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1.
Antiviral Res ; 226: 105880, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608838

RESUMO

Human respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants, young children, and elderly people. However, there are no effective treatments or vaccines available in most countries. In this study, we explored the anti-RSV potential of 2, 4-Di-tert-butylphenol (2, 4-DTBP), a compound derived from Houttuynia cordata Thunb. To overcome the poor solubility of 2, 4-DTBP, we encapsulated it in polymeric micelles and delivered it by inhalation. We found that 2, 4-DTBP-loaded micelles inhibited RSV infection in vitro and improved survival, lung pathology, and viral clearance in RSV-infected mice. Our results suggested that 2, 4-DTBP-loaded micelle is a promising novel therapeutic agent for RSV infection.

2.
Heliyon ; 10(7): e29242, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38623198

RESUMO

Objective: The ultrasonic cardiac output monitor (USCOM), an instrument that monitors the evolution of a patient's hemodynamic status and determines the type of shock, has become an important tool for assessing cardiac pathology and predicting changes in disease, but there are some variations in the instrumental findings for different physical conditions of patients. This article examines whether there are differences in the quality of USCOM waveforms measured in different types of critically ill patients based on clinical characteristics and test parameters. Methods: Baseline data, diagnoses, echocardiograms, ventilation patterns, and USCOM results were retrospectively collected from patients in the emergency intensive care unit. Waveform quality was quantified using the Fremantle score to determine the extent to which age, body mass index (BMI), chronic obstructive pulmonary disease (COPD), respiratory failure, cardiac enlargement, valvular heart disease, and ventilation pattern influenced USCOM waveform quality. Results: Age, body mass index, chronic obstructive pulmonary disease, respiratory failure, right and left heart enlargement, aortic valve disease (excluding aortic stenosis), and ventilation mode did not have a significant effect on USCOM waveform quality in critically ill patients (P > 0.05). Conclusions: Various physical conditions of critically ill patients may have limited effect on the quality of the USCOM waveform, potentially rendering USCOM suitable for early assessment of hemodynamic status during ICU admission.

3.
Angew Chem Int Ed Engl ; : e202404663, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575553

RESUMO

The intrinsic activity assessment of transition metal oxides (TMOs) as key electrocatalysts for the oxygen evolution reaction (OER) has not been standardized due to uncertainties regarding their structure and composition, difficulties in accurately measuring their electrochemically active surface area (ECSA), and deficiencies in mass-transfer (MT) rates in conventional measurements. To address these issues, we utilized an electrodeposition-thermal annealing method to precisely synthesize single-particle TMOs with well-defined structure and composition. Concurrently, we engineered low roughness, spherical surfaces for individual particles, enabling precise measurement of their ECSA. Furthermore, by constructing a conductor-core semiconductor-shell structure, we evaluated the inherent OER activity of perovskite-type semiconductor materials, broadening the scope beyond just conductive TMOs. Finally, using single-particle nanoelectrode technique, we systematically measured individual TMO particles of various sizes for OER, overcoming MT limitations seen in conventional approaches. These improvements have led us to propose a precise and reliable approach to evaluating the intrinsic activity of TMOs, not only validating the accuracy of theoretical calculations but also revealing a strong correlation of OER activity on the melting point of TMOs. This discovery holds significant importance for future high-throughput material research and applications, offering valuable insights in electrocatalysis.

4.
Comput Struct Biotechnol J ; 23: 1288-1297, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38560279

RESUMO

Carbon materials are commonly used for soil carbon sequestration and fertilization, which can also affect crop growth by manipulating the rhizosphere bacterial community. However, the comparison of the differences between active carbon (e.g., organic fertilizers) and stable carbon (e.g., biochar) on rhizosphere microdomains is still unclear. Hence, a trial was implemented to explore the influence of control (CK, no fertilizer; NPK, chemical fertilizer), organic fertilizer (CF-O, organic fertilizer; CF-BO, biochar-based organic fertilizer) and biochar material (CF-B, perishable garbage biochar; CF-PMB, pig manure biochar) on the diversity, composition, and interaction of rice rhizosphere bacterial community through 16 S rRNA gene high-throughput sequencing. Our results demonstrate that organic fertilizer increases bacterial alpha-diversity compared to no-carbon supply treatment to the extend, whereas biochar has the opposite effect. The rhizosphere bacterial community composition showed pronounced variations among the various fertilization treatments. The relative abundance in Firmicutes decreased with organic fertilizer application, whereas that in Chloroflexi and Actinobacteria decreased with biochar application. Bacterial network analysis demonstrate that organic fertilizer enhances the complexity and key taxa of bacterial interactions, while biochar exhibits an opposing trend. The findings of our study indicate that organic fertilizer may contribute to a positive and advantageous impact on bacterial diversity and interaction in rice rhizosphere, whereas the influence of biochar is not as favorable and constructive. This study lays the foundation for elucidating the fate of the rhizosphere bacterial community following different carbon material inputs in the context of sustainable agricultural development.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38593088

RESUMO

Mimicking biological skin enabling direct, intelligent interaction between users and devices, multimodal sensing with optical/electrical (OE) output signals is urgently required. Owing to this, this work aims to logically design a stretchable OE biomimetic skin (OE skin), which can sensitively sense complex external stimuli of pressure, strain, temperature, and localization. The OE skin consists of elastic thin polymer-stabilized cholesteric liquid crystal films, an ion-conductive hydrogel layer, and an elastic protective membrane formed with thin polydimethylsiloxane. The as-designed OE skin exhibits customizable structural color on demand, good thermochromism, and excellent mechanochromism, with the ability to extend the full visible spectrum, a good linearity of over 0.99, fast response speed of 93 ms, and wide temperature range of 119 °C. In addition, the conduction resistance variation of ion-conductive hydrogel exhibits excellent sensing capabilities under pressure, stretch, and temperature, endowing a good linearity of 0.99998 (stretching from 0 to 150%) and high thermal sensitivity of 0.86% per °C. Such an outstanding OE skin provides design concepts for the development of multifunctional biomimetic skin used in human-machine interaction and can find wide applications in intelligent wearable devices and human-machine interactions.

6.
Int Immunopharmacol ; 133: 112071, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636374

RESUMO

Microglia play a pivotal role in the neuroinflammatory response after brain injury, and their proliferation is dependent on colony-stimulating factors. In the present study, we investigated the effect of inhibiting microglia proliferation on neurological damage post intracerebral hemorrhage (ICH) in a mouse model, an aspect that has never been studied before. Using a colony-stimulating factor-1 receptor antagonist (GW2580), we observed that inhibition of microglia proliferation significantly ameliorated neurobehavioral deficits, attenuated cerebral edema, and reduced hematoma volume after ICH. This intervention was associated with a decrease in pro-inflammatory factors in microglia and an increased infiltration of peripheral regulatory CD8 + CD122+ T cells into the injured brain tissue. The CXCR3/CXCL10 axis is the mechanism of brain homing of regulatory CD8 + CD122+ T cells, and the high expression of IL-10 is the hallmark of their synergistic anti-inflammatory effect with microglia. And activated astrocytes around the insult site are a prominent source of CXCL10. Thus, inhibition of microglial proliferation offers a new perspective for clinical translation. The cross-talk between multiple cells involved in the regulation of the inflammatory response highlights the comprehensive nature of neuroimmunomodulation.

7.
J Res Med Sci ; 29: 8, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524748

RESUMO

Background: Myocardial infarction (MI) can lead to higher cellular damage, making cell-free DNA (cfDNA) a potential biomarker for assessing disease severity. The aim of this study is to evaluate survival predictions using cfDNA measurements and assess its correlation with MI. Materials and Methods: A direct fluorescence assay was employed to measure cfDNA content in the blood samples of participants. The inclusion criteria included patients who gave informed consent, suffering from ST-elevation myocardial infraction (STEMI) based on established diagnostic criteria (joint ESC/ACC guidelines), between the age of 18 and 80 years old, and had elevated troponin biomarker levels. The study included 150 patients diagnosed with STEMI and 50 healthy volunteers as controls. Serial monitoring of patients was conducted to track their postdisease status. The rate of change of cfDNA was calculated and daily measurements for 7 days were recorded. Results: Mean levels of cfDNA were found to be 5.93 times higher in patients with STEMI compared to healthy controls, providing clear evidence of a clinical correlation between cfDNA and STEMI. Patients were further categorized based on their survival status within a 90-day period. The study observed a strong predictive relationship between the rate of change of cfDNA during daily measurements and survival outcomes. To assess its predictive capability, a receiver operating characteristics (ROC) curve analysis was performed. The ROC analysis identified an optimal cutoff value of 2.50 for cfDNA, with a sensitivity of 81.5% and specificity of 74.0% in predicting disease outcomes. Conclusion: This study demonstrates a robust association between cfDNA and STEMI, indicating that cfDNA levels can be a valuable early prognostic factor for patients. Serial measurements of cfDNA during early disease onset hold promise as an effective approach for predicting survival outcomes in MI patients.

8.
Vaccines (Basel) ; 12(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38543925

RESUMO

We aim to understand the varicella-zoster virus (VZV) antibody levels in children after vaccination and to construct VZV-IgG centile curves and reference values for children aged 1-7 years. From September to October 2023, a total of 806 children were recruited according to the time intervals of 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination, as well as age groups. A generalized additive model for location, shape, and scale (GAMLSS) was applied to estimate P3, P10, P25, P50, P75, P90, and P97 centile reference values of VZV-IgG, and 95% reference intervals were calculated. A total of 785 children were included in the analysis, with an overall positivity rate of 70.3%, a median antibody concentration of 192.05 (82.89-571.14) mIU/mL, and a positivity rate of 57.7% for one dose of vaccine and 84.2% for two doses. Antibody positivity rates at 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination were 65.1%, 74.4%, 80.4%, 67.7%, and 63.0%, respectively. The GAMLSS results showed that VZV-IgG had a tendency to increase and then decrease after vaccination, and the second dose of vaccination could significantly increase VZV-IgG. Two doses of varicella vaccine should be administered to children in a timely manner and included in the routine vaccination programs.

9.
J Environ Manage ; 355: 120530, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38452622

RESUMO

Antibiotic contamination and excessive nitrate loads are generally concurrent in aquatic ecosystems. However, little is known about the effects of nitrate input on the biodegradation of antibiotics. In this study, the effects of nitrate input on microbial degradation of erythromycin, a typical macrolide antibiotic widely detected in lake sediments, were investigated. The results showed that the nitrate input significantly inhibited the erythromycin removal and such an inhibitory effect was strengthened with the increased input dosages. Nitrate input significantly increased sediment nitrite concentration, indicating enhanced denitrification under high nitrate pressure. Bacterial network module and keystone species analysis showed that nitrate input enriched the keystone species involved in denitrification (e.g., Simplicispira and Denitratisoma). In contrast, some potential erythromycin-degrading bacteria (e.g., Desulfatiglandales, Pseudomonadales, Nitrospira) were inhibited by nitrate input. The variations in dominant bacterial groups implied competition between denitrification and erythromycin degradation in response to nitrate input. Based on the partial least squares path modeling analysis, keystone species (total effect: 0.419) and bacterial module (total effect: 0.403) showed strong association with erythromycin removal percentage. This indicated that the inhibitory effect of nitrate input on erythromycin degradation was mainly explained by bacterial network modules and keystone species. These findings will help us to assess the bioremediation potential of antibiotic-contaminated sediments suffering from excessive nitrogen discharge concurrently.


Assuntos
Eritromicina , Nitratos , Nitratos/análise , Biodegradação Ambiental , Lagos/microbiologia , Ecossistema , Bactérias/metabolismo , Antibacterianos/farmacologia , Sedimentos Geológicos , Desnitrificação
10.
Clin Appl Thromb Hemost ; 30: 10760296241240747, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38528746

RESUMO

Deep venous thrombosis (DVT) has a significant negative impact on surgical and tumor patient's safety and quality of life. There was no specific report on the incidence and risk factors of postoperative lower extremity DVT in cervical cancer patients. Analysis of the risk factors of postoperative DVT in patients with cervical cancer is of great clinical significance for prevention and treatment. We retrospectively analyzed 309 cervical cancer patients treated by the Hubei Cervical Cancer Prevention Center and used a logistic regression model to test the risk variables of postoperative lower extremity deep venous thrombosis in cervical cancer patients. By univariate analyses, the results of the study showed that the incidence of postoperative DVT was significantly increased in cervical cancer patients complicated with old age, obesity, high preoperative plasma D-dimer level, increased preoperative triglyceride level, chronic diseases (hypertension, diabetes, and cardiovascular disease), open surgery, long operation time, intraoperative blood transfusion, advanced tumor stage, and preoperative chemotherapy/radiotherapy. Advanced age, obesity, elevated preoperative D-dimer level, high preoperative triglyceride level, and open surgery were independent risk factors for postoperative lower extremity DVT in patients with cervical cancer by multivariate regression analyses (all P < .05). In gynecologic patients with cervical cancer, there is a high incidence of postoperative lower extremity DVT. Clinicians should develop systematic and comprehensive prevention and treatment measures for the risk factors to lower this morbidity and improve patient prognosis.


Assuntos
Neoplasias do Colo do Útero , Trombose Venosa , Humanos , Feminino , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Trombose Venosa/epidemiologia , Fatores de Risco , Obesidade/complicações , Incidência , Complicações Pós-Operatórias/prevenção & controle , Extremidade Inferior/irrigação sanguínea , Triglicerídeos
11.
Cell Mol Life Sci ; 81(1): 113, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436697

RESUMO

APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.


Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Neoplasias Ovarianas , Grânulos de Estresse , Proteína 1 de Ligação a Y-Box , Feminino , Humanos , Endodesoxirribonucleases , Neoplasias Ovarianas/genética , Fosforilação , Grânulos de Estresse/metabolismo , Proteína 1 de Ligação a Y-Box/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo
12.
Mol Pharm ; 21(4): 1691-1704, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38430187

RESUMO

In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated. The internal microvoids of the cake were characterized by scanning electron microscopy and mercury intrusion porosimetry. Electron paramagnetic resonance was applied to obtain the molecular mobility of the protein during annealing. A large number of VBs were generated in the reconstitution process of unannealed omalizumab and remained for a long period of time. When annealing steps were added, the volume of VBs was dramatically reduced. When annealed at an aggressive temperature (i.e., -6 °C), although the volume of VBs decreased, the aggregation and acidic species increased significantly. Thus, our observations highlight the importance of setting an additional annealing step with a suitable temperature, which contributes to reducing the VBs while maintaining the stability of the high concentration freeze-dried protein formulation.


Assuntos
Omalizumab , Proteínas , Temperatura , Liofilização , Estabilidade de Medicamentos
13.
Planta ; 259(4): 74, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407665

RESUMO

MAIN CONCLUSION: The combined analysis of transcriptome and metabolome provided molecular insight into the dynamics of multiple active ingredients biosynthesis and accumulation across different cultivars of Lycium barbarum. Lycium barbarum L. has a high concentration of active ingredients and is well known in traditional Chinese herbal medicine for its therapeutic properties. However, there are many Lycium barbarum cultivars, and the content of active components varies, resulting in inconsistent quality between Lycium barbarum cultivars. At present, few research has been conducted to reveal the difference in active ingredient content among different cultivars of Lycium barbarum at the molecular level. Therefore, the transcriptome of 'Ningqi No.1' and 'Qixin No.1' during the three development stages (G, T, and M) was constructed in this study. A total of 797,570,278 clean reads were obtained. Between the two types of wolfberries, a total of 469, 2394, and 1531 differentially expressed genes (DEGs) were obtained in the 'G1 vs. G10,' 'T1 vs. T10,' and 'M1 vs. M10,' respectively, and were annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology identifiers. Using these transcriptome data, most DEGs related to the metabolism of the active ingredients in 'Ningqi No.1' and 'Qixin No.1' were identified. Moreover, a widely targeted metabolome analysis of the metabolites of 'Ningqi 1' and 'Qixin 1' fruits at the maturity stage revealed 1,135 differentially expressed metabolites (DEMs) in 'M1 vs. M10,' and many DEMs were associated with active ingredients such as flavonoids, alkaloids, terpenoids, and so on. We further quantified the flavonoid, lignin, and carotenoid contents of the two Lycium barbarum cultivars during the three developmental stages. The present outcome provided molecular insight into the dynamics of multiple active ingredients biosynthesis and accumulation across different cultivars of Lycium barbarum, which would provide the basic data for the formation of Lycium barbarum fruit quality and the breeding of outstanding strains.


Assuntos
Lycium , Lycium/genética , Transcriptoma/genética , Melhoramento Vegetal , Metaboloma , Carotenoides , Flavonoides/genética
14.
Angew Chem Int Ed Engl ; : e202400129, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409630

RESUMO

Probing biomolecular interactions at cellular interfaces is crucial for understanding and interfering with life processes. Although affinity binders with site specificity for membrane proteins are unparalleled molecular tools, a high demand remains for novel multi-functional ligands. In this study, a synthetic peptide (APQQ) with tight and specific binding to the untargeted extracellular loop of CD81 evolved from a genetically encoded peptide pool. With tailored affinity, APQQ flexibly accesses, site-specifically binds, and forms a complex with CD81, enabling in-situ tracking of the dynamics and activity of this protein in living cells, which has rarely been explored because of the lack of ligands. Furthermore, APQQ triggers the relocalization of CD81 from diffuse to densely clustered at cell junctions and modulates the interplay of membrane proteins at cellular interfaces. Motivated by these, efficient suppression of cancer cell migration, and inhibition of breast cancer metastasis were achieved in vivo.

15.
J Emerg Med ; 66(3): e341-e345, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38403563

RESUMO

BACKGROUND: The estimated serum osmolality is a measurement of solutes in the blood, including sodium, glucose, and urea, but also includes ethanol and toxic alcohols (e.g., methanol, ethylene glycol, diethylene glycol, isopropyl alcohol, propylene glycol) when present. These rarely measured toxic alcohols can elevate the serum osmolality, giving the true measured osmolality. The difference between that and a calculated osmolality is the osmolal gap, which can be elevated in many clinical scenarios such as renal failure, ingestion of toxic alcohols, diabetic ketoacidosis, shock, and others. CASE REPORT: We report a patient with a history of alcohol use disorder who came to the Emergency Department with an abnormally elevated osmolal gap in the setting of altered mental status. The patient's increased osmolal gap was further investigated while he was promptly treated with fomepizole, thiamine, and urgent hemodialysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We discuss the differential diagnosis for substances that increase the osmolal gap with respective ranges of elevation. This case demonstrates that although osmolal gap elevation is often attributed to the presence of toxic alcohols, other common etiologies may account for the gap, including acute renal failure and multiple myeloma.


Assuntos
Alcoolismo , Cetoacidose Diabética , Mieloma Múltiplo , Masculino , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Etanol , Metanol , Etilenoglicol , Concentração Osmolar
16.
BMC Cardiovasc Disord ; 24(1): 119, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383333

RESUMO

INTRODUCTION: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. PATIENT CONCERNS: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. DIAGNOSIS: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). INTERVENTIONS: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. OUTCOMES: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. CONCLUSION: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation.


Assuntos
Hidrogéis , Infarto do Miocárdio , Humanos , Ratos , Camundongos , Animais , Suínos , Coelhos , Ovinos , Hidrogéis/uso terapêutico , Qualidade de Vida , Infarto do Miocárdio/tratamento farmacológico , Coração , Injeções
17.
Respir Res ; 25(1): 100, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402153

RESUMO

BACKGROUND: Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. Recently, increasing evidence supports activated inflammation and gasdermin D (GSDMD)-mediated pyroptosis in macrophage are closely associated with ALI. Basic helix-loop-helix family member e40 (Bhlhe40) is a transcription factor that is comprehensively involved in inflammation. However, there is little experimental evidence connecting Bhlhe40 and GSDMD-driven pyroptosis. The study sought to verify the hypothesis that Bhlhe40 is required for GSDMD-mediated pyroptosis in lipopolysaccharide (LPS)-induced inflammatory injury. METHOD: We performed studies using Bhlhe40-knockout (Bhlhe40 -/-) mice, small interfering RNA (siRNA) targeting Bhlhe40 and pyroptosis inhibitor disulfiram to investigate the potential roles of Bhlhe40 on LPS-induced ALI and the underlying mechanisms. RESULTS: Bhlhe40 was highly expressed in total lung tissues and macrophages of LPS-induced mice. Bhlhe40-/- mice showed alleviative lung pathological injury and inflammatory response upon LPS stimulation. Meanwhile, we found that Bhlhe40 deficiency significantly suppressed GSDMD-mediated pyroptosis in macrophage in vivo and in vitro. By further mechanistic analysis, we demonstrated that Bhlhe40 deficiency inhibited GSDMD-mediated pyroptosis and subsequent ALI by repressing canonical (caspase-1-mediated) and non-canonical (caspase-11-mediated) signaling pathways in vivo and in vitro. CONCLUSION: These results indicate Bhlhe40 is required for LPS-induced ALI. Bhlhe40 deficiency can inhibit GSDMD-mediated pyroptosis and therefore alleviate ALI. Targeting Bhlhe40 may be a potential therapeutic strategy for LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Animais , Camundongos , Lipopolissacarídeos/toxicidade , Piroptose , Macrófagos/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/prevenção & controle , Lesão Pulmonar Aguda/metabolismo , Caspases/efeitos adversos , Inflamação , RNA Interferente Pequeno , Proteínas de Homeodomínio/efeitos adversos , Fatores de Transcrição Hélice-Alça-Hélice Básicos
18.
Case Rep Oncol ; 17(1): 370-376, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415269

RESUMO

Introduction: Malignant melanoma most commonly occurs in the skin. Primary malignant melanoma of endometrium is quite rare. Its diagnosis depends on clinical characteristics and pathological examination. It usually exhibits high degree of tumor histology, early onset of distant metastases, and unfavorable prognoses. Case Presentation: In this paper, we report a case of a 73-year-old woman with primary malignant melanoma of endometrium. This patient denied a history of nevus removal or any family medical history of cancer. She was admitted to the hospital for irregular vaginal bleeding after menopause and performed an endometrial biopsy. Pathological of the scrapings suggested malignant melanoma. She subsequently underwent a radical surgery. The final pathology diagnosis was primary malignant melanoma of endometrium, and BRAF gene mutation was detected. The tumor staged as IVB according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Thus, she then started adjuvant chemotherapy. This patient is currently on oral targeted therapy and is still being followed up. Conclusion: Mucosal melanoma is infrequent, and primary malignant melanoma of endometrial is a rare subtype. To the best of our knowledge, malignant melanoma originating from endometrium has never been reported before. It has a high degree of malignancy and is prone to early metastasis. Further investigations are warranted to explore its underlying pathogenesis, management, and outcomes.

19.
Am J Sports Med ; 52(3): 710-720, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38353544

RESUMO

BACKGROUND: Extracorporeal shock wave therapy (ESWT) promotes tissue healing by modulating inflammation, which has implications for meniscal tear healing in the avascular zone. PURPOSE: To evaluate the effects of a single dose of radial ESWT on the healing process and inflammation of the meniscus and knee joints after meniscal tears in the avascular zone. STUDY DESIGN: Controlled laboratory study. METHODS: Avascular tears were induced in the medial meniscus (MM) of 72 Sprague-Dawley rats. One week postoperatively, the rats received a single session of radial ESWT with a Power+ handpiece (ESWT group; n = 36) or with a fake handpiece (sham-ESWT group; n = 36). The rats were then euthanized at 2, 4, or 8 weeks postoperatively. The MMs were harvested for analysis of healing (hematoxylin-eosin, safranin O-Fast Green, and collagen type 2 staining) and inflammation (interleukin [IL]-1ß and IL-6 staining). Lateral menisci and synovia were obtained to evaluate knee joint inflammation (enzyme-linked immunosorbent assay of IL-1ß and IL-6). Cartilage degeneration was assessed in the femurs and tibial plateaus using safranin O-Fast Green staining. RESULTS: The ESWT group showed significantly better meniscal healing scores than the sham-ESWT group at 4 (P = .0066) and 8 (P = .0050) weeks postoperatively. The IL-1ß level was significantly higher in the sham-ESWT group than in the ESWT group at 2 (MM: P = .0009; knee joint: P = .0160) and 8 (MM: P = .0399; knee joint: P = .0001) weeks. The IL-6 level was significantly lower in the sham-ESWT group than in the ESWT group at 2 (knee joint: P = .0184) and 4 (knee joint: P = .0247) weeks but higher at 8 weeks (MM: P = .0169; knee joint: P = .0038). The sham group had significantly higher osteoarthritis scores than the ESWT group at 4 (tibial plateau: P = .0157) and 8 (femur: P = .0048; tibial plateau: P = .0359) weeks. CONCLUSION: A single dose of radial ESWT promoted meniscal tear healing in the avascular zone, modulated inflammatory factors in the menisci and knee joints in rats, and alleviated cartilage degeneration. CLINICAL RELEVANCE: Radial ESWT can be considered a potential option for improving meniscal tear healing in the avascular zone because of its ability to modulate inflammation.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Traumatismos do Joelho , Lacerações , Osteoartrite , Corantes de Rosanilina , Animais , Ratos , Ratos Sprague-Dawley , Interleucina-6 , Inflamação/terapia
20.
Pest Manag Sci ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385791

RESUMO

BACKGROUND: Apolygus lucorum, a major cotton pest, has undergone a significant expansion of the FMRFaR gene within the GPCR superfamily, resulting in two classes of GPCR, namely FMRFaR (A54-55) and newly duplicated FMRFaR-like (A56-62). Notably, FMRFaR-like genes, particularly A62, show enhanced expression in the legs and wings of adults, indicating their potential role in locomotion. Employing A62 as a representative of FMRFaR-like, our study investigates the influence of FMRFa, FMRFaR, and FMRFaR-like on locomotion and development of A. lucorum. RESULTS: FMRFaR and FMRFa exhibit comparable temporal and tissue expression patterns, whereas the FMRFaR-like genes within A. lucorum exhibit completely distinct evolutionary and expression patterns compared to classical FMRFaR. RNA interference (RNAi) experiments revealed that suppressing FMRFa expression results in complete lethality in A. lucorum, but neither FMRFaR nor A62 exhibit the same effect after RNAi. Suppressing the expression of FMRFa only decreases the expression of the A54 gene simultaneously, suggesting that A54 may function as a classical FMRFaR activated by FMRFa. RNAi of A62 leads to wing malformation and a significant reduction in spontaneous movement behavior in A. lucorum. Further transcriptomic analysis revealed that A62 affects the A. lucorum's movement behavior through energy metabolism pathways and motor protein pathways. CONCLUSION: Our study unveils the unique and complex roles of FMRFa and its receptor in A. lucorum. These findings provide valuable insights into potential targets for pest control strategies aimed at managing A. lucorum populations in cotton fields. © 2024 Society of Chemical Industry.

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