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1.
Mycology ; 15(1): 91-100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558843

RESUMO

Although rare, trans-kingdom infection features an interesting infection biology concept, in which highly versatile pathogenic attributes allow successful infections in evolutionarily highly divergent species. Corynespora cassiicola is a phytopathogenic fungus and occasionally causes human infections. Herein, we report a phaeohyphomycosis case caused by C. cassiicola. Given that sporadic reports may contribute to a lack of awareness of the transmission route, clinical manifestations, and diagnostic and clinical management, we systematically reviewed the cases reported thus far. Nine patients were identified and included in the pooled analysis, 88.9% (8/9) of whom were reported after 2010. All patients were from Asian, African, and Latin American countries, among whom 77.8% (7/9) were farmers or lived in areas with active agriculture. Exposed body parts were the major affected infection area, and clinical manifestations were mainly non-specific inflammatory reactions. Although biochemical and morphological examinations confirmed the presence of fungal infection, molecular analysis was used for the final diagnosis, with 77.8% (7/9) being identified by internal transcribed spacer sequencing. Whereas voriconazole, terbinafine, and AmB, either alone or in combination, resulted in successful infection resolution in most cases (5/9; 55.5%), those suffering from invasive facial infections and CARD9 deficiency showed poor outcomes. Our patient is the third case of invasive facial infection caused by C. cassiicola and was successfully treated with intravenous LAmB followed by oral voriconazole combined with topical antifungal irrigation. Molecular identification of fungus and prompt antifungal treatment is pivotal in the clinical success of patients suspected to have phaeohyphomycosis. Moreover, as evidenced by our data, itraconazole treatment is not recommended.

2.
Food Chem X ; 22: 101292, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38559439

RESUMO

Polygonatum kingianum Coll. et (Hemsl) is a famous Chinese traditional food and medicine analogous plant. The rhizome of P. kingianum showed a decrease in levels of alkaloids, amino acids and derivatives, terpenoids, and an increase in organic acid and saccharides when it was processed by the traditional method of "Nine Cycles of Steaming and Sun-Drying". The relative content of 341 metabolites were increased (fold change, FC > 2; variable importance in projection, VIP > 1 and P-value, P < 0.05); while 456 metabolites were decreased (FC < 0.5, VIP > 1, and P < 0.05). The changes in chemical components result in a decrease in numb taste and an increase in sweetness. The increased antioxidant activity was observed in the processed samples. Together, this work has advanced the mechanism of reducing numb taste and enhancing antioxidant activity in the resource plants, such as P. kingianum, processed by the traditional method.

3.
Pediatr Surg Int ; 40(1): 104, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600320

RESUMO

OBJECTIVE: Children with congenital anorectal malformation (CAM) experience challenges with defecation. This study aims to assess defecation in preschool-age children with CAM and to evaluate the correlation between pelvic floor muscle developed assessed by magnetic resonance imaging (MRI) and postoperative defecation. METHODS: We collected clinical data and MRI results from 89 male children with CAM. The bowel function scores for children with Perineal (cutaneous) fistula, Rectourethral fistula(Prostatic or Bulbar), and Rectovesical fistula were computed. MRI scans were subjected to image analysis of the striated muscle complex (SMC). The association between pelvic floor muscle score and bowel function score was examined using the Cochran-Armitage Trend Test. RESULTS: We observed that 77.4% of the SMC scores by MRI for Perineal fistula were good. The Rectourethral fistula SMC score was 40.6% for moderate and 59.4% for poor. The SMC score for Rectovesical fistula was 100% for moderate. Furthermore, 77.4% of patients with Perineal fistula had bowel function scores (BFS) ≥ 17 points. Among those with Rectourethral fistula and Rectovesical fistula, 12.5% and 0 had BFS ≥ 17 points, respectively. An analysis of muscle development and bowel function in patients with Rectovesical fistula, Rectourethral fistula, and Perineal fistula revealed a correlation between SMC development and BFS. Subgroup analysis showed that the Perineal fistula had statistical significance; however, the Rectourethral fistula and Rectovesical fistula were not statistically significant. CONCLUSION: A correlation exists between pelvic floor muscle development and postoperative defecation in children with Perineal fistula.


Assuntos
Malformações Anorretais , Fístula Retal , Doenças Uretrais , Fístula da Bexiga Urinária , Fístula Urinária , Criança , Pré-Escolar , Humanos , Masculino , Reto/cirurgia , Defecação , Diafragma da Pelve/diagnóstico por imagem , Diafragma da Pelve/cirurgia , Fístula Retal/cirurgia , Canal Anal/diagnóstico por imagem , Canal Anal/cirurgia , Canal Anal/anormalidades , Fístula Urinária/cirurgia , Doenças Uretrais/cirurgia , Imageamento por Ressonância Magnética
4.
Int Immunopharmacol ; 132: 111970, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608472

RESUMO

OBJECTIVES: As antibiotics become more prevalent, accuracy and safety are critical. Moxifloxacin (MXF) have been reported to have immunomodulatory effects on a variety of immune cells and even anti-proliferative and pro-apoptotic effects, but the mechanism of action is not fully clear. METHODS: Peripheral blood mononuclear cells (PBMC) from experimental groups of healthy adults (n = 3) were treated with MXF (10ug/ml) in vitro for 24 h. Single-cell sequencing was performed to investigate differences in the response of each immune cell to MXF. Flow cytometry determined differential gene expression in subsets of most damaged NK cells. Pseudo-time analysis identified drivers that influence MXF-stimulated cell differentiation. Detection of mitochondrial DNA and its involvement in the mitochondrial respiratory chain pathway clarifies the origin of MXF-induced stress injury. RESULTS: Moxifloxacin-environmental NK cells are markedly reduced: a new subset of NK cells emerges, and immediate-early-response genes in this subset indicate the presence of an early activation response. The inhibitory receptor-dominant subset shows enhanced activation, leading to increased expression of cytokines and chemokines. The near-mature subset showed greater cytotoxicity and the most pronounced cellular damage. CD56bright cells responded by antagonizing the regulation of activation and inhibitory signals, demonstrating a strong cleavage capacity. The severe depletion of mitochondrial genes was focused on apoptosis induced by the mitochondrial respiratory chain complex. CONCLUSION: NK cells exhibit heightened sensitivity to the MXF environment. Different NK subsets upregulate the expression of cytokines and chemokines through different activation pathways. Concurrently, MXF induces impairment of the mitochondrial oxidative phosphorylation system, culminating in apoptosis.

5.
Skin Res Technol ; 30(4): e13698, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634154

RESUMO

BACKGROUND: Dermoscopy is a common method of scalp psoriasis diagnosis, and several artificial intelligence techniques have been used to assist dermoscopy in the diagnosis of nail fungus disease, the most commonly used being the convolutional neural network algorithm; however, convolutional neural networks are only the most basic algorithm, and the use of object detection algorithms to assist dermoscopy in the diagnosis of scalp psoriasis has not been reported. OBJECTIVES: Establishment of a dermoscopic modality diagnostic framework for scalp psoriasis based on object detection technology and image enhancement to improve diagnostic efficiency and accuracy. METHODS: We analyzed the dermoscopic patterns of scalp psoriasis diagnosed at 72nd Group army hospital of PLA from January 1, 2020 to December 31, 2021, and selected scalp seborrheic dermatitis as a control group. Based on dermoscopic images and major dermoscopic patterns of scalp psoriasis and scalp seborrheic dermatitis, we investigated a multi-network fusion object detection framework based on the object detection technique Faster R-CNN and the image enhancement technique contrast limited adaptive histogram equalization (CLAHE), for assisting in the diagnosis of scalp psoriasis and scalp seborrheic dermatitis, as well as to differentiate the major dermoscopic patterns of the two diseases. The diagnostic performance of the multi-network fusion object detection framework was compared with that between dermatologists. RESULTS: A total of 1876 dermoscopic images were collected, including 1218 for scalp psoriasis versus 658 for scalp seborrheic dermatitis. Based on these images, training and testing are performed using a multi-network fusion object detection framework. The results showed that the test accuracy, specificity, sensitivity, and Youden index for the diagnosis of scalp psoriasis was: 91.0%, 89.5%, 91.0%, and 0.805, and for the main dermoscopic patterns of scalp psoriasis and scalp seborrheic dermatitis, the diagnostic results were: 89.9%, 97.7%, 89.9%, and 0.876. Comparing the diagnostic results with those of five dermatologists, the fusion framework performs better than the dermatologists' diagnoses. CONCLUSIONS: Studies have shown some differences in dermoscopic patterns between scalp psoriasis and scalp seborrheic dermatitis. The proposed multi-network fusion object detection framework has higher diagnostic performance for scalp psoriasis than for dermatologists.


Assuntos
Dermatite Seborreica , Psoríase , Neoplasias Cutâneas , Humanos , Couro Cabeludo , Inteligência Artificial , Redes Neurais de Computação , Dermoscopia/métodos , Neoplasias Cutâneas/diagnóstico
6.
J Neurotrauma ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38553903

RESUMO

Traumatic brain injury (TBI)-a severe clinical problem-is compounded by a lack of effective treatments and impeded intracranial metabolic waste clearance. The glymphatic system and meningeal lymphatic vessels are instrumental in TBI pathophysiology and crucial for clearing harmful substances. Cannabidiol (CBD) has the potential to address metabolic imbalances and improve cognitive functions in neurodegenerative diseases, but its specific effect on TBI remains unclear. Using a fluid percussion injury model, we adopted a comprehensive approach that included behavioral testing, various imaging techniques, and deep cervical lymph node (dCLN) ligation to evaluate CBD's effects on neurological outcomes and lymphatic clearance in a TBI mouse model. Our results demonstrated that CBD markedly enhanced motor, memory, and cognitive functions, correlating with reduced levels of detrimental neural proteins. CBD also expedited the removal of intracranial tracers, increased cerebral blood flow, and improved tracer migration from lymphatic vessels to dCLNs. Intriguingly, CBD treatment modified aquaporin-4 polarization and diminished neuroinflammatory indicators. A key observation was that disrupting efferent lymphatic channels nullified CBD's positive effects on waste removal and cognitive enhancements, whereas its anti-inflammatory benefits continued. This finding suggests that CBD's ability to improve waste clearance may operate via the lymphatic system, thereby improving neurological outcomes in TBI patients. Therefore, our study underscores CBD's potential therapeutic role in TBI management.

7.
JAMA Netw Open ; 7(3): e241765, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38477921

RESUMO

Importance: With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. Objective: To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir. Design, Setting, and Participants: This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir. Interventions: Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60. Main Outcomes and Measures: The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set. Results: The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case. Conclusions and Relevance: In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.


Assuntos
Adenosina , COVID-19 , Recidiva , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Tratamento Farmacológico da COVID-19 , China , Ritonavir , SARS-CoV-2 , Adenosina/análogos & derivados
8.
CNS Neurosci Ther ; 30(3): e14673, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468459

RESUMO

AIM: We aim to identify the specific CD4+ T-cell subtype influenced by brain-to-CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI). METHOD: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4+ T-cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time-of-flight analysis (CyTOF) or fluorescence-activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4+ T cells, specifically CD11b-positive CD4+ T cells, within the affected region. The population of CD4+ CD11b+ T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine-1-phosphate receptor-1 (S1PR1) on these cells. Administration of CD4+ CD11b+ T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy. CONCLUSION: The infiltration of CD4+ CD11b+ T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain-to-CLN signaling.


Assuntos
Edema Encefálico , Lesões Encefálicas Traumáticas , Vasos Linfáticos , Humanos , Animais , Edema Encefálico/patologia , Linfócitos T , Lesões Encefálicas Traumáticas/patologia , Encéfalo/patologia , Apoptose , Citocinas , Vasos Linfáticos/patologia , Linfócitos T CD4-Positivos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Modelos Animais de Doenças
9.
Sci Rep ; 14(1): 3559, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347043

RESUMO

This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone.


Assuntos
Hematoma Subdural Crônico , Humanos , Estudos Retrospectivos , Atorvastatina/uso terapêutico , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/tratamento farmacológico , Tomografia Computadorizada por Raios X , Dexametasona/uso terapêutico
10.
Artigo em Inglês | MEDLINE | ID: mdl-38383980

RESUMO

BACKGROUND: Hypertensive heart disease (HHD) is a common cause of cardiovascular disease and mortality worldwide, and its burden is increasing with aging populations. OBJECTIVES: This study aimed to estimate the prevalence and mortality rates of HHD in mainland China and Taiwan Province using data from the Global Burden of Disease Study 2019 (GBD 2019), and forecast the development trend of HHD from 2020 to 2024. METHODS: We obtained data on number of cases, deaths, crude prevalence rate, crude death rate, age-standardized prevalence rate (ASPR), and age-standardized death rate (ASDR) for mainland China and Taiwan Province from 1990 to 2019 from the GBD 2019. Joinpoint software was used to estimate average annual percentage change (AAPC) with 95% confidence intervals, and the number of HHD cases in China from 2022 to 2024 was predicted by the exponential smoothing method. RESULTS: Between 1990 and 2019, HHD cases and deaths increased in mainland China, but the ASPR and ASDR decreased by 5.96% and 48.72%, respectively. In Taiwan Province, ASPR and ASDR decreased by 7.66% and 52.14%, respectively. The number of HHD cases and death rates varied by region, age, and sex, with a higher number of cases in mainland China than in Taiwan Province. By 2024, the number of HHD cases in mainland China was projected to be over 9.6 million cases, and in Taiwan Province, it was projected to surpass 120,000 cases. CONCLUSION: The differences in HHD cases between mainland China and Taiwan Province in terms of age and sex indicated the need for effective prevention and control measures, especially targeting the elderly population. These findings can inform policymakers and health professionals in the development of targeted prevention and treatment strategies and resource allocation for HHD in China.

11.
J Neurotrauma ; 41(5-6): 660-670, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38204204

RESUMO

Cardiac injury is a common complication following traumatic brain injury (TBI) that can lead to poor clinical outcomes. Angiotensin II type 2 receptor (AT2R) activation exerts protective roles in the brain and heart, yet its potential impact on TBI or TBI-induced cardiac deficits remains elusive. The goal of this study was to investigate the influence of AT2R activation on recovery after TBI-induced cognitive and cardiac injury using the selective nonpeptide AT2R agonist compound 21 (C21). TBI was induced by cortical impact injury in male adult C57BL/6J mice, and the mice received C21 (0.03 mg/kg, intraperitoneally) starting from 24 h after TBI and continuing once daily. C21 facilitated cognitive function recovery until 1 month after TBI. C21 alleviated blood-brain barrier leakage and brain edema and inhibited the expression of proinflammatory cytokines in the brain after 3 consecutive days of treatment. C21 improved cerebral blood flow after 1 month, although the lesion volume was not affected. C21 also reduced the expression of proinflammatory cytokines in the heart after a 3-day consecutive treatment. Meanwhile, C21 benefited cardiac function, as identified by increased left ventricular ejection fraction 1 month after TBI. In addition, C21 alleviated TBI-induced cardiac hypertrophy and fibrosis; however, blood pressure was not affected. Our results demonstrate that AT2R activation ameliorates TBI-induced neurological and cardiac deficits.


Assuntos
Lesões Encefálicas Traumáticas , Imidazóis , Receptor Tipo 2 de Angiotensina , Sulfonamidas , Tiofenos , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Volume Sistólico , Função Ventricular Esquerda , Encéfalo , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Citocinas
12.
Cytokine ; 175: 156451, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38163400

RESUMO

OBJECTIVE: This study aims to investigate the effect of lysine demethylase 5B (KDM5B)-mediated dimethyl-lysine 4 histone H3 (H3K4me2) demethylation on immune microenvironment remodeling in pancreatic cancer. METHODS: Pan 02 mouse pancreatic cancer cell lines were cultured and used to establish tumor model in vivo. RT-qPCR and Western blot were used to detect the expression of stimulator of interferon gene (STING) and KDM5B in pancreatic cancer tissues and Pan 02 cells. The specific demethylation domain of KDM5B was detected by isothermal titration calorimetry binding assay. The regulatory roles of KDM5B in cell apoptosis and remodeling of immune microenvironment in vitro and in vivo were explored after loss-of functions in KDM5B. RESULTS: KDM5B was highly expressed but STING was poorly expressed in pancreatic cancer tissues and Pan 02 cells. After knockdown of KDM5B, CD8+ T cells recognized and killed Pan 02 cells, which promoted the infiltration of CD8+ T cells in Pan 02 cells, thus improving the anti-tumor ability. The PHD domain in KDM5B specifically bound to H3K4me2 peptide and inhibition of KDM5B induced STING expression. Knockdown of KDM5B up-regulated STING expression to promote apoptosis, thus regulating the immune microenvironment and inhibiting the growth of tumor in mice. Meanwhile, knockdown of KDM5B and STING simultaneously counteracted the knockdown effect of KDM5B. CONCLUSION: Inhibition of KDM5B can promote the expression of STING through H3K4me2 demethylation, which promoted the recognition and killing of Pan 02 cells by CD8+ T cells, thus improving the anti-tumor ability and regulating the immune microenvironment.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias Pancreáticas , Animais , Camundongos , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Expressão Gênica , Histonas/metabolismo , Lisina/metabolismo , Microambiente Tumoral
13.
Theranostics ; 14(1): 304-323, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164141

RESUMO

Rationale: Meningeal lymphatic vessels (MLVs) are essential for the clearance of subdural hematoma (SDH). However, SDH impairs their drainage function, and the pathogenesis remains unclear. Herein, we aimed to understand the pathological mechanisms of MLV dysfunction following SDH and to test whether atorvastatin, an effective drug for SDH clearance, improves meningeal lymphatic drainage (MLD). Methods: We induced SDH models in rats by injecting autologous blood into the subdural space and evaluated MLD using Gadopentetate D, Evans blue, and CFSE-labeled erythrocytes. Whole-mount immunofluorescence and transmission electron microscopy were utilized to detect the morphology of MLVs. Phosphoproteomics, western blot, flow cytometry, and in vitro experiments were performed to investigate the molecular mechanisms underlying dysfunctional MLVs. Results: The basal MLVs were detected to have abundant valves and play an important role in draining subdural substances. Following SDH, these basal MLVs exhibited disrupted endothelial junctions and dilated lumen, leading to impaired MLD. Subsequent proteomics analysis of the meninges detected numerous dephosphorylated proteins, primarily enriched in the adherens junction, including significant dephosphorylation of ERK1/2 within the meningeal lymphatic endothelial cells (LECs). Subdural injection of the ERK1/2 kinase inhibitor PD98059 resulted in dilated basal MLVs and impaired MLD, resembling the dysfunctional MLVs observed in SDH. Moreover, inhibiting ERK1/2 signaling severely disrupted intercellular junctions between cultured LECs. Finally, atorvastatin was revealed to protect the structure of basal MLVs and accelerate MLD following SDH. However, these beneficial effects of atorvastatin were abolished when combined with PD98059. Conclusion: Our findings demonstrate that SDH induces ERK1/2 dephosphorylation in meningeal LECs, leading to disrupted basal MLVs and impaired MLD. Additionally, we reveal a beneficial effect of atorvastatin in improving MLD.


Assuntos
Sistema Glinfático , Vasos Linfáticos , Ratos , Animais , Atorvastatina/farmacologia , Células Endoteliais , Sistema de Sinalização das MAP Quinases , Hematoma Subdural
14.
J Transl Med ; 22(1): 97, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263066

RESUMO

Atherosclerosis is a chronic, progressive, inflammatory disease that occurs in the arterial wall. Despite recent advancements in treatment aimed at improving efficacy and prolonging survival, atherosclerosis remains largely incurable. In this review, we discuss emerging single-cell sequencing techniques and their novel insights into atherosclerosis. We provide examples of single-cell profiling studies that reveal phenotypic characteristics of atherosclerosis plaques, blood, liver, and the intestinal tract. Additionally, we highlight the potential clinical applications of single-cell analysis and propose that combining this approach with other techniques can facilitate early diagnosis and treatment, leading to more accurate medical interventions.


Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Medicina de Precisão , Artérias , Fígado
15.
Mol Cell Biochem ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294731

RESUMO

Subdural hematoma (SDH) drains into the extracranial lymphatic system through the meningeal lymphatic vessels (mLVs) but the formation of SDH impairs mLVs. Because vitamin D (Vit D) can protect the endothelial cells, we hypothesized that Vit D may enhance the SDH clearance. SDH was induced in Sprague-Dawley rats and treated with Vit D or vehicle. Hematoma volume in each group was measured by H&E staining and hemoglobin quantification. Evans blue (EB) quantification and red blood cells injection were used to evaluated the drainage of mLVs. Western blot analysis and immunofluorescence were conducted to assess the expression of lymphatic protein markers. We also examined the inflammatory factors levels in subdural space by ELISA. Vit D treatment significantly reduced SDH volume and improved the drainage of SDH to cervical lymph nodes. The structure of mLVs in SDH rats were protected by Vit D, and the expressions of LYVE1, PROX1, FOXC2, and VE-cadherin were increased after Vit D treatment. The TNF-α, IL-6, and IL-8 levels were reduced in Vit D group. In vitro, Vit D also increased the VE-cadherin expression levels under inflammation. Vit D protects the structure of mLVs and enhances the absorption of SDH, partly by the anti-inflammatory effect of Vit D.

17.
Small ; : e2308002, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38084459

RESUMO

In order to reveal the dynamic response characteristic of thin film thermocouples (TFTCs), the nichrome/nisil (NiCr/NiSi) TFTCs are prepared onto the glass substrate. With short pulse infrared laser system, NiCr/NiSi TFTCs are dynamically calibrated. The thermoelectric electromotive force (TEF) curves of NiCr/NiSi TFTCs are recorded by the memory hicorder system, which could reflect TEF signals with resolution ratio in nanosecond and microvolt, simultaneously. With increasing laser energy from 15.49 to 29.59 mJ, TEF curves display more and more violent oscillation, even negative value. The results show that the bounce of thermal energy happens between two interfaces of TFTCs because the thermal conductivity of glass and air is significantly lower than that of NiSi/NiCr TFTCs. The bounce of thermal energy results in the obvious decrease of nNiCr and nNiSi , as well as oscillation of TEF. For laser energy in 29.59 mJ, the bounce of thermal energy in NiCr film could result in nNiCr < nNiSi . Then, TEF value appears abnormal negative value. Based on the results, the complex thermal energy transport process in TFTCs dynamic calibration is revealed, which results in the oscillation of thermal energy and TEF signal.

18.
Heliyon ; 9(11): e21316, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37942163

RESUMO

The presented study examines the chemical composition and antioxidant activity of the petroleum ether fraction of Rosmarinus officinalis (PEF-RO), which was obtained via 75 % ethanol extraction followed by petroleum ether extraction. The obtained fractions were analyzed by gas chromatography-mass spectrometry (GC-MS). The in vitro antioxidant activity of PEF-RO was investigated using various assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate (ABTS) free radical scavenging, and ferric reducing antioxidant power (FRAP) method. A total of 82 chemical components were successfully identified, totaling 10.06 % of PEF-RO content. The identified components consisted of 24 hydrocarbons, 14 ketones, 16 alcohols, 4 phenols, 14 esters, and 10 other compounds. Notably, verbenone (2.4377 %), vitamin A (0.6854 %), trans-geraniol (0.5998 %), linolenic acid (0.5713 %), and 1,8-eucalyptol (0.5323 %) were the most abundant compounds, and there are many trace components in PEF-RO. PEF-RO's IC50 values of DPPH and ABTS free radical scavenging were determined as 0.36 mg/mL and 0.19 mg/mL, respectively. FRAP-method was employed to measure the total antioxidant energy of PEF-RO, which displayed good antioxidant activity. The obtained data provides the foundation for the comprehensive development and utilization of Rosmarinus officinalis.

19.
Mol Med Rep ; 28(6)2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37921069

RESUMO

Insulin growth factor­1 (IGF­1) is an endocrine regulator that plays an important role in normal growth and development. IGF­1 mediated effects may result in protecting macrophages from immunometabolic response. However, it is unclear whether IGF­1 has a protective effect on fatty acid­induced macrophages damage. In the present study, THP­1 cells were differentiated into macrophages and stimulated with palmitic acid (PA) in the absence or presence of IGF­1. Macrophages apoptosis was measured by Cell Counting Kit­8 assay, flow cytometry, Hoechst 33342 staining and western blotting. The mitochondrial damage was evaluated using JC­1 staining and mitochondrial reactive oxygen species detection. The activation of mitophagy was assessed using immunofluorescence and western blotting. As a result, IGF­1 significantly restored the survival rate in macrophages, while the apoptosis was inhibited through mitochondrial pathway. In addition, IGF­1 protected the mitochondrial damage induced by PA. Furthermore, PA induced mitophagy via phosphatase and tensin homolog­induced putative kinase protein 1/Parkin, which was reversed by IGF­1. Taken together, the present study demonstrated the protective effect of IGF­1 on PA­induced mitochondrial apoptosis in macrophages, which might provide a potential therapeutic strategy for treatment of lipotoxicity.


Assuntos
Insulina , Ácido Palmítico , Insulina/farmacologia , Ácido Palmítico/toxicidade , Fator de Crescimento Insulin-Like I/farmacologia , Apoptose , Mitofagia , Espécies Reativas de Oxigênio/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
20.
Heliyon ; 9(10): e20680, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37860513

RESUMO

In this study, total alkaloids from Hemsleya chinensis were extracted and tested for their antioxidant properties. To optimize extraction methods, a single factor experiment was conducted to determine the total alkaloid concentrations of H. chinensis using the L9 (34) orthogonal design test method and the BP neural network (BPNN), resulting in the optimum extraction conditions for total alkaloids. The optimal conditions for H. chinensis alkaloids extraction with acid water are: HCl concentration is 0.50 %, extraction temperature is 85 °C, material-liquid ratio is 1:64.5, and extraction rate of alkaloids is 0.2785 ± 0.0003 mg/mL. The alkaloid from H. chinensis exhibited antioxidant activity in a quantity-effect relationship with activity. These findings showed that the procedure to be reasonable, the alkaloid extraction efficiency to be high, and the method could be used to extract the alkaloids of H. chinensis, improving the development of natural and healthy medicinal resources for the pharmaceutical and food industries.

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