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1.
Ren Fail ; 46(2): 2378210, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39090966

RESUMEN

Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism.Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1ß (DN group was 34%, M2 group was 13%, p < 0.01) and MCP-1 (DN group was 49%, M2 group was 16%, p < 0.01) in the glomeruli. It was also proven that M2 macrophages alleviate mesangial cell injury caused by a high glucose environment. M2 macrophage tracking showed that the infused M2 macrophages migrated to the kidney, and the number of M2 macrophages in the kidney reached a maximum on day 3. Moreover, the ratio of M2 to M1 macrophages was 2.3 in the M2 infusion group, while 0.4 in the DN group (p < 0.01). Mechanistically, M2 macrophages downregulated Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 in mesangial cells.Conclusions: Multiple infusions of M2 macrophages significantly alleviated inflammation in the kidney and hindered the progression of DN at least partially by abrogating the M1/M2 homeostasis disturbances and suppressing the JAK2/STAT3 pathway in glomerular mesangial cells. M2 macrophage infusion may be a new therapeutic strategy for DN treatment.


Asunto(s)
Nefropatías Diabéticas , Janus Quinasa 2 , Macrófagos , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Janus Quinasa 2/metabolismo , Nefropatías Diabéticas/metabolismo , Factor de Transcripción STAT3/metabolismo , Ratones , Macrófagos/metabolismo , Masculino , Células Mesangiales/metabolismo , Modelos Animales de Enfermedad , Glomérulos Renales/patología , Glomérulos Renales/metabolismo , Quimiocina CCL2/metabolismo , Ratones Endogámicos C57BL , Interleucina-1beta/metabolismo
2.
Cancer Cell Int ; 24(1): 272, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39097730

RESUMEN

BACKGROUND: DEAD-box RNA helicase 19 A (DDX19A) is overexpressed in cervical squamous cell carcinoma. However, its role in gastric cancer remains unclear. The present study aimed to explore the role and underlying mechanism of DDX19A in the development of gastric cancer. METHODS: The expression of DDX19A in gastric cancer and paracancerous tissues was evaluated through quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The biological functions of DDX19A in gastric cancer were determined using CCK8, plate colony-forming, and Transwell migration assays. The specific mechanism of DDX19A in gastric cancer cells was studied using western blotting, RNA-binding protein immunoprecipitation, mRNA half-life detection, and nuclear and cytoplasmic RNA isolation. RESULTS: DDX19A was highly expressed in gastric cancer and positively associated with malignant clinicopathological features and poor prognosis. Additionally, DDX19A promoted gastric cancer cell proliferation, migration, and epithelial-mesenchymal transition phenotypes. Mechanistically, DDX19A activated the PI3K/AKT pathway by upregulating phosphatidylinositol-3-kinase (PIK3CA) expression. Furthermore, DDX19A interacted with PIK3CA mRNA, stabilized it, and facilitated its export from the nucleus. CONCLUSIONS: Our study reveals a novel mechanism whereby DDX19A promotes the proliferation and migration of gastric cancer cells by enhancing the stability and nuclear export of PIK3CA mRNA, thereby activating the PI3K/AKT pathway.

3.
Food Chem ; 460(Pt 1): 140532, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39053283

RESUMEN

Larimichthys crocea (LYC) holds significant economic value as a marine fish species. However, inaccuracies in labeling its origin can adversely affect consumer interests. Herein, a laser assisted rapid evaporative ionization mass spectrometry (LA-REIMS) and machine learning (ML) was developed for geographical authentication. When compared to iKnife, the LA demonstrated to be superior owing to reduced thermal damage to sample tissue, enhanced automation, and ease of use. Analysis of LYC from six distinct geographical origins across China revealed a total of 798 ions, which were then subjected to six classifiers to establish ML models. Following hyperparameter optimization and feature engineering, the Chi2(15%)-KNN model exhibited the highest training and testing accuracy, achieving 98.4 ± 0.9% and 98.5 ± 1.4%, respectively. This LA-REIMS/ML methodology offers a rapid, accurate, and intelligent solution for tracing the origin of LYC, thereby providing valuable technical support for the establishment of traceability systems in the aquatic product industry.

4.
Heliyon ; 10(13): e34091, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39055835

RESUMEN

We report a case of a 72-year-old female who presented with fever, abdominal pain, and diarrhea accompanied by leukopenia, anemia, and thrombocytopenia. The diagnosis of acute aplastic anemia was confirmed through bone marrow aspiration. Treatment included glucocorticoids, immunoglobulin therapy, and plasma exchange. Subsequently, the patient developed gastrointestinal bleeding and abdominal Computed Tomography (CT) revealed perforation of the transverse colon. Pathological examination of surgically removed diseased tissue confirmed mucor infection. Despite receiving antifungal therapy with amphotericin B, the patient's condition deteriorated due to the sepsis progression. Mucor infection in immunocompromised patients should be vigilant, and early diagnosis may help improve prognosis.

5.
J Clin Lipidol ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38981820

RESUMEN

BACKGROUND AND PURPOSE: Currently little is known about the joint association of lipoprotein (a) [Lp(a)] and Lipoprotein-associated phospholipase A2 (Lp-PLA2) with stroke recurrence. METHODS: In this prospective multicenter cohort study, 10,675 consecutive acute ischemic stroke (IS) and transient ischemic attack patients (TIA) with Lp(a) and Lp-PLA2 were enrolled. The association of stroke recurrence within 1 year with Lp(a) and Lp-PLA2 was assessed using Cox proportional hazards models and Kaplan-Meier curves. The interaction between Lp(a) and Lp-PLA2 with stroke recurrence was evaluated by multiplicative and additive scales. RESULTS: A significant joint association of Lp(a) and Lp-PLA2 with the risk of stroke recurrence was observed. Multivariate cox regression analysis demonstrated that the combination of elevated Lp(a) (≥ 50 mg/dL) and Lp-PLA2 (≥175.1 ng/ml) was independently associated with the risk of stroke recurrence (adjusted hazard ratio: 1.42; 95 % CI: 1.15-1.76). Both significant multiplicative [(exp(ß3):1.63, 95 % CI: 1.17-2.29, P = 0.004] and additive interaction (RERI:0.55, 95 % CI: 0.20-0.90, P = 0.002; AP: 0.39, 95 %CI, 0.24-0.53) were observed between Lp(a) and Lp-PLA2. CONCLUSIONS: Our results indicated that Lp(a) and Lp-PLA2 have a joint association with the risk of stroke recurrence in IS/TIA patients. Patients with concomitant presence of elevated Lp(a) and Lp-PLA2 have greater risk of stroke recurrence.

6.
Animals (Basel) ; 14(13)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38998035

RESUMEN

As the sheep industry rapidly moves towards modernization, digitization, and intelligence, there is a need to build breeding farms integrated with big data. By collecting individual information on sheep, precision breeding can be conducted to improve breeding efficiency, reduce costs, and promote healthy breeding practices. In this context, the accurate identification of individual sheep is essential for establishing digitized sheep farms and precision animal husbandry. Currently, scholars utilize deep learning technology to construct recognition models, learning the biological features of sheep faces to achieve accurate identification. However, existing research methods are limited to pattern recognition at the image level, leading to a lack of diversity in recognition methods. Therefore, this study focuses on the small-tailed Han sheep and develops a sheep face recognition method based on three-dimensional reconstruction technology and feature point matching, aiming to enrich the theoretical research of sheep face recognition technology. The specific recognition approach is as follows: full-angle sheep face images of experimental sheep are collected, and corresponding three-dimensional sheep face models are generated using three-dimensional reconstruction technology, further obtaining three-dimensional sheep face images from three different perspectives. Additionally, this study developed a sheep face orientation recognition algorithm called the sheep face orientation recognition algorithm (SFORA). The SFORA incorporates the ECA mechanism to further enhance recognition performance. Ultimately, the SFORA has a model size of only 5.3 MB, with accuracy and F1 score reaching 99.6% and 99.5%, respectively. During the recognition task, the SFORA is first used for sheep face orientation recognition, followed by matching the recognition image with the corresponding three-dimensional sheep face image based on the established SuperGlue feature-matching algorithm, ultimately outputting the recognition result. Experimental results indicate that when the confidence threshold is set to 0.4, SuperGlue achieves the best matching performance, with matching accuracies for the front, left, and right faces reaching 96.0%, 94.2%, and 96.3%, respectively. This study enriches the theoretical research on sheep face recognition technology and provides technical support.

7.
Sleep Breath ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012435

RESUMEN

PURPOSE: To continuously and dynamically monitor the sleep status of patients in the acute phase of cerebral infarction, and to investigate the characteristics of acute cerebral infarction(ACI)associated with sleep-disordered breathing (SDB), variations in sleep structure, and changes in sleep circadian rhythms. METHODS: Patients with ACI within 48 h of onset who were admitted to the Department of Neurology at Kailuan General Hospital from November 2020 to December 2022 were selected. Detailed baseline information such as age, gender, smoking history, drinking history, were recorded for the selected participants. From the beginning of their hospitalization, the selected participants were monitored for their sleep status continuously for 5 days using the Intelligent Mattress-based Sleep Monitoring Platform System(IMSMPS). Based on the heart rate data obtained from the monitoring, the interdaily stability (IS) and intradaily variability (IV) of the sleep circadian rhythm were calculated. RESULTS: 1,367 patients with ACI were selected. Monitoring results over 5 days indicated 147 cases (10.75%) without SDB, and 1,220 cases (89.25%) with SDB. Among the group with SDB, there were 248 cases (18.14%) with continuous mild SDB, 395 cases (28.90%) with moderate SDB, 295 cases (21.58%) with severe SDB, and 282 cases (20.63%) that fluctuated between different severity levels. Within this fluctuating group, 152 cases (53.90%) fluctuated between two severity levels, 120 cases (42.55%) between three levels, and 10 cases (3.55%) among all four levels. There were statistically significant differences (P < 0.05) in the sleep latency, sleep efficiency, non-rapid eye movement stages 1-2, rapid eye movement, proportion of non-rapid eye movement, proportion of rapid eye movement, wake after sleep onset, time out of bed, number of awakenings, respiratory variability index, and heart rate variability index among patients with ACI monitored from day 1 to 5. However, other monitored sleep structure parameters did not show statistically significant differences (P > 0.05). The coefficient of variation for all sleep monitoring parameters ranged between 14.54 and 36.57%. The IV in the SDB group was higher than in the group without SDB (P < 0.05), and the IS was lower than in the group without SDB (P < 0.05). CONCLUSION: Patients in the acute phase of cerebral infarction have a high probability of accompanying SDB. The sleep structure of these patients shows significant variability based on the onset time of the stroke, and some patients experience fluctuations among different severity levels of SDB. ACI accompanied by SDB can further reduce the IS of a patient's sleep circadian rhythm and increase its IV.

8.
ACG Case Rep J ; 11(7): e01403, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38988718

RESUMEN

Autoimmune optic papillitis is a rare disorder that causes progressive visual loss, often treated with rituximab (RTX). However, its use is not without risks. Here, we present a 51-year-old man who experienced vision loss because of autoimmune optic papillitis, which was well-controlled with RTX. Four years later, the patient developed abdominal pain and diarrhea and was found to have RTX-induced Crohn's disease (CD). The patient failed treatment with azathioprine, but was subsequently able to achieve clinical and endoscopic remission of his CD with ustekinumab, while continuing RTX therapy for autoimmune optic papillitis. This case report describes the efficacy of the anti-interleukin 12/23 monoclonal antibody in inducing remission of RTX-induced CD.

9.
World J Clin Cases ; 12(18): 3596-3602, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38983430

RESUMEN

BACKGROUND: The bacterium Eikenella, classified as a gram-negative member of the phylum Proteobacteria, is distinguished by its rarity, corrosive nature, facultative anaerobic properties, and conditional pathogenicity. It represents the sole species within its genus-Eikenella corrodens (E. corrodens)-and can be found colonizing both human and animal oral and nasopharyngeal regions. Additionally, it occasionally inhabits the gastrointestinal or urogenital tracts. However, its slow growth rate can be attributed to its high nutritional requirements. However, there is an uneven distribution of construction and diagnostic capacity in China which poses undeniable challenges for the clinical examination and analysis of this case, especially in the basic hospitals. CASE SUMMARY: Here we presented a case of empyema associated with E. corrodens infection in a 67-year-old male patient without any previous history of infectious diseases in our primary hospital in Dongguan district of China. The patient was admitted due to recurrent worsening cough, sputum production, and dyspnea for 3 d, which had persisted for over 20 years. Moreover, the patient experienced a one-hour episode of unconsciousness. Upon admission, immediate comprehensive examinations were conducted on the patient which subsequently led to his admission to the intensive care unit. Meanwhile, the patient presented with drowsiness and profuse sweating along with bilateral conjunctival edema observed during initiation of non-invasive ventilation, suggesting empyema. A significant amount of coffee-colored malodorous pleural fluid was drained during the procedure above and sent to the laboratory department for inspection. Finally, laboratory culture results confirmed the presence of E. corrodens infection in the pleural fluid sample. The patient received antimicrobial therapy until died on day 22 in the hospital. CONCLUSION: In this report, we presented a case of empyema associated with E. corrodens infection. Multiple courses of morphological examination, viable culture analysis, and biochemical identification revealed its difficulties in detecting distinctive characteristics, as well as a detection model worth promoting. It's just that there were still certain deficiencies in terms of morphological assessment, biochemical identification, and drug susceptibility testing.

10.
Nat Commun ; 15(1): 5998, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39013916

RESUMEN

Using renewable electricity to convert CO2 into CO offers a sustainable route to produce a versatile intermediate to synthesize various chemicals and fuels. For economic CO2-to-CO conversion at scale, however, there exists a trade-off between selectivity and activity, necessitating the delicate design of efficient catalysts to hit the sweet spot. We demonstrate here that copper co-alloyed with isolated antimony and palladium atoms can efficiently activate and convert CO2 molecules into CO. This trimetallic single-atom alloy catalyst (Cu92Sb5Pd3) achieves an outstanding CO selectivity of 100% (±1.5%) at -402 mA cm-2 and a high activity up to -1 A cm-2 in a neutral electrolyte, surpassing numerous state-of-the-art noble metal catalysts. Moreover, it exhibits long-term stability over 528 h at -100 mA cm-2 with an FECO above 95%. Operando spectroscopy and theoretical simulation provide explicit evidence for the charge redistribution between Sb/Pd additions and Cu base, demonstrating that Sb and Pd single atoms synergistically shift the electronic structure of Cu for CO production and suppress hydrogen evolution. Additionally, the collaborative interactions enhance the overall stability of the catalyst. These results showcase that Sb/Pd-doped Cu can steadily carry out efficient CO2 electrolysis under mild conditions, challenging the monopoly of noble metals in large-scale CO2-to-CO conversion.

11.
Medicine (Baltimore) ; 103(28): e38912, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38996123

RESUMEN

BACKGROUND: Polycystic ovary syndrome (PCOS) infertility has attracted great attention from researchers due to its high incidence. Numerous studies have shown that Chinese medicine is effective in treating this disease, but there is a wide variety of Chinese medicine therapies available, and there is a lack of comparative evaluation of the efficacy of various Chinese medicine combination therapies in the clinic, which requires further in-depth exploration. This study aims to evaluate the efficacy of a combined traditional Chinese medicine (TCM) therapy for the treatment of infertility with PCOS using network meta-analysis (NMA). METHODS: In PubMed, web of Science, Cochrane Library, Embase, China Knowledge Network, Wanfang Data, VIP Database, China Biomedical Literature Database (SinoMed) databases, searchs were conducted for information about the randomized controlled trials (RCTs) of combined TCM therapy for the treatment of infertility with PCOS. Quality evaluation was performed using the Cochrane 5.3 risk of bias assessment tool, and NMA using Stata 16.0. RESULTS: This study comprised 28 RCTs using 8 combined TCM therapies in total. The results of the NMA showed that moxibustion + herbal, fire acupuncture + herbal, acupuncture + herbal, electroacupuncture + herbal, and acupoint application + herbal improved the clinical pregnancy rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Additionally, ear point pressure + herbal enema + herbal, acupuncture and moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal improved the ovulation rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal are the 3 most effective therapies for improving the clinical pregnancy rate. Fire acupuncture + herbal, acupuncture + herbal, and ear point pressure + herbal enema + herbal are the 3 most effective therapies for improving the ovulation rate. CONCLUSION: The combined TCM therapy demonstrated better efficacy for the treatment of infertility with PCOS compared to acupuncture, herbal, and western medicines monotherapy. However, the optimal treatment therapy varied depending on the outcome indicators. Further large sample, high-quality, and standardized RCTs are needed to verify these findings.


Asunto(s)
Infertilidad Femenina , Medicina Tradicional China , Síndrome del Ovario Poliquístico , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/terapia , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Femenino , Infertilidad Femenina/terapia , Infertilidad Femenina/etiología , Infertilidad Femenina/tratamiento farmacológico , Medicina Tradicional China/métodos , Terapia Combinada , Metaanálisis en Red , Embarazo , Terapia por Acupuntura/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Índice de Embarazo
12.
Sleep Biol Rhythms ; 22(3): 353-362, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38962800

RESUMEN

There is limited research on the circadian rhythm and sleep state in patients with acute cerebral infarction (ACI) accompanied by sleep-breathing disorders (SDB). This study aims to provide a scientific basis for individualized diagnosis and treatment for stroke-related SDB patients. The SC-500 sleep monitor was used to continuously monitor 1367 ACI patients over 5 days. Based on the apnea-hypopnea index (AHI), patients were divided into non-SDB group (normal) and SDB group (mild, moderate, severe, fluctuating). Interdaily stability (IS) and intradaily variability (IV) were calculated through heart rate monitoring, and sleep states and their correlations were analyzed. Compared to the non-SDB group, patients with moderate-to-severe ACI accompanied by SDB showed decreased IS, increased IV, and sleep fragmentation. Significant statistical differences were observed in total sleep time (TST), rapid eye movement latency (REML), sleep efficiency (SE), non-rapid eye movement stages 1-2 (NREM stages1-2), non-rapid eye movement stages 3-4 (NREM stages 3-4), proportion of non-rapid eye movement (NREM%), wake after sleep onset (WASO), and number of awakenings (NOA) between the SDB group and the non-SDB group (P < 0.05). AHI showed a strong negative correlation with IS and a strong positive correlation with IV. AHI was positively correlated with sleep latency (SL), REML, NREM stages1-2, NREM%, proportion of rapid eye movement (REM%), WASO, time out of bed (TOB), and NOA, and negatively correlated with TST, SE, NREM stages 3-4, and rapid eye movement (REM), all with statistical significance (P < 0.05). There were significant statistical differences in the Mini-Mental State Examination (MMSE) between patients with and without SDB, and among mild, moderate, severe, and fluctuating groups (P < 0.05). Patients with moderate-to-severe ACI accompanied by SDB are more likely to experience changes in circadian rhythm and sleep states, which in turn affect cognitive functions. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-024-00516-1.

13.
Medicine (Baltimore) ; 103(30): e39086, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058847

RESUMEN

RATIONALE: Severe congenital neutropenia (SCN) is a rare and heterogeneous genetic disease. By describing the diagnosis and treatment of a child with SCN and periodontitis, this case provides a reference for the oral health management of a child with SCN and periodontitis. PATIENT CONCERNS: We describe a boy with clinical manifestations of oral bleeding, neutropenia, recurrent fever, and other recurrent infections. The absolute neutrophil count (ANC) was <0.50 × 109/L most of the time. Morphological examination of bone marrow cells showed active granulocyte hyperplasia and dysmaturation. DIAGNOSES: According to the clinical manifestations, hematological examination and gene detection results, the child was diagnosed as SCN with chronic periodontitis. INTERVENTIONS: Periodontal treatment was performed after informed consent was obtained from the child guardian. These included supragingival and subgingival cleaning, hydrogen peroxide and saline irrigation, placement of iodoglycerin in the gingival sulcus, and oral hygiene instruction. Hematopoietic stem cell transplantation (HSCT) was performed later. OUTCOMES: One month after initial periodontal treatment, oral hygiene was well maintained and gingival swelling had subsided. Probing depth (PD) index on periodontal probing and bleeding was significantly reduced. However, there was no significant change in blood routine and other indicators before and after periodontal treatment. CONCLUSION: Once SCN is diagnosed, individualized treatment plans can be developed according to the characteristics of the disease and its impact on oral health, which can effectively control the interaction between SCN and periodontal disease and reduce the occurrence of serious infection.


Asunto(s)
Síndromes Congénitos de Insuficiencia de la Médula Ósea , Neutropenia , Humanos , Masculino , Neutropenia/congénito , Neutropenia/terapia , Neutropenia/diagnóstico , Síndromes Congénitos de Insuficiencia de la Médula Ósea/complicaciones , Síndromes Congénitos de Insuficiencia de la Médula Ósea/diagnóstico , Niño , Salud Bucal , Periodontitis Crónica/terapia , Periodontitis Crónica/complicaciones , Periodontitis Crónica/diagnóstico , Higiene Bucal , Trasplante de Células Madre Hematopoyéticas/métodos , Periodontitis/terapia , Periodontitis/complicaciones
14.
Genes (Basel) ; 15(7)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-39062672

RESUMEN

In the present study, the mitochondrial genomic characteristics of Acanthopsetta nadeshnyi have been reported and have depicted the phylogenetic relationship among Pleuronectidae. Combined with a comparative analysis of 13 PCGs, the TN93 model was used to review the neutral evolution and habitat evolution catalysis of the mitogenome to verify the distancing and purification selectivity of the mitogenome in Pleuronectidae. At the same time, a species differentiation and classification model based on mitogenome analysis data was established. This study is expected to provide a new perspective on the phylogenetic relationship and taxonomic status of A. nadeshnyi and lay a foundation for further exploration of environmental and biological evolutionary mechanisms.


Asunto(s)
Evolución Molecular , Genoma Mitocondrial , Filogenia , Animales , Peces Planos/genética , Peces Planos/clasificación
15.
Heliyon ; 10(11): e32377, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38947486

RESUMEN

Acute kidney injury (AKI) frequently emerges as a consequential non-neurological sequel to traumatic brain injury (TBI), significantly contributing to heightened mortality risks. The intricate interplay of oxidative stress in the pathophysiology of TBI underscores the centrality of the Keap1-Nrf2/HO-1 signaling pathway as a pivotal regulator in this context. This study endeavors to elucidate the involvement of the Keap1-Nrf2/HO-1 pathway in modulating oxidative stress in AKI subsequent to TBI and concurrently explore the therapeutic efficacy of dimethyl fumarate (DMF). A rat model of TBI was established via the Feeney free-fall method, incorporating interventions with varying concentrations of DMF. Assessment of renal function ensued through measurements of serum creatinine and neutrophil gelatinase-associated lipocalin. Morphological evaluation of renal pathology was conducted employing quantitative hematoxylin and eosin staining. The inflammatory response was scrutinized by quantifying interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α levels. Oxidative stress levels were discerned through quantification of malondialdehyde and superoxide dismutase. The apoptotic cascade was examined via the terminal deoxynucleotidyl transferase dUTP deletion labeling assay. Western blotting provided insights into the expression dynamics of proteins affiliated with the Keap1-Nrf2/HO-1 pathway and apoptosis. The findings revealed severe kidney injury, heightened oxidative stress, inflammation, and apoptosis in the traumatic brain injury model. Treatment with DMF effectively reversed these changes, alleviating oxidative stress by activating the Keap1-Nrf2/HO-1 signaling pathway, ultimately conferring protection against AKI. Activating Keap1-Nrf2/HO-1 signaling pathway may be a potential therapeutic strategy for attenuating oxidative stress-induced AKI after TBI.

16.
Int Urol Nephrol ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955940

RESUMEN

PURPOSE: This investigation sought to validate the clinical precision and practical applicability of AI-enhanced three-dimensional sonographic imaging for the identification of anterior urethral stricture. METHODS: The study enrolled 63 male patients with diagnosed anterior urethral strictures alongside 10 healthy volunteers to serve as controls. The imaging protocol utilized a high-frequency 3D ultrasound system combined with a linear stepper motor, which enabled precise and rapid image acquisition. For image analysis, an advanced AI-based segmentation process using a modified U-net algorithm was implemented to perform real-time, high-resolution segmentation and three-dimensional reconstruction of the urethra. A comparative analysis was performed against the surgically measured stricture lengths. Spearman's correlation analysis was executed to assess the findings. RESULTS: The AI model completed the entire processing sequence, encompassing recognition, segmentation, and reconstruction, within approximately 5 min. The mean intraoperative length of urethral stricture was determined to be 14.4 ± 8.4 mm. Notably, the mean lengths of the urethral strictures reconstructed by manual and AI models were 13.1 ± 7.5 mm and 13.4 ± 7.2 mm, respectively. Interestingly, no statistically significant disparity in urethral stricture length between manually reconstructed and AI-reconstructed images was observed. Spearman's correlation analysis underscored a more robust association of AI-reconstructed images with intraoperative urethral stricture length than manually reconstructed 3D images (0.870 vs. 0.820). Furthermore, AI-reconstructed images provided detailed views of the corpus spongiosum fibrosis from multiple perspectives. CONCLUSIONS: The research heralds the inception of an innovative, efficient AI-driven sonographic approach for three-dimensional visualization of urethral strictures, substantiating its viability and superiority in clinical application.

18.
Int Immunopharmacol ; 138: 112591, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38981220

RESUMEN

Tripartite motif (Trim) 31 is important for numerous inflammatory diseases. However, whether Trim31 regulates airway inflammation in asthma remains undetermined. The present work explored the role of Trim31 in airway inflammation in asthmatic mice established by ovalbumin (OVA) stimulation. Trim31 expression was markedly downregulated in the lungs of asthmatic mice. Compared with wild-type (WT) mice, Trim31-/- mice showed more severe pathological changes accompanied by increased inflammatory cell infiltration after OVA induction. House dust mite (HDM) stimulation evoked airway epithelial cell injury and inflammation, which were exacerbated by Trim31 silencing or attenuated by Trim31 overexpression. Further examination revealed that Trim31 deficiency exacerbated the activation of the NLRP3 inflammasome in OVA-induced asthmatic mice and HDM-stimulated airway epithelial cells. The inhibition of NLRP3 markedly diminished the Trim31 silencing-mediated enhancement of HDM-induced injury and inflammation in airway epithelial cells. In conclusion, this work demonstrates that Trim31 acts as a crucial mediator of airway inflammation in asthma. Trim31 deficiency may contribute to the progression of asthma by increasing NLRP3 inflammasome activation, suggesting that Trim31 is a potential therapeutic target for asthma.


Asunto(s)
Asma , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Ovalbúmina , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Animales , Femenino , Humanos , Ratones , Asma/inmunología , Asma/metabolismo , Modelos Animales de Enfermedad , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Inflamasomas/metabolismo , Pulmón/patología , Pulmón/inmunología , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Ovalbúmina/inmunología , Pyroglyphidae/inmunología , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/deficiencia , Ubiquitina-Proteína Ligasas/metabolismo
19.
Acta Trop ; 257: 107283, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38955322

RESUMEN

Toxoplasmosis, a zoonotic parasitic disease caused by Toxoplasma gondii (T. gondii), is prevalent worldwide. The fact should be emphasized that a considerable proportion of individuals infected with T. gondii may remain asymptomatic; nevertheless, the condition can have severe implications for pregnant women or immunocompromised individuals. The current treatment of toxoplasmosis primarily relies on medication; however, traditional anti-toxoplasmosis drugs exhibit significant limitations in terms of efficacy, side effects, and drug resistance. The life cycles of T. gondii are characterized by distinct stages and its body morphology goes through dynamic alterations during the growth cycle that are intricately governed by a wide array of post-translational modifications (PTMs). Ubiquitin (Ub) signaling and ubiquitin-like (Ubl) signaling are two crucial post-translational modification pathways within cells, regulating protein function, localization, stability, or interactions by attaching Ub or ubiquitin-like proteins (Ubls) to target proteins. While these signaling mechanisms share some functional similarities, they have distinct regulatory mechanisms and effects. T. gondii possesses both Ub and Ubls and plays a significant role in regulating the parasite's life cycle and maintaining its morphology through PTMs of substrate proteins. Investigating the role and mechanism of protein ubiquitination in T. gondii will provide valuable insights for preventing and treating toxoplasmosis. This review explores the distinctive characteristics of Ub and Ubl signaling in T. gondii, with the aim of inspiring research ideas for the identification of safer and more effective drug targets against toxoplasmosis.


Asunto(s)
Transducción de Señal , Toxoplasma , Toxoplasmosis , Ubiquitina , Toxoplasma/metabolismo , Toxoplasma/fisiología , Toxoplasma/efectos de los fármacos , Ubiquitina/metabolismo , Humanos , Toxoplasmosis/parasitología , Toxoplasmosis/tratamiento farmacológico , Toxoplasmosis/metabolismo , Animales , Proteínas Protozoarias/metabolismo , Ubiquitinación , Procesamiento Proteico-Postraduccional , Ubiquitinas/metabolismo , Estadios del Ciclo de Vida
20.
Angew Chem Int Ed Engl ; : e202411166, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008335

RESUMEN

Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially, N-Boc pyrroles and alkynes are converted into N-bridged compounds through a Diels-Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site-selective peripheral editing of the benzene ring. Furthermore, this proof-of-concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.

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