Millennium MLC, HD120 MLC, and Halcyon, Elekta’s MLCi/i2 and Agility, and Accuray’s InCise 2 MLC and TomoTherapy. In terms of clinical application evaluation, focusing on radiotherapy plans for nasopharyngeal carcinoma, we reviewed comparative studies on the dosimetry performance of multi-leaf collimators and the effects of relevant parameters on dose distribution. We hope this review on the design and application evaluation of multi-leaf collimators can provide a reference for more innovative design and accelerator selection and parameter setting in clinical individualized treatment.

18.
Acta Pharmaceutica Sinica B ; (6): 1231-1245, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-971770

RESUMEN

Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.

19.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-971069

RESUMEN

OBJECTIVES@#To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI).@*METHODS@#A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge.@*RESULTS@#Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05).@*CONCLUSIONS@#Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.


Asunto(s)
Niño , Humanos , Ácido Valproico/uso terapéutico , Proteína HMGB1 , Proyectos Piloto , Factor de Necrosis Tumoral alfa , Enfermedades Neuroinflamatorias , Proteína con Dominio Pirina 3 de la Familia NLR , Estudios Prospectivos , Lesiones Traumáticas del Encéfalo/patología
20.
Front Cell Dev Biol ; 11: 1291170, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38328305

RESUMEN

Introduction: Plaque rupture in atherosclerosis contributes to various acute cardiovascular events. As a new sulfide-containing donor, S-propargyl-cysteine (SPRC) has been reported to play a beneficial role in cardioprotection, potentially through its anti-inflammatory, anti-oxidative and anti-atherogenic activities. Our previous study observed an increase in eNOS phosphorylation in endothelial cells. However, it remains unclear whether SPRC influences vascular smooth muscle cells (VSMCs) within the plaque and if this effect contributes to plaque stabilization. Methods: An atherosclerotic unstable plaque mouse model was established by subjecting ApoE-/- mice to tandem stenosis of the right carotid artery along with a Western diet. Daily SPRC administration was conducted for 13 weeks. Plaque morphology and stability were assessed using MRI scanning and histopathological staining. In our in vitro studies, we stimulated human artery vascular smooth muscle cells (HAVSMCs) with platelet-derived growth factor-BB (PDGF-BB), both with and without 100 µM SPRC treatment. Cell phenotype was assessed using both Western blot and Real-time PCR. Cell proliferation was assessed using the BrdU cell proliferation kit and immunofluorescence of Ki-67, while cell migration was measured using scratch wound healing and transwell assay. MiR-143-3p overexpression and knockdown experiments were used to investigate whether it mediates the effect of SPRC on VSMC phenotype. Results and Discussion: SPRC treatment reduced plasma lipid levels, increased collagen content and decreased cell apoptosis in atherosclerotic plaques, indicating improved plaque stability. Both in vivo and in vitro studies elucidated the role of SPRC in preserving the contractile phenotype of VSMCs through up-regulation of miR-143-3p expression. Furthermore, SPRC suppressed the pro-proliferation and pro-migration effects of PDGF-BB on HAVSMCs. Overall, these findings suggest that the inhibitory effect of SPRC on phenotype switch from contractile to synthetic VSMCs may contribute to its beneficial role in enhancing plaque stability.

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