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1.
Eur J Med Res ; 29(1): 262, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698484

RESUMO

OBJECTIVES: Pituitary abscess (PA) accounts for only 0.3-0.5% of sellar masses, and the lack of specific clinical symptoms makes diagnosing PA difficult without a surgical biopsy. In clinical practice, PA is often mistaken for cystic pituitary adenoma, craniopharyngioma, and Rathke's cyst. Thus, this study aims to investigate challenges in diagnosing PA and evaluate the importance of combining intraoperative surgery with postoperative antibiotic treatment. METHODS: We conducted a retrospective analysis of 19 patients diagnosed with PA through histopathology. All patients underwent transsphenoidal surgery (TSS) for pituitary adenomas after undergoing comprehensive preoperative evaluations, including routine tests, endocrine assay, and imaging examination. Furthermore, we compared different treatments for pituitary abscess (PA) to determine the most effective approach for achieving a favorable prognosis. RESULTS: The most prevalent symptom of PA was headache, especially in the frontal-temporal and vertex regions, ranging from mild to moderate severity. Hypopituitarism-related symptoms were also frequently observed, including hypaphrodisia, cold sensitivity, fatigue, weight loss, polyuria, and amenorrhea. Twelve patients exhibited abnormalities in endocrinology examinations. Diagnosing PA correctly is challenging. In our study, none of the patients were correctly diagnosed with PA prior to surgery, and many sellar lesions were misdiagnosed. The favorable prognosis was largely attributed to surgical intervention and active postoperative antibiotic therapy. CONCLUSIONS: Given the lack of clarity in preoperative diagnosis, typical intraoperative findings and effective antibiotics treatment are more indicative of the correct diagnosis than other tests. In terms of therapy, optimal surgical intervention and active postoperative antibiotic treatment contribute to resolving the challenges posed by PA.


Assuntos
Doenças da Hipófise , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/cirurgia , Doenças da Hipófise/terapia , Idoso , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/terapia , Neoplasias Hipofisárias/patologia , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/terapia , Abscesso/diagnóstico , Abscesso/terapia , Antibacterianos/uso terapêutico
2.
Heliyon ; 10(7): e28957, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601682

RESUMO

Background: Cushing disease (CD) is a rare clinical neuroendocrine disease. CD is characterized by abnormal hypercortisolism induced by a pituitary adenoma with the secretion of adrenocorticotropic hormone. Individuals with CD usually exhibit atrophy of gray matter volume. However, little is known about the alterations in topographical organization of individuals with CD. This study aimed to investigate the structural covariance networks of individuals with CD based on the gray matter volume using graph theory analysis. Methods: High-resolution T1-weighted images of 61 individuals with CD and 53 healthy controls were obtained. Gray matter volume was estimated and the structural covariance network was analyzed using graph theory. Network properties such as hubs of all participants were calculated based on degree centrality. Results: No significant differences were observed between individuals with CD and healthy controls in terms of age, gender, and education level. The small-world features were conserved in individuals with CD but were higher than those in healthy controls. The individuals with CD showed higher global efficiency and modularity, suggesting higher integration and segregation as compared to healthy controls. The hub nodes of the individuals with CD were Short insular gyri (G_insular_short_L), Anterior part of the cingulate gyrus and sulcus (G_and_S_cingul-Ant_R), and Superior frontal gyrus (G_front_sup_R). Conclusions: Significant differences in the structural covariance network of patients with CD were found based on graph theory. These findings might help understanding the pathogenesis of individuals with CD and provide insight into the pathogenesis of this CD.

3.
Theriogenology ; 219: 147-156, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38430799

RESUMO

The supplementation of sperm culture media with serum is quite common, and improves both sperm survival and motility. However, the link between serum and sperm remains poorly understood. The present study is the first investigation of the effects on sperm quality and function of endogenous porcine serum exosomes in medium used for culturing boar sperm. Scanning electron microscopy (SEM) confirmed that serum-derived exosomes from both castrated boars (cbsExos) and sows (ssExos) exhibited typical nanostructural morphology and expressed CD63, CD9, and Alix, as shown by Western blotting. At 17 °C, the progressive motility and membrane integrity of sperm were significantly increased after incubation of fresh boar semen for 7 days with cbsExos-4 (8 × 1010 particles/mL) or ssExos-16 (32 × 1010 particles/mL). Moreover, cbsExos-4 and ssExos-16 were found to be effective sperm additives, improving mitochondrial transmembrane potential (ΔΨm) and adenosine triphosphate (ATP) content, total antioxidant activity (T-AOC), superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity while reducing reactive oxygen species (ROS) levels, and malondialdehyde (MDA) content following preservation at 17 °C after a 5-day incubation. Both fluorescence and SEM showed that the serum exosomes bound directly to the sperm membrane, suggesting an interaction that could influence sperm-zona pellucida binding. Overall, this study provides new insights into the potential benefits of adding cbsExos and ssExos to enhance the quality of boar sperm during ambient temperature preservation, which may lead to advancements in sperm preservation strategies.


Assuntos
Exossomos , Preservação do Sêmen , Suínos , Animais , Masculino , Feminino , Sêmen/metabolismo , Exossomos/metabolismo , Motilidade dos Espermatozoides , Espermatozoides/metabolismo , Análise do Sêmen/veterinária , Preservação do Sêmen/veterinária , Antioxidantes/metabolismo
4.
Acta Neurochir (Wien) ; 166(1): 68, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319454

RESUMO

BACKGROUND: Schwannomas are the most common intrathoracic neurogenic tumors. In the past, they were often treated by traditional open surgery. Video-assisted thoracic surgery (VATS) has also been used for some large tumors. Recently, minimally invasive posterior neurosurgical technique provides a new option for some of these tumors. METHOD: Here, we describe the specific steps involved in the O-arm guided minimally invasive removal of intrathoracic epidural schwannoma, as well as its advantages and limitations. CONCLUSION: O-arm guided minimally invasive resection of intrathoracic epidural schwannoma is safe and effective and causes little damage.


Assuntos
Neurilemoma , Cirurgia Assistida por Computador , Humanos , Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Procedimentos Neurocirúrgicos
5.
Nat Commun ; 14(1): 8257, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38086851

RESUMO

Accurate navigation and targeting are critical for neurological interventions including biopsy and deep brain stimulation. Real-time image guidance further improves surgical planning and MRI is ideally suited for both pre- and intra-operative imaging. However, balancing spatial and temporal resolution is a major challenge for real-time interventional MRI (i-MRI). Here, we proposed a deep unrolled neural network, dubbed as LSFP-Net, for real-time i-MRI reconstruction. By integrating LSFP-Net and a custom-designed, MR-compatible interventional device into a 3 T MRI scanner, a real-time MRI-guided brain intervention system is proposed. The performance of the system was evaluated using phantom and cadaver studies. 2D/3D real-time i-MRI was achieved with temporal resolutions of 80/732.8 ms, latencies of 0.4/3.66 s including data communication, processing and reconstruction time, and in-plane spatial resolution of 1 × 1 mm2. The results demonstrated that the proposed method enables real-time monitoring of the remote-controlled brain intervention, and showed the potential to be readily integrated into diagnostic scanners for image-guided neurosurgery.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Biópsia , Procedimentos Neurocirúrgicos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos
6.
J Craniofac Surg ; 34(5): 1448-1451, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37410572

RESUMO

OBJECTIVE: Adrenocorticotrophic hormone excessive secretion in pituitary-dependent Cushing disease (CD) patients may lead to anatomic variations of the nasal-sphenoidal corridor as a result of hormone-induced abnormal soft tissue change. However, there is still a lack of data on anatomic dimensions in CD patients. In this study, magnetic resonance images were analyzed to determine the anatomic variations of the nasal cavity and sphenoid sinus in CD patients. METHODS: A retrospective radiographic analysis was conducted on CD patients undergoing endonasal transsphenoidal surgery as primary treatment between January 2013 and December 2017. A total of 97 CD patients and 100 controls were included. The nasal and sphenoidal anatomic dimensions of CD patients were compared with the control group. RESULTS: Both sides of nasal cavity height, middle nasal meatus width, and inferior nasal meatus width in CD patients were narrower than that of controls. When compared with controls, the ratio of the middle turbinate to middle nasal meatus and the ratio of inferior turbinate to inferior nasal meatus was found to increase on both sides in CD patients. Intercarotid distance of CD patients was shorter than that of controls. The most prevalent pneumatization pattern of CD patients was postsellar, followed by sellar, presellar, and conchal. CONCLUSIONS: Cushing disease patients have nasal and sphenoidal anatomic variations affecting the endonasal transsphenoidal surgical corridor, especially the shorter intercarotid distance. The neurosurgeon should be aware of these anatomic variations, and adapt surgical techniques and optimal approaches to reach the sella safely.


Assuntos
Hipersecreção Hipofisária de ACTH , Sela Túrcica , Humanos , Sela Túrcica/diagnóstico por imagem , Sela Túrcica/cirurgia , Estudos Retrospectivos , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/cirurgia , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/cirurgia , Conchas Nasais , Seio Esfenoidal/diagnóstico por imagem , Seio Esfenoidal/cirurgia
7.
J Clin Med ; 11(22)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36431325

RESUMO

PURPOSE: Transsphenoidal surgery is the first-line treatment for Cushing's disease (CD), even with negative preoperative magnetic resonance imaging (MRI) results. Some patients with persistent or recurring hypercortisolism have negative MRI findings after the initial surgery. We aimed to analyze the efficacy of repeat surgery in two groups of patients and determine if there is an association between positive MRI findings and early remission. PATIENTS AND METHODS: Clinical, imaging, and biochemical information of 42 patients who underwent repeat surgery by a single neurosurgeon between 2002 and 2021 was retrospectively analyzed. We compared the endocrinological, histopathological, and surgical outcomes before and after repeat surgery among 14 CD patients with negative MRI findings and 28 patients with positive MRI findings. RESULTS: Immediate remission was achieved in 29 patients (69.0%) who underwent repeat surgery. Among all patients, 28 (66.7%) had MRI findings consistent with solid lesions. There was no significant difference in remission rates between the recurrence and persistence groups (77.8% vs. 57.1%, odds ratio = 2.625, 95% confidence interval = 0.651 to 10.586). Patients in remission after repeat surgery were not associated with positive MRI findings (odds ratio = 3.667, 95% confidence interval = 0.920 to 14.622). CONCLUSIONS: In terms of recurrence, repeat surgery in patients with either positive or negative MRI findings showed reasonable remission rates. For persistent disease with positive MRI findings, repeat surgery is still an option; however, more solid evidence is needed to determine if negative MRI findings are predictors for failed reoperations for persistent hypercortisolism.

8.
Clin Endocrinol (Oxf) ; 97(1): 81-90, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35170794

RESUMO

OBJECTIVES: Cushing's disease (CD) is most common endogenous Cushing's syndrome. This study aimed to assess iron alternations in deep grey matter in CD. DESIGN: A cross-sectional study was performed. PATIENTS: In this study, 48 active CD patients, 39 remitted CD patients and 52 healthy control (HC) subjects underwent magnetic resonance imaging. MEASUREMENTS: Quantitative susceptibility mapping (QSM). RESULTS: Decreased susceptibility values were found in the bilateral putamen, caudate, red nucleus, subthalamic nucleus and pulvinar nuclei of the thalamus (TL-PLV) in active and remitted patients with CD compared with HCs. Interestingly, in remitted patients with CD, altered susceptibility values were significantly correlated with altered brain volumes in TL-PLV, while TL-PLV may play an essential role as a general regulatory hub for adaptive and flexible cognition. CONCLUSION: Chronic exposure to hypercortisolism may be related to iron distribution and significantly correlated with altered brain volumes and clinical features in patients with CD.


Assuntos
Síndrome de Cushing , Hipersecreção Hipofisária de ACTH , Estudos Transversais , Síndrome de Cushing/patologia , Humanos , Ferro , Imageamento por Ressonância Magnética/métodos , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/patologia
9.
Front Neurol ; 12: 680375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621232

RESUMO

Objective: This study reviews our experiences in surgical clipping of previously coiled aneurysms, emphasizing on recurrence mechanism of intracranial aneurysms (IAs) and surgical techniques for different types of recurrent IAs. Method: We performed a retrospective study on 12 patients who underwent surgical clipping of aneurysms following endovascular treatment between January 2010 and October 2020. The indications for surgery, surgical techniques, and clinical outcomes were analyzed. Result: Twelve patients with previously coiled IAs were treated with clipping in this study, including nine females and three males. The reasons for the patients having clipping were as follows: early surgery (treatment failure in two patients, postoperative early rebleeding in one patient, and intraprocedural aneurysm rupture during embolization in one patient) and late surgery (aneurysm recurrence in five patients, SAH in one, mass effect in one, and aneurysm regrowth in one). All aneurysms were clipped directly, and coil removal was performed in four patients. One patient died (surgical mortality, 8.3%), 1 patient (8.3%) experienced permanent neurological morbidity, and the remaining 10 patients (83.4%) had good outcomes. Based on our clinical data and previous studies, we classified the recurrence mechanism of IAs into coil compaction, regrowth, coil migration, and coil loosening. Then, we elaborated the specific surgical planning and timing of surgery depending on the recurrence type of IAs. Conclusion: Surgical clipping can be a safe and effective treatment strategy for the management of recurrent coiled IAs, with acceptable morbidity and mortality in properly selected cases. Our classification of recurrent coiled aneurysms into four types helps to assess the optimal surgical approach and the associated risks in managing them.

10.
J Cancer ; 12(7): 2083-2091, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754007

RESUMO

Objective: To identify critical roles played by NEK2 in prolactinomas and to clarify the corresponding underlying mechanisms. Methods: We performed RNA-seq on MMQ cell lines treated with the dopamine receptor agonist cabergoline (CAB) to identify genes involved in prolactinoma progression and dopamine receptor-agonist (DA) sensitivity. NEK2 was then selected for further study. The expression of NEK2 was examined using quantitative real-time PCR, western immunoblotting, and immunohistochemistry - both in pituitary adenomas (PA) and in normal pituitary tissue. We used gain-of-function and loss-of-function assays to explore the biologic roles of NEK2 in cell growth in vivo and in vitro. Co-immunoprecipitation was also used to detect the binding between NEK2 and USP7. Results: Herein, we reported that NEK2 was upregulated in prolactinomas, particularly dopamine-resistant prolactinomas. NEK2 overexpression significantly promoted pituitary tumor GH3 and MMQ cell proliferation, and it impaired cellular sensitivity to CAB. Conversely, knockdown of NEK2 inhibited GH3 and MMQ cell growth, and sensitized the cells to CAB. Mechanistically, NEK2 regulated cell proliferation via the Wnt-signaling pathway; and in addition, we demonstrated that USP7 interacted with, deubiquitylated, and stabilized NEK2. Conclusions: Collectively, our results suggest that NEK2 might be a potential therapeutic target for prolactinoma.

11.
Eur J Endocrinol ; 184(4): 565-574, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33730688

RESUMO

DESIGN: Cushing's disease (CD) is a rare clinical syndrome characterized by chronic exposure to hypercortisolism due to an adrenocorticotropic hormone-secreting pituitary adenoma. The adverse effects of chronic exposure to hypercortisolism on the human brain remain unclear. The purpose of this study was to assess the prevalence of cerebral microbleeds (CMBs) in CD patients and their associations with clinical characteristics. METHODS: In this study, 48 active CD patients, 39 remitted CD patients, and 52 healthy control (HC) subjects underwent MRI. CD patients also underwent neuropsychological testing and clinical examinations. The number, locations, and volumes of CMBs were assessed on quantitative susceptibility mapping (QSM) images and with the Microbleed Anatomical Rating Scale. The correlation between CMBs and clinical characteristics was explored. RESULTS: The prevalence of CMBs among active and remitted CD patients was higher than that among HCs (16.3%, 20.5%, and 3.3%, respectively). Moreover, the age of CD patients with CMBs were much younger than HCs with CMBs. Furthermore, the increased number of CMBs in active CD patients was associated with increased cerebrospinal fluid (CSF) volumes in remitted CD patients. CONCLUSIONS: Chronic exposure to hypercortisolism may be relevant to CMBs and significantly correlated with altered brain volumes in CD.


Assuntos
Encéfalo/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Imageamento por Ressonância Magnética/métodos , Hipersecreção Hipofisária de ACTH/complicações , Adulto , Idoso , Encéfalo/patologia , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/patologia , Estudos Transversais , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/patologia , Suscetibilidade a Doenças/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/epidemiologia , Hipersecreção Hipofisária de ACTH/patologia , Prevalência
12.
Front Hum Neurosci ; 15: 604433, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613209

RESUMO

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson's disease (PD). Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively. Results: Pearson's correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R 2 = 0.283, p = 0.016) but not on the non-tremor total score (R 2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R 2' = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R 2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R 2 = 0.290, p = 0.021), but not on the total score (R 2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R 2' = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor. Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response.

13.
World Neurosurg ; 148: e275-e281, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412326

RESUMO

OBJECTIVE: Cushing disease (CD) is a rare clinical disease in which brain structural and function are impaired as the result of excessive cortisol. However, little is known whether rich-club organization changes in patients with CD, as visualized on resting-state magnetic resonance imaging (fMRI), can reverse to normal conditions after transsphenoidal surgery (TSS). In this study, we aimed to investigate whether the functional connectivity of rich-club organization is affected and whether any abnormal changes may reverse after TSS. METHODS: In this study, 38 patients with active CD, 33 with patients with CD in remission, and 41 age-, sex-, and education-matched healthy control participants underwent resting-state fMRI. Brain functional connectivity was constructed based on fMRI and rich club was calculated with graph theory approach. We constructed the functional brain networks for all participants and calculated rich-club connectivity based on fMRI. RESULTS: We identified left precuneus, right precuneus, left middle cingulum, right middle cingulum, right inferior temporal, right middle temporal, right lingual, right postcentral, right middle occipital, and right precentral regions as rich club nodes. Compared with healthy control participants, rich-club connectivity was significantly lower in patients with active CD (P < 0.001). Moreover, abnormal rich-club connectivity improved to normal after TSS. CONCLUSIONS: Our results show rich-club organization was disrupted in patients with active CD with excessive cortisol production. TSS can reverse abnormal rich-club connectivity. Rich club may be a new indicator to investigate the outcomes of TSS and to increase our understanding of the effect of excessive cortisol on brain functional connectivity in patients with CD.


Assuntos
Adenoma Hipofisário Secretor de ACT/cirurgia , Conectoma , Substância Cinzenta/patologia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Neoplasias Hipofisárias/cirurgia , Adenoma Hipofisário Secretor de ACT/complicações , Adolescente , Adulto , Mapeamento Encefálico , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Hidrocortisona/sangue , Hipofisectomia/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Neuroimagem , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/patologia , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/complicações , Indução de Remissão , Osso Esfenoide/cirurgia , Adulto Jovem
14.
J Parkinsons Dis ; 11(1): 199-210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33325395

RESUMO

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been reported to be effective for camptocormia in Parkinson's disease (PD). However, the association between clinical effectiveness and the stimulated volumes or structural connectivity remains unexplored. OBJECTIVE: To investigate the effectiveness of STN-DBS for treating camptocormia in PD and its association with volumes of tissue activated (VTA) and structural connectivity. METHODS: We reviewed video recordings of patients who had undergone STN-DBS. The total and upper camptocormia (TCC and UCC) angles were measured to quantify changes in camptocormia. The Movement Disorders Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) was used to assess motor symptoms. Pre- and postoperative brain images were collected for modeling volume of VTA and structural connectivity using Lead-DBS software. RESULTS: Participants included 36 patients with PD (8 with TCC-camptocormia and 2 with UCC-camptocormia) treated with bilateral STN-DBS. After surgery, patients showed a significant improvement in postural alignment at follow-up (mean follow-up duration: 6.0±2.2 months). In the entire sample, higher structural connectivity to the right supplementary motor area (SMA) and right lateral premotor cortex along the dorsal plane (PMd) was associated with larger postsurgical improvements in axial signs and TCC angles after stimulation was turned on. In patients diagnosed with camptocormia, larger improvement in camptocormia angles after STN-DBS was associated with a larger VTA overlap with STN (R = 0.75, p = 0.032). CONCLUSION: This study suggests that both VTA overlap with STN and structural connectivity to cortical motor regions are associated with the effectiveness of STN-DBS for managing camptocormia in PD.


Assuntos
Estimulação Encefálica Profunda , Córtex Motor/patologia , Atrofia Muscular Espinal/terapia , Rede Nervosa/patologia , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/terapia , Curvaturas da Coluna Vertebral/terapia , Núcleo Subtalâmico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Atrofia Muscular Espinal/etiologia , Atrofia Muscular Espinal/patologia , Atrofia Muscular Espinal/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Índice de Gravidade de Doença , Curvaturas da Coluna Vertebral/etiologia , Curvaturas da Coluna Vertebral/patologia , Curvaturas da Coluna Vertebral/fisiopatologia
15.
Aging (Albany NY) ; 12(22): 22550-22563, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159013

RESUMO

XL388 is a highly efficient and orally-available ATP-competitive PI3K-mTOR dual inhibitor. Its activity against glioma cells was studied here. In established and primary human glioma cells, XL388 potently inhibited cell survival and proliferation as well as cell migration, invasion and cell cycle progression. The dual inhibitor induced significant apoptosis activation in glioma cells. In A172 cells and primary human glioma cells, XL388 inhibited Akt-mTORC1/2 activation by blocking phosphorylation of Akt and S6K1. XL388-induced glioma cell death was only partially attenuated by a constitutively-active mutant Akt1. Furthermore, it was cytotoxic against Akt1-knockout A172 glioma cells. XL388 downregulated MAF bZIP transcription factor G (MAFG) and inhibited Nrf2 signaling, causing oxidative injury in glioma cells. Conversely, antioxidants, n-acetylcysteine, pyrrolidine dithiocarbamate and AGI-106, alleviated XL388-induced cytotoxicity and apoptosis in glioma cells. Oral administration of XL388 inhibited subcutaneous A172 xenograft growth in severe combined immunodeficient mice. Akt-S6K1 inhibition and MAFG downregulation were detected in XL388-treated A172 xenograft tissues. Collectively, XL388 efficiently inhibits human glioma cell growth, through Akt-mTOR-dependent and -independent mechanisms.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Sulfonas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos SCID , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Reprod Fertil Dev ; 32(14): 1212-1222, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33019961

RESUMO

Melatonin (MLT) is an efficient antioxidant that protects spermatozoa against damages caused by oxidative stress. In this study, to maintain good function of Onychostoma macrolepis spermatozoa during semen preservation invitro at 4°C, different concentrations of MLT (0.5, 1 and 2µM) were added to the semen. After storage (0, 24, 48 and 72h), 1µM MLT in semen markedly improved sperm quality, as reflected by better plasma membrane integrity, the relative steady level of reactive oxygen species (ROS) and slower rate of decrease in mitochondrial membrane potential. Activated spermatozoa in semen with 1µM MLT had higher kinematic performance (i.e. percentage of motile and progressive spermatozoa and the beat cross frequency; P<0.05) and longer duration of sperm motility (P<0.05) compared with spermatozoa in semen withother MLT concentrations. Furthermore, 1µM MLT maintained higher ATP concentrations in spermatozoa during semen storage and significantly improved the fertilising capacity of spermatozoa after 72h semen storage compared with the other MLT concentrations. To expand wild resources of O. macrolepis, 1µM MLT can be used as a semen additive to maintain better sperm function and enhance sperm fertilising capacity in artificial insemination (AI).


Assuntos
Trifosfato de Adenosina/metabolismo , Fertilização/efeitos dos fármacos , Melatonina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sêmen/efeitos dos fármacos , Sêmen/metabolismo , Espermatozoides/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Cyprinidae , Masculino , Preservação do Sêmen , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo
17.
Front Cell Dev Biol ; 8: 302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32457903

RESUMO

Intracerebral hemorrhage (ICH) is a particularly severe form of stroke, and reactive astrogliosis is a common response following injury to the central nervous system (CNS). Mesenchymal stem cells (MSCs) are reported to promote neurogenesis and alleviate the late side effects in injured brain regions. Gap junctions (Gjs) are abundant in the brain, where the richest connexin (Cx) is Cx43, most prominently expressed in astrocytes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor regulating antioxidant reactions. Here, we aimed to explore whether bone marrow MSCs (BM-MSCs) could alleviate brain injury and protect astrocytes from apoptosis, by regulating Cx43 and Nrf2. We validated the effect of BM-MSC transplantation in an ICH model in vivo and in vitro and detected changes using immunofluorescence, as well as protein and mRNA expression of glial fibrillary acidic protein (GFAP), vimentin (VIM), Cx43, Nrf2, and heme oxygenase-1 (HO-1). Our results showed that BM-MSC transplantation attenuated brain injury after ICH and upregulated VIM expression in vivo and in vitro. Additionally, Cx43 upregulation and Nrf2 nuclear translocation were observed in astrocytes cocultured with BM-MSC. Knockdown of Cx43 by siRNA restrained Nrf2 nuclear translocation. Cx43 and Nrf2 had a connection as determined by immunofluorescence and coimmunoprecipitation. We demonstrated that astrocytes undergo astroglial-mesenchymal phenotype switching and have anti-apoptotic abilities after BM-MSC transplantation, where Cx43 upregulation triggers Nrf2 nuclear translocation and promotes its phase II enzyme expression. The Cx43/Nrf2 interaction of astrocytes after BM-MSC transplantation may provide an important therapeutic target in the management of ICH.

18.
Front Oncol ; 10: 502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32328466

RESUMO

Chordoid glioma (CG) of the third ventricle is a rare type of brain tumor. Here, we present a case, review of the literature and proposed a treatment strategy for this rare tumor. Here, A 33-years-old woman presented with the menstrual disorder and progressive obesity. Magnetic resonance imaging showed a large irregularly circular tumor in the third ventricle. The tumor was subtotally resected by microsurgery via the right modified port approach. Immunohistochemical staining was positive for glial fibrillary acidic protein (GFAP), Vimentin and transcription termination factor-1 (TTF-1), and the Ki-67 proliferation index was low (5%), which indicating CG. Residual tumor decreased after treated by Gamma Knife radiosurgery (GKRS) with a dose of 15 Gy. During 30 months of follow-up, the tumor did not recur, and the patient suffered no complications. The diagnosis of CG requires a combination of clinical presentation, neuroimaging, and pathology. The ideal therapy is gross total resection (GTR) of the tumor. However, GTR is usually difficult and carries a high risk of postoperative complications because of the tumor location. This case indicates that planed subtotal resection followed by GKRS with a proper marginal dose could be a good treatment strategy for CG.

19.
Aging (Albany NY) ; 12(7): 6306-6323, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32271159

RESUMO

Intracerebral hemorrhage (ICH) is a common acute nervous system disease with high mortality and severe disability. Mesenchymal stem cells (MSCs) have been reported to promote neurogenesis and to alleviate side effects in areas of brain injury areas. The Hippo pathway regulates diverse cellular processes, including cell survival, proliferation, differentiation, and organ size. Here, we found that transplantation of bone marrow MSCs (BM-MSCs) into the brains of mice could alleviate ICH-mediated injury and protect astrocytes from apoptosis by regulating mammalian sterile 20-like kinase (MST)1 and Yes-associated protein (YAP). Knocking down of MST1 by si-RNA triggered YAP nuclear translocation. We further demonstrated that astrocytes undergo astroglial-mesenchymal phenotype switching and become capable of proliferating after BM-MSC transplantation via the Hippo signaling pathway. Together, our identification of the Hippo pathway in mediating the beneficial effects of BM-MSCs may provide a novel therapeutic target in the treatment and management of ICH.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Astrócitos/metabolismo , Lesões Encefálicas , Proteínas de Ciclo Celular/metabolismo , Hemorragia Cerebral/complicações , Transplante de Células-Tronco Mesenquimais/métodos , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Apoptose , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/terapia , Sobrevivência Celular , Modelos Animais de Doenças , Via de Sinalização Hippo , Células-Tronco Mesenquimais , Camundongos , Transdução de Sinais , Resultado do Tratamento , Proteínas de Sinalização YAP
20.
Thyroid ; 30(9): 1236-1244, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32212919

RESUMO

Background: Diagnosis of thyrotropin (TSH)-secreting pituitary adenomas (TSHoma) before surgery remains a challenge, especially for microadenomas. We aimed to establish a short-term somatostatin analogue (SSA) test to differentiate TSHomas from other causes of syndromes of inappropriate secretion of TSH (IST), mainly resistance to thyroid hormone ß (RTHß). Materials and Methods: We first evaluated the sensitivity and specificity of SSA test in a training cohort (TSHoma, n = 32; RTHß, n = 20). The test was then validated in an independent cohort (TSHoma, n = 9; RTHß, n = 2). We finally applied the SSA test in 12 perceptively enrolled IST cases with negative imaging findings and absent thyroid hormone receptor beta (THRB) mutations or mixed hormone imbalances. Results: Both TSHoma and RTHß patients showed a decrease of TSH at the start of the SSA test, but the velocity of the TSH suppression slowly decreased in RTHß patients after 2 hours. The suppression ratio of TSH at 24 hours versus 2 and 0 hours was significantly greater in TSHoma patients compared with RTHß patients (70.58% ± 18.6% vs. 6.01% ± 25.41%, p < 0.0001, 79.83% ± 12.79% vs. 51.16% ± 13.62%, p < 0.0001, respectively). The 24- versus 2-hour suppression ratio showed the best diagnostic accuracy at a cut point of 44.46% in the training cohort, with a sensitivity of 95.00%, a specificity of 93.75%, and a positive predictive value (PPV) of 88.89%. The accuracy was confirmed in the validation cohort. Three out of 12 patients in the prospective cohort showed a TSH suppression ratio greater than 44.46% and all developed microadenomas during follow-up. Conclusions: A short-term SSA test provides an alternative diagnostic approach for TSHomas. A positive SSA test result is suggestive for a TSHoma even before positive findings become apparent on pituitary imaging. However, studies including larger number of patients, especially those with RTHß, are needed to confirm our findings.


Assuntos
Adenoma/diagnóstico , Adenoma/metabolismo , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/metabolismo , Somatostatina/análogos & derivados , Tireotropina/metabolismo , Adolescente , Adulto , Idoso , Área Sob a Curva , Diferenciação Celular , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipófise/metabolismo , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Síndrome da Resistência aos Hormônios Tireóideos/diagnóstico , Adulto Jovem
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