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1.
Mov Disord ; 38(4): 537-544, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36718795

RESUMO

Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by recurrent and transient episodes of involuntary movements, including dystonia, chorea, ballism, or a combination of these, which are typically triggered by sudden voluntary movement. Disturbance of the basal ganglia-thalamo-cortical circuit has long been considered the cause of involuntary movements. Impairment of the gating function of the basal ganglia can cause an aberrant output toward the thalamus, which in turn leads to excessive activation of the cerebral cortex. Structural and functional abnormalities in the basal ganglia, thalamus, and cortex and abnormal connections between these brain regions have been found in patients with PKD. Recent studies have highlighted the role of the cerebellum in PKD. Insufficient suppression from the cerebellar cortex to the deep cerebellar nuclei could lead to overexcitation of the thalamocortical pathway. Therefore, this literature review aims to provide a comprehensive overview of the current research progress to explore the neural circuits and pathogenesis of PKD and promote further understanding and outlook on the pathophysiological mechanism of movement disorders. © 2023 International Parkinson and Movement Disorder Society.


Assuntos
Coreia , Discinesias , Distonia , Transtornos dos Movimentos , Humanos
2.
Mov Disord ; 37(3): 545-552, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34820915

RESUMO

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Coreia , Distonia , Proteínas de Membrana , Adolescente , Criança , Feminino , Humanos , Masculino , Coreia/genética , Distonia/genética , Proteínas de Membrana/metabolismo , Mutação/genética , Fenótipo
3.
Int J Mol Sci ; 23(19)2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36233293

RESUMO

Thyroid cancer remains the most common endocrine malignancy worldwide, and its incidence has steadily increased over the past four years. Papillary Thyroid Cancer (PTC) is the most common differentiated thyroid cancer, accounting for 80-85% of all thyroid cancers. Mitochondrial proteins (MRPs) are an important part of the structural and functional integrity of the mitochondrial ribosomal complex. It has been reported that MRPL9 is highly expressed in liver cancer and promotes cell proliferation and migration, but it has not been reported in PTC. In the present study we found that MRPL9 was highly expressed in PTC tissues and cell lines, and lentivirus-mediated overexpression of MRPL9 promoted the proliferation and migration ability of PTC cells, whereas knockdown of MRPL9 had the opposite effect. The interaction between MRPL9 and GGCT (γ-glutamylcyclotransferase) was found by immunofluorescence and co-immunoprecipitation experiments (Co-IP). In addition, GGCT is highly expressed in PTC tissues and cell lines, and knockdown of GGCT/MRPL9 in vivo inhibited the growth of subcutaneous xenografts in nude mice and inhibited the formation of lung metastases. Mechanistically, we found that knockdown of GGCT/MRPL9 inhibited the MAPK/ERK signaling pathway. In conclusion, our study found that the interaction of GGCT and MRPL9 modulates the MAPK/ERK pathway, affecting the proliferation and migration of PTC cells. Therefore, GGCT/MRPL9 may serve as a potential biomarker for PTC monitoring and PTC treatment.


Assuntos
Sistema de Sinalização das MAP Quinases , Neoplasias da Glândula Tireoide , gama-Glutamilciclotransferase , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , gama-Glutamilciclotransferase/genética
4.
J Sep Sci ; 44(5): 992-1004, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33352011

RESUMO

The Lilium lancifolium Thunb. is a herb with multiple functions in both medicine and food in China, and its extracts have shown antidepressant effects. In this study, fresh bulbs of Lilium lancifolium Thunb. were processed to study the effects of different drying processes on changes in its main chemical components. We found that different drying methods can affect the chemical constituents of the herb. Among these components, Regaloside A has been found as the characteristic component. Here, Cell Counting Kit-8 assay, and Western blotting were used to evaluate the neuroprotective antidepressant effects of Regaloside A. The results showed the cell survival rate was improved, the phosphorylation levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphatidylinositol 3 kinase, protein kinase B, and mammalian target of rapamycin were increased after Regaloside A treatment. In general, different drying methods have a significant influence on the chemical composition of the herb, and Regaloside A may be the main chemical component of the herb. It can alleviate the damage of corticosterone in SH-SY5Y cells, and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling mediated by brain-derived neurotrophic factor/tyrosine kinase receptor B may play an important role in the neuroprotective antidepressant effects of Regaloside A.


Assuntos
Antidepressivos/farmacologia , Dessecação , Lilium/química , Extratos Vegetais/farmacologia , Antidepressivos/química , Antidepressivos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Corticosterona , Humanos , Espectrometria de Massas , Simulação de Acoplamento Molecular , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células Tumorais Cultivadas
5.
Andrologia ; 53(6): e14056, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33763906

RESUMO

Germplasm cryopreservation and expansion of gonocytes/prospermatogonia or spermatogonial stem cells (SSCs) are important; however, it's difficult in cattle. Since inhibitors of Mek1/2 and Gsk3ß (2i) can enhance pluripotency maintenance, effects of 2i-based medium on the cultivation of bovine prospermatogonia from the cryopreserved tissues were examined. The testicular tissues of newborn bulls were well cryopreserved. High mRNA levels of prospermatogonium/SSC markers (PLZF, GFRα-1) and pluripotency markers (Oct4/Pouf5, Sox2, Nanog) were detected and the PLZF+ /GFRα-1+ prospermatogonia were consistently identified immunohistochemically in the seminiferous cords. Using differential plating and Percoll-based centrifugation, 41.59% prospermatogonia were enriched and they proliferated robustly in 2i medium. The 2i medium boosted mRNA abundances of Pouf5, Sox2, Nanog, GFRα-1, PLZF, anti-apoptosis gene Bcl2, LIF receptor gene LIFR and enhanced PLZF protein expression, but suppressed mRNA expressions of spermatogonial differentiation marker c-kit and pro-apoptotic gene Bax, in the cultured prospermatogonia. It also alleviated H2 O2 -induced apoptosis of the enriched cells and decreased histone H3 lysine (K9) trimethylation (H3K9me3) and its methylase Suv39h1/2 mRNA level in the cultured seminiferous cords. Overall, 2i medium improves the cultivation of bovine prospermatogonia isolated from the cryopreserved testes, by inhibiting Suv39h1/2-mediated H3K9me3 through Mek1/2 and Gsk3ß signalling, evidencing successful cryopreservation and expansion of bovine germplasm.


Assuntos
Células-Tronco Germinativas Adultas , Espermatogônias , Animais , Bovinos , Criopreservação , Meios de Cultura , Masculino , Testículo
6.
BMC Genomics ; 20(1): 743, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615399

RESUMO

BACKGROUND: The distribution and deposition of fat tissue in different parts of the body are the key factors affecting the carcass quality and meat flavour of chickens. Intramuscular fat (IMF) content is an important factor associated with meat quality, while abdominal fat (AbF) is regarded as one of the main factors affecting poultry slaughter efficiency. To investigate the differentially expressed genes (DEGs) and molecular regulatory mechanisms related to adipogenic differentiation between IMF- and AbF-derived preadipocytes, we analysed the mRNA expression profiles in preadipocytes (0d, Pre-) and adipocytes (10d, Ad-) from IMF and AbF of Gushi chickens. RESULTS: AbF-derived preadipocytes exhibited a higher adipogenic differentiation ability (96.4% + 0.6) than IMF-derived preadipocytes (86.0% + 0.4) (p < 0.01). By Ribo-Zero RNA sequencing, we obtained 4403 (2055 upregulated and 2348 downregulated) and 4693 (2797 upregulated and 1896 downregulated) DEGs between preadipocytes and adipocytes in the IMF and Ad groups, respectively. For IMF-derived preadipocyte differentiation, pathways related to the PPAR signalling pathway, ECM-receptor interaction and focal adhesion pathway were significantly enriched. For AbF-derived preadipocyte differentiation, the steroid biosynthesis pathways, calcium signaling pathway and ECM-receptor interaction pathway were significantly enriched. A large number of DEGs related to lipid metabolism, fatty acid metabolism and preadipocyte differentiation, such as PPARG, ACSBG2, FABP4, FASN, APOA1 and INSIG1, were identified in our study. CONCLUSION: This study revealed large transcriptomic differences between IMF- and AbF-derived preadipocyte differentiation. A large number of DEGs and transcription factors that were closely related to fatty acid metabolism, lipid metabolism and preadipocyte differentiation were identified in the present study. Additionally, the microenvironment of IMF- and AbF-derived preadipocyte may play a significant role in adipogenic differentiation. This study provides valuable evidence to understand the molecular mechanisms underlying adipogenesis and fat deposition in chickens.


Assuntos
Gordura Abdominal/citologia , Adipogenia , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Músculos/citologia , Gordura Abdominal/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Diferenciação Celular , Galinhas , Metabolismo dos Lipídeos , Músculos/metabolismo , Análise de Sequência de RNA
7.
Yi Chuan ; 41(2): 125-136, 2019 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-30803943

RESUMO

The vertebrate heart tube originates from cardiogenic mesodermal cells in the early embryo, and subsequently elongates by progressive addition of second heart field (SHF) progenitor cells from adjacent pharyngeal mesoderm and splanchnic mesoderm. Insufficient addition of SHF cells to the heart tube causes the failure of maximal elongation of the heart tube, which results in a series of developmental defects including the most common congenital birth defects, such as right ventricular dysplasia and outflow tract septation, and alignment anomalies. SHF cells form an atypical, apicobasally polarized epithelium which is characterized by apical monocilia, and dynamic actin-rich basal filopodia. In this review, we summarize recent research progresses of actin cytoskeleton in the deployment process of mouse SHF progenitor cells, and reveal the significance of actin cytoskeleton in SHF development, especially in the deployment of SHF cells to the outflow tract, to provide theoretical reference for elucidating and understanding the biological characteristics of SHF deployment.


Assuntos
Citoesqueleto de Actina/fisiologia , Coração/embriologia , Mesoderma/citologia , Miocárdio/citologia , Células-Tronco/citologia , Animais , Camundongos , Organogênese
8.
Anal Chem ; 90(8): 5430-5438, 2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29551058

RESUMO

Single cell proteomic analysis provides crucial information on cellular heterogeneity in biological systems. Herein, we describe a nanoliter-scale oil-air-droplet (OAD) chip for achieving multistep complex sample pretreatment and injection for single cell proteomic analysis in the shotgun mode. By using miniaturized stationary droplet microreaction and manipulation techniques, our system allows all sample pretreatment and injection procedures to be performed in a nanoliter-scale droplet with minimum sample loss and a high sample injection efficiency (>99%), thus substantially increasing the analytical sensitivity for single cell samples. We applied the present system in the proteomic analysis of 100 ± 10, 50 ± 5, 10, and 1 HeLa cell(s), and protein IDs of 1360, 612, 192, and 51 were identified, respectively. The OAD chip-based system was further applied in single mouse oocyte analysis, with 355 protein IDs identified at the single oocyte level, which demonstrated its special advantages of high enrichment of sequence coverage, hydrophobic proteins, and enzymatic digestion efficiency over the traditional in-tube system.


Assuntos
Nanopartículas/química , Óleos/química , Oócitos/química , Peptídeos/análise , Proteômica , Análise de Célula Única , Ar , Animais , Células HeLa , Humanos , Camundongos , Oócitos/citologia , Tamanho da Partícula , Propriedades de Superfície
9.
J Exp Zool B Mol Dev Evol ; 330(8): 406-416, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30460778

RESUMO

Bovine bone marrow mesenchymal stem cells (bBMSC) are potential stem cell source which can be used for multipurpose. However, their application is limited because the in vitro maintenance of these cells is usually accompanied by aging and multipotency losing. Considering transforming growth factor-ß (TGF-ß) pathway inhibitor Repsox is beneficial for cell reprogramming, here we investigated its impacts on the maintenance and differentiation of bBMSC. The bBMSC were enriched and characterized by morphology, immunofluorescent staining, flow cytometry, and multilineage differentiation. The impacts of Repsox on their proliferation, apoptosis, cell cycle, multipotency, and differentiation were examined by Cell Counting Kit-8 (CCK-8), real-time polymerase chain reaction, induced differentiation and specific staining. The results showed that highly purified cluster of diffrentiation 73+ (CD73 + )/CD90 + /CD105 + /CD34 - /CD45 - bBMSC with adipogenic, osteogenic, and chondrogenic differentiation capacities were enriched. Repsox treatments (5 µM, 48 hr) enhanced the messenger RNA mRNA levels of the proliferation gene (telomerase reverse transcriptase [ TERT]; basic fibroblast growth factor [ bFGF]), apoptosis-related gene ( bax and Bcl2), antiapoptosis ratio ( Bcl2/bax), and pluripotency marker gene ( Oct4, Sox2, and Nanog), instead of changing the cell cycle, in bBMSC. Repsox treatments also enhanced the osteogenic differentiation but attenuated the chondrogenic differentiation of bBMSC, concomitant with decreased Smad2 and increased Smad3/4 expressions in TGF-ß pathway. Collectively, inhibiting TGF-ß/Smad signaling by Repsox regulates the in vitro maintenance and differentiation of bBMSC.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/fisiologia , Pirazóis/farmacologia , Piridinas/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Células da Medula Óssea , Bovinos , Diferenciação Celular/efeitos dos fármacos , Condrogênese/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Osteogênese/fisiologia , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Proteína Smad4/genética , Proteína Smad4/metabolismo
10.
Appl Microbiol Biotechnol ; 101(23-24): 8395-8404, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29067484

RESUMO

ChKRED20 is an efficient and robust anti-Prelog ketoreductase that can catalyze the reduction of ketones to chiral alcohols as pharmaceutical intermediates with great industrial potential. To overcome its limitation on the bioreduction of ortho-substituted acetophenone derivatives, the X-ray crystal structure of the apo-enzyme of ChKRED20 was determined at a resolution of 1.85 Å and applied to the molecular modeling and reshaping of the catalytic cavity via three rounds of iterative saturation mutagenesis together with alanine scanning and recombination. The mutant Mut3B was achieved with expanded catalytic scope that covered all the nine substrates tested as compared with two substrates for the wild type. It exhibited 13-20-fold elevated k cat/K m values relative to the wild type or to the first gain-of-activity mutant, while retaining excellent stereoselectivity toward seven of the substrates (98-> 99% ee). Another mutant 29G10 displayed complementary selectivity for eight of the ortho-substituted acetophenone derivatives, with six of them delivering excellent stereoselectivity (90-99% ee). Its k cat/K m value toward 1-(2-fluorophenyl)ethanone was 5.6-fold of the wild type. The application of Mut3B in elevated substrate concentrations of 50-100 g/l was demonstrated in 50-ml reactions, achieving 75-> 99% conversion and > 99% ee.


Assuntos
Chryseobacterium/enzimologia , Cetonas/metabolismo , Mutagênese , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Cristalografia por Raios X , Cinética , Modelos Moleculares , Proteínas Mutantes/química , Oxirredutases/química , Conformação Proteica , Especificidade por Substrato
11.
Acta Neurochir (Wien) ; 159(4): 689-694, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28124740

RESUMO

Trigeminal neuralgia (TN) secondary to arterivenous malformations (AVMs) is relatively rare. We here report on a case of TN caused by cerebellar AVMs that was successfully treated by total AVMs resection in conjunction with microvasecular decompression (MVD) in one stage. In addition, we perform a review of the literature about the treatment of TN caused by cerebellar AVMs.


Assuntos
Cerebelo/cirurgia , Descompressão Cirúrgica/efeitos adversos , Complicações Pós-Operatórias , Neuralgia do Trigêmeo/cirurgia , Artérias/cirurgia , Cerebelo/irrigação sanguínea , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Masculino , Pessoa de Meia-Idade , Neuralgia do Trigêmeo/etiologia
12.
Acta Neurochir (Wien) ; 159(10): 1925-1937, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28766024

RESUMO

BACKGROUND: Intraoperative neurophysiologic monitoring of the extraocular cranial nerve (EOCN) is not commonly performed because of technical difficulty and risk, reliability of the result and predictability of the postoperative function of the EOCN. METHODS: We performed oculomotor nerve (CN III) and abducens nerve (CN VI) intraoperative monitoring in patients with skull base surgery by recording the spontaneous muscle activity (SMA) and compound muscle action potential (CMAP). Two types of needle electrodes of different length were percutaneously inserted into the extraocular muscles with the free-hand technique. We studied the relationships between the SMA and CMAP and postoperative function of CN III and CN VI. RESULTS: A total of 23 patients were included. Nineteen oculomotor nerves and 22 abducens nerves were monitored during surgery, respectively. Neurotonic discharge had a positive predictive value of less than 50% and negative predictive value of more than 80% for postoperative CN III and CN VI dysfunction. The latency of patients with postoperative CN III dysfunction was 2.79 ± 0.13 ms, longer than that with intact CN III function (1.73 ± 0.11 ms). One patient had transient CN VI dysfunction, whose CMAP latency (2.54 ms) was longer than that of intact CN VI function (2.11 ± 0.38 ms). There was no statistically significant difference between patients with paresis and with intact function. CONCLUSIONS: The method of intraoperative monitoring of EOCNs described here is safe and useful to record responses of SMA and CMAP. Neurotonic discharge seems to have limited value in predicting the postoperative function of CN III and CN VI. The onset latency of CMAP longer than 2.5 ms after tumor removal is probably relevant to postoperative CN III and CN VI dysfunction. However, a definite quantitative relationship has not been found between the amplitude and stimulation intensity of CMAP and the postoperative outcome of CN III and CN VI.


Assuntos
Nervo Abducente/cirurgia , Eletromiografia/métodos , Monitorização Neurofisiológica Intraoperatória/métodos , Nervo Oculomotor/cirurgia , Base do Crânio/cirurgia , Nervo Abducente/fisiologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Nervo Oculomotor/fisiologia , Procedimentos Ortopédicos/métodos , Reprodutibilidade dos Testes , Adulto Jovem
13.
Beijing Da Xue Xue Bao Yi Xue Ban ; 46(3): 383-8, 2014 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-24943015

RESUMO

OBJECTIVE: To evaluate the accuracy of parents' perception of whether their child is a picky eater and the specific food category the children avoideating according to the food frequency questionnaire. METHODS: This research selected 1 663 infants aged 4-36 months receiving non-diary complimentary food from maternal, infants, nutrition and growth study (MING Study) in 8 Chinese cities in which a combination of systematic cluster random sampling and purposive sampling was used. The general information, dietary status and picky eating status were collected through a self-designed questionnaire from the caregiver of the children. According to the parents' perception, the children were classified into picky/non-picky groups or avoid/non-avoid to a specific food category groups. Mann-Whitney U test was used to compare between the groups. RESULTS: The reported percentage of picky eaters increased from 7.37% in 4-6 months old infants to 36.20% in 25-36 months old infants. Most picky infants in 4-6 months and 7-12 months old infants avoided eating dairy food (25% and 24%); while most picky toddlers aged 13-24 months and 25-36 months avoided eating vegetables (26.92% and 47.46%). The infants aged 4-6 months and 7-12 months who were perceived as picky by their parents took more kinds of food (8 and 19.5 kinds) than those who were not (6 and 18 kinds), while the picky toddlers aged 13-24 months and 25-36 months took fewer kinds of food (28.5 and 34 kinds for picky eaters, 31 and 37 kinds for non-picky eaters). The parents of infants aged 4-6 months judged correctly in every category of food without any statistical significance; the parents of 7-12 months old infants judged correctly only in dairy food and eggs with statistical significance; those of 13-24 months old infants judged correctly in every food category except for vegetables with statistically significant difference in the category of eggs; those of 25-36 months old toddlers misjudged in dairy, beans and grains with no statistically significant difference in every category. CONCLUSION: Parents tend to misjudge their children's picky eating behavior before the first 12 months of the child, and tend to make a more accurate perception after the 12th month.


Assuntos
Comportamento Infantil , Preferências Alimentares , Pais , Pré-Escolar , Humanos , Lactente , Verduras
14.
Ageing Res Rev ; 99: 102363, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38838785

RESUMO

The basolateral amygdala (BLA) is the subregion of the amygdala located in the medial of the temporal lobe, which is connected with a wide range of brain regions to achieve diverse functions. Recently, an increasing number of studies have focused on the participation of the BLA in many neuropsychiatric disorders from the neural circuit perspective, aided by the rapid development of viral tracing methods and increasingly specific neural modulation technologies. However, how to translate this circuit-level preclinical intervention into clinical treatment using noninvasive or minor invasive manipulations to benefit patients struggling with neuropsychiatric disorders is still an inevitable question to be considered. In this review, we summarized the role of BLA-involved circuits in neuropsychiatric disorders including Alzheimer's disease, perioperative neurocognitive disorders, schizophrenia, anxiety disorders, depressive disorders, posttraumatic stress disorders, autism spectrum disorders, and pain-associative affective states and cognitive dysfunctions. Additionally, we provide insights into future directions and challenges for clinical translation.

15.
World J Diabetes ; 15(6): 1263-1271, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38983812

RESUMO

BACKGROUND: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM). AIM: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels. METHODS: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy. RESULTS: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-ß), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-ß was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control. CONCLUSION: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.

16.
Adv Healthc Mater ; : e2401649, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38938121

RESUMO

Immune checkpoint blockade (ICB) has significantly improved the prognosis of patients with cancer, although the majority of such patients achieve low response rates; consequently, new therapeutic approaches are urgently needed. The upregulation of sialic acid-containing glycans is a common characteristic of cancer-related glycosylation, which drives disease progression and immune escape via numerous pathways. Herein, the development of self-assembled core-shell nanoscale coordination polymer nanoparticles loaded with a sialyltransferase inhibitor, referred to as NCP-STI which effectively stripped diverse sialoglycans from cancer cells, providing an antibody-independent pattern to disrupt the emerging Siglec-sialic acid glyco-immune checkpoint is reported. Furthermore, NCP-STI inhibits sialylation of the concentrated nucleoside transporter 1 (CNT1), promotes the intracellular accumulation of anticancer agent gemcitabine (Gem), and enhances Gem-induced immunogenic cell death (ICD). As a result, the combination of NCP-STI and Gem (NCP-STI/Gem) evokes a robust antitumor immune response and exhibits superior efficacy in restraining the growth of multiple murine tumors and pulmonary metastasis. Collectively, the findings demonstrate a novel form of small molecule-based chemo-immunotherapy approach which features sialic acids blockade that enables cooperative effects of cancer cell chemosensitivity and antitumor immune responses for cancer treatment.

17.
Dalton Trans ; 53(20): 8803-8811, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38716557

RESUMO

Two photochromic Cd(II)-CPs were obtained based on the viologen ligand using different synthetic routes, named {[Cd4(p-BDC)4(CPB)2(H2O)2]·2H2O·EtOH}n (1) and {[Cd(p-BDC)(CPB)(H2O)]·(L)·DMF}n (2) (p-H2BDC = 1,4-benzene-dicarboxylate, HCPB·Cl = 1-(4-carboxyphenyl)-4,4'-bipyridinium·Cl, L = 2,4-dinitrochlorobenzene, and DMF = N,N-dimethylformamide), respectively. Due to different coordination modes, the two Cd(II)-CPs show different structures. Compound 1 exhibits a three-dimensional (3D) framework with bimetallic nodes, while compound 2 displays a 2-fold interpenetrated (4,4) net topology. Notably, the two Cd(II)-CPs exhibit substantial disparities in photo/thermochromism, which can be attributed to variations in donor-acceptor (D-A) distances arising from structural differences. Compound 1 showed visually sensitive photo- and thermochromic behavior due to multi-pathway electron transfer and short D-A distances, which is relatively rare in electron-transfer type photochromic systems. In contrast, 2 only demonstrates insensitive photochromic behavior, with a slight deepening of the color observed after 2 hours of UV light, which is due to the mono-pathway electron transfer and long D-A distance. Moreover, we first combined Cd(II)-viologen CPs with polydimethylsiloxane (PDMS) to prepare a 1@PDMS flexible UV imaging film. 1@PDMS exhibits excellent bendability and stretchability and maintains good photochromic properties after 100 bending cycles. To demonstrate the rapid color response and distinct color contrast of 1, its application in anti-counterfeiting is also demonstrated.

18.
World J Clin Cases ; 12(15): 2568-2577, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38817233

RESUMO

BACKGROUND: The measurement of triceps skinfold (TSF) thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution. Despite its clinical utility, the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated. AIM: To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality. METHODS: This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey. Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness. Subjects were classified into subgroups reflective of their respective TSF thickness trajectory. We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality, including contributory factors. RESULTS: Upon adjustment for multiple confounding factors, we discerned that males in the 'Class 2: Thin-stable' and 'Class 3: Thin-moderate' TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the 'Class 1: Extremely thin' subgroup. In the mediation analyses, the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality. For females, a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort. CONCLUSION: In males and non-elderly females, lower TSF thickness trajectories are significantly predictive of heightened mortality risk, independent of single-point TSF thickness, body mass index, and waist circumference.

19.
Neuropharmacology ; 257: 110032, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852839

RESUMO

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.

20.
J Cancer Res Clin Oncol ; 150(6): 317, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914670

RESUMO

INTRODUCTION: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer. METHODOLOGY: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting. RESULTS: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3'UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression. CONCLUSIONS: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC.


Assuntos
Neoplasias da Mama , Antígeno CD24 , Proliferação de Células , Progressão da Doença , MicroRNAs , RNA Longo não Codificante , Humanos , Antígeno CD24/genética , Antígeno CD24/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , MicroRNAs/genética , Animais , Camundongos , RNA Longo não Codificante/genética , Camundongos Nus , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Movimento Celular/genética , Camundongos Endogâmicos BALB C , Prognóstico
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