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1.
Mol Med ; 30(1): 152, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289602

RESUMO

VEXAS syndrome, an uncommon yet severe autoimmune disorder stemming from a mutation in the UBA1 gene, is the focus of this paper. The overview encompasses its discovery, epidemiological traits, genetic underpinnings, and clinical presentations. Delving into whether distinct genotypes yield varied clinical phenotypes in VEXAS patients, and the consequent adjustment of treatment strategies based on genotypic and clinical profiles necessitates thorough exploration within the clinical realm. Additionally, the current therapeutic landscape and future outlook are examined, with particular attention to the potential therapeutic roles of IL-6 inhibitors and JAK inhibitors, alongside an elucidation of prevailing limitations and avenues for further research. This study contributes essential theoretical groundwork and clinical insights for both diagnosing and managing VEXAS syndrome.


Assuntos
Interleucina-6 , Inibidores de Janus Quinases , Enzimas Ativadoras de Ubiquitina , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Inibidores de Janus Quinases/uso terapêutico , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Mutação , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/genética , Doenças Autoimunes/diagnóstico
2.
Front Pharmacol ; 15: 1377055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828450

RESUMO

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.

3.
Dalton Trans ; 53(10): 4598-4606, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38349531

RESUMO

From paddle-wheel starting material Na3Ru2(CO3)4·6H2O, a family of edge-sharing bi-octahedral (ESBO) diruthenium(IV,IV) compounds formulated as Ru2O2(CO3)2(H2O)2L2·nH2O [L = piperazine (1) or 2-methylpiperazine (2), n = 4, and L = 2,2-dimethylpiperazine (3), n = 12] and Ru2O2(CO3)2(OH)4{M(H2O)4}2·nH2O [M = Mg (4), n = 4, and Ni (5), n = 2] were prepared and structurally characterized. The Ru28+ dimer is chelated and bridged by two CO32- and two µ-O in a trans manner, and the Ru-Ru distances fall in the range 2.3808(6)-2.4001(4) Å. Compound 2 shows the shortest Ru-Ru distance for all known ESBO Ru2 compounds reported thus far. Increasing -CH3 groups of terminal piperazine ligands coordinated to the Ru(µ-O)2(µ-O3C)2Ru core, and according to Raman spectra experiments combined with theoretical calculations, the intense bands of compounds 1-3 appearing at ∼360 cm-1 can be assigned to the stretching of Ru-Ru bonds.

4.
BMC Pediatr ; 24(1): 66, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245681

RESUMO

BACKGROUND: Langerhans cell histiocytosis affecting the thyroid commonly presents with nonspecific clinical and radiological manifestations. Thyroid Langerhans cell histiocytosis is typically characterized by non-enhancing hypodense lesions with an enlarged thyroid on computed tomography medical images. Thyroid involvement in LCH is uncommon and typically encountered in adults, as is salivary gland involvement. Therefore, we present a unique pediatric case featuring simultaneous salivary and thyroid involvement in LCH. CASE PRESENTATION: A 3-year-old boy with complaints of an anterior neck mass persisting for 1 to 2 months, accompanied by mild pain, dysphagia, and hoarseness. A physical examination revealed a 2.5 cm firm and tender mass in the left anterior neck. Laboratory examinations revealed normal thyroid function test levels. Ultrasonography revealed multiple heterogeneous hypoechoic nodules with unclear and irregular margins in both lobes of the thyroid. Contrast-enhanced neck computed tomography revealed an enlarged thyroid gland and bilateral submandibular glands with non-enhancing hypointense nodular lesions, and multiple confluent thin-walled small (< 1.5 cm) cysts scattered bilaterally in the lungs. Subsequently, a left thyroid excisional biopsy was performed, leading to a histopathological diagnosis of LCH. Immunohistochemical analysis of the specimen demonstrated diffuse positivity for S-100, CD1a, and Langerin and focal positivity for CD68. The patient received standard therapy with vinblastine and steroid, and showed disease regression during regular follow-up of neck ultrasonography. CONCLUSIONS: Involvement of the thyroid and submandibular gland as initial diagnosis of Langerhans cell histiocytosis is extremely rare. It is important to investigate the involvement of affected systems. A comprehensive survey and biopsy are required to establish a definitive diagnosis.


Assuntos
Histiocitose de Células de Langerhans , Tireoidite , Pré-Escolar , Humanos , Masculino , Biópsia , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/complicações , Pescoço/patologia , Tireoidite/complicações
5.
Front Plant Sci ; 14: 1240028, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38078087

RESUMO

Introduction: Tilia miqueliana is an endemic species whose population is declining. The permeability barrier and mechanical constraint of the pericarp (seed coat) are important causes of its seed dormancy. Although there has been considerable research on this subject, questions remain regarding how the permeability barrier and mechanical constraint of the seed coat are eliminated during dormancy release and how water enters the seed. Therefore, protecting the species by improving its germination/dormancy breaking in the laboratory is urgent. Methods: In this study, the changes in the cellular structure, mechanical properties, and components of the Tilia miqueliana seed coat after an H2SO4-gibberellic acid (GA3) treatment were analyzed during dormancy release. Various analyses (e.g., magnetic resonance imaging, scanning electron microscopy, and paraffin section detection) revealed the water gap and water channel. Results: The H2SO4 treatment eliminated the blockage at the micropyle and hilum of the seeds. Water entered the seeds through the water gap (micropyle) rather than through the hilum or seed coat, after which it dispersed along the radicle, hypocotyl, and cotyledon to the endosperm. During the cold stratification period, the cellular structure was damaged and an increasing number of holes appeared on the inner and outer surfaces of the seed coat. Vickers hardness tests showed that GA3 decreased the seed coat hardness. Additionally, the seed coat lignin and total phenol contents continuously decreased during the cold stratification period. Notably, the Liquid chromatography-mass spectrometry (LC-MS) analysis of the seed coat detected polyethylene glycol (osmoregulator), which may have destabilized the water potential balance inside and outside the seed and increased the water content to levels required for germination, ultimately accelerating seed dormancy release. Discussion: This sophisticated and multi-level study reveals how H2SO4 and GA3 eliminate the permeability barrier and mechanical constraints of the seed coat during dormancy release of Tilia miqueliana seeds. This will be beneficial to artificially assist the natural regeneration and population expansion of Tilia miqueliana.

6.
Mater Today Bio ; 20: 100639, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37197743

RESUMO

Neural tissue engineering (NTE) has made remarkable strides in recent years and holds great promise for treating several devastating neurological disorders. Selecting optimal scaffolding material is crucial for NET design strategies that enable neural and non-neural cell differentiation and axonal growth. Collagen is extensively employed in NTE applications due to the inherent resistance of the nervous system against regeneration, functionalized with neurotrophic factors, antagonists of neural growth inhibitors, and other neural growth-promoting agents. Recent advancements in integrating collagen with manufacturing strategies, such as scaffolding, electrospinning, and 3D bioprinting, provide localized trophic support, guide cell alignment, and protect neural cells from immune activity. This review categorises and analyses collagen-based processing techniques investigated for neural-specific applications, highlighting their strengths and weaknesses in repair, regeneration, and recovery. We also evaluate the potential prospects and challenges of using collagen-based biomaterials in NTE. Overall, this review offers a comprehensive and systematic framework for the rational evaluation and applications of collagen in NTE.

7.
Insights Imaging ; 14(1): 68, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37093321

RESUMO

BACKGROUND: To develop an artificial intelligence (AI) model with radiomics and deep learning (DL) features extracted from CT images to distinguish benign from malignant ovarian tumors. METHODS: We enrolled 149 patients with pathologically confirmed ovarian tumors. A total of 185 tumors were included and divided into training and testing sets in a 7:3 ratio. All tumors were manually segmented from preoperative contrast-enhanced CT images. CT image features were extracted using radiomics and DL. Five models with different combinations of feature sets were built. Benign and malignant tumors were classified using machine learning (ML) classifiers. The model performance was compared with five radiologists on the testing set. RESULTS:  Among the five models, the best performing model is the ensemble model with a combination of radiomics, DL, and clinical feature sets. The model achieved an accuracy of 82%, specificity of 89% and sensitivity of 68%. Compared with junior radiologists averaged results, the model had a higher accuracy (82% vs 66%) and specificity (89% vs 65%) with comparable sensitivity (68% vs 67%). With the assistance of the model, the junior radiologists achieved a higher average accuracy (81% vs 66%), specificity (80% vs 65%), and sensitivity (82% vs 67%), approaching to the performance of senior radiologists. CONCLUSIONS:  We developed a CT-based AI model that can differentiate benign and malignant ovarian tumors with high accuracy and specificity. This model significantly improved the performance of less-experienced radiologists in ovarian tumor assessment, and may potentially guide gynecologists to provide better therapeutic strategies for these patients.

8.
Front Immunol ; 14: 1277683, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38162662

RESUMO

Elevated CA-125 levels, polyserous effusions (such as pleural effusion, ascites, etc.) in young women with systemic lupus erythematosus (SLE) may signal pseudo-pseudo Meigs' syndrome (PPMS), after excluding other causes. We describe a 32-year-old SLE patient with recurrent bilateral pleural effusions and unexplained hypercalcemia for 10 months. Extensive evaluations revealed no infections or tumors. Cytokine analysis showed elevated interleukin (IL) levels, especially IL-6 in pleural effusion. Treatment with immunosuppressive therapy resulted in reduced cancer antigen (CA) 125 levels and decreased effusion volume, demonstrating a positive response to intervention in this case of PPMS.


Assuntos
Lúpus Eritematoso Sistêmico , Síndrome de Meigs , Derrame Pleural , Adulto , Feminino , Humanos , Ascite/diagnóstico , Ascite/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome de Meigs/diagnóstico , Síndrome de Meigs/tratamento farmacológico , Síndrome de Meigs/complicações , Derrame Pleural/diagnóstico , Derrame Pleural/tratamento farmacológico
9.
World J Clin Cases ; 10(32): 11812-11826, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36405270

RESUMO

BACKGROUND: Prostate artery embolization (PAE) is a promising minimally invasive therapy that improves lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). Transurethral resection of the prostate (TURP) is the gold standard therapy for LUTS/BPH. AIM: To evaluate the efficacy and safety of PAE vs TURP on LUTS related to BPH. METHODS: A literature review was performed to identify all published articles on PAE vs TURP for LUTS/BPH. Sources included PubMed, Embase, Cochrane library databases, and Chinese databases before June 2022. A systematic review and meta-analysis were conducted. Outcome measurements were combined by calculating the mean difference with a 95% confidence interval. Statistical analysis was carried out using Review Manager 5.3. RESULTS: Eleven studies involving 1070 participants were included. Compared with the TURP group, the PAE group had a similar effect on the International Index of Erectile Function (IPSS) score, Peak urinary flow rate (Qmax), postvoid residual volume (PVR), Prostate volume (PV), prostatic specific antigen (PSA), The International Index of Erectile Function short form (IIEF-5) scores, and erectile dysfunction during 24 mo follow-up. Lower quality of life (QoL) score, lower rate of retrograde ejaculation and shorter hospital stay in the PAE group. There was no participant death in either group. A higher proportion of haematuria, urinary incontinence and urinary stricture was identified in the TURP group. CONCLUSION: PAE may be an appropriate option for elderly patients, patients who are not candidates for surgery, and patients who do not want to risk the potential adverse effects of TURP. Studies with large cases and long follow-up time are needed to validate results.

10.
Orphanet J Rare Dis ; 17(1): 296, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35906705

RESUMO

BACKGROUND: In patients with mucopolysaccharidosis (MPS), systematic assessment and management of cervical instability, cervicomedullary and thoracolumbar junction spinal stenosis and spinal cord compression averts or arrests irreversible neurological damage, improving outcomes. However, few studies have assessed thoracic spinal involvement in MPS IVa patients. We aimed to evaluate thoracic spinal abnormalities in MPS IVa patients and identify associated image manifestations by CT and MRI study. RESULTS: Data of patients diagnosed and/or treated for MPS IVa at MacKay Memorial Hospital from January 2010 to December 2020 were extracted from medical records and evaluated retrospectively. Computed tomography (CT), plain radiography and magnetic resonance imaging (MRI) findings of MPS IVa-related spinal abnormalities were reviewed. Spine CT and plain radiography findings of 12 patients (6 males and 6 females with median age 7.5 years, range 1-28 years) revealed two subtypes of spinal abnormalities: thoracic kyphosis apex around T2 (subtype 1, n = 8) and thoracic kyphosis apex around T5 (subtype 2, n = 4). Spine CT and plain radiography clearly identified various degrees of thoracic kyphosis with apex around T2 or T5 in MPS IVa patients. Square-shaped to mild central beaking in middle thoracic vertebral bodies was observed in subtype 1 patients, while greater degrees of central beaking in middle thoracic vertebral bodies was observed in subtype 2 patients. CONCLUSIONS: Spine CT findings clearly identify new radiological findings of thoracic kyphosis apex around T2 or T5 in MPS IVa patients. The degrees of central beaking at middle thoracic vertebral bodies may be a critical factor associated with different image presentations of thoracic kyphosis.


Assuntos
Cifose , Mucopolissacaridoses , Mucopolissacaridose IV , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Mucopolissacaridose IV/diagnóstico , Projetos Piloto , Estudos Retrospectivos , Coluna Vertebral , Adulto Jovem
11.
J Cardiothorac Surg ; 17(1): 100, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505367

RESUMO

BACKGROUND: The study was aimed to compare the efficacy and safety of different sedation protocols of dexmedetomidine-remifentanil and propofol-remifentanil for percutaneous closure of atrial septal defects (ASD) under transthoracic echocardiography (TTE) guidance. MATERIAL AND METHODS: From March 2020 to January 2021, of 114 patients screened, 59 ASD patients scheduled for percutaneous closure under TTE guidance were randomly allocated into the dexmedetomidine-remifentanil (D-R) group (n = 29) and the propofol-remifentanil (P-R) group (n = 30). The incidence of hemodynamic and respiratory adverse events, arterial blood gas analysis, induction and recovery time, pain score, infusion rate of remifentanil, satisfaction of the surgeon and patient, additional sedatives were collected for analysis and comparison. RESULTS: The induction time was longer in the D-R group than that in the P-R group (17.66 ± 2.65 min vs 11.43 ± 1.48 min; difference, 6.22 min; 95% CI 5.10 to 7.35; P < 0.001). No differences were observed in the 2 groups in terms of the additional sedatives, infusion rate of remifentanil, pain score, recovery time (P > 0.05). There was no difference between the two groups regarding the incidence of cardiovascular adverse events (6 [20.7%] vs 4 [13.3%]; difference, 7.4%; 95% CI - 11.7 to 26.5%; P = 0.506). Respiratory adverse events occurred in 1 patient (3.4%) in the D-R group, and 8 patients (26.7%) in the P-R group (difference, 23.3%; 95% CI 6.2 to 40.5%; P = 0.026). The incidence of hypercapnia was significantly lower in the D-R group (4 [13.8%]) than in the P-R group (13 [43.3%]; difference, 29.5%; 95% CI 7.8 to 51.2%; P = 0.012). CONCLUSIONS: Except for more rapid the induction time and higher the surgeon satisfaction score in the propofol-remifentanil protocol, the efficacy was similar between two sedation protocols. The hemodynamic stability was comparable, the dexmedetomidine-remifentanil protocol had superior airway security due to fewer hypercapnia and respiratory adverse events.


Assuntos
Comunicação Interatrial , Hipnóticos e Sedativos , Protocolos Clínicos , Dexmedetomidina/efeitos adversos , Combinação de Medicamentos , Comunicação Interatrial/cirurgia , Humanos , Hipercapnia/epidemiologia , Hipnóticos e Sedativos/efeitos adversos , Dor , Propofol/efeitos adversos , Remifentanil/efeitos adversos , Resultado do Tratamento
12.
Kaohsiung J Med Sci ; 38(4): 321-335, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34989110

RESUMO

Circular RNAs (circRNAs) are implicated in the regulation of tumor progression via the "competitive endogenous RNAs (ceRNAs)" mechanism. We intended to explore the molecular mechanism of circRNA WW domain containing adaptor with coiled-coil (circWAC) in breast cancer (BC) progression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were applied to analyze RNA and protein expression. Cell proliferation, migration, invasion, apoptosis, glycolysis, and tumorigenesis in nude mice were assessed to analyze the role of circWAC/microRNA-599 (miR-599)/E2F transcription factor 3 (E2F3) axis in BC. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA-pull down assay were performed to verify intermolecular interactions. CircWAC was up-regulated in BC tissues and cell lines. CircWAC knockdown restrained the proliferation, migration, invasion, and glycolysis and promoted the apoptosis of BC cells. CircWAC acted as miR-599 sponge, and miR-599 interference largely reversed circWAC silencing-induced effects in BC cells. MiR-599 interacted with the 3' untranslated region (3'UTR) of E2F3, and miR-599 overexpression-induced suppressive effect on cellular malignant potential was overturned by the accumulation of E2F3 in BC cells. Eukaryotic initiation factor 4A3 (eIF4A3) induced the expression of circWAC in BC cells. CircWAC knockdown suppressed xenograft tumor growth in vivo. Our results demonstrated that eIF4A3-induced circWAC promoted the proliferation, migration, invasion, and glycolysis and suppressed the apoptosis of BC cells through mediating miR-599/E2F3 axis, which provided novel potential targets for BC therapy.


Assuntos
Neoplasias da Mama , MicroRNAs , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , RNA Helicases DEAD-box , Fator de Transcrição E2F3/genética , Fator de Transcrição E2F3/metabolismo , Fator de Iniciação 4A em Eucariotos , Feminino , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética
13.
Front Genet ; 12: 743560, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712268

RESUMO

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two most common rheumatic diseases in the world. Although there are standard methods for the diagnosis of both RA and OA, the differentials in some cases are poor. With deepening research, the role of autophagy in maintaining cell homeostasis and thus enabling cells adapt to external environments has become increasingly prominent. Both RA and OA, two diseases with inherent differences in pathogenesis, gradually show differences in autophagy levels. Our study therefore aims to further understand differences in pathogenesis of RA and OA through in-depth studies of autophagy in RA and OA. We also define appropriate autophagy-related markers as recognition indicators. Differences in autophagy levels between RA and OA were found based on analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment (ssGSEA). These differences were mainly caused by 134 differentially expressed genes (DEGs). In two autophagy-related genes, CXCR4 and SERPINA1, there existed significant statistical difference between RA and OA. An autophagy related index (ARI) was thus successfully constructed based on CXCR4 and SERPINA by binary logistic regression of the generalized linear regression (GLR) algorithm. Pearson analysis indicated that the expression of CXCR4, SERPINA1, and ARI were closely correlated with autophagy scores and immune infiltration. Moreover, ARI showed high disease identification through receiver operating characteristic (ROC) analysis (AUCtesting cohort = 0.956, AUCtraining cohort = 0.867). These results were then verified in GSE12021 independent cohort. In conclusion, ARI associated with autophagy and immune infiltration was successfully constructed for accurately identifying OA and RA. The index, thus, has great potential in clinical applications.

14.
Chin Med J (Engl) ; 134(18): 2175-2185, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34483252

RESUMO

BACKGROUND: Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis. METHODS: In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-ß (TGF-ß), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student's t test or analysis of variance were used for statistical analysis. RESULTS: In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ±â€Š0.02 vs. 0.07 ±â€Š0.02, t = 8.66, P = 0.001), TGF-ß (0.54 ±â€Š0.05 vs. 0.09 ±â€Š0.06, t = 10.00, P < 0.001), p-Smad2/3 (0.58 ±â€Š0.06 vs. 0.07 ±â€Š0.03, t = 12.86, P < 0.001) and α-collagen I (0.27 ±â€Š0.02 vs. 0.16 ±â€Š0.01, t = 7.01, P = 0.002), and increased Ang II secretion (62.27 ±â€Š7.32 vs. 9.56 ±â€Š1.68, t = 12.16, P < 0.001). Interestingly, Ang II increased the number of macrophage exosomes, and the protein levels of Alix (1.45 ±â€Š0.15 vs. 1.00 ±â€Š0.10, t = 4.32, P = 0.012), AT1R (4.05 ±â€Š0.64 vs. 1.00 ±â€Š0.09, t = 8.17, P = 0.001), and glyceraldehyde-3-phosphate dehydrogenase (2.13 ±â€Š0.36 vs. 1.00 ±â€Š0.10, t = 5.28, P = 0.006) were increased in exosomes secreted by the same number of macrophages, indicating a positive loop between Ang II and exosomes production. CONCLUSIONS: Exosomes mediate intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.


Assuntos
Exossomos , Fibrose Pulmonar , Angiotensina II , Animais , Bleomicina/toxicidade , Fibroblastos , Pulmão , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Receptor Tipo 1 de Angiotensina
15.
Gerontology ; 67(6): 718-728, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33853071

RESUMO

INTRODUCTION: Prospective memory (PM) is a multiphasic cognitive function important for autonomy and functional independence but is easily disrupted by pathological aging processes. Through cognitive simulation of perceptual experiences, mental imagery could be an effective compensatory strategy to enhance PM performance. Nevertheless, relevant research in individuals with amnestic mild cognitive impairment (MCI) has been limited, and the underlying mechanism of the therapeutic effect has not been sufficiently elucidated. The present study aimed to examine complex PM performances and the effect of mental imagery on each phase in older adults with MCI and to investigate the underlying cognitive mechanism from a process perspective. METHODS: Twenty-eight MCI and 32 normal aging controls completed a seminaturalistic PM task, in addition to a series of neuropsychological tests. Participants from each group were randomly assigned to a mental imagery condition or a standard repeated encoding condition before performing the PM task. Four indices were used to measure performance in the intention formation, intention retention, intention initiation, and intention execution phases of PM. Performances in each phase was compared between the 2 diagnostic groups and the 2 instruction conditions. RESULTS: The MCI group performed worse than the normal aging group in the intention formation and intention retention phases. The participants in the mental imagery condition performed significantly better than those in the standard condition during the intention formation, intention retention, and intention execution phases, regardless of the diagnostic group. Moreover, there was a significant interaction between the group and condition during intention retention, showing that people with MCI benefited even more from mental imagery than normal aging in this phase. Performance in the intention retention phase predicted performance in the intention initiation and intention execution phases. DISCUSSION: PM deficits in MCI mainly manifest during planning and retaining intentions. Mental imagery was able to promote performance in all but the initiation phase, although a trend for improvement was observed in this phase. The effects of mental imagery may be exerted in the intention retention phase by strengthening the PM cue-action bond, thereby facilitating the probability of intention initiation and bolstering fidelity to the original plan during intention execution.


Assuntos
Disfunção Cognitiva , Memória Episódica , Idoso , Disfunção Cognitiva/terapia , Humanos , Intenção , Transtornos da Memória/psicologia , Testes Neuropsicológicos
16.
J Appl Clin Med Phys ; 22(2): 126-137, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33426800

RESUMO

INTRODUCTION: This study aimed to investigate the feasibility of generating pseudo dual-energy CT (DECT) from one 120-kVp CT by using convolutional neural network (CNN) to derive additional information for quantitative image analysis through phantom study. METHODS: Dual-energy scans (80/140 kVp) and single-energy scans (120 kVp) were performed for five calibration phantoms and two evaluation phantoms on a dual-source DECT scanner. The calibration phantoms were used to generate training dataset for CNN optimization, while the evaluation phantoms were used to generate testing dataset. A CNN model which takes 120-kVp images as input and creates 80/140-kVp images as output was built, trained, and tested by using Caffe CNN platform. An in-house software to quantify contrast enhancement and synthesize virtual monochromatic CT (VMCT) for CNN-generated pseudo DECT was implemented and evaluated. RESULTS: The CT numbers in 80-kVp pseudo images generated by CNN are differed from the truth by 11.57, 16.67, 13.92, 12.23, 10.69 HU for syringes filled with iodine concentration of 2.19, 4.38, 8.75, 17.5, 35 mg/ml, respectively. The corresponding results for 140-kVp CT are 3.09, 9.10, 7.08, 9.81, 7.59 HU. The estimates of iodine concentration calculated based on the proposed method are differed from the truth by 0.104, 0.603, 0.478, 0.698, 0.795 mg/ml for syringes filled with iodine concentration of 2.19, 4.38, 8.75, 17.5, 35 mg/ml, respectively. With regards to image quality enhancement, VMCT synthesized by using pseudo DECT shows the best contrast-to-noise ratio at 40 keV. CONCLUSION: In conclusion, the proposed method should be a practicable strategy for iodine quantification in contrast enhanced 120-kVp CT without using specific scanner or scanning procedure.


Assuntos
Iodo , Tomografia Computadorizada por Raios X , Estudos de Viabilidade , Humanos , Imagens de Fantasmas
17.
Cancer Med ; 10(2): 728-736, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33405394

RESUMO

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. However, due to the lack of reliable prognostic biomarkers for PTC, overtreatment has been on the rise. Therefore, our research aims to identify new and promising prognostic biomarkers and provide fresh perspectives for clinical decision making. METHODS: The RNA-seq data and clinical data of PTC samples were obtained from The Cancer Genome Atlas data portal. GSE64912 and GSE83520 datasets were downloaded through the GEOquery R package. The difference in the expression of oxoglutarate dehydrogenase like (OGDHL) between PTC and normal tissues was explored by the Wilcoxon test. Kaplan-Meier (KM) and Cox regression analyses were used to further explore the prognostic value of OGDHL. The tumor microenvironments of PTC patients were explored based on ssGSEA and Tumor Immune Estimation Resource online database. Gene Set Enrichment Analysis (GSEA) was performed to explore the biological processes associated with OGDHL. RESULTS: The expression level of OGDHL in PTC was significantly altered compared to that in normal tissues (p < 0.05). Various biological processes associated with OGDHL were also explored through GSEA. KM analysis suggested that the low-OGDHL group had a better overall survival [OS, p = 3.49e-03, hazard ratio (HR) = 4.567]. The receiver operating characteristic curve also indicated the favorable prognostic potential of OGDHL. Moreover, OGDHL was proved to be an independent prognostic indicator in Cox analysis (p = 1.33e-02, HR = 0.152). In the analysis of the tumor microenvironment, the low-OGDHL group showed a lower immune score and stromal score, while tumor purity was higher. The expression of OGDHL was also closely correlated with the infiltration of immune cells. CONCLUSION: Our study elucidated the influence of OGDHL on the prognosis of PTC and demonstrated its potential as a novel biomarker, which would provide new insights into the prognosis monitoring and clinical decision making in PTC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Complexo Cetoglutarato Desidrogenase/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Microambiente Tumoral/imunologia , Estudos de Casos e Controles , Biologia Computacional , Seguimentos , Humanos , Prognóstico , Curva ROC , Taxa de Sobrevida , Câncer Papilífero da Tireoide/imunologia , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/metabolismo
18.
Front Aging Neurosci ; 12: 239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903858

RESUMO

The current study compared attention profiles and functional connectivity of frontal regions in patients with early-stage subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD). Twenty patients with SIVD, 32 patients with AD, and 23 subjects with normal cognition (NC) received cognition and resting-state functional MRI (rs-fMRI) evaluations. The Cognitive Abilities Screening Instrument (CASI) was used to assess global cognition, and simple attention, processing speed, divided attention, and vigilance/sustained attention were evaluated using the Digit Span Forward, Trail Making Test, Symbol Digit Modality Test, and Conners Continuous Performance Test, respectively. Voxel-based regional homogeneity (ReHo) derived from rs-fMRI data was analyzed to identify significant clusters, which were further correlated with attention profiles. Although the patients with SIVD and AD had comparable global cognitive ability, those with SIVD exhibited worse divided attention and vigilance/sustained attention than those with AD. Compared with the NC group, the patients with SIVD exhibited decreased ReHo within the right middle frontal gyrus (MFG) and left anterior cingulate gyrus (ACG), whereas the patients with AD exhibited increased ReHo within the right orbital part of frontal regions. Correlations between these three clusters with attention exhibited distinct patterns according to the dementia subtype, as did attention indices with significance in predicting global cognition. In summary, our study suggested that worse attention performance was associated with functional disconnection within the frontal regions among patients with SIVD than in those with AD. Frontal functional disconnection may underlie the pathogenesis responsible for defective divided attention, vigilance/sustained attention, and notable within-group variations identified in SIVD.

19.
Dement Geriatr Cogn Disord ; 47(4-6): 375-384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31466053

RESUMO

BACKGROUND: An increasing number of studies suggest the importance of prospective memory (ProM) due to its functional relevance and sensitivity to neuropathology. However, its relevant neural substrates have not been sufficiently explored. OBJECTIVES: The present study aimed to investigate the relationship between structural connectivity and both objective and subjective ProM measures in a group of non-demented people with subjective memory complaints, and to examine the potential of ProM measures to detect the difference between subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in the pre-dementia stage. METHOD: Thirty-sevennon-dementedparticipants aged above 50 years were recruited from an outpatient Neurology Clinic; 13 of them fulfilled the criteria of MCI and 24 of SCD. All subjects received comprehensive neuropsychological tests, including the adapted version of the Cambridge Prospective Memory Test, as well as the Taiwan version of the Prospective and Retrospective Memory Questionnaire. The diffusion tensor imaging technique with tract-based spatial statistics was applied to measure cerebral microstructural changes. RESULTS: Time-based ProM performance was significantly correlated with microstructural integrity of the right superior longitudinal fasciculus, while the event-based one was associated with that of the left superior longitudinal fasciculus and the genu of the corpus callosum among all participants and in the SCD group. After controlling for age, the correlation remained significant between event-based ProM performance and the left superior longitudinal fasciculus among all participants and in the MCI group, as well as between event-based ProM performance and the genu among all participants. Although self-reported ProM failures in real life was associated with fiber disruption of the left superior longitudinal fasciculus among all participants and within the MCI group, an inverse relationship was also observed with that of the corpus callosum in the SCD group even after controlling for age. As compared to the SCD group, people with MCI performed significantly worse on time-based ProM tasks and reported more ProM failures in daily life. CONCLUSIONS: ProM was related to the integrity of interhemispheric commissural fibers and association fibers that connect the frontal lobe with posterior regions, with a task-specific laterality effect. Time-based ProM tasks and self-reported ProM questionnaire may be sensitive to early pathological cognitive deterioration, while the concomitant aging process and individual awareness level may respectively confound the results of evaluation.


Assuntos
Lateralidade Funcional , Transtornos da Memória/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Corpo Caloso/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Fibras Nervosas , Testes Neuropsicológicos , Estudos Retrospectivos , Inquéritos e Questionários , Taiwan
20.
Braz J Med Biol Res ; 52(7): e8222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291381

RESUMO

Monoclonal gammopathy of renal significance (MGRS) can present with different morphologic features and lead to kidney failure. The Henoch-Schönlein purpura nephritis (HSPN) that cannot be relieved by treatment with glucocorticoid and immunosuppressive agents suggests the presence of monoclonal gammopathy in adult patients. The present study reports on a single case of HSPN associated with IgA-κMGRS. The patient who suffered from recurrent skin purpura for 6 months and nephrotic syndrome for 2 months was admitted to our hospital. Bone marrow biopsy showed monoclonal gammopathy of undetermined significance. Kidney biopsy indicated a Henoch-Schönlein purpura nephritis (HSPN, ISKDC classified as type III) with positive staining with κ-light chain in the glomeruli and renal tubular epithelial cells. Furthermore, skin biopsy showed leukocytoclastic vasculitis and negative staining for Congo red and light chain. Given both the renal and cutaneous involvement, the patient was considered to have HSPN associated with IgA-κMGRS. The patient experienced an exacerbation in his purpura-like lesions and clinical status after treatment with glucocorticoid and immunosuppressive agents. Consequently, the patient was put on a regimen that included dexamethasone (20 mg on the 1st, 4th, 8th, and 11th days of each month, iv) and bortezomib (2.4 mg on the 1st, 4th, 8th, and 11th days of each month, iv). Eight weeks after treatment, he had complete resolution of his cutaneous purpura and his biochemical parameters improved. The latent presence of MGRS in cases of HSPN should be considered in adult patients. Increased cognizance and correct treatment options could improve patient outcomes.


Assuntos
Vasculite por IgA/complicações , Nefrite/complicações , Paraproteinemias/etiologia , Glucocorticoides/administração & dosagem , Humanos , Vasculite por IgA/tratamento farmacológico , Vasculite por IgA/patologia , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nefrite/tratamento farmacológico , Nefrite/patologia , Paraproteinemias/tratamento farmacológico , Paraproteinemias/patologia
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