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1.
Heliyon ; 10(6): e27833, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38560678

RESUMO

3-n-butylphthalide (NBP) contains one of the main active ingredients of celery seed. It has a series of pharmacological mechanisms, including reconstitution of microcirculation, protection of mitochondrial function, inhibition of oxidative stress, and inhibition of neuronal apoptosis. Based on the complex multi-targeting of NBP pharmacological mechanisms, the clinical applications of NBP are increasing, and more and more clinical studies and animal experiments have focused on NBP. In this study, we used male Sprague Dawley rats as an animal model to elucidate the intervention effect of butylphthalide on high altitude cerebral edema (HACE), and also compared the effect of butylphthalide and rhodiola rosea on HACE. Firstly, we measured the changes of body weight and brain water content and observed the pathological changes of brain tissues. In addition, the contents of inflammatory factors, oxidative stress and brain neurotransmitters were assessed by enzyme-linked immunoassay kits, and finally, the expression of apoptotic proteins in brain tissues was determined by western blotting. The results showed that NBP reduced brain water content, attenuated brain tissue damage, altered inflammatory factors, oxidative stress indicators, and brain neurotransmitter levels, and in addition NBP inhibited the expression of Caspase-related apoptotic proteins. Therefore, NBP has the potential to treat and prevent HACE.

3.
Front Immunol ; 15: 1359859, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562941

RESUMO

Background: Acute rejection (AR) after liver transplantation (LT) remains an important factor affecting the prognosis of patients. CD8+ T cells are considered to be important regulatory T lymphocytes involved in AR after LT. Our previous study confirmed that autophagy mediated AR by promoting activation and proliferation of CD8+ T cells. However, the underlying mechanisms regulating autophagy in CD8+ T cells during AR remain unclear. Methods: Human liver biopsy specimens of AR after orthotopic LT were collected to assess the relationship between JNK and CD8+ T cells autophagy. The effect of JNK inhibition on CD8+ T cells autophagy and its role in AR were further examined in rats. Besides, the underlying mechanisms how JNK regulated the autophagy of CD8+ T cells were further explored. Results: The expression of JNK is positive correlated with the autophagy level of CD8+ T cells in AR patients. And similar findings were obtained in rats after LT. Further, JNK inhibitor remarkably inhibited the autophagy of CD8+ T cells in rat LT recipients. In addition, administration of JNK inhibitor significantly attenuated AR injury by promoting the apoptosis and downregulating the function of CD8+ T cells. Mechanistically, JNK may activate the autophagy of CD8+ T cells through upregulating BECN1 by inhibiting the formation of Bcl-2/BECN1 complex. Conclusion: JNK signaling promoted CD8+ T cells autophagy to mediate AR after LT, providing a theoretical basis for finding new drug targets for the prevention and treatment of AR after LT.


Assuntos
Transplante de Fígado , Ratos , Humanos , Animais , Transplante de Fígado/efeitos adversos , Linfócitos T CD8-Positivos , Sistema de Sinalização das MAP Quinases , Apoptose , Autofagia
4.
bioRxiv ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38585869

RESUMO

To gain insight into how ERG translocations cause prostate cancer, we performed single cell transcriptional profiling of an autochthonous mouse model at an early stage of disease initiation. Despite broad expression of ERG in all prostate epithelial cells, proliferation was enriched in a small, stem-like population with mixed-luminal basal identity (called intermediate cells). Through a series of lineage tracing and primary prostate tissue transplantation experiments, we find that tumor initiating activity resides in a subpopulation of basal cells that co-express the luminal genes Tmprss2 and Nkx3.1 (called BasalLum) but not in the larger population of classical Krt8+ luminal cells. Upon ERG activation, BasalLum cells give rise to the highly proliferative intermediate state, which subsequently transitions to the larger population of Krt8+ luminal cells characteristic of ERG-positive human cancers. Furthermore, this proliferative population is characterized by an ERG-specific chromatin state enriched for NFkB, AP-1, STAT and NFAT binding, with implications for TF cooperativity. The fact that the proliferative potential of ERG is enriched in a small stem-like population implicates the chromatin context of these cells as a critical variable for unmasking its oncogenic activity.

5.
bioRxiv ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38645223

RESUMO

Lineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage plasticity remain poorly understood. Here, we describe a versatile in vivo platform to identify and interrogate the molecular determinants of neuroendocrine lineage transformation at different stages of prostate cancer progression. Adenocarcinomas reliably develop following orthotopic transplantation of primary mouse prostate organoids acutely engineered with human-relevant driver alterations (e.g., Rb1-/-; Trp53-/-; cMyc+ or Pten-/-; Trp53-/-; cMyc+), but only those with Rb1 deletion progress to ASCL1+ neuroendocrine prostate cancer (NEPC), a highly aggressive, androgen receptor signaling inhibitor (ARSI)-resistant tumor. Importantly, we show this lineage transition requires a native in vivo microenvironment not replicated by conventional organoid culture. By integrating multiplexed immunofluorescence, spatial transcriptomics and PrismSpot to identify cell type-specific spatial gene modules, we reveal that ASCL1+ cells arise from KRT8+ luminal epithelial cells that progressively acquire transcriptional heterogeneity, producing large ASCL1+;KRT8- NEPC clusters. Ascl1 loss in established NEPC results in transient tumor regression followed by recurrence; however, Ascl1 deletion prior to transplantation completely abrogates lineage plasticity, yielding adenocarcinomas with elevated AR expression and marked sensitivity to castration. The dynamic feature of this model reveals the importance of timing of therapies focused on lineage plasticity and offers a platform for identification of additional lineage plasticity drivers.

6.
bioRxiv ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38659913

RESUMO

BRAFV600E mutation occurs in 46% of melanomas and drives high levels of ERK activity and ERK-dependent proliferation. However, BRAFV600E is insufficient to drive melanoma in GEMM models, and 82% of human benign nevi harbor BRAFV600E mutations. We show here that BRAFV600E inhibits mesenchymal migration by causing feedback inhibition of RAC1 activity. ERK pathway inhibition induces RAC1 activation and restores migration and invasion. In cells with BRAFV600E, mutant RAC1, overexpression of PREX1, PREX2, or PTEN inactivation restore RAC1 activity and cell motility. Together, these lesions occur in 48% of BRAFV600E melanomas. Thus, although BRAFV600E activation of ERK deregulates cell proliferation, it prevents full malignant transformation by causing feedback inhibition of cell migration. Secondary mutations are, therefore, required for tumorigenesis. One mechanism underlying tumor evolution may be the selection of lesions that rescue the deleterious effects of oncogenic drivers.

7.
Cell Mol Biol Lett ; 29(1): 46, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561669

RESUMO

BACKGROUND: Small extracellular vesicles (sEV) are closely associated with the development and metastasis of many types of mammalian cancer. Glycoconjugates are highly expressed on sEV and play important roles in sEV biogenesis and their interaction with other cells. However, the study on vesicular glycoconjugates are far behind proteins and nucleic acids. Especially, the functions of sialic acids which are the terminal components of glycoconjugates, are poorly understood in sEV. METHODS: Sialic acid levels on sEV from plasma and bladder cancer cells were determined by ELISA and lectin blotting. Effects of sialylation on sEV uptake were determined by flow cytometry. Vesicular glycoproteins bearing sialic acids responsible for sEV uptake was identified by proteomics and density gradient centrifugation, and their site-specific sialylation functions were assayed by N-glycosylation site mutation. Effects of integrin ß1 bearing sialic acids on the pro-metastatic function of sEV in vivo were explored using Balb/c nu/nu mice. RESULTS: (1) Increased sialic acid levels were observed in sEV from malignant bladder cancer cells. (2) Elimination of sialic acids on sEV impaired sEV uptake by recipient cells. (3) Vesicular integrin ß1 bearing sialic acids was identified to play a key role in sEV uptake. (4) Desialylation of the hybrid domain of vesicular integrin ß1 inhibited its binding to matrix fibronectin, and reduced sEV entry into recipient cells. (5) Sialylation on integrin ß1 affected pro-metastatic function of sEV in Balb/c nu/nu mice. CONCLUSIONS: Taken together, our findings indicate important functional roles of sialic acids in sEV uptake and reprogramming plasticity of surrounding normal epithelial cells.


Assuntos
Vesículas Extracelulares , Neoplasias da Bexiga Urinária , Animais , Camundongos , Vesículas Extracelulares/metabolismo , Glicoconjugados , Integrina beta1/metabolismo , Mamíferos , Ácido N-Acetilneuramínico/metabolismo , Ácidos Siálicos/metabolismo
8.
Anticancer Agents Med Chem ; 24(5): 348-357, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375808

RESUMO

BACKGROUND: Bladder cancer is the most common malignant tumor of the urinary system. Nevertheless, current therapies do not provide satisfactory results. It is imperative that novel strategies should be developed for treating bladder cancer. OBJECTIVES: To evaluate the effect of a broad-spectrum anti-parasitic agent, Ivermectin, on bladder cancer cells in vitro and in vivo. METHODS: CCK-8 and EdU incorporation assays were used to evaluate cell proliferation. Apoptosis was detected by flow cytometry, TUNEL assay, and western blotting. Flow cytometry and DCFH-DA assay were used to analyze the reactive oxygen species (ROS) levels. DNA damage was determined by Neutral COMET assay and γ H2AX expression. Proteins related to apoptosis and DNA damage pathways were determined by WB assay. Xenograft tumor models in nude mice were used to investigate the anti-cancer effect of Ivermectin in vivo. RESULTS: Our study showed that in vitro and in vivo, Ivermectin inhibited the growth of bladder cancer cells. In addition, Ivermectin could induce apoptosis, ROS production, DNA damage, and activate ATM/P53 pathwayrelated proteins in bladder cancer cells. CONCLUSIONS: According to these findings, Ivermectin may be a potential therapeutic candidate against bladder cancer due to its significant anti-cancer effect.


Assuntos
Antineoplásicos , Neoplasias da Bexiga Urinária , Camundongos , Animais , Humanos , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Camundongos Nus , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Estresse Oxidativo , Proliferação de Células , Dano ao DNA , Apoptose , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-38397670

RESUMO

Pain interferes with one's work and social life and, at a personal level, daily activities, mood, and sleep quality. However, little research has been conducted on pain interference and its socioecological determinants among the working poor. Noting the clinical/policy decision needs and the technical challenges of isolating the intricately interrelated socioecological factors' unique contributions to pain interference and quantifying the relative contributions of each factor in an interpretable manner to inform clinical and policy decision-making, we deployed a novel random forest algorithm to model and quantify the unique contribution of a diverse ensemble of environmental, sociodemographic, and clinical factors to pain interference. Our analyses revealed that features representing the internal built environment of the working poor, such as the size of the living space, air quality, access to light, architectural design conducive to social connection, and age of the building, were assigned greater statistical importance than other more commonly examined predisposing factors for pain interference, such as age, occupation, the severity and locations of pain, BMI, serum blood sugar, and blood pressure. The findings were discussed in the context of their benefit in informing community pain screening to target residential areas whose built environment contributed most to pain interference and informing the design of intervention programs to minimize pain interference among those who suffered from chronic pain and showed specific characteristics. The findings support the call for good architecture to provide the spirit and value of buildings in city development.


Assuntos
Poluição do Ar , Dor Crônica , Trabalhadores Pobres , Humanos , Algoritmo Florestas Aleatórias
10.
Int Orthop ; 48(1): 201-209, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37632530

RESUMO

PURPOSE: This retrospective cohort study aimed to evaluate the efficacy and safety of percutaneous endoscopic lumbar decompression (PELD) in elderly patients with lumbar spinal stenosis (LSS). STUDY DESIGN: A matched retrospective study. SETTING: The research was conducted in Beijing Chaoyang Hospital, Capital Medical University, China. METHODS: This study included patients treated with PELD for LSS from September 2016 to September 2020. Patients with LSS aged ≥ 80 years were screened according to the inclusion and exclusion criteria as the study group, and then the same number of patients with LSS aged 50-80 years were matched according to gender, stenosis type, and surgical segment as the control group. Preoperative patient status was assessed using the Charlson comorbidity index (CCI) and the American Society of Anesthesiologists (ASA) physical status classification score. Clinical outcomes were assessed using the visual analog scale (VAS), Oswestry Disability Index (ODI) scores, modified Macnab criteria, radiological parameters and complication rates. RESULTS: A total of 624 LSS patients met the screening criteria between September 2016 and September 2020, with 47 LSS patients ≥ 80 years old serving as the study group. Forty-seven LSS patients aged 50-80 years were matched to the study group according to gender, stenosis type, and stenosis segment. The CCI score (1.77 ± 1.67) and ASA classification (2.62 ± 0.74) of the study group were significantly higher than the CCI score (0.66 ± 0.96) and ASA classification (1.28 ± 0.54) of the control group, and the difference was statistically significant. Compared with preoperative data, postoperative ODI, leg pain VAS scores and back pain VAS scores were significantly improved in both groups (p < 0.05). However, no significant difference was found between two groups in preoperative and postoperative ODI, leg pain VAS scores and back pain VAS scores (p > 0.05). The operation time and postoperative hospital stay in control group were significantly lower than those in study (p < 0.05), but there was no significant difference in blood loss between the two groups (p > 0.05). Besides, overall radiological parameters were comparable in elder and younger patients (p > 0.05), and disc height (DH), lumbar lordosis and segmental lordosis decreased after two year follow-up in both groups (p < 0.05). In addition, complication rates were similar between the two groups (p > 0.05), and no serious complications and deaths were found. LIMITATIONS: Single-centre retrospective design, non-randomized sample, small sample size. CONCLUSION: Although elderly LSS patients (≥ 80 years old) are less fit and have more comorbidities, satisfactory outcomes can be achieved with PELD, comparable to those of LSS patients < 80 years old, and without increased complications.


Assuntos
Lordose , Estenose Espinal , Idoso , Humanos , Idoso de 80 Anos ou mais , Estenose Espinal/cirurgia , Estenose Espinal/complicações , Estudos Retrospectivos , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Lordose/complicações , Lordose/cirurgia , Descompressão Cirúrgica/efeitos adversos , Vértebras Lombares/cirurgia , Dor nas Costas/etiologia , Resultado do Tratamento
11.
Ophthalmol Ther ; 13(1): 337-351, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37982983

RESUMO

INTRODUCTION: The use of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to treat malignant glaucoma (MG) has been described in the literature since the 1980s. However, the technique has been reported to have a short-term effect, with a notable relapse rate. In the present study, we report the efficacy and durability of a modified Nd:YAG laser treatment methodology for treatment of pseudophakic or aphakic MG. METHODS: Patients with chronic angle-closure glaucoma and deemed at high risk of developing post-operative MG received prophylactic peripheral iridectomy during their conventional operation beginning in 2017. When the diagnosis of pseudophakic or aphakic MG was confirmed, a thorough Nd:YAG laser capsulo/zonulo-hyaloido-vitreolysis (CZHV) was performed through iridectomy, along with standardized pre- and post-laser medications. This retrospective case series includes 14 eyes of 11 patients with MG who had surgical preset iridectomy and modified Nd:YAG laser CZHV between 2017 and 2022. Outcome measures included resolution and recurrence of MG and incidence of treatment complications. RESULTS: The mean follow-up was 27.1 ± 15.0 months (range, 12-48). Long-term resolution of MG was obtained in all included eyes at the end of the follow-up. Six eyes (42.9%) achieved long-term resolution with a single Nd:YAG laser intervention. Eight eyes (57.1%) achieved long-term resolution following two to three laser interventions, with two eyes (14.3%) experiencing recurrence. There was no complication during the follow-up. At the final visit, a significant reduction (P = 0.0001) in the mean intraocular pressure (IOP) was observed (13.1 ± 2.8 mmHg) compared to presentation (21.4 ± 6.3 mmHg). CONCLUSION: The modified Nd:YAG laser treatment methodology is a minimally invasive option to manage pseudophakic or aphakic MG with sustained effectiveness. Reduced inflammatory reactions due to prophylactic peripheral iridectomy, rapid diagnosis, and timely treatment initiation have all contributed to the favorable outcomes associated with this modified treatment methodology.

12.
Int J Surg ; 110(2): 1068-1078, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37924501

RESUMO

AIM: This paper aimed to explore the application of three-dimensional (3D) printing in cardiovascular diseases, to reach an insight in this field and prospect the future trend. METHODS: The articles were selected from the Web of Science Core Collection database. Excel 2019, VOSviewer 1.6.16, and CiteSpace 6.1.R6 were used to analyze the information. RESULTS: A total of 467 papers of 3D printing in cardiovascular diseases were identified, and the first included literature appeared in 2000. A total of 692 institutions from 52 countries participated in the relevant research, while the United States of America contributed to 160 articles and were in a leading position. The most productive institution was Curtin University , and Zhonghua Sun who has posted the most articles ( n =8) was also from there. The Frontiers in Cardiovascular Medicine published most papers ( n =25). The Journal of Thoracic and Cardiovascular Surgery coveted the most citations ( n =520). Related topics of frontiers will still focus on congenital heart disease, valvular heart disease, and left atrial appendage closure. CONCLUSIONS: The authors summarized the publication information of the application of 3D printing in cardiovascular diseases related literature from 2000 to 2023, including country and institution of origin, authors, and publication journal. This study can reflect the current hotspots and novel directions for the application of 3D printing in cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/cirurgia , Bibliometria , Impressão Tridimensional , Bases de Dados Factuais , Instalações de Saúde
13.
Orthop Surg ; 16(2): 471-480, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38112436

RESUMO

BACKGROUND: Arthroscopic surgery has been established as an efficacious intervention for the treatment of rotator cuff tears. The primary aim of this study was to analyze the modifications in the lateral acromial angle (LAA) subsequent to rotator cuff repair surgery using single-row rivet fixation and double-row rivet fixation techniques. Furthermore, we sought to investigate the influence of LAA on the prognosis of rotator cuff repair surgery. METHOD: This observational study retrospectively enrolled 105 patients diagnosed with degenerative rotator cuff tears who underwent arthroscopic rotator cuff repair between 2016 and 2019. Following the exclusion of two patients with subscapularis or superior labrum anterior and posterior (SLAP) tears, as well as three patients who were lost to follow-up, a cohort of 100 patients was included for clinical and imaging evaluation. Among these individuals, 50 were assigned to the double-row repair group, whereas the remaining 50 comprised the single-row repair group. Bilateral shoulder magnetic resonance imaging (MRI) scans were conducted no less than 24 months post-surgery. Experienced arthroscopic surgeons, blinded to the LAA measurements, assessed the rotator interval (RI) using a control MRI. Functional assessment was performed using the University of California, Los Angeles (UCLA) quick disability of the shoulder and arm, shoulder and hand (qDASH) score. The Wilcoxon signed-rank test for dependent samples was employed to compare data between the pre- and post-intervention groups. Pearson correlation coefficients were calculated to evaluate the relationship between different parameters. RESULTS: The study population consisted of 73 female patients and 27 male patients, with a mean age of 58.32 ± 5.29 years and a mean follow-up duration of 25.88 ± 8.11 months. Preoperatively, the mean LAA was 75.81° ± 11.28°, RI was 4.78 ± 0.62, UCLA score was 17.54 ± 2.44, and qDASH score was 2.45 ± 0.25. The average tear size was 8.95 ± 2.11 mm. A statistically significant difference in LAA was observed between the preoperative and postoperative measurements, with the double-row repair group exhibiting a greater LAA than the single-row repair group. Finally, a significant correlation was identified between LAA, RI, and qDASH scores after a 24-month follow-up period. CONCLUSION: According to our findings, the utilization of double-row rivet fixation has a greater LAA angle than single-row rivet fixation. Moreover, this preservation of LAA is significantly associated with the functional recovery of the shoulder joint.


Assuntos
Lesões do Manguito Rotador , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Acrômio/diagnóstico por imagem , Acrômio/cirurgia , Estudos Retrospectivos , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Ombro , Artroscopia/métodos , Imageamento por Ressonância Magnética , Resultado do Tratamento
15.
J Cancer Res Ther ; 19(6): 1597-1602, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38156927

RESUMO

OBJECTIVE: To investigate the drug loading and release rate of epirubicin-loaded thermosensitive liquid embolic agents in vitro. MATERIALS AND METHODS: The drug loading and stability of epirubicin-loaded thermosensitive liquid embolic agents with or without iopromide were determined by high-performance liquid chromatography, and the same method was used to determine the drug release rate of thermosensitive liquid embolic agents at different time points. RESULTS: For epirubicin-loaded thermosensitive liquid embolic agents without iopromide, the average drug loading after filtration by membrane was (0.78 ± 0.02) mg and the drug loading rate was (16.1 ± 0.35)%, while the average drug loading without membrane was (0.73 ± 0.06) mg and the drug loading rate was (15.07 ± 1.17)%. After adding iopromide, the drug loading capacity was measured from 0 h-24 h solution and the drug loading was calculated indirectly and conclude that the drug loading capacity of thermosensitive liquid embolic agents decreased or disappeared. The sustained release rate of epirubicin from 0 to 48 hours was 42.65% in 48 hours. CONCLUSION: Epirubicin can be successfully loaded into the thermosensitive liquid embolic agents with good stability and sustained release. After adding iopromide, the drug loading capacity of thermosensitive liquid embolic agents decreased or disappeared.


Assuntos
Iohexol , Humanos , Epirubicina , Preparações de Ação Retardada , Liberação Controlada de Fármacos
16.
BMC Psychiatry ; 23(1): 760, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848849

RESUMO

BACKGROUND: Cognitive and emotional impairment are among the core features of schizophrenia; assessment of vocal emotion recognition may facilitate the detection of schizophrenia. We explored the differences between cognitive and social aspects of emotion using vocal emotion recognition and detailed clinical characterization. METHODS: Clinical symptoms and social and cognitive functioning were assessed by trained clinical psychiatrists. A vocal emotion perception test, including an assessment of emotion recognition and emotional intensity, was conducted. One-hundred-six patients with schizophrenia (SCZ) and 230 healthy controls (HCs) were recruited. RESULTS: Considering emotion recognition, scores for all emotion categories were significantly lower in SCZ compared to HC. Considering emotional intensity, scores for anger, calmness, sadness, and surprise were significantly lower in the SCZs. Vocal recognition patterns showed a trend of unification and simplification in SCZs. A direct correlation was confirmed between vocal recognition impairment and cognition. In diagnostic tests, only the total score of vocal emotion recognition was a reliable index for the presence of schizophrenia. CONCLUSIONS: This study shows that patients with schizophrenia are characterized by impaired vocal emotion perception. Furthermore, explicit and implicit vocal emotion perception processing in individuals with schizophrenia are viewed as distinct entities. This study provides a voice recognition tool to facilitate and improve the diagnosis of schizophrenia.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Emoções , Cognição , Ira , Percepção , Expressão Facial , Percepção Social
17.
J Control Release ; 364: 312-325, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37884210

RESUMO

Cell membrane-derived particles (Mp) are rounded membrane-enclosed particles that are shed from tumor cells. Mp are formed from tumor membranes and are capable of tumor targeting and immunotherapeutic agents because they share membrane homology with parental cells; thus, they are under consideration as a drug delivery vehicle. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein with enzymatic functionality, is highly expressed in Mp and extracellular vesicles (EV) from prostate cancer (PCa) with poor clinical prognosis. Although PSMA expression was previously shown in EV and Mp isolated from cell lines and from the blood of patients with high-grade PCa, no pathophysiological effects have been linked to PCa-derived Mp. Here, we compared Mp from PSMA-expressing (PSMA-Mp) and PSMA-non-expressing (WT-Mp) cells side by side in vitro and in vivo. PSMA-Mp can transfer PSMA and new phenotypic characteristics to the tumor microenvironment. The consequence of PSMA transfer to cells and increased secretion of vascular endothelial growth factor-A (VEGF-A), pro-angiogenic and pro-lymphangiogenic mediators, with increased 4E binding protein 1 (4EBP-1) phosphorylation.


Assuntos
Neoplasias da Próstata , Fator A de Crescimento do Endotélio Vascular , Masculino , Humanos , Neoplasias da Próstata/patologia , Membrana Celular/metabolismo , Microambiente Tumoral
18.
Sci Rep ; 13(1): 13421, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37591924

RESUMO

Myodural bridge (MDB) is a dense connective tissue between suboccipital muscle and dura mater. However, there are few reports on the development and maturation of the human MDB. This study aims to explore the developmental relationship between suboccipital muscle and MDB. 30 head and neck specimens from human fetuses (F) ranging from the 12th to 41st week (W) were made into histological sections. The F12W sections showed evidence that the dura mater dominated by fibroblasts, attached to the posterior atlanto-axial membrane (PAAM) which completely sealed the atlanto-axial space. In the F13W stage, myofibrils of the suboccipital muscle fibers increased significantly in number. At the F14W stage, a gap was observed at the caudal end of the PAAM. Numerous myodural bridge-like structures were observed blending into the dura mater through the gap. At the F19W stage, muscle cells mature. Starting at the F21W stage, the MDB were observed as fibroblasts that cross the atlanto-axial interspace and attach to the dura mater. Therefore, the traction generated by the suboccipital muscles seems to promote the maturity of MDB. This study will provide new morphological knowledge to support future research on the function of the human MDB and regulating the development mechanism of MDB.


Assuntos
Dura-Máter , Feto , Humanos , Dura-Máter/embriologia , Fibroblastos , Cabeça , Fibras Musculares Esqueléticas
19.
Quant Imaging Med Surg ; 13(7): 4526-4539, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37456285

RESUMO

Background: Paraspinal muscle fat infiltration is closely related to the occurrence and development of lumbar spine disorders and postoperative complications. This study aimed to explore the effects of age, sex, muscle, and level on paraspinal muscle fat infiltration among Chinese adults to identify the best single level of assessing whole-level paraspinal muscle fat infiltration and to define the standardized identification thresholds for paraspinal muscle fat infiltration by means of magnetic resonance imaging. Methods: This was a single-center, cross-sectional study conducted on 336 asymptomatic Chinese volunteers aged 20 to 69 years recruited from Beijing and surrounding communities through designed advertisements from May 2022 to October 2022. The fat signal fraction of multifidus (FSFMF), erector spinae (FSFES), psoas major (FSFPM), and the sum of multifidus, erector spinae, and psoas major (FSFTotal) at lumbar levels L1-L5 were measured with magnetic resonance imaging. The Student t-test and Mann-Whitney test were performed, and Pearson correlations and intraclass correlation coefficients were determined. Subgroups were compared using analysis of variance followed by a post hoc Bonferroni test or Kruskal-Wallis test. Results: FSFTotal (14.02%±4.71% vs. 10.34±4.08%; P<0.001), FSFMF (21.14%±6.77% vs. 16.21%±6.26%; P<0.001), and FSFES (15.97%±5.56% vs. 12.37%±4.80%; P<0.001) were higher in females than in males and increased with age and lumbar level, whereas FSFPM did not significantly differ by age (all P values >0.05) or sex (P=0.12) and showed a decreasing trend from L1 to L5. The FSFTotal at L4 showed both the strongest correlation (Pearson correlation coefficient =0.95; P<0.001) and agreement (intraclass correlation coefficient =0.92; P<0.001) with the whole-level FSFTotal. Pathological paraspinal muscle fat infiltration identification thresholds of FSFTotal, FSFMF, FSFES, and FSFPM were 10.0-33.9%, 19.2-47.4%, 16.2-43.6%, and 4.8%, respectively, in each age (range, 20-69 years) and sex group. Conclusions: In asymptomatic Chinese adults, paraspinal muscle fat infiltration can be influenced by age, sex, muscle type, and location. The L4 level can serve as an optimal substitution in whole-level fat infiltration measurement. We present the first data concerning the identification thresholds of pathological paraspinal muscle fat infiltration, which will provide a valuable resource for researchers in the field.

20.
Behav Sci (Basel) ; 13(5)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37232650

RESUMO

A healthy relationship between supervisors and postgraduates is critical for their academic achievements and personal development. This paper quantitatively discusses such a relationship from the viewpoint of differential game theory. First, a mathematic model was established to describe the evolutionary dynamics of the academic level of the supervisor-postgraduate community, which is related to the two parties' positive and negative efforts. Then, the objective function aimed at maximizing the individual and total benefit of the community was constructed. After that, the differential game relationships in the non-cooperative, cooperative and Stackelberg scenarios were formulated and solved. A comparison of the three game scenarios showed that the optimal academic level and total benefit of the community were 22% higher in the cooperative scenario than in the non-cooperative and Stackelberg game scenarios. Moreover, the influence of model parameters on the game results was analyzed. The results indicate that, for the supervisor-led Stackelberg game, when the sharing cost ratio is increased to a specific level, the supervisor's optimal benefit will not be further improved.

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